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PubMed1989

Dynamics of a tightly coupled mechanism for flagellar rotation. Bacterial motility, chemiosmotic coupling, protonmotive force.

The bacterial flagellar motor is a molecular engine that couples the flow of protons across the cytoplasmic membrane to rotation of the flagellar filament. We analyze the steady-state behavior of an explicit mechanical model in which a fixed number of protons carries the filament through one revolution. Predictions of this model are compared with experimentally determined relationships between protonmotive force, proton flux, torque, and speed. All such tightly coupled mechanisms produce the same torque when the motor is stalled but vary greatly in their behavior at high speed. The speed at zero load predicted by our model is limited by the rates of association and dissociation of protons at binding sites on the rotor and by the mobility of force generators containing transmembrane channels that interact with these sites. Our analysis suggests that more could be learned about the motor if it were driven by an externally applied torque backwards (at negative speed) or forwards at speeds greater than the zero-load speed.

Bacterial Physiological Phenomena↗

PubMed2003

Characterizing proteolytic cleavage site activity using bio-basis function neural networks.

MOTIVATION: In protein chemistry, proteomics and biopharmaceutical development, there is a desire to know not only where a protein is cleaved by a protease, but also the susceptibility of its cleavage sites. The current tools for proteolytic cleavage prediction have often relied purely on regular expressions, or involve models that do not represent biological data well. RESULTS: A novel methodology for characterizing proteolytic cleavage site activities has been developed, which incorporates two fundamental features: activity class prediction and the use of an amino acid similarity matrix for (non-parametric) neural learning. The first solved the problem of predicting proteolytic efficiency. The second significantly improved the robustness in prediction and reduced the time complexity for learning. This study shows that activity class prediction is successful when applying this methodology to the prediction and characterization of Trypsin cleavage sites and the prediction of HIV protease cleavage sites. AVAILABILITY: Requests for software and data should be made respectively to Dr Zheng Rong Yang and Miss Rebecca Thomson.

Amino Acid Sequence↗

PubMed1998

Students' misconceptions about perceived physiological responses.

Students' misconceptions about scientific phenomena can arise from at least two possible sources, the students' personal experience with those phenomena and things learned in the classroom. Misconceptions have been studied in a variety of science disciplines, but little attention has been given to the faulty models that students have for physiological processes. In this study 393 undergraduates in three different research universities were asked to predict the changes in heart rate and strength of cardiac contraction and breathing frequency and depth of breathing (physiological parameters that can be directly and personally perceived) under conditions that result in predicted that heart rate would increase but that the strength of contraction would decrease or stay unchanged. Approximately one-half of the students predicted that breathing frequency would increase but depth of breathing would decrease (also erroneous). Explanations for these erroneous predictions were elicited, and the reasons offered revealed significant misconceptions about cardiac and respiratory mechanics. The persistence of such misconceptions was demonstrated in a small group of first-year medical students. A general approach to detecting and remediating misconceptions is discussed.

Adult↗

PubMed2003

Infant perception of non-native consonant contrasts that adults assimilate in different ways.

Numerous findings suggest that non-native speech perception undergoes dramatic changes before the infant's first birthday. Yet the nature and cause of these changes remain uncertain. We evaluated the predictions of several theoretical accounts of developmental change in infants' perception of non-native consonant contrasts. Experiment 1 assessed English-learning infants' discrimination of three isiZulu distinctions that American adults had categorized and discriminated quite differently, consistent with the Perceptual Assimilation Model (PAM: Best, 1995; Best et al., 1988). All involved a distinction employing a single articulatory organ, in this case the larynx. Consistent with all theoretical accounts, 6-8 month olds discriminated all contrasts. However, 10-12 month olds performed more poorly on each, consistent with the Articulatory-Organ-matching hypothesis (AO) derived from PAM and Articulatory Phonology (Studdert-Kennedy & Goldstein, 2003), specifically that older infants should show a decline for non-native distinctions involving a single articulatory organ. However, the results may also be open to other interpretations. The converse AO hypothesis, that non-native between-organ distinctions will remain highly discriminable to older infants, was tested in Experiment 2, using a non-native Tigrinya distinction involving lips versus tongue tip. Both ages discriminated this between-organ contrast well, further supporting the AO hypothesis. Implications for theoretical accounts of infant speech perception are discussed.

Discrimination Learning↗

PubMed1998

Artificial neural networks in outcome prediction.

Artificial neural networks have been successfully used for pattern recognition and outcome prediction in several clinical settings. The advantage of a neural network is the ability of the model to capture nonlinearities and complex interactions between factors related to the outcome of interest. Neural networks also differ from other decision support systems in that the learning occurs by example through training and not by programming or pre-defined rules. Promising surgical applications include preoperative estimation of surgical risk and quality control within a hospital or health care system. An optimal system would estimate the outcome for the individual patient using all the prognostic and risk information inherent in the available patient characteristics.

