Open-tubular capillary electrochromatography/electrospray ionization-mass spectrometry using polymeric surfactant as a stationary phase coating

We describe the use of the polymeric surfactant poly(sodium undecylenic sulfate) (poly-SUS) as a stationary phase coating in open-tubular capillary electrochromatography (OT-CEC) coupled with electrospray ionization-mass spectrometry (ESI-MS) for the analysis of beta-blocker and benzodiazepine analytes. The production of a polymeric surfactant coating on the capillary inner wall involves (i) adsorption of the cationic polymer poly(diallyldimethylammonium chloride) (PDADMAC) to the inner surface of capillary, and (ii) adsorption of the negatively charged poly-SUS onto the cationic polymer layer via strong physical interaction of the two polymer layers. As compared with micellar electrokinetic chromatography (MEKC) coupled with ESI-MS, the main advantage of this proposed method is minimization of introduction of the monomeric or polymeric surfactant into the mass spectrometer, thus avoiding the interference of the nonvolatile micelle in ESI-MS. The effects of buffer pH and applied voltage on the separation of the analytes are also discussed. Under optimum conditions, four of the five beta-blockers and four benzodiazepines are separated.     

Robust and accurate inference for generalized linear models

In the framework of generalized linear models, the nonrobustness of classical estimators and tests for the parameters is a well known problem, and alternative methods have been proposed in the literature. These methods are robust and can cope with deviations from the assumed distribution. However, they are based on first order asymptotic theory, and their accuracy in moderate to small samples is still an open question. In this paper, we propose a test statistic which combines robustness and good accuracy for moderate to small sample sizes. We combine results from Cantoni and Ronchetti [E. Cantoni, E. Ronchetti, Robust inference for generalized linear models, Journal of the American Statistical Association 96 (2001) 1022–1030] and Robinson, Ronchetti and Young [J. Robinson, E. Ronchetti, G.A. Young, Saddlepoint approximations and tests based on multivariate M-estimators, The Annals of Statistics 31 (2003) 1154–1169] to obtain a robust test statistic for hypothesis testing and variable selection, which is asymptotically χ²-distributed as the three classical tests but with a relative error of order O(n⁻¹). This leads to reliable inference in the presence of small deviations from the assumed model distribution, and to accurate testing and variable selection, even in moderate to small samples.     

“Miniaturized” Linearizations for Quadratic 0/1 Problems

In order to solve a quadratic 0/1 problem, some techniques, consisting in deriving a linear integer formulation, are used. Those techniques, called “linearization”, usually involve a huge number of additional variables. As a consequence, the exact resolution of the linear model is, in general, very difficult. Our aim, in this paper, is to propose “economical” linear models. Starting from an existing linearization (typically the so-called “classical linearization”), we find a new linearization with fewer variables. The resulting model is called “Miniaturized” linearization. Based on this approach, we propose a new linearization scheme for which numerical tests have been performed.     

Detection of Cadmium and Copper Cations Using Amorphous Nitrogenated Carbon Thin Film Electrodes

Nitrogenous amorphous carbon (a‐CN_x) thin films were deposited by radio‐frequency cathodic magnetron sputtering (13.56 MHz) on polished and etched titanium disks. While these films are cheaper to prepare than commonly reported carbon‐based electrodes, the usable electrochemical window in aqueous solution is within the same range and spans from ?1.5 to +1.8 V vs. SCE. The electrochemical reactivity was tested using the ferri‐ferrocyanide redox couple as a function of the thin films preparation parameters. The obtained electrochemical properties allow the use of these a‐CN_x thin films for stripping electroanalysis of cations in water, minimizing potential solvent reactivity. Cadmium and copper were used to test these detection abilities. Better analytical properties (notably sensitivity and linearity) were obtained as compared to a commercial boron doped diamond electrode. Preliminary competition/interaction experiments for these two cations were performed.     

A linearization framework for unconstrained quadratic (0-1) problems

In this paper, we are interested in linearization techniques for the exact solution of the Unconstrained Quadratic (0-1) Problem. Our purpose is to propose “economical” linear formulations. We first extend current techniques in a general linearization framework containing many other schemes and propose a new linear formulation. Numerical results comparing classical, Glover’s and the new linearization are reported.     

A Series of Collaborations between Various Pharmaceutical Companies and Regulatory Authorities Concerning the Analysis of Biomolecules Using Capillary Electrophoresis: Additional Instruments/Buffer

An international project team (including members from US, Canada and UK) was formed from a number of interested biopharmaceutical companies and regulatory authorities to conduct a cross-organisation collaboration exercise. The results of the first comparison with eight different organisations that used instruments of the same equipment model, the same reagents, and the same methodology has been reported previously [1]. This report represents the addition of other instruments using a different run buffer. The relative migration times were different, as expected, prohibiting a direct comparison between companies. The within-organisation variability was low for both relative migration time (<0.34% RSD% for all companies save one) and the peak area (<5% RSD% for all companies save one) when measuring the purity of a representative IgG sample. The apparent molecular weight of bovine serum albumin was measured with good precision (less than 10% RSD% across all companies) to the theoretical value when all data is utilized (67.5 kDa compared to 66.4 kDa). For a representative IgG sample, the three main components, IgG Light Chain, IgG Non-glycosylated Heavy Chain, and IgG Heavy Chain, could not be separated, specifically the IgG Non-glycosylated Heavy Chain and IgG Heavy Chain. When the IgG Non-glycosylated Heavy Chain and IgG Heavy Chain were combined for all organisations, the fractional peak area for the IgG Light Chain and IgG Non-glycosylated Heavy Chain + IgG Heavy Chain peak also showed excellent agreement, with less than 7.5 and 3.5% RSD%, respectively. The value of this exercise is in demonstrating the reliability of CE for the determination of apparent size of biopharmaceutical proteins. This underpins the appropriate use of such CE data in support of regulatory submissions.     

Importance of growth form on production of hybrid antibiotic byStreptomyces lividans TK21 by fed-batch and continuous fermentation

A fermentation strategy, based on the controlled feeding of growthlimiting nutrients in order to maintain metabolic activity for extended periods, has been examined in the case of the production of a hybrid antibiotic by a transformed strain ofStreptomyces lividans TK21. The fed-batch operation did not improve the results obtained with batch operation. Continuous cultures on defined medium showed stable levels of biomass concentration, but antibiotic production ceased when continuous operation was started. The results obtained indicate the critical influence that morphology of the cell aggregates has on metabolic activity. The antibiotic is produced only in culture conditions providing growth in compact mycelial pellets.