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Breast cancer resistance protein (BCRP) is expressed in various tissues, such as the gut, liver, kidney and blood brain barrier (BBB), where it mediates the unidirectional transport of substrates to the apical/luminal side of polarized cells. Thereby BCRP acts as an efflux pump, mediating the elimination or restricting the entry of endogenous compounds or xenobiotics into tissues and it plays important roles in drug disposition, efficacy and safety. Bcrp knockout mice (Bcrp−/−) have been used widely to study the role of this transporter in limiting intestinal absorption and brain penetration of substrate compounds. Here we describe the first generation and characterization of a mouse line humanized for BCRP (hBCRP), in which the mouse coding sequence from the start to stop codon was replaced with the corresponding human genomic region, such that the human transporter is expressed under control of the murine Bcrp promoter. We demonstrate robust human and loss of mouse BCRP/Bcrp mRNA and protein expression in the hBCRP mice and the absence of major compensatory changes in the expression of other genes involved in drug metabolism and disposition. Pharmacokinetic and brain distribution studies with several BCRP probe substrates confirmed the functional activity of the human transporter in these mice. Furthermore, we provide practical examples for the use of hBCRP mice to study drug-drug interactions (DDIs). The hBCRP mouse is a promising model to study the in vivo role of human BCRP in limiting absorption and BBB penetration of substrate compounds and to investigate clinically relevant DDIs involving BCRP.
Superparamagnetic iron oxide nanoparticles (SPION) are extensively used for magnetic resonance imaging (MRI) and magnetic particle imaging (MPI), as well as for magnetic fluid hyperthermia (MFH). We here describe a sequential centrifugation protocol to obtain SPION with well-defined sizes from a polydisperse SPION starting formulation, synthesized using the routinely employed co-precipitation technique. Transmission electron microscopy, dynamic light scattering and nanoparticle tracking analyses show that the SPION fractions obtained upon size-isolation are well-defined and almost monodisperse. MRI, MPI and MFH analyses demonstrate improved imaging and hyperthermia performance for size-isolated SPION as compared to the polydisperse starting mixture, as well as to commercial and clinically used iron oxide nanoparticle formulations, such as Resovist® and Sinerem®. The size-isolation protocol presented here may help to identify SPION with optimal properties for diagnostic, therapeutic and theranostic applications.
We present the novel concept of a combined drilling and melting probe for subsurface ice research. This probe, named “IceMole”, is currently developed, built, and tested at the FH Aachen University of Applied Sciences’ Astronautical Laboratory. Here, we describe its first prototype design and report the results of its field tests on the Swiss Morteratsch glacier. Although the IceMole design is currently adapted to terrestrial glaciers and ice shields, it may later be modified for the subsurface in-situ investigation of extraterrestrial ice, e.g., on Mars, Europa, and Enceladus. If life exists on those bodies, it may be present in the ice (as life can also be found in the deep ice of Earth).
The so-called "compound solar sail", also known as "Solar Photon Thruster" (SPT), holds the potential of providing significant performance advantages over the flat solar sail. Previous SPT design concepts, however, do not consider shadowing effects and multiple reflections of highly concentrated solar radiation that would inevitably destroy the gossamer sail film. In this paper, we propose a novel advanced SPT (ASPT) design concept that does not suffer from these oversimplifications. We present the equations that describe the thrust force acting on such a sail system and compare its performance with respect to the conventional flat solar sail.
The so-called "compound solar sail", also known as "Solar Photon Thruster" (SPT), is a solar sail design concept, for which the two basic functions of the solar sail, namely light collection and thrust direction, are uncoupled. In this paper, we introduce a novel SPT concept, termed the Advanced Solar Photon Thruster (ASPT). This model does not suffer from the simplified assumptions that have been made for the analysis of compound solar sails in previous studies. We present the equations that describe the force, which acts on the ASPT. After a detailed design analysis, the performance of the ASPT with respect to the conventional flat solar sail (FSS) is investigated for three interplanetary mission scenarios: An Earth-Venus rendezvous, where the solar sail has to spiral towards the Sun, an Earth-Mars rendezvous, where the solar sail has to spiral away from the Sun, and an Earth-NEA rendezvous (to near-Earth asteroid 1996FG3), where a large orbital eccentricity change is required. The investigated solar sails have realistic near-term characteristic accelerations between 0.1 and 0.2mm/s2. Our results show that a SPT is not superior to the flat solar sail unless very idealistic assumptions are made.