Natural and engineered kallikrein inhibitors: an emerging pharmacopoeia

The kallikreins and kallikrein-related peptidases are serine proteases that control a plethora of developmental and homeostatic phenomena, ranging from semen liquefaction to skin desquamation and blood pressure. The diversity of roles played by kallikreins has stimulated considerable interest in these enzymes from the perspective of diagnostics and drug design. Kallikreins already have well-established credentials as targets for therapeutic intervention and there is increasing appreciation of their potential both as biomarkers and as targets for inhibitor design. Here, we explore the current status of naturally occurring kallikrein protease-inhibitor complexes and illustrate how this knowledge can interface with strategies for rational re-engineering of bioscaffolds and design of small-molecule inhibitors.

Cardiac health diagnosis using higher order spectra and support vector machine

The Electrocardiogram (ECG) is an important bio-signal representing the sum total of millions of cardiac cell depolarization potentials. It contains important insight into the state of health and nature of the disease afflicting the heart. Heart rate variability (HRV) refers to the regulation of the sinoatrial node, the natural pacemaker of the heart by the sympathetic and parasympathetic branches of the autonomic nervous system. The HRV signal can be used as a base signal to observe the heart's functioning. These signals are non-linear and non-stationary in nature. So, higher order spectral (HOS) analysis, which is more suitable for non-linear systems and is robust to noise, was used. An automated intelligent system for the identification of cardiac health is very useful in healthcare technology. In this work, we have extracted seven features from the heart rate signals using HOS and fed them to a support vector machine (SVM) for classification. Our performance evaluation protocol uses 330 subjects consisting of five different kinds of cardiac disease conditions. We demonstrate a sensitivity of 90% for the classifier with a specificity of 87.93%. Our system is ready to run on larger data sets.

Soundness of workflow nets: classification, decidability, and analysis

Workflow nets, a particular class of Petri nets, have become one of the standard ways to model and analyze workflows. Typically, they are used as an abstraction of the workflow that is used to check the so-called soundness property. This property guarantees the absence of livelocks, deadlocks, and other anomalies that can be detected without domain knowledge. Several authors have proposed alternative notions of soundness and have suggested to use more expressive languages, e.g., models with cancellations or priorities. This paper provides an overview of the different notions of soundness and investigates these in the presence of different extensions of workflow nets.We will show that the eight soundness notions described in the literature are decidable for workflow nets. However, most extensions will make all of these notions undecidable. These new results show the theoretical limits of workflow verification. Moreover, we discuss some of the analysis approaches described in the literature.

Spectral–texture feature extraction using statistical moments with application to object-based vegetation species classification

The use of appropriate features to characterise an output class or object is critical for all classification problems. In order to find optimal feature descriptors for vegetation species classification in a power line corridor monitoring application, this article evaluates the capability of several spectral and texture features. A new idea of spectral–texture feature descriptor is proposed by incorporating spectral vegetation indices in statistical moment features. The proposed method is evaluated against several classic texture feature descriptors. Object-based classification method is used and a support vector machine is employed as the benchmark classifier. Individual tree crowns are first detected and segmented from aerial images and different feature vectors are extracted to represent each tree crown. The experimental results showed that the proposed spectral moment features outperform or can at least compare with the state-of-the-art texture descriptors in terms of classification accuracy. A comprehensive quantitative evaluation using receiver operating characteristic space analysis further demonstrates the strength of the proposed feature descriptors.

The sample complexity of pattern classification with neural networks: the size of the weights is more important than the size of the network

Sample complexity results from computational learning theory, when applied to neural network learning for pattern classification problems, suggest that for good generalization performance the number of training examples should grow at least linearly with the number of adjustable parameters in the network. Results in this paper show that if a large neural network is used for a pattern classification problem and the learning algorithm finds a network with small weights that has small squared error on the training patterns, then the generalization performance depends on the size of the weights rather than the number of weights. For example, consider a two-layer feedforward network of sigmoid units, in which the sum of the magnitudes of the weights associated with each unit is bounded by A and the input dimension is n. We show that the misclassification probability is no more than a certain error estimate (that is related to squared error on the training set) plus A3 √((log n)/m) (ignoring log A and log m factors), where m is the number of training patterns. This may explain the generalization performance of neural networks, particularly when the number of training examples is considerably smaller than the number of weights. It also supports heuristics (such as weight decay and early stopping) that attempt to keep the weights small during training. The proof techniques appear to be useful for the analysis of other pattern classifiers: when the input domain is a totally bounded metric space, we use the same approach to give upper bounds on misclassification probability for classifiers with decision boundaries that are far from the training examples.

Convexity, Classification, and Risk Bounds

Many of the classification algorithms developed in the machine learning literature, including the support vector machine and boosting, can be viewed as minimum contrast methods that minimize a convex surrogate of the 0–1 loss function. The convexity makes these algorithms computationally efficient. The use of a surrogate, however, has statistical consequences that must be balanced against the computational virtues of convexity. To study these issues, we provide a general quantitative relationship between the risk as assessed using the 0–1 loss and the risk as assessed using any nonnegative surrogate loss function. We show that this relationship gives nontrivial upper bounds on excess risk under the weakest possible condition on the loss function—that it satisfies a pointwise form of Fisher consistency for classification. The relationship is based on a simple variational transformation of the loss function that is easy to compute in many applications. We also present a refined version of this result in the case of low noise, and show that in this case, strictly convex loss functions lead to faster rates of convergence of the risk than would be implied by standard uniform convergence arguments. Finally, we present applications of our results to the estimation of convergence rates in function classes that are scaled convex hulls of a finite-dimensional base class, with a variety of commonly used loss functions.

On the consistency of multiclass classification methods

Binary classification methods can be generalized in many ways to handle multiple classes. It turns out that not all generalizations preserve the nice property of Bayes consistency. We provide a necessary and sufficient condition for consistency which applies to a large class of multiclass classification methods. The approach is illustrated by applying it to some multiclass methods proposed in the literature.

Classification with a reject option using a hinge loss

We consider the problem of binary classification where the classifier can, for a particular cost, choose not to classify an observation. Just as in the conventional classification problem, minimization of the sample average of the cost is a difficult optimization problem. As an alternative, we propose the optimization of a certain convex loss function φ, analogous to the hinge loss used in support vector machines (SVMs). Its convexity ensures that the sample average of this surrogate loss can be efficiently minimized. We study its statistical properties. We show that minimizing the expected surrogate loss—the φ-risk—also minimizes the risk. We also study the rate at which the φ-risk approaches its minimum value. We show that fast rates are possible when the conditional probability P(Y=1|X) is unlikely to be close to certain critical values.