Ultrasound and Microbubbles Enhance Uptake of Doxorubicin in Murine Kidneys

The use of ultrasound and microbubble-enhanced drug delivery, commonly referred to as sonoporation, has reached numerous clinical trials and has shown favourable results. Nevertheless, the microbubbles and acoustic path also pass through healthy tissues. To date, the majority of studies have focused on the impact to diseased tissues and rarely evaluated the impact on healthy and collateral tissue. The aim of this study was to test the effect and feasibility of low-intensity sonoporation on healthy kidneys in a mouse model. In our work here, we used a clinical diagnostic ultrasound system (GE Vivid E9) with a C1-5 ultrasound transducer combined with a software modification for 20-µs-long pulses to induce the ultrasound-guided drug delivery of doxorubicin (DOX) in mice kidneys in combination with SonoVue® and Sonazoid™ microbubbles. The acoustic output settings were within the commonly used diagnostic ranges. Sonoporation with SonoVue® resulted in a significant decrease in weight vs. DOX alone (p = 0.0004) in the first nine days, whilst all other comparisons were not significant. Ultrasound alone resulted in a 381% increase in DOX uptake vs. DOX alone (p = 0.0004), whilst SonoVue® (p = 0.0001) and Sonazoid™ (p < 0.0001) further increased the uptake nine days after treatment (419% and 493%, respectively). No long-standing damage was observed in the kidneys via histology. In future sonoporation and drug uptake studies, we therefore suggest including an “ultrasound alone” group to verify the actual contribution of the individual components of the procedure on the drug uptake and to perform collateral damage studies to ensure there is no negative impact of low-intensity sonoporation on healthy tissues.

Expressing Tonal Closure in Music Performance: Auditory and Visual Cues

We examined whether musical performers communicate tonal closure through expressive manipulation of facial expressions and non-pitch features of the acoustic output. Two musicians hummed two versions of Silent Night: one ended on the tonic of the scale and exhibited tonal closure; the other ended on the dominant and was therefore tonally unclosed. In Experiment 1, video-only recordings of the hummed sequences were presented to 15 participants, who judged whether the (imagined) melody was closed or unclosed. Accuracy was reliably above chance, indicating that the musicians expressed tonal closure in facial expressions and listeners decoded these cues. Experiment 2 was conducted to determine whether musicians also communicate tonal closure in acoustic attributes other than pitch. All tones in the hummed melodies were pitched-shifted to a constant mean value, but performances still differed in loudness, microtonal pitch variation, timing, and timbre. Participants judged whether audio-only recordings were closed or unclosed. Accuracy was not above chance overall, but was marginally above chance for judgement of one of the two singers. Results suggest that tonal closure can be mapped onto non-pitch aspects of performance expression, but is primarily restricted to the use of facial expressions.

Universal principles underlying segmental structures in parrot song and human speech

Despite the diversity of human languages, certain linguistic patterns are remarkably consistent across human populations. While syntactic universals receive more attention, there is stronger evidence for universal patterns in the inventory and organization of segments: units that are separated by rapid acoustic transitions which are used to build syllables, words, and phrases. Crucially, if an alien researcher investigated spoken human language how we analyze non-human communication systems, many of the phonological regularities would be overlooked, as the majority of analyses in non-humans treat breath groups, or “syllables” (units divided by silent inhalations), as the smallest unit. Here, we introduce a novel segment-based analysis that reveals patterns in the acoustic output of budgerigars, a vocal learning parrot species, that match universal phonological patterns well-documented in humans. We show that song in four independent budgerigar populations is comprised of consonant- and vowel-like segments. Furthermore, the organization of segments within syllables is not random. As in spoken human language, segments at the start of a vocalization are more likely to be consonant-like and segments at the end are more likely to be longer, quieter, and lower in fundamental frequency. These results provide a new foundation for empirical investigation of language-like abilities in other species.

Evolution of flow characteristics in a centrifugal compressor with an increase in operating speed

Developments in materials, manufacturing and computing methods have catalysed the generation of efficient compressor designs with higher specific power outputs. Centrifugal compressors have become pervasive in environments demanding a combination of higher power with smaller sizes such as unmanned aerial vehicles, micro gas turbines and turbochargers. These compressors are expected to perform optimally in a range of operational speeds and mass flow states with low acoustic emissions. The impact of operating speed on the flow and acoustic characteristics of a ported shroud compressor has been explored in this work. The operation of the open and blocked configurations of the compressor at the design and near surge points each of a lower and a higher speedline was numerically and experimentally investigated. Comparing the results, the model was shown to predict the operation of the compressor for both configurations at the investigated operating points satisfactorily in terms of both performance and dominant acoustic features. With an increase in the velocity and the Mach number due to increased operational speed, changes in the flow behaviour in the inducer and diffuser were observed. An increase in operational speed was shown to generally increase the overall acoustic emission of the compressor for both configurations. The number of distinct tones in the acoustic output and their magnitude were also seen to be a function of operating speed.