@inproceedings{TranTranMatthiesetal.2016, author = {Tran, Ngoc Trinh and Tran, Thanh Ngoc and Matthies, H. G. and Stavroulakis, G. E. and Staat, Manfred}, title = {Shakedown analysis of plate bending analysis under stochastic uncertainty by chance constrained programming}, series = {ECCOMAS Congress 2016, VII European Congress on Computational Methods in Applied Sciences and Engineering. Crete Island, Greece, 5-10 June 2016}, booktitle = {ECCOMAS Congress 2016, VII European Congress on Computational Methods in Applied Sciences and Engineering. Crete Island, Greece, 5-10 June 2016}, editor = {Papadrakakis, M.}, pages = {13 S.}, year = {2016}, language = {en} } @inproceedings{PoghossianBronderSchejaetal.2016, author = {Poghossian, Arshak and Bronder, Thomas and Scheja, S. and Wu, Chunsheng and Metzger-Boddien, C. and Keusgen, M. and Sch{\"o}ning, Michael Josef}, title = {Label-free Electrostatic Detection of DNA Amplification by PCR Using Capacitive Field-effect Devices}, series = {Procedia Engineering}, volume = {Vol. 168}, booktitle = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2016.11.512}, pages = {514 -- 517}, year = {2016}, abstract = {A capacitive field-effect EIS (electrolyte-insulator-semiconductor) sensor modified with a positively charged weak polyelectrolyte of poly(allylamine hydrochloride) (PAH)/single-stranded probe DNA (ssDNA) bilayer has been used for a label-free electrostatic detection of pathogen-specific DNA amplification via polymerase chain reaction (PCR). The sensor is able to distinguish between positive and negative PCR solutions, to detect the existence of target DNA amplicons in PCR samples and thus, can be used as tool for a quick verification of DNA amplification and the successful PCR process.}, language = {en} } @inproceedings{LeichtScholtenSteuerDankertBouffier2016, author = {Leicht-Scholten, Carmen and Steuer-Dankert, Linda and Bouffier, Anna}, title = {Facing Future Challenges: Building Engineers for Tomorrow}, series = {Conference proceedings : new perspectives in science education : 5th Conference edition, Florence, Italy, 17-18 March 2016}, booktitle = {Conference proceedings : new perspectives in science education : 5th Conference edition, Florence, Italy, 17-18 March 2016}, isbn = {978-886292-705-5}, pages = {32 -- 37}, year = {2016}, abstract = {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.}, language = {en} } @article{WuPoghossianBronderetal.2016, author = {Wu, Chunsheng and Poghossian, Arshak and Bronder, Thomas and Sch{\"o}ning, Michael Josef}, title = {Sensing of double-stranded DNA molecules by their intrinsic molecular charge using the light-addressable potentiometric sensor}, series = {Sensors and Actuators B: Chemical}, journal = {Sensors and Actuators B: Chemical}, number = {229}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0925-4005}, doi = {10.1016/j.snb.2016.02.004}, pages = {506 -- 512}, year = {2016}, abstract = {A multi-spot light-addressable potentiometric sensor (LAPS), which belongs to the family of semiconductor field-effect devices, was applied for label-free detection of double-stranded deoxyribonucleic acid (dsDNA) molecules by their intrinsic molecular charge. To reduce the distance between the DNA charge and sensor surface and thus, to enhance the electrostatic coupling between the dsDNA molecules and the LAPS, the negatively charged dsDNA molecules were electrostatically adsorbed onto the gate surface of the LAPS covered with a positively charged weak polyelectrolyte layer of PAH (poly(allylamine hydrochloride)). The surface potential changes in each spot of the LAPS, induced by the layer-by-layer adsorption of a PAH/dsDNA bilayer, were recorded by means of photocurrent-voltage and constant-photocurrent measurements. In addition, the surface morphology of the gate surface before and after consecutive electrostatic adsorption of PAH and dsDNA layers was studied by atomic force microscopy measurements. Moreover, fluorescence microscopy was used to verify the successful adsorption of dsDNA molecules onto the PAH-modified LAPS surface. A high sensor signal of 25 mV was registered after adsorption of 10 nM dsDNA molecules. The lower detection limit is down to 0.1 nM dsDNA. The obtained results demonstrate that the PAH-modified LAPS device provides a convenient and rapid platform for the direct label-free electrical detection of in-solution hybridized dsDNA molecules.