http://nova.newcastle.edu.au/vital/access/services/Feed ${session.getAttribute("locale")} 5 http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:413 2010-04-27T05:48:41.646Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3374 The kinetics of drop penetration were studied by filming single drops of several different fluids (water, PEG200, PEG600, and HPC solutions) as they penetrated into loosely packed beds of glass ballotini, lactose, zinc oxide, and titanium dioxide powders. Measured times ranged from 0.45 to 126 s and depended on the powder particle size, viscosity, surface tensions, and contact angle. The experimental drop penetration times were compared to existing theoretical predictions by M. Denesuk et al. (J. Colloid Interface Sci.158, 114, 1993) and S. Middleman (“Modeling Axisymmetric Flows: Dynamics of Films, Jets, and Drops,” Academic Press, San Diego, 1995) but did not agree. Loosely packed powder beds tend to have a heterogeneous bed structure containing large macrovoids which do not participate in liquid flow but are included implicitly in the existing approach to estimating powder pore size. A new two-phase model was proposed where the total volume of the macrovoids was assumed to be the difference between the bed porosity and the tap porosity. A new parameter, the effective porosity εeff, was defined as the tap porosity multiplied by the fraction of pores that terminate at a macrovoid and are effectively blocked pores. The improved drop penetration model was much more successful at estimating the drop penetration time on all powders and the predicted times were generally within an order of magnitude of the experimental results. 2010-04-27T05:03:38.207Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5776 In this study, we present evidence for the mechanism of neomycin inhibition of skeletal ryanodine receptors (RyRs). In single-channel recordings, neomycin produced monophasic inhibition of RyR open probability and biphasic inhibition of [3H]ryanodine binding. The half maximal inhibitory concentration (IC₅0) for channel blockade by neomycin was dependent on membrane potential and cytoplasmic [Ca²⁺], suggesting that neomycin acts both as a pore plug and as a competitive antagonist at a cytoplasmic Ca²⁺ binding site that causes allosteric inhibition. This novel Ca²⁺/neomycin binding site had a neomycin affinity of 100 nM and a Ca²⁺ affinity of 35 nM, which is 30-fold higher than that of the well-described cytoplasmic Ca²⁺ activation site. Therefore, a new high affinity class of Ca²⁺ binding site(s) on the RyR exists that mediates neomycin inhibition. Neomycin plugging of the channel pore induced brief (1-2 ms) conductance substates at 30% of the fully open conductance, whereas allosteric inhibition caused complete channel closure with durations that depended on the neomycin concentration. We quantitatively account for these results using a dual inhibition model for neomycin that incorporates voltage-dependent pore plugging and Ca²⁺-dependent allosteric inhibition. 2010-04-27T04:50:28.985Z ]]>