Are class II phosphoinositide 3-kinases potential targets for anticancer therapies?

Of the three classes of true phosphoinositide (PI) 3-kinases, the class II subdivision, which consists of three isoforms, PI3K-C2alpha, PI3K-C2beta and PI3K-C2gamma, is the least well understood. There are a number of reasons for this. This class of PI 3-kinase was identified exclusively by PCR and homology cloning approaches and not on the basis of cellular function. Like class I PI 3-kinases, class II PI 3-kinases are activated by diverse receptor types. To complicate the elucidation of class II PI 3-kinase function further, their in vitro substrate specificity is intermediate between the receptor activated class I PI 3-kinases and the housekeeping class III PI 3-kinase. The class II PI 3-kinases are inhibited by the two commonly used PI 3-kinase family selective inhibitors, wortmannin and LY294002, and there are no widely available, specific inhibitors for the individual classes or isoforms. Here the current state of understanding of class II PI 3-kinase function is reviewed, followed by an appraisal as to whether there is enough evidence to suggest that pharmaceutical companies, who are currently targeting the class I PI 3-kinases in an attempt to generate anticancer agents, should also consider targeting the class II PI 3-kinases.

Improvement of classification accuracy for stochastic discrimination - Multi-class classification

In this paper, an improved stochastic discrimination (SD) is introduced to reduce the error rate of the standard SD in the context of multi-class classification problem. The learning procedure of the improved SD consists of two stages. In the first stage, a standard SD, but with shorter learning period is carried out to identify an important space where all the misclassified samples are located. In the second stage, the standard SD is modified by (i) restricting sampling in the important space; and (ii) introducing a new discriminant function for samples in the important space. It is shown by mathematical derivation that the new discriminant function has the same mean, but smaller variance than that of standard SD for samples in the important space. It is also analyzed that the smaller the variance of the discriminant function, the lower the error rate of the classifier. Consequently, the proposed improved SD improves standard SD by its capability of achieving higher classification accuracy. Illustrative examples axe provided to demonstrate the effectiveness of the proposed improved SD.

Grey-box radial basis function modelling: the art of incorporating prior knowledge

A basic principle in data modelling is to incorporate available a priori information regarding the underlying data generating mechanism into the modelling process. We adopt this principle and consider grey-box radial basis function (RBF) modelling capable of incorporating prior knowledge. Specifically, we show how to explicitly incorporate the two types of prior knowledge: the underlying data generating mechanism exhibits known symmetric property and the underlying process obeys a set of given boundary value constraints. The class of orthogonal least squares regression algorithms can readily be applied to construct parsimonious grey-box RBF models with enhanced generalisation capability.

Fully complex-valued radial basis function networks: orthogonal least squares regression and classification

We consider a fully complex-valued radial basis function (RBF) network for regression and classification applications. For regression problems, the locally regularised orthogonal least squares (LROLS) algorithm aided with the D-optimality experimental design, originally derived for constructing parsimonious real-valued RBF models, is extended to the fully complex-valued RBF (CVRBF) network. Like its real-valued counterpart, the proposed algorithm aims to achieve maximised model robustness and sparsity by combining two effective and complementary approaches. The LROLS algorithm alone is capable of producing a very parsimonious model with excellent generalisation performance while the D-optimality design criterion further enhances the model efficiency and robustness. By specifying an appropriate weighting for the D-optimality cost in the combined model selecting criterion, the entire model construction procedure becomes automatic. An example of identifying a complex-valued nonlinear channel is used to illustrate the regression application of the proposed fully CVRBF network. The proposed fully CVRBF network is also applied to four-class classification problems that are typically encountered in communication systems. A complex-valued orthogonal forward selection algorithm based on the multi-class Fisher ratio of class separability measure is derived for constructing sparse CVRBF classifiers that generalise well. The effectiveness of the proposed algorithm is demonstrated using the example of nonlinear beamforming for multiple-antenna aided communication systems that employ complex-valued quadrature phase shift keying modulation scheme. (C) 2007 Elsevier B.V. All rights reserved.

Construction of tunable radial basis function networks using orthogonal forward selection

An orthogonal forward selection (OFS) algorithm based on leave-one-out (LOO) criteria is proposed for the construction of radial basis function (RBF) networks with tunable nodes. Each stage of the construction process determines an RBF node, namely, its center vector and diagonal covariance matrix, by minimizing the LOO statistics. For regression application, the LOO criterion is chosen to be the LOO mean-square error, while the LOO misclassification rate is adopted in two-class classification application. This OFS-LOO algorithm is computationally efficient, and it is capable of constructing parsimonious RBF networks that generalize well. Moreover, the proposed algorithm is fully automatic, and the user does not need to specify a termination criterion for the construction process. The effectiveness of the proposed RBF network construction procedure is demonstrated using examples taken from both regression and classification applications.

Kernel classifier construction using orthogonal forward selection and boosting with Fisher ratio class separability measure

A greedy technique is proposed to construct parsimonious kernel classifiers using the orthogonal forward selection method and boosting based on Fisher ratio for class separability measure. Unlike most kernel classification methods, which restrict kernel means to the training input data and use a fixed common variance for all the kernel terms, the proposed technique can tune both the mean vector and diagonal covariance matrix of individual kernel by incrementally maximizing Fisher ratio for class separability measure. An efficient weighted optimization method is developed based on boosting to append kernels one by one in an orthogonal forward selection procedure. Experimental results obtained using this construction technique demonstrate that it offers a viable alternative to the existing state-of-the-art kernel modeling methods for constructing sparse Gaussian radial basis function network classifiers. that generalize well.

