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Extracting the principal behavior of a probabilistic supervisor through neural networks ensemble.

In this paper, we propose a model of a neural network ensemble that can be trained with a supervisor having two kinds of input-output functions where the occurrence probability of each function is not even. This condition can be likened to a learning condition, in which the learning data are hampered by noise. In this case, the neural network has the impression that the learning supervisor (object) has a probabilistic behavior in which the supervisor generates correct learning data most of the time but occasionally generates erroneous ones. The objective is to train the neural network to approximate the greatest distributed input-output relation, which can be considered to be the principal nature of the supervisor, so that we can obtain a neural network that is able, to some extent, to suppress the ill effect of erroneous data encountered during the learning process.

Algorithms↗

Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men.

Narcolepsy is a sleep disorder caused by disruption of hypocretin (orexin) neurotransmission. Injection of hypocretin-1 acutely suppresses TRH and TSH release in rats. In contrast, subchronic administration does not appear to affect the hypothalamo-pituitary-thyroid ensemble in animals. We explored (in 7 patients and 7 controls) whether hypocretin deficiency impacts circulating TSH levels and circadian timing of TSH release in narcoleptic humans. Plasma TSH concentration profiles (blood samples taken at 10-min intervals during 24 h) and TSH levels in response to TRH injection were analyzed by Cluster, robust regression, approximate entropy (ApEn), and deconvolution. Circulating TSH levels were lower in patients, which was primarily attributable to lower pulse amplitude and nadir concentrations. TSH secretion correlated positively with mean 24-h leptin levels (R2 = 0.46, P = 0.02) and negatively with amount of sleep (R2 = 0.29, P = 0.048). Pattern-synchrony between 24-h leptin and TSH concentrations was demonstrated by significant cross-correlation and cross-ApEn analyses with no differences between controls and patients. Sleep onset was closely associated with a fall in circulating TSH. Features of diurnal rhythmicity of circulating TSH fluctuations were similar in patients and controls, with the acrophase occurring shortly after midnight. Thyroxine and triiodothyronine concentrations were similar in patients and controls and did not display a diurnal rhythm. The response of plasma TSH levels to TRH was also similar in both groups. Sleep patterns in narcoleptics were significantly disorderly compared with controls, as measured by ApEn (P = 0.006). In summary, circulating TSH concentrations are low in hypocretin-deficient narcoleptic men, which could be attributable to their low plasma leptin levels and/or their abnormal sleep-wake cycle.

Adaptation, Physiological↗

Physiologically derived critical evaporative coefficients for protective clothing ensembles.

When work is performed in heavy clothing, evaporation of sweat from the skin to the environment is limited by layers of wet clothing and air. The magnitude of decrement in evaporative cooling is a function of the clothing's resistance to permeation of water vapor. A physiological approach has been used to derive effective evaporative coefficients (he) which define this ability to evaporate sweat. We refined this approach by correcting the critical effective evaporative coefficient (K for sweating efficiency (Ke,eta') since only a portion of the sweat produced under such conditions is evaporated through the clothing. Six acclimated men and women walked at 30% maximal O2 consumption (150-200 W.m-2) at a constant dry bulb temperature as ambient water vapor pressure was systematically increased 1 Torr every 10 min. Critical pressure was defined as the partial pressure of water vapor (Pw) at which thermal balance could no longer be maintained and rectal temperature rose sharply. Each test was performed in various clothing ensembles ranging from cotton shirt and pants to "impermeable" suits. This approach was used to derive he by solving the general heat balance equation, M - W +/- (R + C) = w.he.(Psk - Pw), where M is metabolic heat production, W is external work, R is radiant heat exchange, C is convective heat transfer, w is skin wettedness, and Psk is water vapor pressure of fully wet skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

Orbitofrontal ensemble activity monitors licking and distinguishes among natural rewards.

The classification of rhythmic licking into clusters has proved to be useful for characterizing brain mechanisms that modulate the ingestion of natural rewards (sucrose and water). One cortical area that is responsive to rewarding stimuli is the orbitofrontal cortex (OFC). However, it is not presently known how OFC neurons respond while rodents freely lick for natural rewards and whether these responses are related to the structure of licking clusters. We addressed these issues by showing that temporary inactivation of the OFC decreases the duration and increases the number of clusters and that the activity of OFC neurons changed at precise times before, during, and after the cluster terminates. Furthermore, analysis of the activity of OFC neuronal ensembles showed that they could discriminate cluster onset from termination, predict when a behaving animal will begin a cluster, and distinguish and anticipate between natural rewards. These results provide a new role for the OFC in influencing licking clusters and anticipating specific rewards.

