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At least 505 records · Page 28Linked to original sources

PubMed2004

Emergence of orientation-selective inhibition in the primary visual cortex: a Bayes-Markov computational model.

The recent consensus is that virtually all aspects of response selectivity exhibited by the primary visual cortex are either created or sharpened by cortical inhibitory interneurons. Experimental studies have shown that there are cortical inhibitory cells that are driven by geniculate cells and that, like their cortical excitatory counterparts, are orientation selective, though less sharply tuned. The main goal of this article is to demonstrate how orientation-selective inhibition might be created by the circuitry of the primary visual cortex (striate cortex, V1) from its nonoriented geniculate inputs. To fulfill this goal, first, a Bayes-Markov computational model is developed for the V1 area dedicated to foveal vision. The developed model consists of three parts: (i) a two-layered hierarchical Markov random field that is assumed to generate the activity patterns of the geniculate and cortical inhibitory cells, (ii) a Bayesian computational goal that is formulated based on the maximum a posteriori (MAP) estimation principle, and (iii) an iterative, deterministic, parallel algorithm that leads the cortical circuitry to achieve its assigned computational goal. The developed model is not fully LGN driven and it is not implementable by the neural machinery of V1. The model, then, is transformed into a fully LGN-driven and physiologically plausible form. Computer simulation is used to demonstrate the performance of the developed models.

Action Potentials↗

PubMed1987

Computer modelling of DNA structures involved in chromosome maintenance.

Sequence-dependent DNA bending of synthetic and natural molecules was studied by computer analysis. Modelling of synthetic oligonucleotides and of 107 kb of natural sequences gave results which closely resembled published electrophoretic data, demonstrating the powerful predictive capacity of the procedure. The analysis was extended to the study of DNA structures involved in chromosome maintenance. Centromeric DNAs from yeast were found to have sequences in their functional elements which cause them to be unusually straight. Autonomous replicating sequences were found to have two structural domains, one consisting of unusually straight sequences surrounding the consensus and the other of bending elements in flanking DNA. In addition to a structural homology, centromeric and autonomous replicating sequences share common sequence elements. These observations show that computer modelling of natural sequences is a viable approach to the study of the biological implications of alternative DNA structures.

Base Sequence↗

PubMed2000

Electrolyte and pH dependence of heart rate during hemodialysis: a computer model analysis.

The influence of hemodialysis-induced modifications in extracellular fluid characteristics on heart rate was investigated by using a detailed computer model of sinus-node electrical activity. Changes similar to those occurring in the course of hemodialysis in extracellular concentrations of sodium (from 138 to 140 mM), potassium (from 6 to 3.3 mM), and calcium (from 1.2 to 1.5 mM) ions as well as in pH (from 7.31 to 7.4) and intracellular volume were simulated. The model predicted that such changes may largely influence the rhythm of the sinoatrial node pacemaker, causing the heart rate to range from 69 to 86 bpm. Heart rate increases after removing potassium (up to 7 bpm) and also after calcium perfusion (up to 11 bpm) whereas restoring pH slows heart beat (up to 6 bpm). Extracellular sodium has no significant influence, but the heart rate strictly depends on intracellular sodium concentration (5 bpm/mM). A complex dependence of heart rate on electrolytes and pH was also recognized. Providing extracellular potassium concentration is maintained above 5 mM, heart rate exhibits low sensitivity to changes in calcium and potassium. When potassium concentration is reduced below 4.5 mM, heart rate sensitivity to calcium and potassium increases significantly to 10 and 30 bpm/mM, respectively. A sustained increase in heart rate always corresponds to an increase in intracellular sodium concentration.

Acetylcholine↗

PubMed1992

Modes of binding of 2'-AMP to RNase T1. A computer modeling study.

