Investigation of the species-dependent in vitro metabolism of BAL30630 by stable isotope labeling and isotope exchange experiments analyzed by capillary liquid chromatography coupled to mass spectrometry

The in vitro metabolic profile of BAL30630, an antifungal piperazine propanol derivative, which inhibits the 1,3-beta-d-glucansynthase, was investigated by incubation with microsomes of several species and with rat hepatocytes. For the spotting of the metabolites, mixtures of BAL30630 with a stable isotope (deuterium) labeled analogue were incubated. The metabolic pattern comprises several oxidized metabolites. Based on isotope exchange experiments, their structures could be assigned to epoxide- and hydroxylated metabolites. In hepatocyte incubations, several glucuronides formed from these oxidized metabolites could be observed. From the analysis of the metabolic pattern in microsomes, products of carbamate hydrolysis were characterized. This hydrolysis was highly species dependent. In activated incubations and in rat hepatocytes, those metabolites were further oxidized. In incubations without NADPH activation, the resulting hydrolytic metabolites could be enriched without the subsequent oxidation. Final structural elucidation of the metabolites was performed using accurate mass determination and isotope exchange experiments, in which incubations were analyzed by deuterium exchange and capillary HPLC–QTof-MS and MS/MS. The use of non-radioactive, stabile isotope labeled drug analogues in combination with isotope exchange studies was essential in particular for a defined assignment of the functional groups in the structures of the investigated metabolites.     

Conductance oscillations and transport spectroscopy of a quantum dot

Results are reported for low temperature measurements of the conductance through small regions of a two-dimensional electron gas (2 DEG). An unconventional GaAs heterostructure is used to form a 2 DEG whose density can be tuned by the gate voltage applied to its conductive substrate. Electron beam lithography is used to pattern a narrow channel in the 2 DEG interrupted by two constrictions, defining a small 2 DEG island between them. The conductance is found to oscillate periodically with the gate voltage, namely with electron density. Calculations of the capacitance between the substrate and the island show that the period of oscillation corresponds to adding one electron to the island. The oscillatory behavior results primarily from the discreteness of charge and the Coulomb interaction between electrons. However, the observed temperature dependence of these oscillations requires a more sophisticated treatment which includes the quantized electron energy levels as well. The magnetic field dependence of the oscillations allows us to extract the discrete energy spectrum of the quantum dot in the quantum-Hall regime.     

Lateral scaling in carbon-nanotube field-effect transistors

We have fabricated carbon-nanotube (CN) field-effect transistors with multiple, individually addressable gate segments. The devices exhibit markedly different transistor characteristics when switched using gate segments controlling the device interior versus those near the source and drain. We ascribe this difference to a change from Schottky-barrier modulation at the contacts to bulk switching. We also find that the current through the bulk portion is independent of gate length for any gate voltage, offering direct evidence for ballistic transport in semiconducting carbon nanotubes over at least a few hundred nanometers, even for relatively small carrier velocities.     

The effect of H-dilution on the transport properties of doped a-Si1−x Ge x : H alloys

This paper is concerned with the optimization of growth conditions for a-Si_1-x Ge _x :H alloys. It is shown that H-dilution of source gases selectively improves the band transport of electrons without significantly affecting the recombination center density or the band transport of holes. It is further shown that the beneficial effects of H-dilution are most pronounced in alloys with comparable densities of Si and Ge.     

Parallel arrays of geometric nanowells for assembling curtains of DNA with controlled lateral dispersion

The analysis of individual molecules is evolving into an important tool for biological research, and presents conceptually new ways of approaching experimental design strategies. However, more robust methods are required if these technologies are to be made broadly available to the biological research community. To help achieve this goal we have combined nanofabrication techniques with single-molecule optical microscopy for assembling and visualizing curtains comprised of thousands of individual DNA molecules organized at engineered diffusion barriers on a lipid bilayer-coated surface. Here we present an important extension of this technology that implements geometric barrier patterns comprised of thousands of nanoscale wells that can be loaded with single molecules of DNA. We show that these geometric nanowells can be used to precisely control the lateral distribution of the individual DNA molecules within curtains assembled along the edges of the engineered barrier patterns. The individual molecules making up the DNA curtain can be separated from one another by a user-defined distance dictated by the dimensions of the nanowells. We demonstrate the broader utility of these patterned DNA curtains in a novel, real time restriction assay that we refer to as dynamic optical restriction mapping, which can be used to rapidly identify entire sets of cleavage sites within a large DNA molecule.     