}, language = {en} } @inproceedings{TranTranMatthiesetal.2016, author = {Tran, Ngoc Trinh and Tran, Thanh Ngoc and Matthies, Hermann G. and Stavroulakis, Georgios Eleftherios and Staat, Manfred}, title = {FEM Shakedown of uncertain structures by chance constrained programming}, series = {PAMM Proceedings in Applied Mathematics and Mechanics}, volume = {16}, booktitle = {PAMM Proceedings in Applied Mathematics and Mechanics}, number = {1}, issn = {1617-7061}, doi = {10.1002/pamm.201610346}, pages = {715 -- 716}, year = {2016}, language = {en} } @inproceedings{StaatDuong2016, author = {Staat, Manfred and Duong, Minh Tuan}, title = {Smoothed Finite Element Methods for Nonlinear Solid Mechanics Problems: 2D and 3D Case Studies}, series = {Proceedings of the National Science and Technology Conference on Mechanical - Transportation Engineering (NSCMET 2016), 13th October 2016, Hanoi, Vietnam, Vol.2}, booktitle = {Proceedings of the National Science and Technology Conference on Mechanical - Transportation Engineering (NSCMET 2016), 13th October 2016, Hanoi, Vietnam, Vol.2}, pages = {440 -- 445}, year = {2016}, abstract = {The Smoothed Finite Element Method (SFEM) is presented as an edge-based and a facebased techniques for 2D and 3D boundary value problems, respectively. SFEMs avoid shortcomings of the standard Finite Element Method (FEM) with lower order elements such as overly stiff behavior, poor stress solution, and locking effects. Based on the idea of averaging spatially the standard strain field of the FEM over so-called smoothing domains SFEM calculates the stiffness matrix for the same number of degrees of freedom (DOFs) as those of the FEM. However, the SFEMs significantly improve accuracy and convergence even for distorted meshes and/or nearly incompressible materials. Numerical results of the SFEMs for a cardiac tissue membrane (thin plate inflation) and an artery (tension of 3D tube) show clearly their advantageous properties in improving accuracy particularly for the distorted meshes and avoiding shear locking effects.}, language = {en} } @inproceedings{ValeroBung2016, author = {Valero, Daniel and Bung, Daniel Bernhard}, title = {Interfacial velocity estimation in highly aerated stepped spillway flows with a single tip fibre optical probe and Artificial Neural Networks}, series = {6th IAHR International Junior Researcher and Engineer Workshop on Hydraulic Structures, May 30th to June 1st 2016. L{\"u}beck, Germany}, booktitle = {6th IAHR International Junior Researcher and Engineer Workshop on Hydraulic Structures, May 30th to June 1st 2016. L{\"u}beck, Germany}, doi = {10.15142/T3Q590}, pages = {13 Seiten}, year = {2016}, abstract = {Air-water flows can be found in different engineering applications: from nuclear engineering to huge hydraulic structures. In this paper, a single tip fibre optical probe has been used to record high frequency (over 1 MHz) phase functions at different locations of a stepped spillway. These phase functions have been related to the interfacial velocities by means of Artificial Neural Networks (ANN) and the measurements of a classical double tip conductivity probe. Special attention has been put to the input selection and the ANN dimensions. Finally, ANN have shown to be able to link the signal rising times and plateau shapes to the air-water interfacial velocity.}, language = {en} } @article{ValeroBung2016, author = {Valero, Daniel and Bung, Daniel Bernhard}, title = {Sensitivity of turbulent Schmidt number and turbulence model to simulations of jets in crossflow}, series = {Environmental Modelling and Software}, volume = {82}, journal = {Environmental Modelling and Software}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1364-8152 (electronic)}, doi = {10.1016/j.envsoft.2016.04.030}, pages = {218 -- 228}, year = {2016}, abstract = {Environmental discharges have been traditionally designed by means of cost-intensive and time-consuming experimental studies. Some extensively validated models based on an integral approach have been often employed for water quality problems, as