Evaluation of steerable filter for detection of fibers in flowing suspensions

Steerable filters are concluded to be useful in order to determine the orientation of fibers captured in digital images. The fiber orientation is a key variable in the study of flowing fiber suspensions. Here, digital image analysis based on a filter within the class of steerable filters is evaluated for suitability of finding the position and orientation of fibers suspended in flowing suspensions. In sharp images with small noise levels, the steerable filter succeeds in determining the orientation of artificially generated fibers with well-defined angles. The influence of reduced image quality on the orientation has been quantified. The effect of unsharpness and noise is studied and the results show that the error in orientation is less than 1° for moderate levels. Images from two flow cases, one laminar shear flow and one turbulent, are also analyzed. The fiber orientation distribution is determined in the flow-vorticity plane. For the laminar case a comparison is made to a robust, but computationally more expensive, method involving convolutions with an oriented elliptic filter. A good agreement is found when comparing the resulting fiber orientation distributions obtained with the two methods. For the turbulent case, it is demonstrated that correct results are obtained and that the method can handle overlapping fibers.     

On-line coupling of supercritical fluid extraction with high-performance liquid chromatography for the determination of explosives in vapour phases

An investigation into the selectivity of an iminodiacetic acid (IDA) modified silica gel column for transition and heavy metal ions using non-chelating inorganic eluents has been carried out. A number of eluent parameters were investigated to determine the exact retention mechanism taking place and to control selectivity. The parameters studied were eluent ionic strength and the nature of the inorganic salt used, eluent pH and eluent temperature. The results obtained showed how despite certain metal ions exhibiting similar stability constants with the bonded IDA groups, careful control of each of the above parameters, in particular eluent chloride ion concentration and eluent temperature, could result in large changes in selectivity. Optimal conditions for the isocratic and gradient separation of Mg(II), Ca(II), Mn(II), Cd(II), Co(II), Zn(II) and Pb(II) were determined. An isocratic method using a 0.035 M KCl, 0.065 M KNO3 (pH 2.5) eluent was successfully applied to the determination of Mn(II), Cd(II), Co(II) and Zn(II) at concentrations between 20 and 121 microg/l in a freshwater certified reference material (NIST 1640).     

Determination of dopamine and its metabolites in small volumes of rat brain dialysates using small-bore liquid chromatography with electrochemical detection

A miniaturized liquid chromatographic system with electrochemical detection (LC-ED) was developed and applied to the analysis of dopamine and its metabolites in dialysate samples collected from the rat brain in vivo. An existing LC-ED system was down-scaled using a 1 mm I.D. small-bore column operated at a reduced flow-rate and with an injection volume of 1 microliter. With the small-bore system the limit of detection for dopamine of ca. 0.06 pg was almost 50 times less than with the conventional system, which represents a two-fold improvement in concentration sensitivity. Miniaturization was accomplished with negligible loss in resolution by using a conventional commercial amperometric detector with minor modifications. The results indicate that a number of useful advantages could be realized by the combination of this small-bore LC-ED system and the in vivo brain dialysis method.     

Stereoselective synthesis of optically active bicyclic beta-lactam carboxylic acids that target pilus biogenesis in pathogenic bacteria

Optically active bicyclic beta-lactams were synthesized, starting from 2-H-delta 2-thiazolines and Meldrum's acid derivatives. Several methods to accomplish an ester hydrolysis without damaging the beta-lactam framework were investigated. A rapid CsOH saponification of the beta-lactam methyl esters was developed and protonation of the Cs-carboxylates by Amberlite (IR-120 H+) afforded a series of bicyclic beta-lactam carboxylic acids. Moreover, a convenient method for the synthesis of 2-H-delta 2-thiazolinecarboxylic acid methyl ester 2 was developed. Bicyclic beta-lactam carboxylic acids 7a-g and aldehydes 4a-d were screened for their affinity to the bacterial periplasmic chaperone PapD using a surface plasmon resonance technique. beta-Lactams substituted with large acyl substitutents showed better binding to the chaperone than the native C-terminal peptide PapG 8, demonstrating that bicyclic beta-lactams constitute a new class of potential bacterial chaperone inhibitors.     