The modes of binding of adenosine 2'-monophosphate (2'-AMP) to the enzyme ribonuclease (RNase) T1 were determined by computer modelling studies. The phosphate moiety of 2'-AMP binds at the primary phosphate binding site. However, adenine can occupy two distinct sites--(1) The primary base binding site where the guanine of 2'-GMP binds and (2) The subsite close to the N1 subsite for the base on the 3'-side of guanine in a guanyl dinucleotide. The minimum energy conformers corresponding to the two modes of binding of 2'-AMP to RNase T1 were found to be of nearly the same energy implying that in solution 2'-AMP binds to the enzyme in both modes. The conformation of the inhibitor and the predicted hydrogen bonding scheme for the RNase T1-2'-AMP complex in the second binding mode (S) agrees well with the reported x-ray crystallographic study. The existence of the first mode of binding explains the experimental observations that RNase T1 catalyses the hydrolysis of phosphodiester bonds adjacent to adenosine at high enzyme concentrations. A comparison of the interactions of 2'-AMP and 2'-GMP with RNase T1 reveals that Glu58 and Asn98 at the phosphate binding site and Glu46 at the base binding site preferentially stabilise the enzyme-2'-GMP complex.

Adenosine Monophosphate↗

PubMed2006

Simulation of hemodynamic responses to the valsalva maneuver: an integrative computational model of the cardiovascular system and the autonomic nervous system.

The Valsalva maneuver is a frequently used physiological test in evaluating the cardiovascular autonomic functions in human. Although a large pool of experimental data has provided substantial insights into different aspects of the mechanisms underlying the cardiovascular regulations during the Valsalva maneuver, so far a complete comprehension of these mechanisms and the interactions among them is unavailable. In the present study, a computational model of the cardiovascular system (CVS) and its interaction with the autonomic nervous system (ANS) was developed for the purpose of quantifying the individual roles of the CVS and the ANS in the hemodynamic regulations during the Valsalva maneuver. A detailed computational compartmental parameter model of the global CVS, a system of mathematical equations representing the autonomic nervous reflex regulatory functions, and an empirical cerebral autoregulation (CA) model formed the main body of the present model. Based on simulations of the Valsalva maneuvers at several typical postures, it was demonstrated that hemodynamic responses to the maneuver were not only determined by the ANS-mediated cardiovascular regulations, but also significantly affected by the postural-change-induced hemodynamic alterations preceding the maneuver. Moreover, the large-magnitude overshoot in cerebral perfusion immediately after the Valsalva maneuver was found to result from a combined effect of the circulatory autonomic functions, the CA, and the cerebral venous blood pressure.

Afferent Pathways↗

PubMed1995

A computational model for signal processing by the dorsal cochlear nucleus. II. Responses to broadband and notch noise.

In a previous paper a computational model was developed which was shown to account for most of the essential features of the variety of experimentally observed response maps of type-IV cells in the dorsal cochlear nucleus to pure tones. In the present study, the responses of the same model DCN to broadband noise and notch noise are investigated. It is shown that the previous model qualitatively accounts for the observed responses to these more complex sounds. Predictions of the model for inverted notches and for the behavior of type-IV cell output as notch center is varied for different amplitudes are presented. It is shown that the model is suitable for feature detection of auditory signals and an expansion is given as to how this ability arises from the properties of the stellate, type-II, and type-IV cells and the variations in the connectional patterns that were previously shown to account for the response patterns of type-IV cells to pure tones.

Auditory Perception↗

PubMed1998

The generation of DC potentials in a computational model of the organ of Corti: effects of voltage-dependent K+ channels in the basolateral membrane of the inner hair cell.

A computational model of the organ of Corti is described to assist in the interpretation of electrophysiological data concerning the role of the K+ channels residing in the basolateral membrane of cochlear hair cells. Recent in vivo data from Van Emst et al. (Hear. Res. 88, 27-35 (1995); Hear. Res. 102, 70-80 (1996)) about the effects of selective blocking of K+ channels indicate that these channels affect the magnitude of the summating potential. In order to understand the nature of this effect, the model of Dallos (Hear. Res. 14, 281-291 (1984)) was extended to account for the voltage- and time-dependent properties of the K+ channels in the basolateral membrane of the inner hair cell (IHC) (Kros and Crawford, J. Physiol. 421, 262-291 (1990)). The model shows that the K+ channels induce a shift in the mean IHC basolateral conductance when high-frequency stimuli are present. As a result, cochlear transduction shifts to a different electrical operating state and this is the source of a marked decrease in the stimulus-evoked DC response of the IHC. Extracellularly, in contrast, the magnitude of the DC response increases slightly. At low frequencies, the K+ channels respond to the stimulus waveform on a cycle-by-cycle basis. The waveform distortion associated with this dynamic basolateral impedance induces a further decrease in the intracellular stimulus-evoked DC response of the IHC. Thus, K+ channels in the IHC appear to be directly involved in the generation of the DC receptor potential at low frequencies, but at high frequencies they simply modify the size of the DC response.