Animals↗

A point process framework for relating neural spiking activity to spiking history, neural ensemble, and extrinsic covariate effects.

Multiple factors simultaneously affect the spiking activity of individual neurons. Determining the effects and relative importance of these factors is a challenging problem in neurophysiology. We propose a statistical framework based on the point process likelihood function to relate a neuron's spiking probability to three typical covariates: the neuron's own spiking history, concurrent ensemble activity, and extrinsic covariates such as stimuli or behavior. The framework uses parametric models of the conditional intensity function to define a neuron's spiking probability in terms of the covariates. The discrete time likelihood function for point processes is used to carry out model fitting and model analysis. We show that, by modeling the logarithm of the conditional intensity function as a linear combination of functions of the covariates, the discrete time point process likelihood function is readily analyzed in the generalized linear model (GLM) framework. We illustrate our approach for both GLM and non-GLM likelihood functions using simulated data and multivariate single-unit activity data simultaneously recorded from the motor cortex of a monkey performing a visuomotor pursuit-tracking task. The point process framework provides a flexible, computationally efficient approach for maximum likelihood estimation, goodness-of-fit assessment, residual analysis, model selection, and neural decoding. The framework thus allows for the formulation and analysis of point process models of neural spiking activity that readily capture the simultaneous effects of multiple covariates and enables the assessment of their relative importance.

Action Potentials↗

Dynamic ensemble coding of saccades in the monkey superior colliculus.

The deeper layers of the midbrain superior colliculus (SC) contain a topographic motor map in which a localized population of cells is recruited for each saccade, but how the brain stem decodes the dynamic SC output is unclear. Here we analyze saccade-related responses in the monkey SC to test a new dynamic ensemble-coding model, which proposes that each spike from each saccade-related SC neuron adds a fixed, site-specific contribution to the intended eye movement command. As predicted by this simple theory, we found that the cumulative number of spikes in the cell bursts is tightly related to the displacement of the eye along the ideal straight trajectory, both for normal saccades and for strongly curved, blink-perturbed saccades toward a single visual target. This dynamic relation depends systematically on the metrics of the saccade displacement vector, and can be fully predicted from a quantitative description of the cell's classical movement field. Furthermore, we show that a linear feedback model of the brain stem, which is driven by dynamic linear vector summation of measured SC firing patterns, produces realistic two-dimensional (2D) saccade trajectories and kinematics. We conclude that the SC may act as a nonlinear, vectorial saccade generator that programs an optimal straight eye-movement trajectory.

Action Potentials↗

Fidelity of the ensemble code for visual motion in primate retina.

Sensory experience typically depends on the ensemble activity of hundreds or thousands of neurons, but little is known about how populations of neurons faithfully encode behaviorally important sensory information. We examined how precisely speed of movement is encoded in the population activity of magnocellular-projecting parasol retinal ganglion cells (RGCs) in macaque monkey retina. Multi-electrode recordings were used to measure the activity of approximately 100 parasol RGCs simultaneously in isolated retinas stimulated with moving bars. To examine how faithfully the retina signals motion, stimulus speed was estimated directly from recorded RGC responses using an optimized algorithm that resembles models of motion sensing in the brain. RGC population activity encoded speed with a precision of approximately 1%. The elementary motion signal was conveyed in approximately 10 ms, comparable to the interspike interval. Temporal structure in spike trains provided more precise speed estimates than time-varying firing rates. Correlated activity between RGCs had little effect on speed estimates. The spatial dispersion of RGC receptive fields along the axis of motion influenced speed estimates more strongly than along the orthogonal direction, as predicted by a simple model based on RGC response time variability and optimal pooling. on and off cells encoded speed with similar and statistically independent variability. Simulation of downstream speed estimation using populations of speed-tuned units showed that peak (winner take all) readout provided more precise speed estimates than centroid (vector average) readout. These findings reveal how faithfully the retinal population code conveys information about stimulus speed and the consequences for motion sensing in the brain.

Action Potentials↗

Interactions among an ensemble of chordotonal organ receptors and motor neurons of the crayfish claw.

