Control of fed-batch fermentations

Fed-batch fermentation is used to prevent or reduce substrate-associated growth inhibition by controlling nutrient supply. Here we review the advances in control of fed-batch fermentations. Simple exponential feeding and inferential methods are examined, as are newer methods based on fuzzy control and neural networks. Considerable interest has developed in these more advanced methods that hold promise for optimizing fed-batch techniques for complex fermentation systems. (C) 1999 Elsevier Science Inc. All rights reserved.

Context-free and context-sensitive dynamics in recurrent neural networks

Continuous-valued recurrent neural networks can learn mechanisms for processing context-free languages. The dynamics of such networks is usually based on damped oscillation around fixed points in state space and requires that the dynamical components are arranged in certain ways. It is shown that qualitatively similar dynamics with similar constraints hold for a(n)b(n)c(n), a context-sensitive language. The additional difficulty with a(n)b(n)c(n), compared with the context-free language a(n)b(n), consists of 'counting up' and 'counting down' letters simultaneously. The network solution is to oscillate in two principal dimensions, one for counting up and one for counting down. This study focuses on the dynamics employed by the sequential cascaded network, in contrast to the simple recurrent network, and the use of backpropagation through time. Found solutions generalize well beyond training data, however, learning is not reliable. The contribution of this study lies in demonstrating how the dynamics in recurrent neural networks that process context-free languages can also be employed in processing some context-sensitive languages (traditionally thought of as requiring additional computation resources). This continuity of mechanism between language classes contributes to our understanding of neural networks in modelling language learning and processing.

Visualization of learning in multilayer perceptron networks using principal component analysis

This paper is concerned with the use of scientific visualization methods for the analysis of feedforward neural networks (NNs). Inevitably, the kinds of data associated with the design and implementation of neural networks are of very high dimensionality, presenting a major challenge for visualization. A method is described using the well-known statistical technique of principal component analysis (PCA). This is found to be an effective and useful method of visualizing the learning trajectories of many learning algorithms such as back-propagation and can also be used to provide insight into the learning process and the nature of the error surface.

An adaptive neural-wavelet model for short term load forecasting

This paper proposed a novel model for short term load forecast in the competitive electricity market. The prior electricity demand data are treated as time series. The forecast model is based on wavelet multi-resolution decomposition by autocorrelation shell representation and neural networks (multilayer perceptrons, or MLPs) modeling of wavelet coefficients. To minimize the influence of noisy low level coefficients, we applied the practical Bayesian method Automatic Relevance Determination (ARD) model to choose the size of MLPs, which are then trained to provide forecasts. The individual wavelet domain forecasts are recombined to form the accurate overall forecast. The proposed method is tested using Queensland electricity demand data from the Australian National Electricity Market. (C) 2001 Elsevier Science B.V. All rights reserved.

Probabilistic modelling of CO2 corrosion laboratory data using neural networks

The present paper addresses two major concerns that were identified when developing neural network based prediction models and which can limit their wider applicability in the industry. The first problem is that it appears neural network models are not readily available to a corrosion engineer. Therefore the first part of this paper describes a neural network model of CO2 corrosion which was created using a standard commercial software package and simple modelling strategies. It was found that such a model was able to capture practically all of the trends noticed in the experimental data with acceptable accuracy. This exercise has proven that a corrosion engineer could readily develop a neural network model such as the one described below for any problem at hand, given that sufficient experimental data exist. This applies even in the cases when the understanding of the underlying processes is poor. The second problem arises from cases when all the required inputs for a model are not known or can be estimated with a limited degree of accuracy. It seems advantageous to have models that can take as input a range rather than a single value. One such model, based on the so-called Monte Carlo approach, is presented. A number of comparisons are shown which have illustrated how a corrosion engineer might use this approach to rapidly test the sensitivity of a model to the uncertainities associated with the input parameters. (C) 2001 Elsevier Science Ltd. All rights reserved.

