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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.
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.
Die Menschheit lebt über ihre Verhältnisse: Permanent übersteigt unser Verbrauch die uns jährlich zur Verfügung stehenden Ressourcen. Der Energiebedarf digitaler Anwendungen wird dabei meist unterschätzt. Wie Interaction-Designer:innen einen Beitrag zur Entwicklung nachhaltiger Websites leisten können, ist aktuell nur durch aufwendige Recherche zu beantworten. Die Bachelorarbeit »Seeds« stellt einen Schritt im Prozess zu mehr Nachhaltigkeit dar. Sie umfasst ein Toolkit, bestehend aus einer Website und einem Plugin für gängige Designtools. Dieses bündelt alle Informationen, um das Internet barriereärmer, sozialer, ethischer und eben auch ökologisch verträglicher zu gestalten. Während die Website eine Anlaufstelle für den Wissensaufbau darstellt, unterstützt das Plugin bei der Entwicklung eigener Designs, ohne dass Gestalter:innen den Designprozess verlassen müssen.
Konzeption eines Flagship-Stores mit Wohlfühl- und Erlebnis-Spaces
Die Bedürfnisse von Besuchern und Kunden eines Geschäfts haben sich über die letzten Jahre stark verändert. Sie möchten das ihr Kauf zum Erlebnis wird. Auf Basis dieser Erkenntnis wurde im Rahmen dieser Arbeit zusammen mit den Produkten des Weltmarktführers für Teichtechnik und Aquaristik „OASE – Living Water“ ein Storekonzept geschaffen. Dieses verbindet den Verkaufsraum mit unterschiedlichen Erlebniswelten, welche auf die jeweilig ausgestellte Produktkategorie abgestimmt sind. Zusätzlich eröffnet ein diverser und aufregend gestalteter Gartenbereich der zum Entspannen und Verweilen einlädt. Der herausstechende Aspekt des Konzepts ist, dass die Produkte sowohl als reines Produkt, als auch in verbauter Version in Aktion zu sehen sind. Auf diese Art bietet die Marke „OASE – Living Water“ ein neues Kauf-Erlebnis an.
Die Airysche Spannungsfunktion für die unendliche anisotrope, orthotrope und isotrope Scheibe
(1980)
Solution of plane anisotropic elastostatical boundary value problems by singular integral equations
(1982)
Concentrated Solar Power (CSP) systems are able to store energy cost-effectively in their integrated thermal energy storage (TES). By intelligently combining Photovoltaics (PV) systems with CSP, a further cost reduction of solar power plants is expected, as well as an increase in dispatchability and flexibility of power generation. PV-powered Resistance Heaters (RH) can be deployed to raise the temperature of the molten salt hot storage from 385 °C up to 565 °C in a Parabolic Trough Collector (PTC) plant. To avoid freezing and decomposition of molten salt, the temperature distribution in the electrical resistance heater is investigated in the present study. For this purpose, a RH has been modeled and CFD simulations have been performed. The simulation results show that the hottest regions occur on the electric rod surface behind the last baffle. A technical optimization was performed by adjusting three parameters: Shell-baffle clearance, electric rod-baffle clearance and number of baffles. After the technical optimization was carried out, the temperature difference between the maximum temperature and the average outlet temperature of the salt is within the acceptable limits, thus critical salt decomposition has been avoided. Additionally, the CFD simulations results were analyzed and compared with results obtained with a one-dimensional model in Modelica.
Light-addressable potentiometric sensors for quantitative spatial imaging of chemical species
(2017)
A light-addressable potentiometric sensor (LAPS) is a semiconductor-based chemical sensor, in which a measurement site on the sensing surface is defined by illumination. This light addressability can be applied to visualize the spatial distribution of pH or the concentration of a specific chemical species, with potential applications in the fields of chemistry, materials science, biology, and medicine. In this review, the features of this chemical imaging sensor technology are compared with those of other technologies. Instrumentation, principles of operation, and various measurement modes of chemical imaging sensor systems are described. The review discusses and summarizes state-of-the-art technologies, especially with regard to the spatial resolution and measurement speed; for example, a high spatial resolution in a submicron range and a readout speed in the range of several tens of thousands of pixels per second have been achieved with the LAPS. The possibility of combining this technology with microfluidic devices and other potential future developments are discussed.
The light-addressable potentiometric sensor (LAPS) is an electrochemical sensor with a field-effect structure to detect the variation of the Nernst potential at its sensor surface, the measured area on which is defined by illumination. Thanks to this light-addressability, the LAPS can be applied to chemical imaging sensor systems, which can visualize the two-dimensional distribution of a particular target ion on the sensor surface. Chemical imaging sensor systems are expected to be useful for analysis of reaction and diffusion in various electrochemical and biological samples. Recent developments of LAPS-based chemical imaging sensor systems, in terms of the spatial resolution, measurement speed, image quality, miniaturization and integration with microfluidic devices, are summarized and discussed.
The artificial olfactory image was proposed by Lundström et al. in 1991 as a new strategy for an electronic nose system which generated a two-dimensional mapping to be interpreted as a fingerprint of the detected gas species. The potential distribution generated by the catalytic metals integrated into a semiconductor field-effect structure was read as a photocurrent signal generated by scanning light pulses. The impact of the proposed technology spread beyond gas sensing, inspiring the development of various imaging modalities based on the light addressing of field-effect structures to obtain spatial maps of pH distribution, ions, molecules, and impedance, and these modalities have been applied in both biological and non-biological systems. These light-addressing technologies have been further developed to realize the position control of a faradaic current on the electrode surface for localized electrochemical reactions and amperometric measurements, as well as the actuation of liquids in microfluidic devices.
The light-addressable potentiometric sensor (LAPS) and scanning photo-induced impedance microscopy (SPIM) are two closely related methods to visualise the distributions of chemical species and impedance, respectively, at the interface between the sensing surface and the sample solution. They both have the same field-effect structure based on a semiconductor, which allows spatially resolved and label-free measurement of chemical species and impedance in the form of a photocurrent signal generated by a scanning light beam. In this article, the principles and various operation modes of LAPS and SPIM, functionalisation of the sensing surface for measuring various species, LAPS-based chemical imaging and high-resolution sensors based on silicon-on-sapphire substrates are described and discussed, focusing on their technical details and prospective applications.