ST/b and DBA/2 mice differ in brain alpha-bungarotoxin binding and alpha 7 nicotinic receptor subunit mRNA levels: a quantitative autoradiographic analysis

Inbred mouse strains vary in sensitivity to a number of behavioral and physiological effects produced by nicotine. Differences in sensitivity to nicotine are correlated with variance in the number of brain nicotinic receptors as measured in regionally dissected brain tissue. The studies reported here used quantitative autoradiography and in-situ hybridization methods to measure regional levels of alpha-bungarotoxin (alpha BTX) binding and alpha 7 mRNA levels. Two inbred mouse strains, ST/b and DBA/2, were compared because these strains differ maximally in sensitivity to nicotine-induced seizures and in alpha BTX binding measured in regional brain homogenates. The binding of alpha BTX was significantly greater in the St/b strain in 42 of 127 brain regions that were analyzed, and a trend towards increased binding was seen in many additional brain regions. The most consistent strain differences were found in hippocampal, thalamic and pontine nuclei. Strain differences in alpha 7 mRNA levels were also detected, but these were not as widespread as were the alpha BTX binding differences. The alpha 7 mRNA levels were significantly correlated with alpha BTX binding in both mouse strains which suggests that the strain differences in binding are related, in part, to the levels of alpha 7 mRNA.     

N- and O-glycosylation muteins of recombinant human erythropoietin secreted from BHK-21 cells

Single-site glycomuteins of recombinant human erythropoietin (rhuEpo) were constructed and transiently and stably expressed in BHK-21 cells. The transient expression levels varied among muteins, being highest for mutein rhuEpoGln24 followed by wild-type rhuEpo (rhuEpowt). All other glycomuteins, including rhuEpoGln38, rhuEpoGln83, rhuEpoThr126, and rhuEpoGly126, were secreted at lower levels than rhuEpowt. Muteins expressed in stable cell lines showed similar differences in expression levels. Also each mutein could be affinity-purified from culture supernatants, and was biologically active in vivo. Based on secretion rates from BHK-21 cells, the most potent erythropoietin was rhuEpoGln24. This mutein is also considered to have biologic activities that are superior to rhuEpowt.     

Viscosity measurements of liquids under pressure by using the quartz crystal resonators

A quartz crystal viscometer has been developed for measuring viscosity in liquids under pressure. It employs an AT-cut quartz crystal resonator of fundamental frequency 3 MHz inserted in a variable-volume vessel designed for working up to 80 MPa. Viscosity is determined by two methods from resonance frequency and bandwidth measurements along up to eight different overtones. The resonance frequency allows an absolute measurement of the viscosity but leads to an accuracy limited to 5% whereas the bandwidth technique which works in a relative way provides an accuracy of 2%. The techniques were tested by carrying out measurements in two pure compounds: heptane and toluene. Measurement results demonstrate the feasibility of the technique in this viscosity range. The apparatus was also used to determine the viscosity of n-decane with dissolved methane. The results obtained with these mixtures reveal the applicability of the apparatus for reservoir fluids study.     

Detail-preserving fluid control

We propose a new fluid control technique that uses scale-dependent force control to preserve small-scale fluid detail. Control particles define local force fields and can be generated automatically from either a physical simulation or a sequence of target shapes. We use a multi-scale decomposition of the velocity field and apply control forces only to the coarse-scale components of the flow. Small-scale detail is thus preserved in a natural way avoiding the artificial viscosity often introduced by force-based control methods. We demonstrate the effectiveness of our method for both Lagrangian and Eulerian fluid simulation environments.     

Bootstrap- and permutation-based inference for the Mann–Whitney effect for right-censored and tied data

The Mann–Whitney effect is an intuitive measure for discriminating two survival distributions. Here we analyse various inference techniques for this parameter in a two-sample survival setting with independent right-censoring, where the survival times are even allowed to be discretely distributed. This allows for ties in the data and requires the introduction of normalized versions of Kaplan–Meier estimators from which adequate point estimates are deduced. Asymptotically exact inference procedures based on standard normal, bootstrap, and permutation quantiles are developed and compared in simulations. Here, the asymptotically robust and—under exchangeable data—even finitely exact permutation procedure turned out to be the best. Finally, all procedures are illustrated using a real data set.     

A sufficient condition to test identifiability of nonlinear delayed-differential models with constant delays and multi-inputs

In this paper, an original result in terms of a sufficient condition to test the identifiability of nonlinear delayed-differential models with constant delays and multi-inputs is given. The identifiability is studied for the linearized system and a criterion for linear systems with constant delays is provided, from which the identifiability of the original nonlinear system can be proved. This result is obtained by combining a classical identifiability result for nonlinear ordinary differential systems due to Grewal and Glover (1976) with the identifiability of linear delayed-differential models developed by Orlov, Belkoura, Richard, and Dambrine (2002). This paper is a generalization of Denis-Vidal, Jauberthie, and Joly-Blanchard (2006), which deals with the specific case of nonlinear delayed-differential models with two delays and a single input.     

Liquid chromatographic determination of caffeine and adrenergic stimulants in food supplements sold in Brazilian e-commerce for weight loss and physical fitness

Methyl-xanthines and adrenergic stimulants, such as caffeine and synephrine, are commonly added to food supplements due to their stimulating and thermogenic effects. In addition, the abusive consumption of food supplements with ergogenic and aesthetic purposes has been observed worldwide. This work describes the study of caffeine, p-synephrine, hordenine, octopamine, tyramine, ephedrine and salicin as stimulants in dietary supplements marketed in Brazil for weight loss and physical fitness claims. A total of 94 different products were acquired from 30 Brazilian websites. Thus, the sampling of marketed supplements was performed in virtual commerce (e-commerce) with claims of weight loss, appetite reduction, fat burning and metabolism acceleration. The developed analytical method involved the separation of the stimulants by HPLC with diode array detection (HPLC-DAD) by using a gradient elution of flow rate (0.7–2.5 ml min^?1) and mobile phase composition (0.1% H₃PO₄/methanol). The validated method was applied to the study of 46 dietary supplements. Caffeine, p-synephrine and ephedrine were found to be present as stimulants in 52% of the studied samples marketed as encapsulated or bulk forms. Caffeine was found to be present in concentrations that represent doses from 25.0 to 1476.7 mg day^–1. Synephrine was found in concentrations that represent doses from 59.1 to 127.0 mg day^–1. Ephedrine was found to be associated with caffeine in one formulation at a concentration representing a 26.1 mg day^–1 dosage.