Cationic crosslinking of solid dgeba resins with ytterbium(III) trifluoromethanesulfonate as initiator

Solid bisphenol-A epoxy resin of medium molecular mass was cured using a Lewis acid initiator (ytterbium(III) trifluoromethanesulfonate) in three different proportions (0.5, 1 and 2 phr). A kinetic study was performed in a differential scanning calorimeter. The complete kinetic triplet was determined (activation energy, pre-exponential factor, and integral function of the degree of conversion) for each system. A kinetic analysis was performed with an integral isoconversional procedure (free model), and the kinetic model was determined both with the Coats-Redfern method (the obtained isoconversional value being accepted as the effective activation energy) and through the compensation effect. All the systems followed the same isothermal curing model simulated from non-isothermal ones. The growth-of-nuclei Avrami kinetic model A_3/2 has been proposed as the polymerization kinetic model. The addition of initiator accelerated the reaction especially when 2 phr was added. 0.5 and 1 phr showed very few kinetic differences between them.     

Chiral capillary electrophoresis as predictor for separation of drug enantiomers in continuous flow zone electrophoresis

Separation of the enantiomers of chlorpheniramine and methadone in acidic buffers containing carboxymethyl-betacyclodextrin (CMCD) as chiral selector was investigated by capillary zone electrophoresis. For a range of pH and CMCD concentrations, the mobility difference and resolution of the enantiomers were determined. Then, conditions known to provide well resolved enantiomers and optimized chiral separation were applied to chiral continuous flow electrophoresis. In that approach, a thin film of fluid flowing between two parallel plates is employed as carrier for electrophoresis. The electrolytes and the sample are continuously admitted at one end of the electrophoresis chamber and are fractionated by an array of outlet tubes at the other. The number of pure enantiomeric fractions obtained by chiral continuous flow electrophoresis was found to be directly dependent on the enantiomeric mobility difference. For racemic chlorpheniramine separated in a betaine-acetic acid buffer at a total throughput of 5 mg/h, complete enantiomeric separation is shown to require a mobility difference of about 3 x 10(-9) m2/V s. Furthermore, compared to the previous investigations with hydroxypropyl-beta-cyclodextrin, CMCD was found to permit improved fractionation of methadone enantiomers. With a total racemic drug throughput of about 15 mg/h, continuous flow zone electrophoresis processing with CMCD as chiral selector is shown to have the potential of providing pure enantiomers on a mg/h scale. The results indicate that chiral capillary zone electrophoresis data can be employed as predictor for preparative scale chiral separations based upon continuous flow zone electrophoresis.     

Macroscopic etch anisotropies and microscopic reaction mechanisms: a micromachined structure for the rapid assay of etchant anisotropy

A new technique for the rapid quantification of orientation-dependent etch rates, which uses micromachined test patterns and optical microscopy, has been developed. The etching of silicon in KOH etchants with and without isopropanol was studied. Etch rates measured with this technique are in good agreement with conventionally measured rates. In most cases, the etch rate anisotropies are well described by a simple model that is based on step-flow etching. Kinetic Monte Carlo simulations of etching were used to test the simple model and to generate approximate morphologies of the etched surfaces. Vicinal Si(110) surfaces display unusual, orientation-dependent etch rates in some etchants; the functional form of the etch rate anisotropy suggests that a morphological transition occurs on these highly reactive faces. In moderately concentrated KOH solutions where isopropanol is readily soluble, the measured etch rate anisotropies suggest that isopropanol stabilizes step-flow etching.