Comparisons in Frequency Difference Limens Between Sequential and Simultaneous Listening Conditions in Normal-Hearing Listeners.

Purpose We compared frequency difference limens (FDLs) in normal-hearing listeners under two listening conditions: sequential and simultaneous. Method Eighteen adult listeners participated in three experiments. FDL was measured using a method of limits for comparison frequency. In the sequential listening condition, the tones were presented with a half-second time interval in between, but for the simultaneous listening condition, the tones were presented simultaneously. For the first experiment, one of four reference tones (125, 250, 500, or 750 Hz), which was presented to the left ear, was paired with one of four starting comparison tones (250, 500, 750, or 1000 Hz), which was presented to the right ear. The second and third experiments had the same testing conditions as the first experiment except with two- and three-tone complexes, comparison tones. The subjects were asked if the tones sounded the same or different. When a subject chose "different," the comparison frequency decreased by 10% of the frequency difference between the reference and comparison tones. FDLs were determined when the subjects chose "same" 3 times in a row. Results FDLs were significantly broader (worse) with simultaneous listening than with sequential listening for the two- and three-tone complex conditions but not for the single-tone condition. The FDLs were narrowest (best) with the three-tone complex under both listening conditions. FDLs broadened as the testing frequencies increased for the single tone and the two-tone complex. The FDLs were not broadened at frequencies > 250 Hz for the three-tone complex. Conclusion The results suggest that sequential and simultaneous frequency discriminations are mediated by different processes at different stages in the auditory pathway for complex tones, but not for pure tones.

Synthetic tumor networks for screening drug delivery systems.

Tumor drug delivery is a complex phenomenon affected by several elements in addition to drug or delivery vehicle's physico-chemical properties. A key factor is tumor microvasculature with complex effects including convective transport, high interstitial pressure and enhanced vascular permeability due to the presence of "leaky vessels". Current in vitro models of the tumor microenvironment for evaluating drug delivery are oversimplified and, as a result, show poor correlation with in vivo performance. In this study, we report on the development of a novel microfluidic platform that models the tumor microenvironment more accurately, with physiologically and morphologically realistic microvasculature including endothelial cell lined leaky capillary vessels along with 3D solid tumors. Endothelial cells and 3D spheroids of cervical tumor cells were co-cultured in the networks. Drug vehicle screening was demonstrated using GFP gene delivery by different formulations of nanopolymers. The synthetic tumor network was successful in predicting in vivo delivery efficiencies of the drug vehicles. The developed assay will have critical applications both in basic research, where it can be used to develop next generation delivery vehicles, and in drug discovery where it can be used to study drug transport and delivery efficacy in realistic tumor microenvironment, thereby enabling drug compound and/or delivery vehicle screening.

SyM-BBB: a microfluidic Blood Brain Barrier model.

Current techniques for mimicking the Blood-Brain Barrier (BBB) largely use incubation chambers (Transwell) separated with a filter and matrix coating to represent and to study barrier permeability. These devices have several critical shortcomings: (a) they do not reproduce critical microenvironmental parameters, primarily anatomical size or hemodynamic shear stress, (b) they often do not provide real-time visualization capability, and (c) they require a large amount of consumables. To overcome these limitations, we have developed a microfluidics based Synthetic Microvasculature model of the Blood-Brain Barrier (SyM-BBB). The SyM-BBB platform is comprised of a plastic, disposable and optically clear microfluidic chip with a microcirculation sized two-compartment chamber. The chamber is designed in such a way as to permit the realization of side-by-side apical and basolateral compartments, thereby simplifying fabrication and facilitating integration with standard instrumentation. The individually addressable apical side is seeded with endothelial cells and the basolateral side can support neuronal cells or conditioned media. In the present study, an immortalized Rat Brain Endothelial cell line (RBE4) was cultured in SyM-BBB with a perfusate of Astrocyte Conditioned Media (ACM). Biochemical analysis showed upregulation of tight junction molecules while permeation studies showed an intact BBB. Finally, transporter assay was successfully demonstrated in SyM-BBB indicating a functional model.