Global exponential periodicity of a class of bidirectional associative memory networks with finite distributed delays

In this paper, we study the periodic oscillatory behavior of a class of bidirectional associative memory (BAM) networks with finite distributed delays. A set of criteria are proposed for determining global exponential periodicity of the proposed BAM networks, which assume neither differentiability nor monotonicity of the activation function of each neuron. In addition, our criteria are easily checkable. (c) 2005 Elsevier Inc. All rights reserved.

Global exponential periodicity of a class of neural networks with recent-history distributed delays

In this paper, we propose to study a class of neural networks with recent-history distributed delays. A sufficient condition is derived for the global exponential periodicity of the proposed neural networks, which has the advantage that it assumes neither the differentiability nor monotonicity of the activation function of each neuron nor the symmetry of the feedback matrix or delayed feedback matrix. Our criterion is shown to be valid by applying it to an illustrative system. (c) 2005 Elsevier Ltd. All rights reserved.

Grey-box radial basis function modelling

A fundamental principle in data modelling is to incorporate available a priori information regarding the underlying data generating mechanism into the modelling process. We adopt this principle and consider grey-box radial basis function (RBF) modelling capable of incorporating prior knowledge. Specifically, we show how to explicitly incorporate the two types of prior knowledge: (i) the underlying data generating mechanism exhibits known symmetric property, and (ii) the underlying process obeys a set of given boundary value constraints. The class of efficient orthogonal least squares regression algorithms can readily be applied without any modification to construct parsimonious grey-box RBF models with enhanced generalisation capability.

On combination of SMOTE and particle swarm optimization based radial basis function classifier for imbalanced problems

The combination of the synthetic minority oversampling technique (SMOTE) and the radial basis function (RBF) classifier is proposed to deal with classification for imbalanced two-class data. In order to enhance the significance of the small and specific region belonging to the positive class in the decision region, the SMOTE is applied to generate synthetic instances for the positive class to balance the training data set. Based on the over-sampled training data, the RBF classifier is constructed by applying the orthogonal forward selection procedure, in which the classifier structure and the parameters of RBF kernels are determined using a particle swarm optimization algorithm based on the criterion of minimizing the leave-one-out misclassification rate. The experimental results on both simulated and real imbalanced data sets are presented to demonstrate the effectiveness of our proposed algorithm.

A combined SMOTE and PSO based RBF classifier for two-class imbalanced problems

This contribution proposes a powerful technique for two-class imbalanced classification problems by combining the synthetic minority over-sampling technique (SMOTE) and the particle swarm optimisation (PSO) aided radial basis function (RBF) classifier. In order to enhance the significance of the small and specific region belonging to the positive class in the decision region, the SMOTE is applied to generate synthetic instances for the positive class to balance the training data set. Based on the over-sampled training data, the RBF classifier is constructed by applying the orthogonal forward selection procedure, in which the classifier's structure and the parameters of RBF kernels are determined using a PSO algorithm based on the criterion of minimising the leave-one-out misclassification rate. The experimental results obtained on a simulated imbalanced data set and three real imbalanced data sets are presented to demonstrate the effectiveness of our proposed algorithm.

Asset allocation, cross-class correlation and the structure of property returns

Practical applications of portfolio optimisation tend to proceed on a “top down” basis where funds are allocated first at asset class level (between, say, bonds, cash, equities and real estate) and then, progressively, at sub-class level (within property to sectors, office, retail, industrial for example). While there are organisational benefits from such an approach, it can potentially lead to sub-optimal allocations when compared to a “global” or “side-by-side” optimisation. This will occur where there are correlations between sub-classes across the asset divide that are masked in aggregation – between, for instance, City offices and the performance of financial services stocks. This paper explores such sub-class linkages using UK monthly stock and property data. Exploratory analysis using clustering procedures and factor analysis suggests that property performance and equity performance are distinctive: there is little persuasive evidence of contemporaneous or lagged sub-class linkages. Formal tests of the equivalence of optimised portfolios using top-down and global approaches failed to demonstrate significant differences, whether or not allocations were constrained. While the results may be a function of measurement of market returns, it is those returns that are used to assess fund performance. Accordingly, the treatment of real estate as a distinct asset class with diversification potential seems justified.

A Nyström method for a class of integral equations on the real line with applications to scattering by diffraction gratings and rough surfaces

We propose a Nystr¨om/product integration method for a class of second kind integral equations on the real line which arise in problems of two-dimensional scalar and elastic wave scattering by unbounded surfaces. Stability and convergence of the method is established with convergence rates dependent on the smoothness of components of the kernel. The method is applied to the problem of acoustic scattering by a sound soft one-dimensional surface which is the graph of a function f, and superalgebraic convergence is established in the case when f is infinitely smooth. Numerical results are presented illustrating this behavior for the case when f is periodic (the diffraction grating case). The Nystr¨om method for this problem is stable and convergent uniformly with respect to the period of the grating, in contrast to standard integral equation methods for diffraction gratings which fail at a countable set of grating periods.