OptDesign: extending optimizable k-dissimilarity selection to combinatorial library design

Optimizable k-dissimilarity (OptiSim) selection entails drawing a series of subsamples of size k from a population and choosing the "best" candidate from each such subsample for inclusion in the selection set. By varying the size of the subsample, one can control the balance between representativeness and diversity in the selection set obtained. In the original formulation, a uniform random sampling from among valid candidates was used to draw the subsamples from a single target population. Here we describe in detail two key modifications that serve to extend the OptiSim methodology to vector selection for interdependent variables, specifically as applied to the design of combinatorial sublibraries. The first modification involves pivoting between variables: subsamples are drawn from each reagent pool in turn, with the viability of each candidate being evaluated in isolation as well as in terms of the products it will produce from complementary reagents already selected. The filters applied may be static or dynamic in nature, with molecular weight and hydrophobicity being examples of the former and structural diversity with respect to reagents already selected being an example of the latter. The second key modification is adding the ability to bias the selection of candidate reagents for inclusion in the subsamples. Taken together, these modifications support the efficient generation of multiblock and other sparse matrix designs that are both representative and diverse, and for which "backfilling" of designs edited to remove undesirable reagents or products is straightforward. The method is intrinsically fast and efficient, since enumeration of the full combinatorial is not required- only those candidates actually considered for inclusion need be evaluated. Moreover, because the subsample selection step is separate from the diversity-based selection of the "best" candidate, incorporating such bias in favor of a competing criterion such as low price provides a "natural," nonparametric mechanism for generating designs that are likely to be "good" in a double-objective, Pareto sense.     

Direct continuous supercritical fluid extraction as a novel method of wine analysis. Comparison with conventional indirect extraction and implications for wine variety identification

Direct supercritical fluid extraction (SFE) of wines with carbon dioxide was compared to SFE of the sorbent used for solid-phase extraction of the same wine samples (SPE-SFE). Compared to SPE-SFE, the direct SFE results in amore specific and representative gas chromatographic fingerprint of the wine sample. The multivariate statistical processing of the direct SFE-GC data provides a clear-cut and sharp discrimination among the individual wine varieties while the discrimination based on the SPE-SFE-GC data is relatively poor. This finding reflects the adverse effects of additional analyte-sorbent interactions and sorption/desorption steps involved in SPE-SFE.     

Bound states and dipole polarizability of hydrogen molecular ion H2 in weakly coupled hot plasmas

The effects of hot-dense plasmas on the bound states and the dipole polarizability of the ground state of Coulomb three-body molecular ion H⁺₂ have been investigated using highly correlated basis functions and by considering the Debye shielding approach of plasma modeling. The ground S state and the first excited P state energies along with the dipole polarizability for different shielding parameters are reported.     

Development and validation of a HPLC method for quantification of rivastigmine in rat urine and identification of a novel metabolite in urine by LC‐MS/MS

A sensitive, specific and accurate HPLC method for the quantification of rivastigmine (RSM) in rat urine was developed and validated. The method involves the simple liquid–liquid extraction of RSM and pyridostigmine as an internal standard (IS) from rat urine with tertiary methyl butyl ether. The chromatographic separation of RSM and IS was achieved with 20 mm ammonium acetate buffer (pH 6.5) and acetonitrile (65:35, v/v) delivered at flow‐rate of 1 mL/min on a Kromasil KR‐100. The method was in linear range from 50 to 5000 ng/mL. The validation was done as per FDA guidelines and the results met the acceptance criteria. The method was successfully applied for the quantification of RSM in rat urine. Besides method validation, we have identified two metabolites of RSM in urine. Both the metabolites were characterized by HPLC‐PDA and LC‐MS/MS and it was found that one metabolite is novel. Copyright © 2010 John Wiley & Sons, Ltd.     

Conservation of a prey-predator fishery with predator self limitation based on continuous fishing effort

The paper deals with the problem of selective harvesting in a prey-predator model with predator self limitation. Criteria for local stability and global stability for both the exploited and unexploited system are derived. The effort has been considered as a dynamic variable and taxation as a control instrument to protect the fish populations from over exploitation. Finally, the optimal taxation policy is discussed with the help of control theory.     

