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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.
Solar Sail Trajectory Optimization for Intercepting, Impacting, and Deflecting Near-Earth Asteroids
(2005)
Solar Sail Kinetic Energy Impactor Trajectory Optimization for an Asteroid-Deflection Mission
(2007)
Ice melting probes
(2023)
The exploration of icy environments in the solar system, such as the poles of Mars and the icy moons (a.k.a. ocean worlds), is a key aspect for understanding their astrobiological potential as well as for extraterrestrial resource inspection. On these worlds, ice melting probes are considered to be well suited for the robotic clean execution of such missions. In this chapter, we describe ice melting probes and their applications, the physics of ice melting and how the melting behavior can be modeled and simulated numerically, the challenges for ice melting, and the required key technologies to deal with those challenges. We also give an overview of existing ice melting probes and report some results and lessons learned from laboratory and field tests.
"To assess the habitability of the icy environments in the solar system, for example, on Mars, Europa, and Enceladus, the scientific analysis of material embedded in or underneath their ice layers is very important. We consider self-steering robotic ice melting probes to be the best method to cleanly access these environments, that is, in compliance with planetary protection standards. The required technologies are currently developed and tested."
Innovative interplanetary deep space missions, like a main belt asteroid sample
return mission, require ever larger velocity increments (∆V s) and thus ever
more demanding propulsion capabilities. Providing much larger exhaust velocities than chemical high-thrust systems, electric low-thrust space-propulsion
systems can significantly enhance or even enable such high-energy missions. In
1995, a European-Russian Joint Study Group (JSG) presented a study report
on “Advanced Interplanetary Missions Using Nuclear-Electric Propulsion”
(NEP). One of the investigated reference missions was a sample return (SR)
from the main belt asteroid (19) Fortuna. The envisaged nuclear power plant,
Topaz-25, however, could not be realized and also the worldwide developments
in space reactor hardware stalled. In this paper, we investigate, whether such
a mission is also feasible using a solar electric propulsion (SEP) system and
compare our SEP results to corresponding NEP results.
Solar sailcraft provide a wide range of opportunities for high-energy low-cost missions. To date, most mission studies require a rather demanding performance that will not be realized by solar sailcraft of the first generation.
However, even with solar sailcraft of moderate performance, scientifically relevant missions are feasible. This is demonstrated with a Near Earth Asteroid sample return mission and various planetary rendezvous missions.
Multiple Near-Earth Asteroid Rendezvous and Sample Return Using First Generation Solar Sailcraft
(2005)
Solar Sails for Near- and Medium-Term Scientific Deep Space Missions / W. Sebolt ; B. Dachwald
(2005)
Optimization of Interplanetary Rendezvous Trajectories for Solar Sailcraft Using a Neurocontroller
(2002)
Solar sailcraft of the first generation technology development / Seboldt, Wolfgang ; Dachwald, Bernd
(2003)
Within ESA's Cosmic Vision 2015-2025 plan, a mission to explore the Saturnian System, with special emphasis on its two moons Titan and Enceladus, was selected for study, termed TANDEM (Titan and Enceladus Mission). In this paper, we describe an optimized mission design for a TANDEM-derived solar electric propulsion (SEP) mission. We have chosen the SEP mission scenario for the interplanetary transfer of the TANDEM spacecraft because all feasible gravity assist sequences for a chemical transfer between 2015 and 2025 result in long flight times of about nine years. Our SEP system is based on the German RIT ion engine. For our optimized mission design, we have extensively explored the SEP parameter space (specific impulse, thrust level, power level) and have calculated an optimal interplanetary trajectory for each setting. In contrast to the original TANDEM mission concept, which intends to use two launch vehicles and an all-chemical transfer, our SEP mission design requires only a single Ariane 5 ECA launch for the same payload mass. Without gravity assist, it yields a faster and more flexible transfer with a fight time of less than seven years, and an increased payload ratio. Our mission design proves thereby the capability of SEP even for missions into the outer solar system.
Searching optimal continuous-thrust trajectories is usually a difficult and time-consuming task. The solution quality of traditional optimal-control methods depends strongly on an adequate initial guess because the solution is typically close to the initial guess, which may be far from the (unknown) global optimum. Evolutionary neurocontrol attacks continuous-thrust optimization problems from the perspective of artificial intelligence and machine learning, combining artificial neural networks and evolutionary algorithms. This chapter describes the method and shows some example results for single- and multi-phase continuous-thrust trajectory optimization problems to assess its performance. Evolutionary neurocontrol can explore the trajectory search space more exhaustively than a human expert can do with traditional optimal-control methods. Especially for difficult problems, it usually finds solutions that are closer to the global optimum. Another fundamental advantage is that continuous-thrust trajectories can be optimized without an initial guess and without expert supervision.
There is significant interest in sampling subglacial environments for geobiological studies, but they are difficult to access. Existing ice-drilling technologies make it cumbersome to maintain microbiologically clean access for sample acquisition and environmental stewardship of potentially fragile subglacial aquatic ecosystems. The IceMole is a maneuverable subsurface ice probe for clean in situ analysis and sampling of glacial ice and subglacial materials. The design is based on the novel concept of combining melting and mechanical propulsion. It can change melting direction by differential heating of the melting head and optional side-wall heaters. The first two prototypes were successfully tested between 2010 and 2012 on glaciers in Switzerland and Iceland. They demonstrated downward, horizontal and upward melting, as well as curve driving and dirt layer penetration. A more advanced probe is currently under development as part of the Enceladus Explorer (EnEx) project. It offers systems for obstacle avoidance, target detection, and navigation in ice. For the EnEx-IceMole, we will pay particular attention to clean protocols for the sampling of subglacial materials for biogeochemical analysis. We plan to use this probe for clean access into a unique subglacial aquatic environment at Blood Falls, Antarctica, with return of a subglacial brine sample.
We propose a simple parametric OSSD model that describes the variation of the sail film's optical coefficients with time, depending on the sail film's environmental history, i.e., the radiation dose. The primary intention of our model is not to describe the exact behavior of specific film-coating combinations in the real space environment, but to provide a more general parametric framework for describing the general optical degradation behavior of solar sails.