1. Action potentials of crayfish propodite-dactyl (PD) chordotonal organ receptors and two claw motor neurons, the opener inhibitor (OI) and slow closer excitor CE) were simultaneously monitored during imposed step and ramp movements of the dactyl or while the dactyl was held at various positions. 2. The activities of the cells during imposed displacements were analyzed using peristimulus time histograms and response and contour planes. The proprioceptive fields (PFs) of individual receptors resemble components of the more complex motor neuron PFs. Some receptors are briefly active after each successive opening step, while others do not respond to steps near the closed position but respond as the joint angle increases, becoming active when the claw is held open. Another type of receptor responds to closing movements. 3. Interactions among the various types of receptors and the two motor neurons were detected and analyzed by various statistical methods and intracellular recording techniques. The results indicate that receptors activated during opening movements and when the dactyl is held at open positions excite OI and CE via divergent functional connections. The efficacies of the connections made by a receptor may differ. Receptors activated by closing movements produce hyperpolarizing synaptic potentials in both efferents, possible directly or via interneurons. 4. It is concluded that several types of chordotonal organ receptors form an ensemble of parallel input channels, which modulates the activities of OI and CE and contributes to the generation of the spatial-temporal nonuniformities of their proprioceptive reflex responses.

Animals↗

Representation of wrist joint kinematics by the ensemble of muscle spindles from synergistic muscles.

Proprioceptive information about movement is transmitted to the central nervous system by a variety of receptor types, which are widely distributed among the muscles, joints, and skin. Muscle spindles are known to be an important and reliable source of information for the perception of movement kinematics. Previous studies that focused on the characteristics of single muscle spindle firing patterns have left the impression that each receptor fires in relation to a number of kinematic variables, leaving the following question unanswered: what role is played by the ensemble of muscle spindles within the same muscle or within synergistic muscles? The study described in this paper addressed whether the perception of joint position and velocity is based on the net input of muscle spindles residing in all synergistic muscles crossing a joint. Normal human adults performed a motor coordination task that required perception of joint velocity and dynamic position at the wrist. The task was to open the left hand briskly as the right wrist was passively rotated in the flexion direction through a prescribed target angle. In randomly occurring trials, the tendons to three muscles [extensor carpi radialis (ECR), extensor carpi ulnaris (ECU), and extensor digitorum (ED)] were vibrated either individually or in different combinations during the performance of the motor task. Tendon vibration is known to distort muscle spindle firing patterns, and consequently, kinesthesia. By comparing performance errors with and without tendon vibration, the relative influences of muscle spindles residing in ECR, ECU, and ED were quantified. Vibration of the individual ECR, ECU, or ED tendons produced systematic undershoot errors in performance, consistent with the misperception of wrist velocity and dynamic position. Performance errors were larger when combinations of, rather than individual, muscle tendons were vibrated. The error resulting from simultaneous vibration of ECR and ECU was roughly equal to the sum of the errors produced by vibration of the individual tendons. These effects of vibrating synergistic tendons at the wrist suggest that kinesthesia is derived from the integrated input of muscle spindles from all synergistic muscles.

Adult↗

Simultaneous reorganization in thalamocortical ensembles evolves over several hours after perioral capsaicin injections.

Reorganization of the somatosensory system was quantified by simultaneously recording from single-unit neural ensembles in the whisker regions of the ventral posterior medial (VPM) nucleus of the thalamus and the primary somatosensory (SI) cortex in anesthetized rats before, during, and after injecting capsaicin under the skin of the lip. Capsaicin, a compound that excites and then inactivates a subset of peripheral C and Adelta fibers, triggered increases in spontaneous firing of thalamocortical neurons (10-15 min after injection), as well as rapid reorganization of the whisker representations in both the VPM and SI. During the first hour after capsaicin injection, 57% of the 139 recorded neurons either gained or lost at least one whisker response in their receptive fields (RFs). Capsaicin-related changes continued to emerge for >/=6 h after the injection: Fifty percent of the single-neuron RFs changed between 1-2 and 5-6 h after capsaicin injection. Most (79%) of these late changes represented neural responses that had remained unchanged in the first postcapsaicin mapping; just under 20% of these late changes appeared in neurons that had previously shown no plasticity of response. The majority of the changes (55% immediately after injection, 66% 6 h later) involved "unmasking" of new tactile responses. RF change rates were comparable in SI and VPM (57-49%). Population analysis indicated that the reorganization was associated with a lessening of the "spatial coupling" between cortical neurons-a significant reduction in firing covariance that could be related to distances between neurons. This general loss of spatial coupling, in conjunction with increases in spontaneous firing, may create a situation that is favorable for the induction of synaptic plasticity. Our results indicate that the selective inactivation of a peripheral nociceptor subpopulation can induce rapid and long-evolving (>/=6 h) shifts in the balance of inhibition and excitation in the somatosensory system. The time course of these processes suggest that thalamic and cortical plasticity is not a linear reflection of spinal and brainstem changes that occur following the application of capsaicin.

