Predictive flow-field estimation

We are considering the problem of real-time prediction of 3D turbulent velocity fields based on a small number of scalar measurements. The method of proper orthogonal decomposition (POD) allows for the decomposition of an ensemble of velocity fields into a set of spatial basis functions and a set of temporal coefficients. The computation of the temporal coefficients is by no means a trivial matter, especially when one is faced with a large number of modes. In this paper we discuss the use of radial basis function (RBF) models to capture the discrete time evolution and nonlinear dynamics of the POD coefficients. Further, we propose the use of regularized regression techniques to generate models that provide mappings between the POD coefficients and scalar measurements. As a final step towards real-time prediction, the state-space RBF models and regression measurement models are combined using unscented Kalman filters to produce optimal solutions such that a balance between the state models and measurement models is achieved.The proposed methods are tested for two specific cases. The classical Lorenz model is chosen to demonstrate the use and effectiveness of RBF models as a potential candidate for state models. Flow around a wall-mounted cube in a channel at Re=20,000 is considered as the second case. The aim for the second case is to be able to accurately predict the POD coefficients outside the ensemble. It is shown that a large number of POD coefficients is required to approximate the velocity fields with sufficient accuracy. The RBF models are created based on only the temporal information available from the initial ensemble, and it is shown that the RBF model is able to correctly approximate the high-dimensional phase space. Combined with the unscented Kalman filter it is indeed possible to track the evolution of the POD coefficients for a long time. The robustness of the filter is demonstrated by considering the presence of noise in measurements and using measurement information at time steps greater than the evolution time step.     

Simple and Efficient Process for the Large-Scale Preparation of Agomelatine: An Antidepressant Drug

A simple and efficient process for the large-scale preparation of agomelatine (1), an antidepressant drug is, described. Agomelatine was prepared in a linear manner starting from readily available, inexpensive 2-naphthol. Key steps in the synthesis are Friedel–Crafts acylation of 2-naphthyl acetate with chloroacetyl chloride, reduction of keto intermediate, and nucleophilic displacement of chloro intermediate with sodium diformylamide. A systemic approach was described to streamline the process into a robust scalable process by controlling the impurities.     

Root‐mean‐square‐deviation‐based rapid backbone resonance assignments in proteins

We have shown that the methodology based on the estimation of root‐mean‐square deviation (RMSD) between two sets of chemical shifts is very useful to rapidly assign the spectral signatures of ¹H^N, ¹³C^α, ¹³C^β, ¹³C′, ¹H^α and ¹⁵N spins of a given protein in one state from the knowledge of its resonance assignments in a different state, without resorting to routine established procedures (manual and automated). We demonstrate the utility of this methodology to rapidly assign the 3D spectra of a metal‐binding protein in its holo‐state from the knowledge of its assignments in apo‐state, the spectra of a protein in its paramagnetic state from the knowledge of its assignments in diamagnetic state and, finally, the spectra of a mutant protein from the knowledge of the chemical shifts of the corresponding wild‐type protein. The underlying assumption of this methodology is that, it is impossible for any two amino acid residues in a given protein to have all the six chemical shifts degenerate and that the protein under consideration does not undergo large conformational changes in going from one conformational state to another. The methodology has been tested using experimental data on three proteins, M‐crystallin (8.5 kDa, predominantly β‐sheet, for apo‐ to holo‐state), Calbindin (7.5 kDa, predominantly α‐helical, for diamagnetic to paramagnetic state and apo to holo) and EhCaBP1 (14.3 kDa, α‐helical, the wild‐type protein with one of its mutant). In all the cases, the extent of assignment is found to be greater than 85%. Copyright © 2010 John Wiley & Sons, Ltd.     

Regiochemical effects on molecular stability: a mechanochemical evaluation of 1,4- and 1,5-disubstituted triazoles

Poly(methyl acrylate) chains of varying molecular weight were grown from 1,4- as well as 1,5-disubstituted 1,2,3-triazoles. Irradiating acetonitrile solutions of these polymers with ultrasound resulted in the formal cycloreversion of the triazole units, as determined by a variety of spectroscopic and chemical labeling techniques. The aforementioned reactions were monitored over time, and the rate constant for the cycloreversion of the 1,5-disubstituted triazole was measured to be 1.2 times larger than that of the 1,4-disubstituted congener. The difference was attributed to the increased mechanical deformability of the 1,5-regioisomer as compared to the 1,4-isomer. This interpretation was further supported by computational studies, which employed extended Bell theory to predict the force dependence of the activation barriers for the cycloreversions of both isomers.