Acoustic Stimulation↗

PubMed2004

A computational model for the development of multiple maps in primary visual cortex.

Primary visual cortex contains multiple maps of features of the visual scene, including visual field position, orientation, direction, ocular dominance and spatial frequency. The complex relationships between these maps provide clues to the strategies the cortex uses for representing and processing information. Here we simulate the combined development of all these map systems using a computational model, the elastic net. We show that this model robustly produces combined maps of these four variables that bear a close resemblance to experimental maps. In addition we show that the experimentally observed effects of monocular deprivation and single-orientation rearing can be reproduced in this model, and we make some testable predictions. These results provide strong support for the hypothesis that cortical representations attempt to optimize a trade-off between coverage and continuity.

Brain Mapping↗

PubMed1992

Computer modeling of pole formation in cell division.

The regular position of spindle poles in bi- and multipolar cell divisions is interpreted as the result of expanding caps on the surface of cell nuclei first proposed by Mazia in 1986. In a computer model it is shown that expanding caps position their centers with the maximal distance between them, which is in complete accordance with findings in experimentally influenced cell divisions in which multiple poles are formed.

Cell Division↗

PubMed1990

Plaque fluid and diffusion: study of the cariogenic challenge by computer modeling.

Every cariogenic challenge involves a mixture of convective transport, diffusive transport, and biochemical reactions, plus physico-chemical reactions (including charge-coupling of diffusion), all of which together require numerical methods for their analysis. This presentation describes a one-dimensional finite-difference computer model of the cariogenic process, and some conclusions obtained from it. Sugar clearance from the mouth, together with site-dependent exchange between the bulk saliva and plaque surface via a salivary film, is combined with a finite-difference model of events occurring within the dental plaque. The latter includes: sugar diffusion and pH-dependent acid production; diffusion and dissociation equilibria for two acid end-products of fermentation and their anions (acetate and lactate); diffusion and dissociation equilibria of phosphate buffer; diffusion of potassium and chloride; diffusion of protons and simultaneous equilibration with fixed and mobile buffers. So that proper concentration distributions consistent with local charge neutrality can be ensured, an algorithm called Q-couple is used to impose charge-coupling between the fluxes of different ions including fixed charges. Mineral dissolution and precipitation are modeled as part of the same equilibrium calculations. The predictions of the model are compared with those of an earlier, much simpler one, in which fixed buffers were not included. It is shown that the known concentration of fixed buffer greatly extends the low pH of a Stephan curve. The isoelectric point of the plaque bacteria also appears to be of importance. The effects of various concentrations of mobile buffers, including acetate, are investigated. It is also shown that varying plaque/saliva contact over the known range derived from published studies has a profound effect on the modeled cariogenic challenge.

Computer Simulation↗

PubMed1981

Effect of shifts of the O2 dissociation curve upon alveolar-arterial O2 gradients in computer models of the lung with ventilation-perfusion mismatching.

The effect of a shift of the blood O2 dissociation curve (ODC) on the alveolar-arterial O2 gradient was studied in computer models of the lung with several degrees of VA/Q inequality during air breathing. A shift to the left decreases and a shift to the right increases not only the mixed-venous but also the arterial PO2. Consequently the alveolar-arterial O2 gradient is larger with a left and smaller with a right shift of the ODC. This effect of a shift of the ODC on the alveolar-arterial O2 gradient is negligible in a healthy lung but becomes quite considerable in a diseased lung with a severe mismatching of VA/Q.

Animals↗

PubMedDate not supplied

Performance optimization of left ventricular assistance. A computer model study.