Analysis of Variance↗

Synaptic and temporal ensemble interpretation of spike-timing-dependent plasticity.

We postulate that a simple, three-state synaptic switch governs changes in synaptic strength at individual synapses. Under this switch rule, we show that a variety of experimental results on timing-dependent plasticity can emerge from temporal and spatial averaging over multiple synapses and multiple spike pairings. In particular, we show that a critical window for the interaction of pre- and postsynaptic spikes emerges as an ensemble property of the collective system, with individual synapses exhibiting only a minimal form of spike coincidence detection. In addition, we show that a Bienenstock-Cooper-Munro-like, rate-based plasticity rule emerges directly from such a model. This demonstrates that two apparently separate forms of neuronal plasticity can emerge from a much simpler rule governing the plasticity of individual synapses.

Action Potentials↗

Polymer encapsulation of CdE (E = S, se) quantum dot ensembles via in-situ radical polymerization in miniemulsion.

Cadmium sulfide and cadmium selenide/polymer nanocomposites were prepared via in-situ radical polymerization in miniemulsion. Organically capped CdE (E = S, Se) quantum dots (QDs) were used as the starting materials and ensembles of these dots were encapsulated with no need of further surface treatment. The use of two polymer matrices was investigated: polystyrene (PS) and poly(n-butyl acrylate) (PBA). In both cases, homogenous nanocomposites were obtained and their optical properties were investigated by visible absorption and photoluminescence spectroscopy. Quantum size effects were assigned to the nanocomposites, indicating the integrity of the individual QDs upon polymer encapsulation using the miniemulsion process.

Acrylates↗

A combinational feature selection and ensemble neural network method for classification of gene expression data.

BACKGROUND: Microarray experiments are becoming a powerful tool for clinical diagnosis, as they have the potential to discover gene expression patterns that are characteristic for a particular disease. To date, this problem has received most attention in the context of cancer research, especially in tumor classification. Various feature selection methods and classifier design strategies also have been generally used and compared. However, most published articles on tumor classification have applied a certain technique to a certain dataset, and recently several researchers compared these techniques based on several public datasets. But, it has been verified that differently selected features reflect different aspects of the dataset and some selected features can obtain better solutions on some certain problems. At the same time, faced with a large amount of microarray data with little knowledge, it is difficult to find the intrinsic characteristics using traditional methods. In this paper, we attempt to introduce a combinational feature selection method in conjunction with ensemble neural networks to generally improve the accuracy and robustness of sample classification. RESULTS: We validate our new method on several recent publicly available datasets both with predictive accuracy of testing samples and through cross validation. Compared with the best performance of other current methods, remarkably improved results can be obtained using our new strategy on a wide range of different datasets. CONCLUSIONS: Thus, we conclude that our methods can obtain more information in microarray data to get more accurate classification and also can help to extract the latent marker genes of the diseases for better diagnosis and treatment.

Acute Disease↗

Recognition of protein/gene names from text using an ensemble of classifiers.

This paper proposes an ensemble of classifiers for biomedical name recognition in which three classifiers, one Support Vector Machine and two discriminative Hidden Markov Models, are combined effectively using a simple majority voting strategy. In addition, we incorporate three post-processing modules, including an abbreviation resolution module, a protein/gene name refinement module and a simple dictionary matching module, into the system to further improve the performance. Evaluation shows that our system achieves the best performance from among 10 systems with a balanced F-measure of 82.58 on the closed evaluation of the BioCreative protein/gene name recognition task (Task 1A).

Biomedical Research↗

Predicting protein subcellular locations using hierarchical ensemble of Bayesian classifiers based on Markov chains.

