Quantitative structure-activity relationship analysis of β-amyloid aggregation inhibitors

Inhibiting the aggregation process of the β-amyloid peptide is a promising strategy in treating Alzheimer’s disease. In this work, we have collected a dataset of 80 small molecules with known inhibition levels and utilized them to develop two comprehensive quantitative structure–activity relationship models: a Bayesian model and a decision tree model. These models have exhibited high predictive accuracy: 87% of the training and test sets using the Bayesian model and 89 and 93% of the training and test sets, respectively, by the decision tree model. Subsequently these models were used to predict the activities of several new potential β-amyloid aggregation inhibitors and these predictions were indeed validated by in vitro experiments. Key chemical features correlated with the inhibition ability were identified. These include the electro-topological state of carbonyl groups, AlogP and the number of hydrogen bond donor groups. The results demonstrate the feasibility of the developed models as tools for rapid screening, which could help in the design of novel potential drug candidates for Alzheimer’s disease.     

Stability of noble-gas hydrocarbons in an organic liquid-like environment: HXeCCH in acetylene

Noble-gas hydrides such as HXeCCH are prepared in cryogenic noble-gas matrices where they are stable. Molecular dynamics simulations reported here predict that HXeCCH is chemically stable in clusters of acetylene, and that stability prevails for temperatures of at least 150 K, at which the clusters are liquid-like. The HXeCCH(C(2)H(2))(n) clusters are studied for sizes up to n = 7. Ab Initio Molecular Dynamics trajectories of 10 ps duration are computed using BLYP-D DFT potential. The liquid-like nature of the system at 150 K is reflected in large amplitude motion of intermolecular distances and orientations. In addition, structures, energetics, NBO charges and bonding analysis at equilibrium are also reported. Complexation is found to be energetically favorable, and to increase the stability of the HXeCCH molecule. The significance of the existence of stable liquid-like complexes of noble-gas hydrides is discussed.     

Zariski geometries

A characterization is obtained of the Zariski topology over an algebraically closed field.

     

ɛ-Consistent equilibrium in repeated games

We introduce the concept of ɛ-consistent equilibrium where each player plays a ɛ-best response after every history reached with positive probability. In particular, an ɛ-consistent equilibrium induces an ɛ-equilibrium in any subgame reached along the play path. The existence of ɛ-consistent equilibrium is examined in various repeated games. The main result is the existence in stochastic games with absorbing states. Received January 1995/Revised version October 1996/Final version September 1997     

On some families of cooperative fuzzy games

In a fuzzy cooperative game the players may choose to partially participate in a coalition. A fuzzy coalition consists of a group of participating players along with their participation level. The characteristic function of a fuzzy game specifies the worth of each such coalition. This paper introduces well-known properties of classical cooperative games to the theory of fuzzy games, and studies their interrelations. It deals with convex games, exact games, games with a large core, extendable games and games with a stable core.