Calculations of solute and solvent entropies from molecular dynamics simulations

The translational, rotational and conformational (vibrational) entropy contributions to ligand-receptor binding free energies are analyzed within the standard formulation of statistical thermodynamics. It is shown that the partitioning of the binding entropy into different components is to some extent arbitrary, but an appropriate method to calculate both translational and rotational entropy contributions to noncovalent association is by estimating the configurational volumes of the ligand in the bound and free states. Different approaches to calculating solute entropies using free energy perturbation calculations, configurational volumes based on root-mean-square fluctuations and covariance matrix based quasiharmonic analysis are illustrated for some simple molecular systems. Numerical examples for the different contributions demonstrate that theoretically derived results are well reproduced by the approximations. Calculation of solvent entropies, either using total potential energy averages or van't Hoff plots, are carried out for the case of ion solvation in water. Although convergence problems will persist for large and complex simulation systems, good agreement with experiment is obtained here for relative and absolute ion hydration entropies. We also outline how solvent and solute entropic contributions are taken into account in empirical binding free energy calculations using the linear interaction energy method. In particular it is shown that empirical scaling of the nonpolar intermolecular ligand interaction energy effectively takes into account size dependent contributions to the binding free energy.     

Evidence for shape coexistence at medium spin in Rb

Four previously known rotational bands in ⁷⁶Rb have been extended to moderate spins using the Gammasphere and Microball γ ray and charged particle detector arrays and the ⁴⁰Ca(⁴⁰Ca, 3pn) reaction at a beam energy of 165 MeV. The properties of two of the negative-parity bands can only readily be interpreted in terms of the highly successful Cranked Nilsson-Strutinsky model calculations if they have the same configuration in terms of the number of g9/2 particles, but they result from different nuclear shapes (one near-oblate and the other near-prolate). These data appear to constitute a unique example of shape coexisting structures at medium spins.     

Optimization and characterization of the chiral separation of citalopram and its demethylated metabolites by response-surface methodology

Summary Response-surface modelling and sequential optimization have been used for optimization and characterization of the separation of the enantiomers of citalopram, desmethylcitalopram, and didesmethylcitalopram on an acetylated β-cyclodextrin column. In the model chosen the separation conditions mobile phase methanol content, buffer concentration, column temperature, and pH were varied to investigate their influence on the chromatography. It was found that what is good for selectivity within an enantiomer pair is bad for selectivity between enantiomer pairs. Because within-pair and between-pair selectivity does not reach its optimum at the same conditions, a middle course approach has to be followed. Use of an experimental design for this investigation enabled understanding of the mechanisms of within- and between-pair separation for citalopram, desmethylcitalopram, and didesmethylcitalopram. Sequential optimization can be a quicker means of optimizing a chromatographic separation; response-surface modelling, in addition to enabling optimization of the chromatographic process, also serves as a tool for leaming more about the separation mechanism.     

QSAR with experimental and predictive distributions: an information theoretic approach for assessing model quality

We propose that quantitative structure–activity relationship (QSAR) predictions should be explicitly represented as predictive (probability) distributions. If both predictions and experimental measurements are treated as probability distributions, the quality of a set of predictive distributions output by a model can be assessed with Kullback–Leibler (KL) divergence: a widely used information theoretic measure of the distance between two probability distributions. We have assessed a range of different machine learning algorithms and error estimation methods for producing predictive distributions with an analysis against three of AstraZeneca’s global DMPK datasets. Using the KL-divergence framework, we have identified a few combinations of algorithms that produce accurate and valid compound-specific predictive distributions. These methods use reliability indices to assign predictive distributions to the predictions output by QSAR models so that reliable predictions have tight distributions and vice versa. Finally we show how valid predictive distributions can be used to estimate the probability that a test compound has properties that hit single- or multi- objective target profiles.