TY - JOUR A1 - Zhang, Jin A1 - Heimbach, Tycho A1 - Scheer, Nico A1 - Barve, Avantika A1 - Li, Wenkui A1 - Lin, Wen A1 - He, Handan T1 - Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4–Humanized Mouse Studies With PBPK Modeling JF - Journal of Pharmaceutical Sciences N2 - 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. Y1 - 2016 U6 - http://dx.doi.org/doi.org/10.1016/j.xphs.2016.01.021 SN - 0022-3549 VL - Volume 105 IS - Issue 4 SP - 1398 EP - 1404 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Dallas, Shannon A1 - Salphati, Laurent A1 - Gomez-Zepeda, David A1 - Wanek, Thomas A1 - Chen, Liangfu A1 - Chu, Xiaoyan A1 - Kunta, Jeevan A1 - Mezler, Mario A1 - Menet, Marie-Claude A1 - Chasseigneaux, Stephanie A1 - Declèves, Xavier A1 - Langer, Oliver A1 - Pierre, Esaie A1 - DiLoreto, Karen A1 - Hoft, Carolin A1 - Laplanche, Loic A1 - Pang, Jodie A1 - Pereira, Tony A1 - Andonian, Clara A1 - Simic, Damir A1 - Rode, Anja A1 - Yabut, Jocelyn A1 - Zhang, Xiaolin A1 - Scheer, Nico T1 - Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model JF - Molecular Pharmacology N2 - 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. Y1 - 2016 U6 - http://dx.doi.org/10.1124/mol.115.102079 SN - 1521-0111 VL - 89 IS - 5 SP - 492 EP - 504 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Bernecker, Andreas T1 - Divided we reform? Evidence from US welfare policies JF - Journal of Public Economics N2 - Divided government is often thought of as causing legislative deadlock. I investigate the link between divided government and economic reforms using a novel data set on welfare reforms in US states between 1978 and 2010. Panel data regressions show that, under divided government, a US state is around 25% more likely to adopt a welfare reform than under unified government. Several robustness checks confirm this counter-intuitive finding. Case study evidence suggests an explanation based on policy competition between governor, senate, and house. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.jpubeco.2016.08.003 SN - 0047-2727 VL - 142 SP - 24 EP - 38 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Rieper, Harald A1 - Gebhardt, Andreas A1 - Stucker, Brent T1 - Process parameters for Selective Laser Melting of AgCu7 T2 - DDMC, Fraunhofer Direct Digital Manufacturing Conference, 3 Y1 - 2016 SN - 978-3-8396-1001-5 N1 - DDMC, 2016, Fraunhofer Direct Digital Manufacturing Conference, 3rd, Berlin, DE, 2016-03-16 - 2016-03-17 SP - 171 EP - 176 PB - Fraunhofer-Verlag CY - Stuttgart ER - TY - JOUR A1 - Aimenova, Zh. E. A1 - Digel, Ilya A1 - Eshibaev, А. А. T1 - Dynamics of accumulation of lagochirzin in Lagochilus setulosus phytomass during the growing season and also features of its cultivation in the conditions of a typical sierozem JF - KazNU Bulletin. Biology series N2 - L.setulosus is offered for creation of biopreparation «Setulin», possesing he- mostatic action, the basic reactant of biopreparation is diterpen – lagochirzin. Results under the maintenance and dynamics of diterpen lagochirzin accumula- tion in various parts of L.setulosus are presented: in roots, stalks, leaves, flowers and calyx lobes during the growing season, and also results on conditions of cultivation L.setulosus in the conditions of a typical sierozem are resulted. From the obtained data is visible, that the given species of a plant is endemic. It is established, that dynamics of accumulation of lagochirzin in phytomass accrues from the beginning to the middle of the growing season. The chemical analysis of L.setulosus on a localization of lagochirzin in various organs of a plant, has shown, that the greatest quantity of lagochirzin collects in calyx lobes of the plants. Also it is established, that L.setulosus can be cultivated in the conditions of the typical sierozem, a mineral food is necessary for the given species of plants of Lagochilus genus, except nitric fertilizers. Comparative studying of wild-growing and cultural forms of L.setulosus has shown, that in the cultivated phytomass of plants the maintenance of lagochirzin on 17-20 % higher than in the wild-growing