Empirical evidence for ultrametric structure in multi-layer perceptron error surfaces

Combinatorial optimization problems share an interesting property with spin glass systems in that their state spaces can exhibit ultrametric structure. We use sampling methods to analyse the error surfaces of feedforward multi-layer perceptron neural networks learning encoder problems. The third order statistics of these points of attraction are examined and found to be arranged in a highly ultrametric way. This is a unique result for a finite, continuous parameter space. The implications of this result are discussed.

Learning the dynamics of embedded clauses

Recent work by Siegelmann has shown that the computational power of recurrent neural networks matches that of Turing Machines. One important implication is that complex language classes (infinite languages with embedded clauses) can be represented in neural networks. Proofs are based on a fractal encoding of states to simulate the memory and operations of stacks. In the present work, it is shown that similar stack-like dynamics can be learned in recurrent neural networks from simple sequence prediction tasks. Two main types of network solutions are found and described qualitatively as dynamical systems: damped oscillation and entangled spiraling around fixed points. The potential and limitations of each solution type are established in terms of generalization on two different context-free languages. Both solution types constitute novel stack implementations - generally in line with Siegelmann's theoretical work - which supply insights into how embedded structures of languages can be handled in analog hardware.

Electricity market price spike forecast with data mining techniques

Electricity market price forecast is a changeling yet very important task for electricity market managers and participants. Due to the complexity and uncertainties in the power grid, electricity prices are highly volatile and normally carry with spikes. which may be (ens or even hundreds of times higher than the normal price. Such electricity spikes are very difficult to be predicted. So far. most of the research on electricity price forecast is based on the normal range electricity prices. This paper proposes a data mining based electricity price forecast framework, which can predict the normal price as well as the price spikes. The normal price can be, predicted by a previously proposed wavelet and neural network based forecast model, while the spikes are forecasted based on a data mining approach. This paper focuses on the spike prediction and explores the reasons for price spikes based on the measurement of a proposed composite supply-demand balance index (SDI) and relative demand index (RDI). These indices are able to reflect the relationship among electricity demand, electricity supply and electricity reserve capacity. The proposed model is based on a mining database including market clearing price, trading hour. electricity), demand, electricity supply and reserve. Bayesian classification and similarity searching techniques are used to mine the database to find out the internal relationships between electricity price spikes and these proposed. The mining results are used to form the price spike forecast model. This proposed model is able to generate forecasted price spike, level of spike and associated forecast confidence level. The model is tested with the Queensland electricity market data with promising results. Crown Copyright (C) 2004 Published by Elsevier B.V. All rights reserved.

The applicability of recurrent neural networks for biological sequence analysis

Selection of machine learning techniques requires a certain sensitivity to the requirements of the problem. In particular, the problem can be made more tractable by deliberately using algorithms that are biased toward solutions of the requisite kind. In this paper, we argue that recurrent neural networks have a natural bias toward a problem domain of which biological sequence analysis tasks are a subset. We use experiments with synthetic data to illustrate this bias. We then demonstrate that this bias can be exploitable using a data set of protein sequences containing several classes of subcellular localization targeting peptides. The results show that, compared with feed forward, recurrent neural networks will generally perform better on sequence analysis tasks. Furthermore, as the patterns within the sequence become more ambiguous, the choice of specific recurrent architecture becomes more critical.

Tracking the states of a nonlinear and nonstationary system in the weight-space of artificial neural networks

We propose a novel interpretation and usage of Neural Network (NN) in modeling physiological signals, which are allowed to be nonlinear and/or nonstationary. The method consists of training a NN for the k-step prediction of a physiological signal, and then examining the connection-weight-space (CWS) of the NN to extract information about the signal generator mechanism. We de. ne a novel feature, Normalized Vector Separation (gamma(ij)), to measure the separation of two arbitrary states i and j in the CWS and use it to track the state changes of the generating system. The performance of the method is examined via synthetic signals and clinical EEG. Synthetic data indicates that gamma(ij) can track the system down to a SNR of 3.5 dB. Clinical data obtained from three patients undergoing carotid endarterectomy of the brain showed that EEG could be modeled (within a root-means-squared-error of 0.01) by the proposed method, and the blood perfusion state of the brain could be monitored via gamma(ij), with small NNs having no more than 21 connection weight altogether.

