The philosophical significance of Cox's theorem

Cox's theorem states that, under certain assumptions, any measure of belief is isomorphic to a probability measure. This theorem, although intended as a justification of the subjectivist interpretation of probability theory, is sometimes presented as an argument for more controversial theses. Of particular interest is the thesis that the only coherent means of representing uncertainty is via the probability calculus. In this paper I examine the logical assumptions of Cox's theorem and I show how these impinge on the philosophical conclusions thought to be supported by the theorem. I show that the more controversial thesis is not supported by Cox's theorem. (C) 2003 Elsevier Inc. All rights reserved.

Logic of Violations: A gentzen systems for reasoning with contrary-to-duty obligations

In this paper we present a Gentzen system for reasoning with contrary-to-duty obligations. The intuition behind the system is that a contrary-to-duty is a special kind of normative exception. The logical machinery to formalise this idea is taken from substructural logics and it is based on the definition of a new non-classical connective capturing the notion of reparational obligation. Then the system is tested against well-known contrary-to-duty paradoxes.

Non-positivity of Groenewold operators

A central feature in the Hilbert space formulation of classical mechanics is the quantisation of classical Lionville densities, leading to what may be termed Groenewold operators. We investigate the spectra of the Groenewold operators that correspond to Gaussian and to certain uniform Lionville densities. We show that when the classical coordinate-momentum uncertainty product falls below Heisenberg's limit, the Groenewold operators in the Gaussian case develop negative eigenvalues and eigenvalues larger than 1. However, in the uniform case, negative eigenvalues are shown to persist for arbitrarily large values of the classical uncertainty product.

A potential role for isothermal calorimetry in studies of the effects of thermodynamic non-ideality in enzyme-catalyzed reactions

Attention is drawn to the feasibility of using isothermal calorimetry for the characterization of enzyme reactions under conditions bearing greater relevance to the crowded biological environment, where kinetic parameters are likely to differ significantly from those obtained by classical enzyme kinetic studies in dilute solution. An outline of the application of isothermal calorimetry to the determination of enzyme kinetic parameters is followed by considerations of the nature and consequences of crowding effects in enzyme catalysis. Some of those effects of thermodynamic non-ideality are then illustrated by means of experimental results from calorimetric studies of the effect of molecular crowding on the kinetics of catalysis by rabbit muscle pyruvate kinase. This review concludes with a discussion of the potential of isothermal calorimetry for the experimental determination of kinetic parameters for enzymes either in biological environments or at least in media that should provide reasonable approximations of the crowded conditions encountered in vivo. Copyright (C) 2004 John Wiley Sons, Ltd.

Prediction of HLA-DQ3.2 beta ligands: evidence of multiple registers in class II binding peptides

Motivation: While processing of MHC class II antigens for presentation to helper T-cells is essential for normal immune response, it is also implicated in the pathogenesis of autoimmune disorders and hypersensitivity reactions. Sequence-based computational techniques for predicting HLA-DQ binding peptides have encountered limited success, with few prediction techniques developed using three-dimensional models. Methods: We describe a structure-based prediction model for modeling peptide-DQ3.2 beta complexes. We have developed a rapid and accurate protocol for docking candidate peptides into the DQ3.2 beta receptor and a scoring function to discriminate binders from the background. The scoring function was rigorously trained, tested and validated using experimentally verified DQ3.2 beta binding and non-binding peptides obtained from biochemical and functional studies. Results: Our model predicts DQ3.2 beta binding peptides with high accuracy [area under the receiver operating characteristic (ROC) curve A(ROC) > 0.90], compared with experimental data. We investigated the binding patterns of DQ3.2 beta peptides and illustrate that several registers exist within a candidate binding peptide. Further analysis reveals that peptides with multiple registers occur predominantly for high-affinity binders.