The parish priest on duty : a practical manual for pastors, curates, and theological students preparing for the mission : being a brief summary of the prescribed manner of administering the sacraments, the service of the dead, and sundry other pastoral functions in accordance with the Roman Ritual (The Sacraments) / by H.J. Heuser.

http://www.archive.org/details/theparishpriesto00heusuoft

Protein Docking by the Underestimation of Free Energy Funnels in the Space of Encounter Complexes

Similarly to protein folding, the association of two proteins is driven by a free energy funnel, determined by favorable interactions in some neighborhood of the native state. We describe a docking method based on stochastic global minimization of funnel-shaped energy functions in the space of rigid body motions (SE(3)) while accounting for flexibility of the interface side chains. The method, called semi-definite programming-based underestimation (SDU), employs a general quadratic function to underestimate a set of local energy minima and uses the resulting underestimator to bias further sampling. While SDU effectively minimizes functions with funnel-shaped basins, its application to docking in the rotational and translational space SE(3) is not straightforward due to the geometry of that space. We introduce a strategy that uses separate independent variables for side-chain optimization, center-to-center distance of the two proteins, and five angular descriptors of the relative orientations of the molecules. The removal of the center-to-center distance turns out to vastly improve the efficiency of the search, because the five-dimensional space now exhibits a well-behaved energy surface suitable for underestimation. This algorithm explores the free energy surface spanned by encounter complexes that correspond to local free energy minima and shows similarity to the model of macromolecular association that proceeds through a series of collisions. Results for standard protein docking benchmarks establish that in this space the free energy landscape is a funnel in a reasonably broad neighborhood of the native state and that the SDU strategy can generate docking predictions with less than 5 � ligand interface Ca root-mean-square deviation while achieving an approximately 20-fold efficiency gain compared to Monte Carlo methods.

Integration of relational and hierarchical network information for protein function prediction

BACKGROUND:In the current climate of high-throughput computational biology, the inference of a protein's function from related measurements, such as protein-protein interaction relations, has become a canonical task. Most existing technologies pursue this task as a classification problem, on a term-by-term basis, for each term in a database, such as the Gene Ontology (GO) database, a popular rigorous vocabulary for biological functions. However, ontology structures are essentially hierarchies, with certain top to bottom annotation rules which protein function predictions should in principle follow. Currently, the most common approach to imposing these hierarchical constraints on network-based classifiers is through the use of transitive closure to predictions.RESULTS:We propose a probabilistic framework to integrate information in relational data, in the form of a protein-protein interaction network, and a hierarchically structured database of terms, in the form of the GO database, for the purpose of protein function prediction. At the heart of our framework is a factorization of local neighborhood information in the protein-protein interaction network across successive ancestral terms in the GO hierarchy. We introduce a classifier within this framework, with computationally efficient implementation, that produces GO-term predictions that naturally obey a hierarchical 'true-path' consistency from root to leaves, without the need for further post-processing.CONCLUSION:A cross-validation study, using data from the yeast Saccharomyces cerevisiae, shows our method offers substantial improvements over both standard 'guilt-by-association' (i.e., Nearest-Neighbor) and more refined Markov random field methods, whether in their original form or when post-processed to artificially impose 'true-path' consistency. Further analysis of the results indicates that these improvements are associated with increased predictive capabilities (i.e., increased positive predictive value), and that this increase is consistent uniformly with GO-term depth. Additional in silico validation on a collection of new annotations recently added to GO confirms the advantages suggested by the cross-validation study. Taken as a whole, our results show that a hierarchical approach to network-based protein function prediction, that exploits the ontological structure of protein annotation databases in a principled manner, can offer substantial advantages over the successive application of 'flat' network-based methods.

On Learning Counting Functions With Queries

We investigate the problem of learning disjunctions of counting functions, which are general cases of parity and modulo functions, with equivalence and membership queries. We prove that, for any prime number p, the class of disjunctions of integer-weighted counting functions with modulus p over the domain Znq (or Zn) for any given integer q ≥ 2 is polynomial time learnable using at most n + 1 equivalence queries, where the hypotheses issued by the learner are disjunctions of at most n counting functions with weights from Zp. The result is obtained through learning linear systems over an arbitrary field. In general a counting function may have a composite modulus. We prove that, for any given integer q ≥ 2, over the domain Zn2, the class of read-once disjunctions of Boolean-weighted counting functions with modulus q is polynomial time learnable with only one equivalence query, and the class of disjunctions of log log n Boolean-weighted counting functions with modulus q is polynomial time learnable. Finally, we present an algorithm for learning graph-based counting functions.

Fuzzy ART Choice Functions

Adaptive Resonance Theory (ART) models are real-time neural networks for category learning, pattern recognition, and prediction. Unsupervised fuzzy ART and supervised fuzzy ARTMAP networks synthesize fuzzy logic and ART by exploiting the formal similarity between tile computations of fuzzy subsethood and the dynamics of ART category choice, search, and learning. Fuzzy ART self-organizes stable recognition categories in response to arbitrary sequences of analog or binary input patterns. It generalizes the binary ART 1 model, replacing the set-theoretic intersection (∩) with the fuzzy intersection(∧), or component-wise minimum. A normalization procedure called complement coding leads to a symmetric theory in which the fuzzy intersection and the fuzzy union (∨), or component-wise maximum, play complementary roles. A geometric interpretation of fuzzy ART represents each category as a box that increases in size as weights decrease. This paper analyzes fuzzy ART models that employ various choice functions for category selection. One such function minimizes total weight change during learning. Benchmark simulations compare peformance of fuzzy ARTMAP systems that use different choice functions.

Hippocampal Modulation of Recognition, Conditioning, Timing, and Space: Why So Many Functions?

Advanced Research Projects Agency (ONR N00014-92-J-4015); National Science Foundation (IRI-90-24877); Office of Naval Research (N00014-91-J-1309)