Performance of temporary parallel left ventricular assistance was investigated and the theoretic conditions leading to optimal behavior of the mechanical system were explored. Computer models of nonpulsatile and pulsatile left ventricular assist devices (LVADs) were incorporated into a previously reported closed-loop simulation of the canine cardiovascular system. Assuming the assisted heart was capable of recovery, LVAD performance was assessed based on both myocardial oxygen balance and cardiac output. With a synchronous LVAD, and operating in a counterpulsation mode, these variables were sensitive to the phasing of pump ejection. Maximum reduction in cardiac oxygen consumption, maximum increase in oxygen availability, and maximum increase in cardiac output with the atrio-aortic device were obtained when pump ejection immediately followed aortic valve closure. These variables were directly proportional to the magnitude of bypass volume. The pulsatile asynchronous and nonpulsatile LVAD models affected oxygen balance in a similar manner, but neither performed so well as the synchronous model when equal bypass volumes were used. Ventricular uptake of blood provided a further 27% decrease in oxygen consumption and further 78% increase in oxygen availability than atrial uptake. In summary, the model predicted that the pulsatile synchronous LVAD, filling from the ventricle during heart systole and ejecting into either the ascending or descending aorta just after ventricular systole, would be most beneficial to both myocardial oxygen balance and cardiac output.

Animals↗

PubMed1993

Effects of defibrillation shock energy and timing on 3-D computer model of heart.

We present computer simulations of electrical defibrillation in a three-dimensional model of the ventricles of the heart. In this model, called HEARTSIM, the ventricles are represented by 1473 cubic elements with 3 mm sides. The action potential is described by five discrete states; absolutely refractory, three relatively refractory, and repolarized. Activation is propagated to an element's six orthogonal neighbors with the conduction velocity dependent on the refractory state of the neighbor. Delivery of several extra-stimuli with decrementing coupling intervals results in ventricular fibrillation. Following the onset of ventricular fibrillation, we simulate defibrillation using various electrode configurations, shock energies, and timings. The current density distributions in the heart model resulting from the defibrillation shocks are determined from finite element analysis of the electric fields produced by the delivery of high energy shocks. The simulations suggest that successful defibrillation shocks produce a short period of low activation followed by a complete cessation of activation for a duration of 387 +/- 162 ms. In contrast, unsuccessful shocks produce a significantly shorter period of low activation (70 +/- 12 ms) after which ventricular fibrillation resumes. HEARTSIM mimics the experimentally reported, highly variable response to near-threshold shocks--the energy for successful defibrillation varies widely (20.8 +/- 20.7 J). In addition, the success rate vs. energy curve has a sigmoidal shape that is consistent with experiments. We demonstrate that this variability in the energy requirement results from dynamic variability in the number of elements made refractory by the shock and the relative distribution of the activation pattern at the time of the shock. Further, we show that it may be possible to lower the defibrillation energy requirements by delivery of two successive low energy pulses. The most efficient timing for the second pulse corresponds to the repolarization of the elements that were excited by the first pulse. Thus, when the interval between the two pulses was 85 +/- 18 ms, the defibrillation threshold energy (DFE) is reduced by 30.7 +/- 10% with pulses of 10 ms duration, and 62.6 +/- 7.9% with pulses of 5 ms duration. Our simulations also show that there is a delicate balance of energy between the two pulses that must be reached in order to achieve energy reduction with double pulse defibrillation. In conclusion, HEARTSIM serves as a tool for studying the underlying mechanisms of the effects of DF shocks on ventricular arrhythmias, and assists in evaluation of improved strategies for shock delivery.

Action Potentials↗

PubMed2006

Interplay between computational models and cognitive electrophysiology in visual word recognition.

In this article, we discuss the relevance of electrophysiological data to the enterprise of analyzing and understanding the reading process. Specifically, we detail how the event-related brain potential (ERP) technique (and its magnetic counterpart) can aid in development of models of visual word recognition. Any viable and accurate account of reading must take into account the temporal and anatomical constraints imposed by the fact that reading is a human brain function. We believe that neurophysiological (especially, although not limited to electrophysiological) data can serve an essential reference in the development of biologically realistic models of reading. We assess just how well extant electrophysiological data comport with specific predictions of existing computational models and offer some suggestions for the kinds of research that can address some of the remaining open questions.

Brain↗

PubMed2006

A hybrid mixture discriminant analysis-random forest computational model for the prediction of volume of distribution of drugs in human.