Detecting and sorting targeting peptides wtih neural networks and support vector machines

This paper presents a composite multi-layer classifier system for predicting the subcellular localization of proteins based on their amino acid sequence. The work is an extension of our previous predictor PProwler v1.1 which is itself built upon the series of predictors SignalP and TargetP. In this study we outline experiments conducted to improve the classifier design. The major improvement came from using Support Vector machines as a "smart gate" sorting the outputs of several different targeting peptide detection networks. Our final model (PProwler v1.2) gives MCC values of 0.873 for non-plant and 0.849 for plant proteins. The model improves upon the accuracy of our previous subcellular localization predictor (PProwler v1.1) by 2% for plant data (which represents 7.5% improvement upon TargetP).

Strategies for identifying and predicting islet autoantigen T-cell epitopes in insulin-dependent diabetes mellitus

T cells recognize peptide epitopes bound to major histocompatibility complex molecules. Human T-cell epitopes have diagnostic and therapeutic applications in autoimmune diseases. However, their accurate definition within an autoantigen by T-cell bioassay, usually proliferation, involves many costly peptides and a large amount of blood, We have therefore developed a strategy to predict T-cell epitopes and applied it to tyrosine phosphatase IA-2, an autoantigen in IDDM, and HLA-DR4(*0401). First, the binding of synthetic overlapping peptides encompassing IA-2 was measured directly to purified DR4. Secondly, a large amount of HLA-DR4 binding data were analysed by alignment using a genetic algorithm and were used to train an artificial neural network to predict the affinity of binding. This bioinformatic prediction method was then validated experimentally and used to predict DR4 binding peptides in IA-2. The binding set encompassed 85% of experimentally determined T-cell epitopes. Both the experimental and bioinformatic methods had high negative predictive values, 92% and 95%, indicating that this strategy of combining experimental results with computer modelling should lead to a significant reduction in the amount of blood and the number of peptides required to define T-cell epitopes in humans.

Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules

Efficiency of presentation of a peptide epitope by a MHC class I molecule depends on two parameters: its binding to the MHC molecule and its generation by intracellular Ag processing. In contrast to the former parameter, the mechanisms underlying peptide selection in Ag processing are poorly understood. Peptide translocation by the TAP transporter is required for presentation of most epitopes and may modulate peptide supply to MHC class I molecules. To study the role of human TAP for peptide presentation by individual HLA class I molecules, we generated artificial neural networks capable of predicting the affinity of TAP for random sequence 9-mer peptides. Using neural network-based predictions of TAP affinity, we found that peptides eluted from three different HLA class I molecules had higher TAP affinities than control peptides with equal binding affinities for the same HLA class I molecules, suggesting that human TAP may contribute to epitope selection. In simulated TAP binding experiments with 408 HLA class I binding peptides, HLA class I molecules differed significantly with respect to TAP affinities of their ligands, As a result, some class I molecules, especially HLA-B27, may be particularly efficient in presentation of cytosolic peptides with low concentrations, while most class I molecules may predominantly present abundant cytosolic peptides.

Computational binding assays of antigenic peptides

Computer models can be combined with laboratory experiments for the efficient determination of (i) peptides that bind MHC molecules and (ii) T-cell epitopes. For maximum benefit, the use of computer models must be treated as experiments analogous to standard laboratory procedures. This requires the definition of standards and experimental protocols for model application. We describe the requirements for validation and assessment of computer models. The utility of combining accurate predictions with a limited number of laboratory experiments is illustrated by practical examples. These include the identification of T-cell epitopes from IDDM-, melanoma- and malaria-related antigens by combining computational and conventional laboratory assays. The success rate in determining antigenic peptides, each in the context of a specific HLA molecule, ranged from 27 to 71%, while the natural prevalence of MHC-binding peptides is 0.1-5%.

Knowledge discovery and data mining in biological databases

The new technologies for Knowledge Discovery from Databases (KDD) and data mining promise to bring new insights into a voluminous growing amount of biological data. KDD technology is complementary to laboratory experimentation and helps speed up biological research. This article contains an introduction to KDD, a review of data mining tools, and their biological applications. We discuss the domain concepts related to biological data and databases, as well as current KDD and data mining developments in biology.