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Improved potency of escitalopram on the human serotonin transporter: demonstration of an ex vivo assay technique.
The potency of escitalopram ("Lexapro," s-citalopram, LU-26-054) was compared with that of racemic citalopram ("Celexa") using plasma samples from drug-treated normal controls applied to an assay of human serotonin [5-hydroxytryptamine (5-HT)] transport inhibition in blood platelets. Samples were available for both 4-hour and 24-day drug administration. The data indicated that 5-HT transport inhibition was fully manifest for each drug within 4 hours of administration, without significant increase in platelet transport inhibition by 24-day treatment. In addition, a dose-response relationship could be seen for escitalopram and citalopram with increasing 5-HT transport inhibition observed with increasing dose. It was evident from the data that escitalopram was significantly more potent than its racemate in inhibiting human platelet 5-HT transport. Thirty milligrams of escitalopram approximated the effect of 60 mg of racemic citalopram, and similarly, 10 mg of escitalopram approximated that of 20 mg of its racemate. This is the first demonstration of escitalopram's pharmacodynamic effect on the human 5-HT transporter. The results demonstrate its superior potency at the human 5-HT transporter site.
Immediate rupture of breast implant following trauma.
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Sound processing in amateur musicians and nonmusicians: event-related potential and behavioral indices.
To increase our understanding of auditory neurocognition in musicians, we compared nonmusicians with amateur band musicians in their neural and behavioral sound encoding accuracy. Mismatch negativity and P3a components of the auditory event-related potentials were recorded to changes in basic acoustic features (frequency, duration, location, intensity, gap) and abstract features (melodic contour and interval size). Mismatch negativity was larger in musicians than in nonmusicians for location changes whereas no statistically significant group difference was observed in response to other feature changes or in abstract-feature mismatch negativity. P3a was observed only in musicians in response to location changes. This suggests that when compared with nonmusicians, even amateur musicians have neural sound processing advantages with acoustic information most essential to their musical genre.
The TIR1 protein of Arabidopsis functions in auxin response and is related to human SKP2 and yeast grr1p.
Genetic analysis in Arabidopsis has led to the identification of several genes that are required for auxin response. One of these genes, AXR1, encodes a protein related to yeast Aos1p, a protein that functions to activate the ubiquitin-related protein Smt3p. Here we report the identification of a new gene called TRANSPORT INHIBITOR RESPONSE 1 (TIR1). The tir1 mutants are deficient in a variety of auxin-regulated growth processes including hypocotyl elongation and lateral root formation. These results indicate that TIR1 is also required for normal response to auxin. Further, mutations in TIR1 display a synergistic interaction with mutations in AXR1, suggesting that the two genes function in overlapping pathways. The TIR1 protein contains a series of leucine-rich repeats and a recently identified motif called an F box. Sequence comparisons indicate that TIR1 is related to the yeast protein Grr1p and the human protein SKP2. Because Grr1p and other F-box proteins have been implicated in ubiquitin-mediated processes, we speculate that auxin response depends on the modification of a key regulatory protein(s) by ubiquitin or a ubiquitin-related protein.
Identification of an SCF ubiquitin-ligase complex required for auxin response in Arabidopsis thaliana.
The plant hormone auxin regulates diverse aspects of plant growth and development. We report that in Arabidopsis, auxin response is dependent on a ubiquitin-ligase (E3) complex called SCFTIR1. The complex consists of proteins related to yeast Skp1p and Cdc53p called ASK and AtCUL1, respectively, as well as the F-box protein TIR1. Mutations in either ASK1 or TIR1 result in decreased auxin response. Further, overexpression of TIR1 promotes auxin response suggesting that SCFTIR1 is limiting for the response. These results provide new support for a model in which auxin action depends on the regulated proteolysis of repressor proteins.
Heat-capacity studies near the smectic-A-smectic-C phase transition of azoxy-4,4(')-di-undecyl- alpha -methylcinnamate (AMC-11).
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Thermal-conductivity studies near the smectic-A-smectic-C transition in a liquid-crystal compound.
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Heat-capacity studies near the smectic-C-smectic-I transition of two liquid-crystal compounds.
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Simple explanation of the anomalous transport of heat near two smectic liquid-crystal phase transitions.
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Thermal-conductivity studies near the smectic-C-smectic-I transition of racemic 4-(2'-methylbutyl) phenyl-4'-n-octyloxybiphenyl-4-carboxylate.
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Asymptotic crossover in polymer blends.
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Slow dynamics of segregation in hydrogen-bonded polymer blends.
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Shear suppression of critical fluctuations in a diluted polymer blend.
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Stringlike patterns in critical polymer mixtures under steady shear flow.
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Internal dynamics and elasticity of confined entropic gels
The internal dynamics and elasticity of colloidal gels formed via depletion in confined nearly hard-sphere mixtures are studied via particle-tracking measurements of the self part of the van Hove correlation function, which is found to decay exponentially in space and exhibit a scaling in terms of its first moment. The second moment, or mean-square particle displacement, exhibits a stretched-exponential decay to a plateau and provides a measure of the weak elastic modulus of the gel. A Fourier analysis of the real-space probability distribution yields the intermediate scattering function, which at fixed wave vector exhibits a stretched exponential decay to a nonzero plateau, reminiscent of dynamic behavior observed in a broad class of disordered systems.
Shear viscosity of phase-separating polymer blends with viscous asymmetry.
Rheo-optical measurements of phase separating polymer mixtures under simple shear flow have been used to investigate the influence of domain morphology on the viscosity of emulsionlike polymer blends, in which the morphology under weak shear is droplets of one coexisting phase dispersed in a matrix of the second. The structure and viscosity of low-molecular-weight polybutadiene and polyisoprene mixtures, phase separated by quenching to a temperature inside the coexistence region of the phase diagram, were measured as a function of shear rate and composition. In the weak shear regime, the data are in qualitative agreement with an effective medium model for non-dilute suspensions of slightly deformed interacting droplets. In the strong shear regime, where a stringlike pattern appears en route to a shear-homogenized state, the data are in qualitative agreement with a simple model that accounts for viscous asymmetry in the components.
Anisotropic ordering in sheared binary fluids with viscous asymmetry: experiment and computer simulation.
Optical measurements of the structure and morphology of phase-separating polymer blend under simple shear flow have been performed and the results are compared with computer simulations of sheared phase-separating binary mixtures with viscous asymmetry in the fluid components. Information about the structure is obtained from the two-point composition correlation function. Both experiment and simulation suggest subtle differences in the shear response depending on whether the more viscous phase is dispersed or continuous. Measurements of the string width along the neutral direction suggest power-law decay in the shear rate with an exponent of 1/3 when the more viscous phase is dispersed. The simulations suggest that the mean string width, measured along the velocity-gradient direction in the two-dimensional model calculation, exhibits power-law decay in the shear rate with an exponent of 1/3 independent of which phase is dispersed.