recommended by USEPA (i.e.: CORMIX). In this study, FLOW-3D is employed for a full 3D RANS modelling of two turbulent jet-to-crossflow cases, including free surface jet impingement. Results are compared to both physical modelling and CORMIX to better assess model performance. Turbulence measurements have been collected for a better understanding of turbulent diffusion's parameter sensitivity. Although both studied models are generally able to reproduce jet trajectory, jet separation downstream of the impingement has been reproduced only by RANS modelling. Additionally, concentrations are better reproduced by FLOW-3D when the proper turbulent Schmidt number is used. This study provides a recommendation on the selection of the turbulence model and the turbulent Schmidt number for future outfall structures design studies.}, language = {en} } @inproceedings{NeumannDuelbergSchifferetal.2016, author = {Neumann, Tobias and D{\"u}lberg, Enno and Schiffer, Stefan and Ferrein, Alexander}, title = {A rotating platform for swift acquisition of dense 3D point clouds}, series = {Intelligent Robotics and Applications: 9th International Conference, ICIRA 2016, Tokyo, Japan, August 22-24, 2016, Proceedings, Part I}, volume = {9834}, booktitle = {Intelligent Robotics and Applications: 9th International Conference, ICIRA 2016, Tokyo, Japan, August 22-24, 2016, Proceedings, Part I}, publisher = {Springer}, isbn = {978-3-319-43505-3 (Print)}, doi = {10.1007/978-3-319-43506-0_22}, pages = {257 -- 268}, year = {2016}, language = {en} } @article{HacklMuellerStaatetal.2016, author = {Hackl, Michael and M{\"u}ller, Lars-Peter and Staat, Manfred and Kahmann, Stephanie Lucina and Wegmann, Kilian}, title = {Proximal phalangeal neck fractures of the hand — a biomechanical comparison of three fixation techniques}, series = {Knee surgery, sports traumatology, arthroscopy}, volume = {Volume 24}, journal = {Knee surgery, sports traumatology, arthroscopy}, number = {Supplement 1}, publisher = {Springer}, address = {Berlin}, issn = {0942-2056}, doi = {10.1007/s00167-016-4080-7}, pages = {148 -- 149}, year = {2016}, abstract = {Plate osteosynthesis of displaced proximal phalangeal neck fractures of the hand allows early mobilization due to a stable internal fixation. Nevertheless, joint stiffness—because of soft tissue irritation—represents a common complication leading to high complication rates. Del Pinal et al. recently reported promising clinical results for a new, minimally invasive fixation technique with a cannulated headless intramedullary compression screw. Hence, the aim of this study was to compare plate fixation of proximal phalangeal neck fractures to less two less invasive techniques: Crossed k-wire fixation and intramedullary screw fixation. We hypothesized that these fixation techniques provide inferior stability when compared to plate osteosynthesis.}, language = {en} } @article{FunkeBeckmannKeinzetal.2016, author = {Funke, Harald and Beckmann, Nils and Keinz, Jan and Abanteriba, Sylvester}, title = {Comparison of Numerical Combustion Models for Hydrogen and Hydrogen-Rich Syngas Applied for Dry-Low-NOx-Micromix-Combustion}, series = {ASME Turbo Expo 2016: Turbomachinery Technical Conference and Exposition Volume 4A: Combustion, Fuels and Emissions Seoul, South Korea, June 13-17, 2016}, journal = {ASME Turbo Expo 2016: Turbomachinery Technical Conference and Exposition Volume 4A: Combustion, Fuels and Emissions Seoul, South Korea, June 13-17, 2016}, publisher = {ASME}, address = {New York, NY}, isbn = {978-0-7918-4975-0}, doi = {10.1115/GT2016-56430}, pages = {12}, year = {2016}, abstract = {The Dry-Low-NOₓ (DLN) Micromix combustion technology has been developed as low emission combustion principle for industrial gas turbines fueled with hydrogen or syngas. The combustion process is based on the phenomenon of jet-in-crossflow-mixing. Fuel is injected perpendicular into the air-cross-flow and burned in a multitude of miniaturized, diffusion-like flames. The miniaturization of the flames leads to a significant reduction of NOₓ emissions due to the very short residence time of reactants in the flame. In the Micromix research approach, CFD analyses are validated towards experimental results. The combination of