Computer control for continuous cultivation ofSaccharomyces cerevisiae

Summary An on-line respiratory quotient control system has been developed for the continuous cultivation of baker's yeast. This system is based on moving identification of the microbial dynamics. The optimal dilution rate that was selected as the control variable was determined by minimizing a performance index. Without resorting to complicated microbial analysis, a simple and practical moving model is obtained by continually updating the input and output data. The experimental results indicate the satisfactory controllability of the present system and the possible extention of the proposed method to other bioprocesses.     

Nonlinear control of bioreactors with input multiplicities in dilution rate

Control problems of continuous bioreactors having two input multiplicities in dilution rate on the productivity are analyzed. The nonlinear system is represented by a unity gain linear subsystem cascaded with a nonlinear gain subsystem. A conventional PI controller designed for the linear subsystem followed by the solution of the nonlinear gain equation gives a nonlinear controller. The performance of the nonlinear controller is compared with that of the conventional PI controller and also of the nonlinear controller [1] designed based on the output equation. The present nonlinear PI controller gives a superior performance. A single set of controller settings can be used for both the operating points. Whereas the linear PI controller and the nonlinear controller proposed by Henson and Seborg [1] destabilize the system.     

Automated detection of driver fatigue based on EEG signals using gradient boosting decision tree model

Driver fatigue is increasingly a contributing factor for traffic accidents, so an effective method to automatically detect driver fatigue is urgently needed. In this study, in order to catch the main characteristics of the EEG signals, four types of entropies (based on the EEG signal of a single channel) were calculated as the feature sets, including sample entropy, fuzzy entropy, approximate entropy and spectral entropy. All feature sets were used as the input of a gradient boosting decision tree (GBDT), a fast and highly accurate boosting ensemble method. The output of GBDT determined whether a driver was in a fatigue state or not based on their EEG signals. Three state-of-the-art classifiers, k-nearest neighbor, support vector machine and neural network were also employed. To assess our method, several experiments including parameter setting and classification performance comparison were performed on 22 subjects. The results indicated that it is possible to use only one EEG channel to detect a driver fatigue state. The average highest recognition rate in this work was up to 94.0%, which could meet the needs of daily applications. Our GBDT-based method may assist in the detection of driver fatigue.     

The rate of information transfer of naturalistic stimulation by graded potentials

We present a method to measure the rate of information transfer for any continuous signals of finite duration without assumptions. After testing the method with simulated responses, we measure the encoding performance of Calliphora photoreceptors. We find that especially for naturalistic stimulation the responses are nonlinear and noise is nonadditive, and show that adaptation mechanisms affect signal and noise differentially depending on the time scale, structure, and speed of the stimulus. Different signaling strategies for short- and long-term and dim and bright light are found for this graded system when stimulated with naturalistic light changes.     

Gamma oscillations as a mechanism for selective information transmission

In the past decades, many studies have focussed on the relation between the input and output of neurons with the aim to understand information processing by neurons. A particular aspect of neuronal information, which has not received much attention so far, concerns the problem of information transfer when a neuron or a population of neurons receives input from two or more (populations of) neurons, in particular when these (populations of) neurons carry different types of information. The aim of the present study is to investigate the responses of neurons to multiple inputs modulated in the gamma frequency range. By a combination of theoretical approaches and computer simulations, we test the hypothesis that enhanced modulation of synchronized excitatory neuronal activity in the gamma frequency range provides an advantage over a less synchronized input for various types of neurons. The results of this study show that the spike output of various types of neurons [i.e. the leaky integrate and fire neuron, the quadratic integrate and fire neuron and the Hodgkin–Huxley (HH) neuron] and that of excitatory–inhibitory coupled pairs of neurons, like the Pyramidal Interneuronal Network Gamma (PING) model, is highly phase-locked to the larger of two gamma-modulated input signals. This implies that the neuron selectively responds to the input with the larger gamma modulation if the amplitude of the gamma modulation exceeds that of the other signals by a certain amount. In that case, the output of the neuron is entrained by one of multiple inputs and that other inputs are not represented in the output. This mechanism for selective information transmission is enhanced for short membrane time constants of the neuron.     

Adaptive rescaling maximizes information transmission

Adaptation is a widespread phenomenon in nervous systems, providing flexibility to function under varying external conditions. Here, we relate an adaptive property of a sensory system directly to its function as a carrier of information about input signals. We show that the input/output relation of a sensory system in a dynamic environment changes with the statistical properties of the environment. Specifically, when the dynamic range of inputs changes, the input/output relation rescales so as to match the dynamic range of responses to that of the inputs. We give direct evidence that the scaling of the input/output relation is set to maximize information transmission for each distribution of signals. This adaptive behavior should be particularly useful in dealing with the intermittent statistics of natural signals.     