species. Y1 - 2016 SN - 1563-0218 N1 - Original in russischer Sprache VL - 69 IS - 4 SP - 4 EP - 11 PB - Al-Farabi Kazakh National University CY - Almaty ER - TY - CHAP A1 - Matcha, Heike ED - Herneoja, Aulikki ED - Österlund, Toni ED - Markkanen, Piia T1 - From Designing Buildings from Systems to Designing Systems for Buildings T2 - Complexity & Simplicity - Proceedings of the 34th eCAADe Conference - Volume 1 N2 - We study the novel possibilities computer aided design and production open up for the design of building systems. Such systems today can, via individualized mass production, consist of a larger number and more complex parts than previously and therefore be assembled into more complex wholes. This opens up the possibility of designing specialized systems specifically for single buildings. The common order of starting with a building system and designing a building using this system can be reversed to designing a building first and then developing a system specifically for that building. We present and discuss research that incorporates students design projects into research work and fosters links between research and teaching. KW - Building Systems KW - Parametric Design KW - Parametric Modelling KW - Structuralist Architecture Y1 - 2016 U6 - http://dx.doi.org/10.52842/conf.ecaade.2016.1.237 N1 - Proceedings of the 34th eCAADe Conference, University of Oulu, Oulu, Finland, 22-26 August 2016. SP - 237 EP - 240 PB - ECAADe CY - Oulu, Finland ER - TY - THES A1 - Frotscher, Ralf T1 - Electromechanical modeling and simulation of thin cardiac tissue constructs - smoothed FEM applied to a biomechanical plate problem Y1 - 2016 N1 - Duisburg, Essen, Universität Duisburg-Essen, Diss., 2016 ER - TY - JOUR A1 - Scheer, Nico A1 - Wilson, Ian D. T1 - A comparison between genetically humanized and chimeric liver humanized mouse models for studies in drug metabolism and toxicity JF - Drug Discovery Today N2 - Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug–drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.drudis.2015.09.002 SN - 1359-6446 VL - 21 IS - 2 SP - 250 EP - 263 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Scheer, Nico A1 - Chu, Xiaoyan A1 - Salphati, Laurent A1 - Zamek-Gliszczynski, Maciej J. ED - Nicholls, Glynis T1 - Knockout and humanized animal models to study membrane transporters in drug development T2 - Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development Y1 - 2016 SN - 978-1-78262-379-3 U6 - http://dx.doi.org/10.1039/9781782623793-00298 SP - 298 EP - 332 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Weber, Tobias A1 - Arent, Jan-Christoph A1 - Münch, Lukas A1 - Duhovic, Miro A1 - Balvers, Johannes M. T1 - A fast method for the generation of boundary conditions for thermal autoclave simulation JF - Composites Part A N2 - Manufacturing process simulation enables the evaluation and improvement of autoclave mold concepts early in the design phase. To achieve a high part quality at low cycle times, the thermal behavior of the autoclave mold can be investigated by means of simulations. Most challenging for such a simulation is the generation of necessary boundary conditions. Heat-up and temperature distribution in an autoclave mold are governed by flow phenomena, tooling material and shape, position within the autoclave, and the chosen autoclave cycle. This paper identifies and summarizes the most important factors influencing mold heat-up and how they can be introduced into a thermal simulation. Thermal measurements are used to quantify the impact of the various parameters. Finally, the gained knowledge is applied to develop a semi-empirical approach for boundary condition estimation that enables a simple and fast thermal simulation of the autoclave curing process with reasonably high accuracy for tooling optimization. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.compositesa.2016.05.036 SN - 1359-835X VL - 88 SP - 216 EP - 225 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Svaneborg, Carsten A1 - Karimi-Varzaneh, Hossein Ali A1 - Hojdis, Nils A1 - Fleck, Franz A1 - Everaers, Ralf T1 - Multiscale approach to equilibrating model polymer melts JF - Physical Review E N2 - We present an effective and simple multiscale method for equilibrating Kremer Grest model polymer melts of varying stiffness. In our approach, we progressively equilibrate the melt structure above the tube scale, inside the tube and finally at the monomeric scale. We make use of models designed to be computationally effective at each scale. Density fluctuations in the melt structure above the tube scale are minimized through a Monte Carlo simulated annealing of a lattice polymer model. Subsequently the melt structure below the tube scale is equilibrated via the Rouse dynamics of a force-capped Kremer-Grest model that allows chains to partially interpenetrate. Finally the Kremer-Grest force field is introduced to freeze the topological state and enforce correct monomer packing. We generate 15 melts of 500 chains of 10.000 beads for varying chain stiffness as well as a number of melts with 1.000 chains of 15.000 monomers. To validate the equilibration process we study the time evolution of bulk, collective, and single-chain observables at the monomeric, mesoscopic, and macroscopic length scales. Extension of the present method to longer, branched, or polydisperse chains, and/or larger system sizes is straightforward. Y1 - 2016 U6 - http://dx.doi.org/10.1103/PhysRevE.94.032502 SN - 2470-0053 VL - 94 IS - 032502 PB - AIP Publishing CY - Melville, NY ER - TY - JOUR A1 - Schwab, Lukas A1 - Hojdis, Nils A1 - Lacayo, Jorge A1 - Wilhelm, Manfred T1 - Fourier-Transform Rheology of Unvulcanized, Carbon Black Filled Styrene Butadiene Rubber JF - Macromolecular Materials and Engineering N2 - Rubber materials filled with reinforcing fillers display nonlinear rheological behavior at small strain amplitudes below γ0 < 0.1. Nevertheless, rheological data are analyzed mostly in terms of linear parameters, such as shear moduli (G′, G″), which loose their physical meaning in the nonlinear regime. In this work styrene butadiene rubber filled with carbon black (CB) under large amplitude oscillatory shear (LAOS) is analyzed in terms of the nonlinear parameter I3/1. Three different CB grades are used and the filler load is varied between 0 and 70 phr. It is found that I3/1(φ) is most sensitive to changes of the total accessible filler surface area at low strain amplitudes (γ0 = 0.32). The addition of up to 70 phr CB leads to an increase of I3/1(φ) by a factor of more than ten. The influence of the measurement temperature on I3/1 is pronounced for CB levels above the percolation threshold. Y1 - 2016 U6 - http://dx.doi.org/10.1002/mame.201500356 SN - 1439-2054 VL - 301 IS - 4 SP - 457 EP - 468 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Harish, Ajay B. A1 - Wriggers, Peter A1 - Jungk, Juliane A1 - Hojdis, Nils A1 - Recker, Carla T1 - Mesoscale Constitutive Modeling of Non-Crystallizing Filled Elastomers JF - Computational Mechanics N2 - Elastomers are exceptional materials owing to their ability to undergo large deformations before failure. However, due to their very low stiffness, they are not always suitable for industrial applications. Addition of filler particles provides reinforcing effects and thus enhances the material properties that render them more versatile for applications like tyres etc. However, deformation behavior of filled polymers is accompanied by several nonlinear effects like Mullins and Payne effect. To this day, the physical and chemical changes resulting in such nonlinear effect remain an active area of research. In this work, we develop a heterogeneous (or multiphase) constitutive model at the mesoscale explicitly considering filler particle aggregates, elastomeric matrix and their mechanical interaction through an approximate interface layer. The developed constitutive model is used to demonstrate cluster breakage, also, as one of the possible sources for Mullins effect observed in non-crystallizing filled elastomers. Y1 - 2016 U6 - http://dx.doi.org/10.1007/s00466-015-1251-1 SN - 1432-0924 VL - 57 SP - 653 EP - 677 PB - Springer CY - Berlin ER - TY - BOOK A1 - Altherr, Lena T1 - Algorithmic System Design under Consideration of Dynamic Processes N2 - Nach Stand von Wissenschaft und Technik werden Komponenten hinsichtlich ihrer Eigenschaften, wie Lebensdauer oder Energieeffizienz, optimiert. Allerdings können selbst hervorragende Komponenten zu ineffizienten oder instabilen Systemen führen, wenn ihr Zusammenspiel nur unzureichend berücksichtigt wird. Eine Systembetrachtung schafft ein größeres Optimierungspotential - dem erhöhten Potential steht jedoch auch ein erhöhter Komplexitätsgrad gegenüber. Die vorliegende Arbeit ist im Rahmen des Sonderforschungsbereichs 805 entstanden, dessen Ziel die Beherrschung von Unsicherheit in Systemen des Maschinenbaus ist. Die Arbeit zeigt anhand eines realen Systems aus dem Bereich der Hydraulik, wie Unsicherheit in der Entwicklungsphase beherrscht werden kann. Hierbei ist neu, dass die durch den späteren Betrieb zu erwartende Systemdegradation eines jeden möglichen Systemvorschlags antizipiert werden kann. Dadurch können Betriebs- und Wartungskosten vorausgesagt und minimiert werden und durch eine optimale Betriebs- und Wartungsstrategie die Verfügbarkeit des Systems garantiert werden. Wesentliche Fragen bei der optimalen Auslegung des betrachteten hydrostatischen Getriebes sind dessen physikalische Modellierung, die Darstellung des Optimierungsproblems als gemischt-ganzzahliges lineares Programm, und dessen algorithmische Behandlung zur Lösungsfindung. Hierzu werden Heuristiken zum schnelleren Auffinden sinnvoller Systemtopologien vorgestellt und mittels mathematischer Dekomposition eine Bewertung des dynamischen Verschleiß- und Wartungsverlaufs möglicher Systemvorschläge vorgenommen. Die Arbeit stellt die Optimierung technischer Systeme an der Schnittstelle von Mathematik, Informatik und Ingenieurwesen sowohl gründlich als auch anschaulich und nachvollziehbar dar. KW - Mixed Integer Programming KW - Technical Operations Research KW - Optimization KW - System Design Y1 - 2016 SN - 978-3-8440-4848-3 PB - Shaker CY - Aachen ER - TY - CHAP A1 - Altherr, Lena A1 - Ederer, Thorsten A1 - Lorenz, Ulf A1 - Pelz, Peter F. A1 - Pöttgen, Philipp ED - Lübbecke, Marco E. ED - Koster, Arie ED - Letmathe, Peter ED - Madlener, Reihard ED - Preis, Britta ED - Walther, Grit T1 - Designing a feedback control system via mixed-integer programming T2 - Operations Research Proceedings 2014: Selected Papers of the Annual International Conference of the German Operations Research N2 - Pure analytical or experimental methods can only find a control strategy for technical systems with a fixed setup. In former contributions we presented an approach that simultaneously finds the optimal topology and the optimal open-loop control of a system via Mixed Integer Linear Programming (MILP). In order to extend this approach by a closed-loop control we present a Mixed Integer Program for a time discretized tank level control. This model is the basis for an extension by combinatorial decisions and thus for the variation of the network topology. Furthermore, one is able to appraise feasible solutions using the global optimality gap. KW - Optimal Topology KW - Controller Parameter KW - Level Control System KW - Technical Operation Research KW - Optimal Closed Loop Y1 - 2016 SN - 978-3-319-28695-2 U6 - http://dx.doi.org/10.1007/978-3-319-28697-6_18 SP - 121 EP - 127 PB - Springer CY - Cham ER - TY - CHAP A1 - Rausch, Lea A1 - Leise, Philipp A1 - Ederer, Thorsten A1 - Altherr, Lena A1 - Pelz, Peter F. ED - Papadrakakis, M. ED - Ppadopoulos, V. ED - Stefanou, G. ED - Plevris, V. T1 - A comparison of MILP and MINLP solver performance on the example of a drinking water supply system design problem T2 - ECCOMAS Congress 2016 VII European Congress on Computational Methods in Applied Sciences and Engineering N2 - Finding a good system topology with more than a handful of components is a highly non-trivial task. The system needs to be able to fulfil all expected load cases, but at the same time the components should interact in an energy-efficient way. An example for a system design problem is the layout of