Humans↗

PubMed1994

Probabilistic analysis of human supervised learning and classification.

Probabilistic classification techniques based on Bayesian decision theory are used to analyze human supervised learning and classification. The procedure rests on the assumption that human classification behaviour is based on internal feature states which can be linked to physical feature vectors (corresponding to the system input). In the present approach, this relationship is modeled in terms of additive stochastic error signals. The corresponding random variables describe the additional degrees of bias and variance introduced by the (perceptual) process of internal feature measurement. Estimates of internal feature states are obtained by least-squares minimization. Structure and dimensionality of the resulting internal representation are displayed by plotting the configuration of internal class means, or virtual prototypes. Their temporal evolution reflects the dynamic properties of the learning process. The use of the procedure is demonstrated by analyzing the results of two experiments. First, it is shown that Minimum Distance Classifiers, such as used by Caelli, Rentschler and Scheidler [(1987) Biological Cybernetics, 57, 233-240], are suboptimal in predicting human performance. Second, it is found that extrafoveal learning is much slower than foveal learning and that extrafoveal pattern representations are severely distorted. The latter distortions reveal the existence of limitations for the generalization of supervised learning over space.

Adult↗

PubMed1984

Timing, learning, and forgetting.

A computer-simulation model (AL) was developed for molecular and molar operant conditioning data. AL assumes a simple forgetting rule and all-or-nothing associations between memory representations of responses and reinforcers. AL describes acquisition and steady-state behavior in both concurrent interresponse time (IRT) schedules and in ordinary concurrent schedules. It describes functions relating the relative frequency of an IRT to IRT duration and to reinforcement frequency. AL accurately predicts for ordinary concurrent variable-interval schedules that the log ratio of responses to the two alternatives is a linear function of the log ratio of the reinforcers they deliver, and that the slope of this straight line approximates the degree of undermatching that characterizes the behavior of real animals. In addition, AL successfully describes the fact that in real data of Nevin, Heyman, and others, the probability of a changeover from one response to the other is roughly independent of the number of consecutive responses to the same alternative preceding the changeover. A previous version of AL assimilated data on temporal psychophysics, such as that animals bisect two temporal intervals at the geometric mean, and that the Weber fraction in DRL schedules is approximately constant. AL therefore describes transient and steady-state molecular and molar performances as well as data on temporal psychophysics.

Animals↗

PubMed2004

Distinctiveness and correlation in conceptual structure: behavioral and computational studies.

Patients with category-specific deficits have motivated a range of hypotheses about the structure of the conceptual system. One class of models claims that apparent category dissociations emerge from the internal structure of concepts rather than fractionation of the system into separate substores. This account claims that distinctive properties of concepts in the living domain are vulnerable because of their weak correlation with other features. Given the assumption that mutual activation among correlated properties produces faster activation in the normal system, the authors predicted a disadvantage for the distinctive features of living things for unimpaired adults. Results of a speeded feature verification study supported this prediction, as did a computational simulation in which networks mapped from orthography to semantics.

Adolescent↗

PubMed2001

Relative validity effects with either one or two more valid cues in Pavlovian and instrumental conditioning.

Two experiments investigated the relative validity effect with either 1 or 2 continuously reinforced cues in Wistar rats using appetitive Pavlovian and instrumental preparations. Discrimination training involved 3 compound cues containing a common element (1AX: 1BX: 2CX). In the first true-discrimination group (TD-1), CX was followed by food, but AX and BX were not. In the second true-discrimination group (TD-2), AX and BX but not CX were followed by food. In the third, pseudodiscrimination group (PD), food followed 50% of each compound. Compared with the PD group, there were lower levels of responding to X in Groups TD-1 and TD-2, which did not differ. That is, both TD treatments showed equivalent relative validity effects. There was evidence for a relative validity effect on the context. The Rescorla-Wagner model incorrectly predicts a smaller relative validity effect after the TD-2 than the TD-1 treatment. Comparator theory predicts these results.

Animals↗

PubMed1997

Functional versus aesthetic articulation of maxillary anterior restorations.

The correct orientation of the master model is a frequently overlooked aspect of communication between the clinician and the ceramist. The master model must provide the ceramist with the same perspective of the patient as is seen by the clinician--facing the viewer. Unless precise information is transferred to the laboratory, the ceramist can only estimate horizontal and vertical alignment of the working cast from landmarks taken from the cast itself. It is unwise to leave such appraisal to chance, especially when restoring multiple anterior preparations, where the potential for misalignment of the cast increases with the number of restorations involved. The learning objective of this article is to discuss communication techniques between the clinician and the ceramist for achieving precise and predictable orientation in the treatment of aesthetic anterior restorations.