numerical and experimental methods allows an efficient design and optimization of DLN Micromix combustors concerning combustion stability and low NOₓ emissions. The paper presents a comparison of several numerical combustion models for hydrogen and hydrogen-rich syngas. They differ in the complexity of the underlying reaction mechanism and the associated computational effort. For pure hydrogen combustion a one-step global reaction is applied using a hybrid Eddy-Break-up model that incorporates finite rate kinetics. The model is evaluated and compared to a detailed hydrogen combustion mechanism derived by Li et al. including 9 species and 19 reversible elementary reactions. Based on this mechanism, reduction of the computational effort is achieved by applying the Flamelet Generated Manifolds (FGM) method while the accuracy of the detailed reaction scheme is maintained. For hydrogen-rich syngas combustion (H₂-CO) numerical analyses based on a skeletal H₂/CO reaction mechanism derived by Hawkes et al. and a detailed reaction mechanism provided by Ranzi et al. are performed. The comparison between combustion models and the validation of numerical results is based on exhaust gas compositions available from experimental investigation on DLN Micromix combustors. The conducted evaluation confirms that the applied detailed combustion mechanisms are able to predict the general physics of the DLN-Micromix combustion process accurately. The Flamelet Generated Manifolds method proved to be generally suitable to reduce the computational effort while maintaining the accuracy of detailed chemistry. Especially for reaction mechanisms with a high number of species accuracy and computational effort can be balanced using the FGM model.}, language = {en} } @article{AimenovaDigelEshibaev2016, author = {Aimenova, Zh. E. and Digel, Ilya and Eshibaev, А. А.}, title = {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}, series = {KazNU Bulletin. Biology series}, volume = {69}, journal = {KazNU Bulletin. Biology series}, number = {4}, publisher = {Al-Farabi Kazakh National University}, address = {Almaty}, issn = {1563-0218}, pages = {4 -- 11}, year = {2016}, abstract = {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.}, language = {en} } @misc{GamgamiCzupallaGarciaetal.2016, author = {Gamgami, Farid and Czupalla, Markus and Garcia, Antonio and Agnolon, David}, title = {From planetary transits to spacecraft design: achieving PLATO's pointing performance}, series = {A7. Symposium on technological Requirement for future space astronomy and solar-system science missions}, journal = {A7. Symposium on technological Requirement for future space astronomy and solar-system science missions}, year = {2016}, abstract = {In the last decades, several hundred exoplanets could be detected thanks to space-based observatories, namely CNES' COROT and NASA's Kepler. To expand this quest ESA plans to launch CHEOPS as the f irst small class mission in the cosmic visions program (S1) and PLATO as the 3rd medium class mission, so called M3 . PLATO's primary objective is the detection of Earth like Exoplanets orbiting solar type stars in the habitable zone and characterisation of their bulk properties. This is possible by precise lightcurve measurement via 34 cameras. That said it becomes obvious that accurate pointing is key to achieve the required signal to noise ratio for positive transit detection. The paper will start with a comprehensive overview of PLATO's mission objectives and mission architecture. Hereafter, special focus will be devoted to PLATO's pointing requirements. Understanding the very nature of PLATO's pointing requirements is essential to derive a design baseline to achieve the required performance. The PLATO frequency domain is of particular interest, ranging from 40 mHz to 3 Hz. Due to the very different time-scales involved, the spectral pointing requirement is decomposed into a high frequency part dominated by the attitude control system and the low frequency part dominated by the thermo-elastic properties of the spacecraft's configuration. Both pose stringent constraints on the overall design as well as technology properties to comply with the derived requirements and thus assure a successful mission.