BACKGROUND: The subcellular location of a protein is closely related to its function. It would be worthwhile to develop a method to predict the subcellular location for a given protein when only the amino acid sequence of the protein is known. Although many efforts have been made to predict subcellular location from sequence information only, there is the need for further research to improve the accuracy of prediction. RESULTS: A novel method called HensBC is introduced to predict protein subcellular location. HensBC is a recursive algorithm which constructs a hierarchical ensemble of classifiers. The classifiers used are Bayesian classifiers based on Markov chain models. We tested our method on six various datasets; among them are Gram-negative bacteria dataset, data for discriminating outer membrane proteins and apoptosis proteins dataset. We observed that our method can predict the subcellular location with high accuracy. Another advantage of the proposed method is that it can improve the accuracy of the prediction of some classes with few sequences in training and is therefore useful for datasets with imbalanced distribution of classes. CONCLUSION: This study introduces an algorithm which uses only the primary sequence of a protein to predict its subcellular location. The proposed recursive scheme represents an interesting methodology for learning and combining classifiers. The method is computationally efficient and competitive with the previously reported approaches in terms of prediction accuracies as empirical results indicate. The code for the software is available upon request.

Amino Acid Sequence↗

Expressionview: visualization of quantitative trait loci and gene-expression data in Ensembl.

We present here a software tool for combined visualization of gene-expression data and quantitative trait loci (QTL). The application is implemented as an extension to the Ensembl project and caters for a direct transition from microarray experiments of gene or protein expression levels to the genomic context of individual genes and QTL. It supports the visualization of gene clusters and the selection of functional candidate genes in the context of research on complex traits.

Animals↗

An ensemble model of the male gonadal axis: illustrative application in aging men.

Testosterone (Te) production declines in the aging male, albeit for unknown reasons. Plausible mechanisms include reduced secretion of GnRH, less feedforward by LH, and/or altered feedback by systemic Te. The present study tests all three postulates in a cohort of 10 young (20-35 yr old) and eight older (50-72 yr old) men. The experimental paradigm comprised graded blockade of the GnRH receptor to create four distinct strata of LH and Te pulsatility in each subject. A novel analytical formalism was developed to reconstruct implicit dose-response functions linking 1) virtual GnRH outflow positively to LH secretion, 2) LH pulses positively to Te secretion, and 3) Te concentrations negatively to the size and number of LH secretory bursts. Validation was by direct pituitary sampling in the horse and sheep. Statistical comparisons disclosed that age decreased the efficacy of each of 1) virtual GnRH outflow (P < 0.01), 2) LH drive of Te secretion (P < 0.01), and 3) total, bioavailable and free Te feedback on GnRH-driven LH secretion (P = 0.015). In contrast, age increased the potency of virtual GnRH feedforward (P = 0.013) and did not affect Te's inhibition of LH pulse frequency. Unexplained variance was less than 10%. Robustness was shown by resampling techniques. Accordingly, competitive silencing of one locus of control and ensemble-based analyses identified triple regulatory deficits in the aging male gonadal axis. The generality of the present integrative model suggests utility in parsing interlinked adaptations in other physiological networks.

Adult↗

Dynamics of the pituitary-adrenal ensemble in hypocretin-deficient narcoleptic humans: blunted basal adrenocorticotropin release and evidence for normal time-keeping by the master pacemaker.

Narcolepsy is a sleep disorder caused by disruption of hypocretin (orexin) neurotransmission. It has been suggested that anomalous timing by the biological clock contributes to the symptomatology. Hypocretins stimulate the pituitary-adrenal (PA) axis in rodents. We explored whether hypocretin deficiency disrupts circadian timing and blunts PA hormone release. We deconvolved 24-h plasma profiles of ACTH and cortisol, and determined their circadian rhythm by cosinor analysis in seven hypocretin-deficient narcoleptic males and seven matched controls. Basal and total ACTH production were blunted in narcoleptics [310 +/- 86 vs. 760 +/-160 ng/liter.24 h (P = 0.02) and 920 +/- 147 vs. 1460 +/- 220 ng/liter.24 h (P = 0.04), respectively], whereas pulsatile release did not differ between groups. In contrast, basal, pulsatile and total cortisol secretion were similar in both groups. The cross-approximate entropy of the joint ACTH/cortisol time series was higher in narcoleptics (1.26 +/- 0.07 vs. 1.07 +/- 0.04; P = 0.04), reflecting reduced secretory process regularity. The acrophases of both ACTH and cortisol occurred at similar clock times (approximately 0830 h) in patients and controls, which supports the idea that the master pacemaker is intact in narcolepsy. The reduced (basal) ACTH secretion and the diminished secretory process regularity of the ACTH/cortisol ensemble conjointly suggest that hypocretin deficiency induces changes in the interplay between PA hormones.

Adrenal Glands↗