the drinking water supply of a residential building. It may be reasonable to choose a design of spatially distributed pumps which are connected by pipes in at least two dimensions. This leads to a large variety of possible system topologies. To solve such problems in a reasonable time frame, the nonlinear technical characteristics must be modelled as simple as possible, while still achieving a sufficiently good representation of reality. The aim of this paper is to compare the speed and reliability of a selection of leading mathematical programming solvers on a set of varying model formulations. This gives us empirical evidence on what combinations of model formulations and solver packages are the means of choice with the current state of the art. KW - Technical Operations Research KW - Mixed-Integer Nonlinear Optimisation KW - Solver Per- formance KW - Drinking Water Supply KW - System Design Problem Y1 - 2016 SN - 978-618-82844-0-1 N1 - ECCOMAS Congress 2016 VII European Congress on Computational Methods in Applied Sciences and Engineering, 5–10 June 2016.Crete Island, Greece SP - 8509 EP - 8527 ER - TY - CHAP A1 - Grundmann, Jan Thimo A1 - Biele, Jens A1 - Dachwald, Bernd A1 - Grimm, Christian A1 - Lange, Caroline A1 - Ulamec, Stephan T1 - Small spacecraft for small solar system body science, planetary defence and applications T2 - IEEE Aerospace Conference 2016 N2 - Following the recent successful landings and occasional re-awakenings of PHILAE, the lander carried aboard ROSETTA to comet 67P/Churyumov-Gerasimenko, and the launch of the Mobile Asteroid Surface Scout, MASCOT, aboard the HAYABUSA2 space probe to asteroid (162173) Ryugu we present an overview of the characteristics and peculiarities of small spacecraft missions to small solar system bodies (SSSB). Their main purpose is planetary science which is transitioning from a ‘pure’ science of observation of the distant to one also supporting in-situ applications relevant for life on Earth. Here we focus on missions at the interface of SSSB science and planetary defence applications. We provide a brief overview of small spacecraft SSSB missions and on this background present recent missions, projects and related studies at the German Aerospace Center, DLR, that contribute to the worldwide planetary defence community. These range from Earth orbit technology demonstrators to active science missions in interplanetary space. We provide a summary of experience from recently flown missions with DLR participation as well as a number of studies. These include PHILAE, the lander of ESA’s ROSETTA comet rendezvous mission now on the surface of comet 67P/Churyumov-Gerasimenko, and the Mobile Asteroid Surface Scout, MASCOT, now in cruise to the ~1 km diameter C-type near-Earth asteroid (162173) Ryugu aboard the Japanese sample-return probe HAYABUSA2. We introduce the differences between the conventional methods employed in the design, integration and testing of large spacecraft and the new approaches developed by small spacecraft projects. We expect that the practical experience that can be gained from projects on extremely compressed timelines or with high-intensity operation phases on a newly explored small solar system body can contribute significantly to the study, preparation and realization of future planetary defence related missions. One is AIDA (Asteroid Impact & Deflection Assessment), a joint effort of ESA, JHU/APL, NASA, OCA and DLR, combining JHU/APL’s DART (Double Asteroid Redirection Test) and ESA’s AIM (Asteroid Impact Monitor) spacecraft in a mission towards near-Earth binary asteroid system (65803) Didymos. DLR is currently applying MASCOT heritage and lessons learned to the design of MASCOT2, a lander for the AIM mission to support a bistatic low frequency radar experiment with PHILAE/ROSETTA CONSERT heritage to explore the inner structure of Didymoon which is the designated impact target for DART. Y1 - 2016 SP - 1 EP - 20 ER - TY - CHAP A1 - König, Johannes Alexander A1 - Wolf, Martin T1 - A new definition of competence developing games - and a framework to assess them T2 - ACHI 