}, language = {en} } @article{DiktaReisselHarlass2016, author = {Dikta, Gerhard and Reißel, Martin and Harlaß, Carsten}, title = {Semi-parametric survival function estimators deduced from an identifying Volterra type integral equation}, series = {Journal of multivariate analysis}, journal = {Journal of multivariate analysis}, number = {147}, publisher = {Elsevier}, address = {Amsterdam}, doi = {10.1016/j.jmva.2016.02.008}, pages = {273 -- 284}, year = {2016}, abstract = {Based on an identifying Volterra type integral equation for randomly right censored observations from a lifetime distribution function F, we solve the corresponding estimating equation by an explicit and implicit Euler scheme. While the first approach results in some known estimators, the second one produces new semi-parametric and pre-smoothed Kaplan-Meier estimators which are real distribution functions rather than sub-distribution functions as the former ones are. This property of the new estimators is particular useful if one wants to estimate the expected lifetime restricted to the support of the observation time. Specifically, we focus on estimation under the semi-parametric random censorship model (SRCM), that is, a random censorship model where the conditional expectation of the censoring indicator given the observation belongs to a parametric family. We show that some estimated linear functionals which are based on the new semi-parametric estimator are strong consistent, asymptotically normal, and efficient under SRCM. In a small simulation study, the performance of the new estimator is illustrated under moderate sample sizes. Finally, we apply the new estimator to a well-known real dataset.}, language = {en} } @misc{MoehringWulfhorstCapitainetal.2016, author = {M{\"o}hring, S. and Wulfhorst, H. and Capitain, C. and Roth, J. and Tippk{\"o}tter, Nils}, title = {Fractioning of lignocellulosic biomass: Scale-down and automation of thermal pretreatment for parameter optimization}, series = {Chemie Ingenieur Technik}, volume = {88}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201650288}, pages = {1229}, year = {2016}, abstract = {In order to efficiently convert lignocellulose, it is often necessary to conduct a pretreatment. The biomass considered in this study typically comprises of agricultural and horticultural residues, as well as beechwood. A very environmentally friendly method, namely, fungal pretreatment using white-rot fungi, leads to an enhanced enzymatic hydrolysis. In contrast to other processes presented, the energy input is extremely low. However, the fungal growth on the lignocellulosic substrates takes several weeks at least in order to be effective. Thus, the reduction of chemicals and energy for thermal processing is a target of our current research. Liquid hot water (LHW) and solvent-based pretreatment (OrganoSolv) require more complex equipment, as they depend on high temperatures (160 - 180 °C) and enhanced pressure (up to 20 bar). However, they prove to be promising processes in regard to the fractioning of lignocellulose. For optimal lignin recovery the parameters differ from those established in cellulose extraction. A novel screening system scaled down to a reaction volume of 100 mL has been developed and successfully tested for this purpose.}, language = {en} } @article{FrotscherMuanghongDursunetal.2016, author = {Frotscher, Ralf and Muanghong, Danita and Dursun, G{\"o}zde and Goßmann, Matthias and Temiz Artmann, Ayseg{\"u}l and Staat, Manfred}, title = {Sample-specific adaption of an improved electro-mechanical model of in vitro cardiac tissue}, series = {Journal of Biomechanics}, volume = {49}, journal = {Journal of Biomechanics}, number = {12}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0021-9290 (Print)}, doi = {10.1016/j.jbiomech.2016.01.039}, pages = {2428 -- 2435}, year = {2016}, abstract = {We present an electromechanically coupled computational model for the investigation of a thin cardiac tissue construct consisting of human-induced pluripotent stem cell-derived atrial, ventricular and sinoatrial cardiomyocytes. The mechanical and electrophysiological parts of the finite element model, as well as their coupling are explained in detail. The model is implemented