Ligand-, structure- and pharmacophore-based molecular fingerprints: a case study on adenosine A1, A2A, A2B, and A3 receptor antagonists

FLAP fingerprints are applied in the ligand-, structure- and pharmacophore-based mode in a case study on antagonists of all four adenosine receptor (AR) subtypes. Structurally diverse antagonist collections with respect to the different ARs were constructed by including binding data to human species only. FLAP models well discriminate ??active?? (=highly potent) from ??inactive?? (=weakly potent) AR antagonists, as indicated by enrichment curves, numbers of false positives, and AUC values. For all FLAP modes, model predictivity slightly decreases as follows: A_2BR?>?A_2AR?>?A₃R?>?A₁R antagonists. General performance of FLAP modes in this study is: ligand-?>?structure-?>?pharmacophore- based mode. We also compared the FLAP performance with other common ligand- and structure-based fingerprints. Concerning the ligand-based mode, FLAP model performance is superior to ECFP4 and ROCS for all AR subtypes. Although focusing on the early first part of the A_2A, A_2B and A₃ enrichment curves, ECFP4 and ROCS still retain a satisfactory retrieval of actives. FLAP is also superior when comparing the structure-based mode with PLANTS and GOLD. In this study we applied for the first time the novel FLAPPharm tool for pharmacophore generation. Pharmacophore hypotheses, generated with this tool, convincingly match with formerly published data. Finally, we could demonstrate the capability of FLAP models to uncover selectivity aspects although single AR subtype models were not trained for this purpose.     

Mathematical Force Concept for the One-Way-Coupling of Dynamic Fibers and Turbulent Flows

For the modeling of turbulence effects on the dynamics of a long slender elastic fiber, a mathematical aerodynamic force concept is presented in this work. It yields a correlated random Gaussian force and respectively uncorrelated Gaussian white noise with flow-dependent amplitude in the asymptotic limit on the macroscopic fiber scale. Numerical comparisons of the correlated and uncorrelated force effects on the fiber behavior show coinciding results. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Micromechanical strength analysis of fiber reinforced plastics

Strength of an unidirectional lamina is computed with a representative volume element. An approximative “voxel” meshing method is used in conjunction with continuum damage mechanics to simulate crack growth in the RVE. Two material models for the nonlinear material behaviour of the epoxy resin are compared. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

A mathematical model of clarifier-thickener units

We review a recent analysis of a clarifier-thickener model for flocculated suspensions. The resulting governing PDE is a strongly degenerate convection-diffusion equation with discontinuous flux. A new numerical example illustrates how control actions speed up thickener operation significantly. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Arbitrage conditions for electricity markets with production and storage

Computational Management Science - This work analyzes the notion of arbitrage for market models with electricity production from fuel. Several generators, fuel storage, and the related fuel and...     

Voronoi diagrams and arrangements

We propose a uniform and general framework for defining and dealing with Voronoi diagrams. In this framework a Voronoi diagram is a partition of a domainD induced by a finite number of real valued functions onD. Valuable insight can be gained when one considers how these real valued functions partitionD ×R. With this view it turns out that the standard Euclidean Voronoi diagram of point sets inR ^d along with its order-k generalizations are intimately related to certain arrangements of hyperplanes. This fact can be used to obtain new Voronoi diagram algorithms. We also discuss how the formalism of arrangements can be used to solve certain intersection and union problems.     

Nuclear stopping power in αα anddd collisions

Inelasticαα anddd collisions were studied at a centre-of-mass energy √S _NN=31.2 GeV per nucleon-nucleon collision, using the Split-Field Magnet (SFM) detector at the CERN ISR. In this paper we show the inclusive and semi-inclusive rapidity distributions of protons, compare them with predictions of the Lund model, and calculate the average rapidity loss for participant protons. From the negative particles we calculate the inelasticity of the interaction, the average energy per particle, and the degree of isotropy of the produced hadrons.     

Semi-rigid analogues of the calcium antagonist verapamil: A molecular modelling study

Summary In this work the rigid-analogue approach has been used to obtain information on the active conformation(s) of the calcium antagonist verapamil. A series of semi-rigid analogues of verapamil were synthesized and their biological activities evaluated on guinea-pig heart and aorta. These molecules were analysed by means of molecular modelling techniques.On the basis of the pharmacological profile and conformational analysis of these compounds, two different models for negative inotropic and negative chronotropic activity are proposed. The two actions seem to be due to conformations of the molecules which differ in the orientation of their phenylethylamino groups.