Communication↗

PubMed2005

Using ergodic theory to assess the performance of ecosystem models.

Ecosystem simulation models are designed to assess the flux of energy, water, carbon and nitrogen according to a given vegetation type. The reliability of the modeled results is determined by model validations. Model validations are typically done using classical statistical methods like regression analysis of predicted versus observed values, paired t statistics and error assessment procedures to characterize the quality of current and future model predictions. All these validation efforts concentrate on static aspects of the model but fail to describe the model dynamics. In this paper, we introduce methods from ergodic theory to analyze the dynamic behavior of ecosystem models. We describe (1) how the attractor representation of model behavior can be reconstructed from a time series of model outputs, and (2) what we can learn from the attractor to assess the model dynamics. As an application example, we provide simulation results for two important pine forest ecosystems in Austria, i.e., 23 Cembran pine and 16 Scots pine stands. These stands were simulated with three model parameterizations: one representing a generic, evergreen needle-leaf forest, and two species- specific parameter sets, one for Cembran pine and one for Scots pine. First, we applied standard validation methods to get static measures of model accuracy and precision. Next, we used ergodic theory to assess model dynamics. A comparison of both analyses reveals important issues related to model dynamics, such as the finding that the occurrence of instabilities in model behavior may not be detected by standard validation methods. Using ergodic theory, we were able to reconstruct the attractors of model behavior. In the attractor describing model dynamics for Cembran pine, simulated with the generic, evergreen needle-leaf forest parameter set, we detected instability in model behavior. We identified this instability as a riddled basin configuration, which is a strong indicator for the occurrence of a chaotic model behavior that may result in random predictions. Our results suggest that ergodic theory is a useful tool for assessing inconsistencies in the dynamics of ecosystem model simulations that have not been detected by standard statistical validation methods.

Climate↗

PubMed1980

Neuroleptic-induced acute dyskinesias in squirrel monkeys: correlation with propensity to cause extrapyramidal side effects.

In squirrel monkeys that had undergone repeated treatment with haloperidol at intervals of 7--14 days, subsequent acute administration of haloperidol induced dystonia and dyskinesias. This acute effect of haloperidol was dose-related and occurred at the same doses that impaired Sidman avoidance performance. Chlorpromazine, fluphenazine, metoclopramide, tetrabenazine, and Su-23397, all of which have been associated with extrapyramidal side effects, reliably elicited dyskinesias in these monkeys. Dyskinesias were less mared after thioridazine and absent after clozapine, corresponding to the reported lower incidence of extrapyramidal side effects in the clinic. The non-neuroleptics, baclofen, and diazepam, failed to elicit dyskinesias. In contrast to the dyskinetic syndrome, the incidence of catalepsy or tremor did not accurately predict propensity to elicit extrapyramidal symptomatology. The acute dyskinetic syndrome in squirrel monkeys may therefore serve as an animal model for predicting the ability of antipsychotics to cause extrapyramidal dysfunction, and may yield insight into the mechanisms of these drug-induced motor disorders.

Animals↗

PubMed1980

Local contrast and maintained generalization.

Pigeons received variable-interval reinforcement for key pecking during presentations of horizontal and vertical line-orientation stimuli, while pecks during five intermediate orientations were extinguished. Lowest peck rates were observed during presentations of negative stimuli adjacent to the positive orientations while peck rate during 45 degrees (the intermediate negative orientation) was relatively high, i.e., there were negative contrast shoulders. When peck rates were manipulated in the positive orientations, peck rate in neithboring orientations changed in the opposite direction. Contrast shoulders faded after prolonged training. A second type of contrast, local contrast, was correlated with similarity of preceding stimulus and different average peck rates during different stages of the discrimination process. The data suggest that sequential local contrast accompanying the formation of a discrimination contributes to the form of generalization gradients. Blough's model of stimulus control predicts the changes in gradient form described here, but may not accurately depict the underlying process responsible for gradient form.

Animals↗

PubMed1995

A model for realism of confidence judgments: implications for underconfidence in sensory discrimination.

In a recent issue of this journal, Björkman, Justlin, and Winman (1993) presented a model of the calibration of subjective confidence judgments for sensory discrimination which they called "subjective distance theory." They proposed that there was a robust underconfidence bias in such judgments, that the model predicted such a bias, and that two different models were needed for the calibration of subjective confidence for cognitive judgments and for sensory ones. This paper addresses issues they raised. It points out that they have not presented a new model, but rather a portion of a more general one, the "decision-variable partition model" originally proposed in Ferrell and McGoey (1980). This paper explores properties of the model and shows, contrary to Björkman, Juslin, and Winman's hypotheses, that the model does not predict underconfidence, that the "hard-easy effect" can be observed with sensory discriminations, and that the model fits not only sensory, but also cognitive judgments.