A computational approach is described that can predict the VD(ss) of new compounds in humans, with an accuracy of within 2-fold of the actual value. A dataset of VD values for 384 drugs in humans was used to train a hybrid mixture discriminant analysis-random forest (MDA-RF) model using 31 computed descriptors. Descriptors included terms describing lipophilicity, ionization, molecular volume, and various molecular fragments. For a test set of 23 proprietary compounds not used in model construction, the geometric mean fold-error (GMFE) was 1.78-fold (+/-11.4%). The model was also tested using a leave-class out approach wherein subsets of drugs based on therapeutic class were removed from the training set of 384, the model was recast, and the VD(ss) values for each of the subsets were predicted. GMFE values ranged from 1.46 to 2.94-fold, depending on the subset. Finally, for an additional set of 74 compounds, VD(ss) predictions made using the computational model were compared to predictions made using previously described methods dependent on animal pharmacokinetic data. Computational VD(ss) predictions were, on average, 2.13-fold different from the VD(ss) predictions from animal data. The computational model described can predict human VD(ss) with an accuracy comparable to predictions requiring substantially greater effort and can be applied in place of animal experimentation.

Algorithms↗

PubMed2005

Cue-guided search: a computational model of selective attention.

Selective visual attention in a natural environment can be seen as the interaction between the external visual stimulus and task specific knowledge of the required behavior. This interaction between the bottom-up stimulus and the top-down, task-related knowledge is crucial for what is selected in the space and time within the scene. In this paper, we propose a computational model for selective attention for a visual search task. We go beyond simple saliency-based attention models to model selective attention guided by top-down visual cues, which are dynamically integrated with the bottom-up information. In this way, selection of a location is accomplished by interaction between bottom-up and top-down information. First, the general structure of our model is briefly introduced and followed by a description of the top-down processing of task-relevant cues. This is then followed by a description of the processing of the external images to give three feature maps that are combined to give an overall bottom-up map. Second, the development of the formalism for our novel interactive spiking neural network (ISNN) is given, with the interactive activation rule that calculates the integration map. The learning rule for both bottom-up and top-down weight parameters are given, together with some further analysis of the properties of the resulting ISNN. Third, the model is applied to a face detection task to search for the location of a specific face that is cued. The results show that the trajectories of attention are dramatically changed by interaction of information and variations of cues, giving an appropriate, task-relevant search pattern. Finally, we discuss ways in which these results can be seen as compatible with existing psychological evidence.

Algorithms↗

PubMed1988

A computer model of the electrogram: what causes fractionation?

Fractionated electrograms are frequently recorded during mapping studies in patients with coronary artery disease and ventricular tachycardia. The authors developed a computer model of electrogram generation based on the biophysics of volume conductor fields. They show that fractionated electrograms can be produced as otherwise uniform wavefronts of activation encounter regions of increased cellular coupling resistance. Because of this, local activation may not correspond to the largest or most rapid deflection in a polyphasic, fractionated electrogram.

Animals↗

PubMed2002

N-Myristoylethanolamine-cholesterol (1:1) complex: first evidence from differential scanning calorimetry, fast-atom-bombardment mass spectrometry and computational modelling.

The interaction of N-myristoylethanolamine (NMEA) with cholesterol is investigated by differential scanning calorimetry (DSC), fast-atom-bombardment mass spectrometry (FAB-MS) and computational modelling. Addition of cholesterol to NMEA leads to a new phase transition at 55 degrees C besides the chain-melting transition of NMEA at 72.5 degrees C. The enthalpy of the new transition increases with cholesterol content up to 50 mol%, but decreases thereafter, vanishing at 80 mol%. The enthalpy of the chain-melting transition of NMEA decreases with an increase in cholesterol; the transition disappears at 50 mol%. FAB-MS spectra of mixtures of NMEA and cholesterol provide clear signatures of the formation of ([NMEA+cholesterol]+) ([NMEA+cholesterol+Na]+). These results are consistent with the formation of a 1:1 complex between NMEA and cholesterol. Molecular modelling studies support this experimental finding and provide a plausible structural model for the complex, which highlights multiple H-bond interactions between the hydroxy group of cholesterol and the hydroxy and carbonyl groups of NMEA besides appreciable dispersion interaction between the hydrocarbon domains of the two molecules.

Calorimetry, Differential Scanning↗