Linear and quadratic models of point process systems: Contributions of patterned input to output

In the 1880's Volterra characterised a nonlinear system using a functional series connecting continuous input and continuous output. Norbert Wiener, in the 1940's, circumvented problems associated with the application of Volterra series to physical problems by deriving from it a new series of terms that are mutually uncorrelated with respect to Gaussian processes. Subsequently, Brillinger, in the 1970's, introduced a point-process analogue of Volterra's series connecting point-process inputs to the instantaneous rate of point-process output. We derive here a new series from this analogue in which its terms are mutually uncorrelated with respect to Poisson processes. This new series expresses how patterned input in a spike train, represented by third-order cross-cumulants, is converted into the instantaneous rate of an output point-process. Given experimental records of suitable duration, the contribution of arbitrary patterned input to an output process can, in principle, be determined. Solutions for linear and quadratic point-process models with one and two inputs and a single output are investigated. Our theoretical results are applied to isolated muscle spindle data in which the spike trains from the primary and secondary endings from the same muscle spindle are recorded in response to stimulation of one and then two static fusimotor axons in the absence and presence of a random length change imposed on the parent muscle. For a fixed mean rate of input spikes, the analysis of the experimental data makes explicit which patterns of two input spikes contribute to an output spike.     

Neural network comparing two-rate-encoded inputs entering in parallel

Presented computational model of a neural network is able to compare two regular input frequencies. The comparison is based on detection of inter-spike interval differences of the two frequencies. This detection is continuous and the network dynamically changes its output according to the changes in the input frequencies. The entire network is composed of biologically plausible parts. A combination of such simple comparators might be involved in the information processing in the central nervous system.     

Enzyme logic gates for the digital analysis of physiological level upon injury

A biocomputing system composed of a combination of AND/IDENTITY logic gates based on the concerted operation of three enzymes: lactate oxidase, horseradish peroxidase and glucose dehydrogenase was designed to process biochemical information related to pathophysiological conditions originating from various injuries. Three biochemical markers: lactate, norepinephrine and glucose were applied as input signals to activate the enzyme logic system. Physiologically normal concentrations of the markers were selected as logic 0 values of the input signals, while their abnormally increased concentrations, indicative of various injury conditions were defined as logic 1 input. Biochemical processing of different patterns of the biomarkers resulted in the formation of norepi-quinone and NADH defined as the output signals. Optical and electrochemical means were used to follow the formation of the output signals for eight different combinations of three input signals. The enzymatically processed biochemical information presented in the form of a logic truth table allowed distinguishing the difference between normal physiological conditions, pathophysiological conditions corresponding to traumatic brain injury and hemorrhagic shock, and abnormal situations (not corresponding to injury). The developed system represents a biocomputing logic system applied for the analysis of biomedical conditions related to various injuries. We anticipate that such biochemical logic gates will facilitate decision-making in connection to an integrated therapeutic feedback-loop system and hence will revolutionize the monitoring and treatment of injured civilians and soldiers.     

A model for dual channel segmentation of the EEG signal

Dual channel segmentation of the EEG signal has been developed. The purpose was to divide the signals into segments, according to information common for the two channels. The criterion for segmentation was based on the changes in the cross-spectrum of the two signals. It has been shown theoretically, as well as by simulation studies and by analysis of real EEG data that this method is sensitive to changes common for both channels, whereas segmentation does not occur as a result of changes in each channel separately.     

Regularized common spatial patterns with subject-to-subject transfer of EEG signals

In the context of brain-computer interface (BCI) system, the common spatial patterns (CSP) method has been used to extract discriminative spatial filters for the classification of electroencephalogram (EEG) signals. However, the classification performance of CSP typically deteriorates when a few training samples are collected from a new BCI user. In this paper, we propose an approach that maintains or improves the recognition accuracy of the system with only a small size of training data set. The proposed approach is formulated by regularizing the classical CSP technique with the strategy of transfer learning. Specifically, we incorporate into the CSP analysis inter-subject information involving the same task, by minimizing the difference between the inter-subject features. Experimental results on two data sets from BCI competitions show that the proposed approach greatly improves the classification performance over that of the conventional CSP method; the transformed variant proved to be successful in almost every case, based on a small number of available training samples.     