2016 : The Ninth International Conference on Advances in Computer-Human Interactions N2 - There are different types of games that try to make use of the motivation of a gaming situation in learning contexts. This paper introduces the new terminology ‘Competence Developing Game’ (CDG) as an umbrella term for all games with this intention. Based on this new terminology, an assessment framework has been developed and validated in scope of an empirical study. Now, all different types of CDGs can be evaluated according to a defined and uniform set of assessment criteria and, thus, are comparable according to their characteristics and effectiveness. KW - Serious Games KW - Gamification KW - Business Simulations KW - Assessment Y1 - 2016 SN - 978-1-61208-468-8 N1 - Proceeding of the Ninth International Conference on Advances in Computer-Human Interactions (ACHI 2016), Venice. SP - 95 EP - 97 ER - TY - CHAP A1 - Hallmann, Marcus A1 - Heidecker, Ansgar A1 - Schlotterer, Markus A1 - Dachwald, Bernd T1 - GTOC8: results and methods of team 15 DLR T2 - 26th AAS/AIAA Space Flight Mechanics Meeting, Napa, CA N2 - This paper describes the results and methods used during the 8th Global Trajectory Optimization Competition (GTOC) of the DLR team. Trajectory optimization is crucial for most of the space missions and usually can be formulated as a global optimization problem. A lot of research has been done to different type of mission problems. The most demanding ones are low thrust transfers with e.g. gravity assist sequences. In that case the optimal control problem is combined with an integer problem. In most of the GTOCs we apply a filtering of the problem based on domain knowledge. Y1 - 2016 N1 - 26th AAS/AIAA Space Flight Mechanics Meeting, February 14-18, 2016, Napa, California, U.S.A. Napa, CA ER - TY - CHAP A1 - Leicht-Scholten, Carmen A1 - Steuer-Dankert, Linda A1 - Bouffier, Anna T1 - Facing Future Challenges: Building Engineers for Tomorrow T2 - Conference proceedings : new perspectives in science education : 5th Conference edition, Florence, Italy, 17-18 March 2016 N2 - Future engineers are increasingly confronted with the so-called Megatrends which are the big social challenges society has to cope with. These Megatrends, such as “Silver Society”, “Globalization”, “Mobility” and “Female Shift” require an application-oriented perspective on Diversity especially in the engineering field. Therefore, it is necessary to enable future engineers not only to look at the technical perspectives of a problem, but also to be able to see the related questions within societies they are developing their artefacts for. The aim of teaching engineering should be to prepare engineers for these requirements and to draw attention to the diverse needs in a globalized world. Bringing together technical knowledge and social competences which go beyond a mere training of the so-called “soft skills”, is a new approach followed at RWTH Aachen University, one of the leading technical universities in Germany. RWTH Aachen University has established the bridging professorship “Gender and Diversity in Engineering” (GDI) which educates engineers with an interdisciplinary approach to expand engineering limits. In the frame of a sustainable teaching concept the research group under the leadership of Prof. Carmen Leicht-Scholten has developed an approach which imparts a supplication-specific Gender and Diversity expertise to engineers. In workshops students gain theoretical knowledge about Gender and Diversity and learn how to transfer their knowledge in their special field of study and later work. To substantiate this, the course participants have to solve case studies from real life. The cases which are developed in collaboration with non-profit organizations and enterprises from economy rise the students to challenges which are inspired by professional life. Evaluation shows the success of this approach as well as an increasing demand for such teaching formats. KW - Diversity KW - Engineering Education KW - Gender KW - Higher Education Y1 - 2016 SN - 978-886292-705-5 SP - 32 EP - 37 ER -