Assignment of the absolute configuration at the sulfur atom of thioridazine metabolites by the analysis of their chiroptical properties: The case of thioridazine 2-sulfoxide

Thioridazine (THD) is a commonly prescribed phenotiazine neuroleptic drug, which is extensively biotransformed in the organism producing as main metabolites sulfoxides and a sulfone by sulfur oxidation Significant differences have been observed in the activity of the THD enantiomers as well as for its main metabolites, and enantioselectivity phenomena have been proved in the metabolic pathway. Here the assignment of the absolute configuration at the sulfur atom of enantiomeric THD-2-sulfoxide (THD-2-SO) has been carried out by circular dichroism (CD) spectroscopy The stereoisomers were separated by HPLC on Chiralpak AS column, recording the CD spectra for the two collected enantiomeric fractions The theoretical electronic CD spectrum has been obtained by the TDDFT/B3LYP/6-31G*. as Boltzmann averaging of the contributions calculated for the most stable conformations of the drug The comparison of the simulated and experimental spectra allowed the absolute configuration at the sulfur atom of the four THD-2-SO stereoisomers to be assigned The developed method should be useful for a reliable correlation between stereochemistry and activity and/or toxicity

Fast Structure-Based Assignment of 15N HSQC Spectra of Selectively 15N-Labeled Paramagnetic Proteins

A novel strategy for fast NMR resonance assignment of N-15 HSQC spectra of proteins is presented. It requires the structure coordinates of the protein, a paramagnetic center, and one or more residue-selectively N-15-labeled samples. Comparison of sensitive undecoupled N-15 HSQC spectra recorded of paramagnetic and diamagnetic samples yields data for every cross-peak on pseudocontact shift, paramagnetic relaxation enhancement, cross-correlation between Curie-spin and dipole-dipole relaxation, and residual dipolar coupling. Comparison of these four different paramagnetic quantities with predictions from the three-dimensional structure simultaneously yields the resonance assignment and the anisotropy of the susceptibility tensor of the paramagnetic center. The method is demonstrated with the 30 kDa complex between the N-terminal domain of the epsilon subunit and the theta subunit of Escherichia Coll DNA polymerase III. The program PLATYPUS was developed to perform the assignment, provide a measure of reliability of the assignment, and determine the susceptibility tensor anisotropy.

Structure revision and assignment of absolute stereochemistry of a marine C-21 bisfuranoterpene

The C-21 bisfuranoterpene (-)-isotetradehydrofurospongin-1 (6), previously isolated from a Western Australian Spongia sp., has been reisolated from a specimen of Spirastrella papilosa collected during scientific trawling operations in the Great Australian Eight. A 2D NMR analysis of 6 has prompted reassignment of the published structure 5, while degradation and chiral HPLC analysis have allowed determination of the absolute stereochemistry.

A note on the multiple partners assignment game

In the assignment game of Shapley and Shubik [Shapley, L.S., Shubik, M., 1972. The assignment game. I. The core, International journal of Game Theory 1, 11-130] agents are allowed to form one partnership at most. That paper proves that, in the context of firms and workers, given two stable payoffs for the firms there is a stable payoff which gives each firm the larger of the two amounts and also one which gives each of them the smaller amount. Analogous result applies to the workers. Sotomayor [Sotomayor, M., 1992. The multiple partners game. In: Majumdar, M. (Ed.), Dynamics and Equilibrium: Essays in Honor to D. Gale. Mcmillian, pp. 322-336] extends this analysis to the case where both types of agents may form more than one partnership and an agent`s payoff is multi-dimensional. Instead, this note concentrates in the total payoff of the agents. It is then proved the rather unexpected result that again the maximum of any pair of stable payoffs for the firms is stable but the minimum need not be, even if we restrict the multiplicity of partnerships to one of the sides. (C) 2009 Elsevier B.V. All rights reserved.

Adjusting prices in the multiple-partners assignment game

Starting with an initial price vector, prices are adjusted in order to eliminate the excess demand and at the same time to keep the transfers to the sellers as low as possible. In each step of the auction, to which set of sellers should those transfers be made is the key issue in the description of the algorithm. We assume additively separable utilities and introduce a novel distinction by considering multiple sellers owing multiple identical objects and multiple buyers with an exogenously defined quota, consuming more than one object but at most one unit of a seller`s good and having multi-dimensional payoffs. This distinction induces a necessarily more complicated construction of the over-demanded sets than the constructions of these sets for the other assignment games. For this approach, our mechanism yields the buyer-optimal competitive equilibrium payoff, which equals the buyer-optimal stable payoff. The symmetry of the model allows to getting the seller-optimal stable payoff and the seller-optimal competitive equilibrium payoff can then be also derived.

Credit assignment: The memory representation of dynamic task events

The experiment examined the influence of memory for prior instances on aircraft conflict detection. Participants saw pairs of similar aircraft repeatedly conflict with each other. Performance improvements suggest that participants credited the conflict status of familiar aircraft pairs to repeated static features such as speed, and dynamic features such as aircraft relative position. Participants missed conflicts when a conflict pair resembled a pair that had repeatedly passed safely. Participants either did not attend to, or interpret, the bearing of aircraft correctly as a result of false memory-based expectations. Implications for instance models and situational awareness in dynamic systems are discussed.