Aging effect of diethanolamine derived precursor sol on TiO<Subscript>2</Subscript> films deposited at different annealing temperatures

A diethanolamine stabilized precursor sol has been utilized for studying the effect of sol aging and annealing temperature on key properties of TiO₂ films. X-ray diffraction investigations have shown increased crystallite size in the films as a function of both sol aging and the thermal treatment. Fourier transform infrared studies have elucidated that cleavage of the bond involving diethanolamine and the alkoxide in the films requires high temperature annealing treatment upon the use of aged sol for the deposition of the films. Multiple step chronoamperometry has shown the ion storage capacity of the films increases as a function of sol aging, with the highest extent of Li ion insertion being obtained for films produced from as-prepared and aged sols and subsequently annealed at, 300 and 350 °C, respectively. Films with excellent optical quality were obtained. Ellipsometry revealed that the refractive indices of the films vary from 1.67 to 2.02. The highest thickness obtained in these films was nearly 900 nm. The bandgaps of the films for both direct and indirect transitions decreased as a function of precursor sol’s aging. In addition, although the indirect bandgap values have shown a decrease with increasing annealing temperature, the direct bandgap values reveal a slight increase as a function of annealing temperature.     

LES study of diesel flame/wall interaction and mixing mechanisms at different wall distances

In this paper, the flame-wall interaction of reacting diesel spray under engine like conditions is investigated using large eddy simulations. The aim of this study is to understand the influence of the distance between the wall and the spray nozzle on the air entrainment rate, which is a key variable in formation/oxidation process of soot. Three experimental cases are investigated, a free jet case and two wall impingement cases with a distance from nozzle to wall of 30 mm and 50 mm, which are considered as characteristic wall impingement distances for light- and heavy-duty bores in diesel engines, respectively. The optical soot measurements imply a positive influence of wall on the rate of soot oxidation. Numerical simulations are employed to elucidate importance of different mechanisms for the air entrainment, i.e., air entrainment prior to flame lift-off position, enhanced mixing due to the wall impingement and enhanced mixing by the entrainment wave. The results show that oxidation process after the end of injection is driven by a different mixing mechanism depending on the distance to the wall. The 30 mm case resulted in a “mixing boost”, where the dominant mixing mechanism is the wall impingement vortex mixing, which gives rise to the fastest soot decay among the cases. The mixing in the 50 mm case is governed by a late wall impingement vortex mixing, giving rise to a low, but a constant air entrainment rate, i.e., a “mixing plateau”. The free jet case resulted in mixing governed by the entrainment wave mechanism. Both wall impingement cases have faster soot oxidation rate compared with the free jet case, but due to a different underlying mixing process. LES is shown to be able to replicate the line-of-sight measurements of natural OH* chemiluminescence and distribution of soot region from the optical soot diagnostics.     

On further application of r as a metric for validation of QSAR models

Validation is a crucial aspect for quantitative structure–activity relationship (QSAR) model development. External validation is considered, in general, as the most conclusive proof of predictive capacity of a QSAR model. In the absence of truly external data set, external validation is usually performed on test set compounds, which are members of the original data set but not used in model development exercise. In the case of small data sets, QSAR researchers experience problem in model development due to the fact that the developed models may be less reliable on account of the small number of training set compounds and such models may also show poor external predictability because the models may not have captured all necessary features required for the particular structure–activity relationships. The present paper attempts to show that ‘true r_(LOO)’ statistic calculated based on the model derived from the undivided data set with application of variable selection strategy at each cycle of leave‐one‐out (LOO) validation may reflect external validation characteristics of the developed model thus obviating the requirement of splitting of the data set into training and test sets. This approach may be helpful in the case of small data sets as it uses all available data for model development and validation thus making the resulting model more reliable. Copyright © 2009 John Wiley & Sons, Ltd.     

Calculations of D‐wave bound states and resonance states of the screened helium atom using correlated exponential wave functions

We have investigated the effects of screened Coulomb (Yukawa) potentials on the bound ^1,3D states and the doubly excited ^1,3 D^e resonance states of helium atom using highly correlated exponential basis functions. The Density of resonance states are calculated using stabilization method. Highly correlated exponential basis functions are used to consider the correlation effect between the charged particles. A total of 18 resonances (nine each for ¹ D^e and ³ D^e states) below the n = 2 He ⁺ threshold has been calculated. For each spin states, this includes four members in the 2pnp series, three members in the 2snd series, and two members in 2pnf series. The resonance energies and widths for various screening parameters ranging from infinity to a small value for these ^1,3 D^e resonance states are reported along with the bound‐excited 1s3d ^1,3 D state energies. Overall behavior of the spectral profile of 1s3d ¹D state of helium atom due to electron‐electron and electron‐nucleus screening are also presented. Accurate resonance energies and widths are also reported for He in vacuum. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010