Information capacity and its approximations under metabolic cost in a simple homogeneous population of neurons

We calculate and analyze the information capacity-achieving conditions and their approximations in a simple neuronal system. The input–output properties of individual neurons are described by an empirical stimulus–response relationship and the metabolic cost of neuronal activity is taken into account. The exact (numerical) results are compared with a popular “low-noise” approximation method which employs the concepts of parameter estimation theory. We show, that the approximate method gives reliable results only in the case of significantly low response variability. By employing specialized numerical procedures we demonstrate, that optimal information transfer can be near-achieved by a number of different input distributions. It implies that the precise structure of the capacity-achieving input is of lesser importance than the value of capacity. Finally, we illustrate on an example that an innocuously looking stimulus–response relationship may lead to a problematic interpretation of the obtained Fisher information values.     

100% Classification Accuracy Considered Harmful: The Normalized Information Transfer Factor Explains the Accuracy Paradox

The most widely spread measure of performance, accuracy, suffers from a paradox: predictive models with a given level of accuracy may have greater predictive power than models with higher accuracy. Despite optimizing classification error rate, high accuracy models may fail to capture crucial information transfer in the classification task. We present evidence of this behavior by means of a combinatorial analysis where every possible contingency matrix of 2, 3 and 4 classes classifiers are depicted on the entropy triangle, a more reliable information-theoretic tool for classification assessment.Motivated by this, we develop from first principles a measure of classification performance that takes into consideration the information learned by classifiers. We are then able to obtain the entropy-modulated accuracy (EMA), a pessimistic estimate of the expected accuracy with the influence of the input distribution factored out, and the normalized information transfer factor (NIT), a measure of how efficient is the transmission of information from the input to the output set of classes.The EMA is a more natural measure of classification performance than accuracy when the heuristic to maximize is the transfer of information through the classifier instead of classification error count. The NIT factor measures the effectiveness of the learning process in classifiers and also makes it harder for them to “cheat” using techniques like specialization, while also promoting the interpretability of results. Their use is demonstrated in a mind reading task competition that aims at decoding the identity of a video stimulus based on magnetoencephalography recordings. We show how the EMA and the NIT factor reject rankings based in accuracy, choosing more meaningful and interpretable classifiers.     

Redundancy reducing processes in single neurons

Interaction mechanisms between excitatory and inhibitory impulse sequences operating on neurons play an important role for the processing of information by the nervous system. For instance, the convergence of excitatory and inhibitory influences on retinal ganglion cells to form their receptive fields has been taken as an example for the process of neuronal sharpening by lateral inhibition. In order to analyze quantitatively the functional behavior of such a system, Shannon's entropy method for multiple access channels has been applied to biological two-inputs-one-output systems using the theoretical model developed by Tsukada et al. (1979). Here we give an extension of this procedure from the point of view to reduce redundancy of information in the input signal space of single neurons and attempt to obtain a new interpretation for the information processing of the system. The concept for the redundancy reducing mechanism in single neurons is examined and discussed for the following two processes. The first process is concerned with a signal space formed by superposing two random sequences on the input of a neuron. In this process, we introduce a coding technique to encode the inhibitory sequence by using the timing of the excitatory sequence, which is closely related to an encoding technique of multiple access channels with a correlated source (Marko, 1966, 1970, 1973; Slepian and Wolf, 1973) and which is an invariant transformation in the input signal space without changing the information contents of the input. The second process is concerned with a procedure of reducing redundant signals in the signal space mentioned before. In this connection, it is an important point to see how single neurons reduce the dimensionality of the signal space via transformation with a minimum loss of effective information. For this purpose we introduce the criterion that average transmission of information from signal space to the output does not change when redundant signals are added. This assumption is based on the fact that two signals are equivalent if and only if they have identical input-output behavior. The mechanism is examined and estimated by using a computer-simulated model. As the result of such a simulation we can estimate the minimal segmentation in the signal space which is necessary and sufficient for temporal pattern sensitivity in neurons.     

