Simultaneous determination of midazolam and its three hydroxy metabolites in human plasma by electron-capture gas chromatography without derivatization

Electron-capture gas chromatography was carried out to determine midazolam and its three hydroxy metabolites (1-hydroxymethylmidazolam, 4-hydroxymidazolam and 1-hydroxymethyl-4-hydroxymidazolam) in human plasma. The assay involves extraction from plasma, buffered to pH 9.3, into cyclohexane-dichloromethane (6:4) and analysis by gas chromatography. The use of an HP-17 cross-linked, capillary column makes derivatization unnecessary. The sensitivity of the method was 2-3 ng/ml for midazolam, 1-hydroxymethylmidazolam and 4-hydroxymidazolam, and 20 ng/ml for 1-hydroxymethyl-4-hydroxymidazolam. The extraction recovery of midazolam, 1-hydroxymethylmidazolam, 4-hydroxymidazolam and 1-hydroxymethyl-4-hydroxymidazolam was 99.3 +/- 2.4, 67.0 +/- 4.6, 92.7 +/- 4.7 and 28.7 +/- 6.3%, respectively. This gas chromatographic assay was used to assess the concentration-time profiles of midazolam and its metabolites in human plasma after rectal and intravenous administration of midazolam.     

Substrate specificity analysis of protein kinase complex Dbf2-Mob1 by peptide library and proteome array screening

Background  

The mitotic exit network (MEN) is a group of proteins that form a signaling cascade that is essential for cells to exit mitosis in Saccharomyces cerevisiae. The MEN has also been implicated in playing a role in cytokinesis. Two components of this signaling pathway are the protein kinase Dbf2 and its binding partner essential for its kinase activity, Mob1. The components of MEN that act upstream of Dbf2-Mob1 have been characterized, but physiological substrates for Dbf2-Mob1 have yet to be identified.     

Steady streaming around a spherical drop displaced from the velocity antinode in an acoustic levitation field

The steady (acoustic) streaming associated with a sphericaldrop displaced from the velocity antinode of a standing waveis studied. The ratio of the particle size to the acoustic wavelengthis treated as small but non-zero, and the solution is developedin the form of a two-term expansion in terms of the correspondingsmallness parameter. The drop viscosity is assumed to be muchhigher than that of the surrounding fluid, which is the casefor a drop in a gas medium. There are essentially three distinctregions where the steady streaming flow is analysed: insidethe drop (internal circulation), in the Stokes shear-wave layerat the surface on the gas side, and the gas outside the Stokeslayer (the outer streaming region). Solutions for the internalcirculation and the outer streaming are obtained in the limitof small Reynolds number. Despite the gas-to-liquid viscosity ratio being small, the outerstreaming may be dramatically affected by the fact that thesphere is liquid as opposed to solid. The parameter that measuresthe effect of liquidity is essentially the viscosity ratio dividedby the relative (to the particle size) thickness of the Stokeslayer. The case of a solid sphere is recovered by letting thisparameter go to zero.     

Contribution of spectral cues to human sound localization

The contribution of spectral cues to human sound localization was investigated by removing cues in 1/2-, 1- or 2-octave bands in the frequency range above 4 kHz. Localization responses were given by placing an acoustic pointer at the same apparent position as a virtual target. The pointer was generated by filtering a 100-ms harmonic complex with equalized head-related transfer functions (HRTFs). Listeners controlled the pointer via a hand-held stick that rotated about a fixed point. In the baseline condition, the target, a 200-ms noise burst, was filtered with the same HRTFs as the pointer. In other conditions, the spectral information within a certain frequency band was removed by replacing the directional transfer function within this band with the average transfer of this band. Analysis of the data showed that removing cues in 1/2-octave bands did not affect localization, whereas for the 2-octave band correct localization was virtually impossible. The results obtained for the 1-octave bands indicate that up-down cues are located mainly in the 6-12-kHz band, and front-back cues in the 8-16-kHz band. The interindividual spread in response patterns suggests that different listeners use different localization cues. The response patterns in the median plane can be predicted using a model based on spectral comparison of directional transfer functions for target and response directions.     

Fidelity of three-dimensional-sound reproduction using a virtual auditory display

The fidelity of reproducing free-field sounds using a virtual auditory display was investigated in two experiments. In the first experiment, listeners directly compared stimuli from an actual loudspeaker in the free field with those from small headphones placed in front of the ears. Headphone stimuli were filtered using head-related transfer functions (HRTFs), recorded while listeners were wearing the headphones, in order to reproduce the pressure signatures of the free-field sounds at the eardrum. Discriminability was investigated for six sound-source positions using broadband noise as a stimulus. The results show that the acoustic percepts of real and virtual sounds were identical. In the second experiment, discrimination between virtual sounds generated with measured and interpolated HRTFs was investigated. Interpolation was performed using HRTFs measured for loudspeaker positions with different spatial resolutions. Broadband noise bursts with flat and scrambled spectra were used as stimuli. The results indicate that, for a spatial resolution of about 6 degrees, the interpolation does not introduce audible cues. For resolutions of 20 degrees or more, the interpolation introduces audible cues related to timbre and position. For intermediate resolutions (10 degrees - 15 degrees) the data suggest that only timbre cues were used.