Attention↗

PubMed1996

Behavioral, structural and neurochemical asymmetries in the avian brain: a model system for studying visual development and processing.

The emphasis of this review is on the visual systems and lateralized visually guided behavior in several avian species. Lateral asymmetry is known to be present in the tectofugal visual projections to the forebrain of the pigeon and in the thalamofugal visual projections to the forebrain of the chicken. These structural asymmetries are discussed in the context of the behavioral and neurochemical asymmetries. While recognizing the need to investigate the organization of both of the visual pathways within one avian species; this review reasons inductively that the lateralized organization of the two visual pathways leads to binocular input to the right hemisphere via the thalamofugal visual system and to the left hemisphere via the tectofugal visual system. For each system, input to the other hemisphere is primarily monocular. This specialization of the hemispheres for visual processing has predictable effects on behavior. The role of asymmetrical light stimulation of the eyes of the embryo in determining the lateralizations in the visual pathways and some behaviors is discussed, as are other lateralizations generated or altered by imprinting and passive avoidance learning.

Animals↗

PubMed2005

Incremental online learning in high dimensions.

Locally weighted projection regression (LWPR) is a new algorithm for incremental nonlinear function approximation in high-dimensional spaces with redundant and irrelevant input dimensions. At its core, it employs nonparametric regression with locally linear models. In order to stay computationally efficient and numerically robust, each local model performs the regression analysis with a small number of univariate regressions in selected directions in input space in the spirit of partial least squares regression. We discuss when and how local learning techniques can successfully work in high-dimensional spaces and review the various techniques for local dimensionality reduction before finally deriving the LWPR algorithm. The properties of LWPR are that it (1) learns rapidly with second-order learning methods based on incremental training, (2) uses statistically sound stochastic leave-one-out cross validation for learning without the need to memorize training data, (3) adjusts its weighting kernels based on only local information in order to minimize the danger of negative interference of incremental learning, (4) has a computational complexity that is linear in the number of inputs, and (5) can deal with a large number of-possibly redundant-inputs, as shown in various empirical evaluations with up to 90 dimensional data sets. For a probabilistic interpretation, predictive variance and confidence intervals are derived. To our knowledge, LWPR is the first truly incremental spatially localized learning method that can successfully and efficiently operate in very high-dimensional spaces.

Algorithms↗

PubMed1996

Artificial neural networks: current status in cardiovascular medicine.

Artificial neural networks are a form of artificial computer intelligence that have been the subject of renewed research interest in the last 10 years. Although they have been used extensively for problems in engineering, they have only recently been applied to medical problems, particularly in the fields of radiology, urology, laboratory medicine and cardiology. An artificial neural network is a distributed network of computing elements that is modeled after a biologic neural system and may be implemented as a computer software program. It is capable of identifying relations in input data that are not easily apparent with current common analytic techniques. The functioning artificial neural network's knowledge is built on learning and experience from previous input data. On the basis of this prior knowledge, the artificial neural network can predict relations found in newly presented data sets. In cardiology, artificial neural networks have been successfully applied to problems in the diagnosis and treatment of coronary artery disease and myocardial infarction, in electrocardiographic interpretation and detection of arrhythmias and in image analysis in cardiac radiography and sonography. This report focuses on the current status of artificial neural network technology in cardiovascular medical research.

Cardiology↗

PubMed2005

Dynamic response-by-response models of matching behavior in rhesus monkeys.

We studied the choice behavior of 2 monkeys in a discrete-trial task with reinforcement contingencies similar to those Herrnstein (1961) used when he described the matching law. In each session, the monkeys experienced blocks of discrete trials at different relative-reinforcer frequencies or magnitudes with unsignalled transitions between the blocks. Steady-state data following adjustment to each transition were well characterized by the generalized matching law; response ratios undermatched reinforcer frequency ratios but matched reinforcer magnitude ratios. We modelled response-by-response behavior with linear models that used past reinforcers as well as past choices to predict the monkeys' choices on each trial. We found that more recently obtained reinforcers more strongly influenced choice behavior. Perhaps surprisingly, we also found that the monkeys' actions were influenced by the pattern of their own past choices. It was necessary to incorporate both past reinforcers and past choices in order to accurately capture steady-state behavior as well as the fluctuations during block transitions and the response-by-response patterns of behavior. Our results suggest that simple reinforcement learning models must account for the effects of past choices to accurately characterize behavior in this task, and that models with these properties provide a conceptual tool for studying how both past reinforcers and past choices are integrated by the neural systems that generate behavior.

Animals↗