A Comparison Study of Canonical Correlation Analysis Based Methods for Detecting Steady-State Visual Evoked Potentials

Canonical correlation analysis (CCA) has been widely used in the detection of the steady-state visual evoked potentials (SSVEPs) in brain-computer interfaces (BCIs). The standard CCA method, which uses sinusoidal signals as reference signals, was first proposed for SSVEP detection without calibration. However, the detection performance can be deteriorated by the interference from the spontaneous EEG activities. Recently, various extended methods have been developed to incorporate individual EEG calibration data in CCA to improve the detection performance. Although advantages of the extended CCA methods have been demonstrated in separate studies, a comprehensive comparison between these methods is still missing. This study performed a comparison of the existing CCA-based SSVEP detection methods using a 12-class SSVEP dataset recorded from 10 subjects in a simulated online BCI experiment. Classification accuracy and information transfer rate (ITR) were used for performance evaluation. The results suggest that individual calibration data can significantly improve the detection performance. Furthermore, the results showed that the combination method based on the standard CCA and the individual template based CCA (IT-CCA) achieved the highest performance.     

Pattern orthogonalization via channel decorrelation by adaptive networks

The early processing of sensory information by neuronal circuits often includes a reshaping of activity patterns that may facilitate further processing in the brain. For instance, in the olfactory system the activity patterns that related odors evoke at the input of the olfactory bulb can be highly similar. Nevertheless, the corresponding activity patterns of the mitral cells, which represent the output of the olfactory bulb, can differ significantly from each other due to strong inhibition by granule cells and peri-glomerular cells. Motivated by these results we study simple adaptive inhibitory networks that aim to separate or even orthogonalize activity patterns representing similar stimuli. Since the animal experiences the different stimuli at different times it is difficult for the network to learn the connectivity based on their similarity; biologically it is more plausible that learning is driven by simultaneous correlations between the input channels. We investigate the connection between pattern orthogonalization and channel decorrelation and demonstrate that networks can achieve effective pattern orthogonalization through channel decorrelation if they simultaneously equalize their output levels. In feedforward networks biophysically plausible learning mechanisms fail, however, for even moderately similar input patterns. Recurrent networks do not have that limitation; they can orthogonalize the representations of highly similar input patterns. Even when they are optimized for linear neuronal dynamics they perform very well when the dynamics are nonlinear. These results provide insights into fundamental features of simplified inhibitory networks that may be relevant for pattern orthogonalization by neuronal circuits in general.     

Identification and control of dissolved oxygen in hybridoma cell culture in a shear sensitive environment

The productivity of mammalian cells can be enhanced by facilitating adequate oxygen transfer into the cultivation medium. However, current methods of controlling dissolved oxygen (DO) fail to account for alterations in medium composition during the course of the fermentation. These changes, which directly affect gas solubility and overall mass transfer coefficient, may be significant and deteriorate controller's performance in the long run. In this paper, the applications of Generalized Predictive Controllers (GPC) to DO control were investigated in a shear sensitive environment and compared to PID and Model Predictive Controllers (MPC). Input and output data for system identification were initially generated by varying the composition of oxygen fed into the bioreactor from 0 to 0.21 mol % while keeping the total inlet gas flow rate at 8.75 vvm. The process was identified using an AutoRegressive model with eXogeneous inputs (ARX) model and tested on different data sets. The model parameters were then correlated with the overall mass transfer coefficients. In simulation tests, the output of the PID controller switched from minimum to maximum values while more continuous control signals were obtained with the MPC and GPC controllers. When tested in a cell-free medium, all three controllers were able to track setpoint changes with some chattering observed in the control signals. The GPC outperformed the MPC and PID controllers when applied to the cultivation of hybridoma cells.     

Microwave irradiation and instrumental behavior in rats: Unitized irradiation and behavioral evaluation facility

A facility for the exposure of small animals to pulse-modulated microwave radiation ( PM MWR ) concurrent with their performance of operant behavioral tasks is described. The computer-managed facility comprises an array of 32 individual waveguide exposure cells, each enclosing instrumental conditioning apparatus within a plastic subhousing. The distribution of the microwave electric field intensity within the waveguide was measured by a nonperturbing probe and the modifications induced by the behavioral apparatus and animal within the waveguide determined. Input and interior voltage standing wave ratios are presented to characterize the design of the chambers and to demonstrate the suitability of the chambers for whole-body irradiation of rat. The specific absorption rate (SAR) is presented utilizing data derived from incremental thermometric examination of saline loads and of selected sites in rat carcasses. This is compared with the whole-body SAR derived from the input/ output energy balance equation for the waveguide. The results of continuous monitoring of the SAR by the latter method, while unrestrained rats were engaged in operant and exploratory behavior within the waveguide, are utilized to derive a relationship between chamber input power and the dose rate for adult rats behaviorally active within the waveguide. From these data, we conclude that the experimental array provides a practical method for exposing a large number of animals to PM MWR for long periods of time and coincident with the establishment and/or performance of complex operant behavior.