Fast-convergent iterative scheme for filtering velocity signals and finding Kolmogorov scales

The present fundamental knowledge of fluid turbulence has been established primarily from hot- and cold-wire measurements. Unfortunately, however, these measurements necessarily suffer from contamination by noise since no certain method has previously been available to optimally filter noise from the measured signals. This limitation has impeded our progress of understanding turbulence profoundly. We address this limitation by presenting a simple, fast-convergent iterative scheme to digitally filter signals optimally and find Kolmogorov scales definitely. The great efficacy of the scheme is demonstrated by its application to the instantaneous velocity measured in a turbulent jet.

Time evolution in the unimolecular master equation at low temperatures: full spectral solution with scalable iterative methods and high precision

A new method is presented to determine an accurate eigendecomposition of difficult low temperature unimolecular master equation problems. Based on a generalisation of the Nesbet method, the new method is capable of achieving complete spectral resolution of the master equation matrix with relative accuracy in the eigenvectors. The method is applied to a test case of the decomposition of ethane at 300 K from a microcanonical initial population with energy transfer modelled by both Ergodic Collision Theory and the exponential-down model. The fact that quadruple precision (16-byte) arithmetic is required irrespective of the eigensolution method used is demonstrated. (C) 2001 Elsevier Science B.V. All rights reserved.

Fast, scalable master equation solution algorithms. IV. Lanczos iteration with diffusion approximation preconditioned iterative inversion

In this paper we propose a second linearly scalable method for solving large master equations arising in the context of gas-phase reactive systems. The new method is based on the well-known shift-invert Lanczos iteration using the GMRES iteration preconditioned using the diffusion approximation to the master equation to provide the inverse of the master equation matrix. In this way we avoid the cubic scaling of traditional master equation solution methods while maintaining the speed of a partial spectral decomposition. The method is tested using a master equation modeling the formation of propargyl from the reaction of singlet methylene with acetylene, proceeding through long-lived isomerizing intermediates. (C) 2003 American Institute of Physics.

Fast, scalable master equation solution algorithms. III. Direct time propagation accelerated by a diffusion approximation preconditioned iterative solver

In this paper we propose a novel fast and linearly scalable method for solving master equations arising in the context of gas-phase reactive systems, based on an existent stiff ordinary differential equation integrator. The required solution of a linear system involving the Jacobian matrix is achieved using the GMRES iteration preconditioned using the diffusion approximation to the master equation. In this way we avoid the cubic scaling of traditional master equation solution methods and maintain the low temperature robustness of numerical integration. The method is tested using a master equation modelling the formation of propargyl from the reaction of singlet methylene with acetylene, proceeding through long lived isomerizing intermediates. (C) 2003 American Institute of Physics.

A comparative study of iterative Chebyshev and Lanczos implementations of the boundary inhomogeneity method for quantum scattering

We have recently developed a scaleable Artificial Boundary Inhomogeneity (ABI) method [Chem. Phys. Lett.366, 390–397 (2002)] based on the utilization of the Lanczos algorithm, and in this work explore an alternative iterative implementation based on the Chebyshev algorithm. Detailed comparisons between the two iterative methods have been made in terms of efficiency as well as convergence behavior. The Lanczos subspace ABI method was also further improved by the use of a simpler three-term backward recursion algorithm to solve the subspace linear system. The two different iterative methods are tested on the model collinear H+H2 reactive state-to-state scattering.

Contrasts in the basins of attraction of structurally identical iterative root finding methods

A numerical comparison is performed between three methods of third order with the same structure, namely BSC, Halley’s and Euler–Chebyshev’s methods. As the behavior of an iterative method applied to a nonlinear equation can be highly sensitive to the starting points, the numerical comparison is carried out, allowing for complex starting points and for complex roots, on the basins of attraction in the complex plane. Several examples of algebraic and transcendental equations are presented.

Automatic assignment of absolute configuration from 1D NMR data

Opposite enantiomers exhibit different NMR properties in the presence of an external common chiral element, and a chiral molecule exhibits different NMR properties in the presence of external enantiomeric chiral elements. Automatic prediction of such differences, and comparison with experimental values, leads to the assignment of the absolute configuration. Here two cases are reported, one using a dataset of 80 chiral secondary alcohols esterified with (R)-MTPA and the corresponding 1H NMR chemical shifts and the other with 94 13C NMR chemical shifts of chiral secondary alcohols in two enantiomeric chiral solvents. For the first application, counterpropagation neural networks were trained to predict the sign of the difference between chemical shifts of opposite stereoisomers. The neural networks were trained to process the chirality code of the alcohol as the input, and to give the NMR property as the output. In the second application, similar neural networks were employed, but the property to predict was the difference of chemical shifts in the two enantiomeric solvents. For independent test sets of 20 objects, 100% correct predictions were obtained in both applications concerning the sign of the chemical shifts differences. Additionally, with the second dataset, the difference of chemical shifts in the two enantiomeric solvents was quantitatively predicted, yielding r2 0.936 for the test set between the predicted and experimental values.

A denoising approach for iterative side information creation in distributed video coding

In distributed video coding, motion estimation is typically performed at the decoder to generate the side information, increasing the decoder complexity while providing low complexity encoding in comparison with predictive video coding. Motion estimation can be performed once to create the side information or several times to refine the side information quality along the decoding process. In this paper, motion estimation is performed at the decoder side to generate multiple side information hypotheses which are adaptively and dynamically combined, whenever additional decoded information is available. The proposed iterative side information creation algorithm is inspired in video denoising filters and requires some statistics of the virtual channel between each side information hypothesis and the original data. With the proposed denoising algorithm for side information creation, a RD performance gain up to 1.2 dB is obtained for the same bitrate.