in the open source finite element code Code_Aster and is employed for the simulation of a thin circular membrane deflected by a monolayer of autonomously beating, circular, thin cardiac tissue. Two cardio-active drugs, S-Bay K8644 and veratridine, are applied in experiments and simulations and are investigated with respect to their chronotropic effects on the tissue. These results demonstrate the potential of coupled micro- and macroscopic electromechanical models of cardiac tissue to be adapted to experimental results at the cellular level. Further model improvements are discussed taking into account experimentally measurable quantities that can easily be extracted from the obtained experimental results. The goal is to estimate the potential to adapt the presented model to sample specific cell cultures.}, language = {en} } @inproceedings{EngelThieringerTippkoetter2016, author = {Engel, Mareike and Thieringer, Julia and Tippk{\"o}tter, Nils}, title = {Linking bioprocess engineering and electrochemistry for sustainable biofuel production}, series = {Young Researchers Symposium, YRS 2016. Proceedings}, booktitle = {Young Researchers Symposium, YRS 2016. Proceedings}, publisher = {Fraunhofer Verlag}, address = {Karlsruhe}, pages = {49 -- 53}, year = {2016}, abstract = {Electromicrobial engineering is an emerging, highly interdisciplinary research area linking bioprocesses with electrochemistry. In this work, microbial electrosynthesis (MES) of biobutanol is carried out during acetone-butanol-ethanol (ABE) fermentations with Clostridium acetobutylicum. A constant electric potential of -600mV (vs. Ag/AgCl) with simultaneous addition of the soluble redox mediator neutral red is used in order to study the electron transfer between the working electrode and the bacterial cells. The results show an earlier initiation of solvent production for all fermentations with applied potential compared to the conventional ABE fermentation. The f inal butanol concentration can be more than doubled by the application of a negative potential combined with addition of neutral red. Moreover a higher biofilm formation on the working electrode compared to control cultivations has been observed. In contrast to previous studies, our results also indicate that direct electron transfer (DET) might be possible with C. acetobutylicum. The presented results make microbial butanol production economically attractive and therefore support the development of sustainable production processes in the chemical industry aspired by the "Centre for resource-efficient chemistry and raw material change" as well as the the project "NanoKat" working on nanostructured catalysts in Kaiserslautern.}, language = {en} } @inproceedings{JungStaatMueller2016, author = {Jung, Alexander and Staat, Manfred and M{\"u}ller, Wolfram}, title = {Effect of wind on flight style optimisation in ski jumping}, series = {15th International Symposium on Computer Simulation in Biomechanics ; July 9th-11th 2015, Edinburgh, UK}, booktitle = {15th International Symposium on Computer Simulation in Biomechanics ; July 9th-11th 2015, Edinburgh, UK}, publisher = {The University of Edinburgh ; Loughborough University}, address = {Edinburgh}, pages = {53 -- 54}, year = {2016}, language = {en} } @inproceedings{Finger2016, author = {Finger, Felix}, title = {Comparative Performance and Benefit Assessment of VTOL and CTOL UAVs}, series = {Deutscher Luft- und Raumfahrtkongress (DLRK) 2016, 13.-15.9.2016}, booktitle = {Deutscher Luft- und Raumfahrtkongress (DLRK) 2016, 13.-15.9.2016}, pages = {10 Seiten}, year = {2016}, language = {en} } @article{ZhangHeimbachScheeretal.2016, author = {Zhang, Jin and Heimbach, Tycho and Scheer, Nico and Barve, Avantika and Li, Wenkui and Lin, Wen and He, Handan}, title = {Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4-Humanized Mouse Studies With PBPK Modeling}, series = {Journal of Pharmaceutical Sciences}, volume = {Volume 105}, journal = {Journal of Pharmaceutical Sciences}, number = {Issue 4}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0022-3549}, doi = {doi.org/10.1016/j.xphs.2016.01.021}, pages = {1398 -- 1404}, year = {2016}, abstract = {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.}, language = {en} }