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- avalanche (5)
- Earthquake (4)
- LAPS (4)
- field-effect sensor (4)
- frequency mixing magnetic detection (4)
- CellDrum (3)
- Heparin (3)
- capacitive field-effect sensor (3)
- hydrogen peroxide (3)
- impedance spectroscopy (3)
Accurate determination of free-surface dynamics has attracted much research attention during the past decade and has important applications in many environmental and water related areas. In this study, the free-surface dynamics in several turbulent flows commonly found in nature were investigated using a synchronised setup consisting of an ultrasonic sensor and a high-speed video camera. Basic sensor capabilities were examined in dry conditions to allow for a better characterisation of the present sensor model. The ultrasonic sensor was found to adequately reproduce free-surface dynamics up to the second order, especially in two-dimensional scenarios with the most energetic modes in the low frequency range. The sensor frequency response was satisfactory in the sub-20 Hz band, and its signal quality may be further improved by low-pass filtering prior to digitisation. The application of the USS to characterise entrapped air in high-velocity flows is also discussed.
NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir.