@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} } @article{WilsonWilsonScheeretal.2017, author = {Wilson, Ian D. and Wilson, Claire E. and Scheer, Nico and Dickie, A.P. and Schreiter, K. and Wilson, E. M. and Riley, R. J. and Wehr, R. and Bial, J.}, title = {The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice}, series = {Biochemical pharmacology}, volume = {Volume 135}, journal = {Biochemical pharmacology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-2968}, doi = {10.1016/j.bcp.2017.03.015}, pages = {139 -- 150}, year = {2017}, language = {en} } @inproceedings{MatareSchifferFerrein2019, author = {Matar{\´e}, Victor and Schiffer, Stefan and Ferrein, Alexander}, title = {golog++ : An integrative system design}, series = {CogRob 2018. Cognitive Robotics Workshop : Proceedings of the 11th Cognitive Robotics Workshop 2018 co-located with 16th International Conference on Principles of Knowledge Representation and Reasoning (KR 2018) Tempe, AZ, USA, October 27th, 2018}, booktitle = {CogRob 2018. Cognitive Robotics Workshop : Proceedings of the 11th Cognitive Robotics Workshop 2018 co-located with 16th International Conference on Principles of Knowledge Representation and Reasoning (KR 2018) Tempe, AZ, USA, October 27th, 2018}, editor = {Steinbauer, Gerald and Ferrein, Alexander}, issn = {1613-0073}, pages = {29 -- 35}, year = {2019}, language = {en} } @inproceedings{RuettersWeinheimerBragard2018, author = {R{\"u}tters, Ren{\´e} and Weinheimer, Marius and Bragard, Michael}, title = {Teaching Control Theory with a Simplified Helicopter Model and a Classroom Fitting Hardware Test-Bench}, series = {2018 IEEE 59th International Scientific Conference on Power and Electrical Engineering of Riga Technical University (RTUCON)}, booktitle = {2018 IEEE 59th International Scientific Conference on Power and Electrical Engineering of Riga Technical University (RTUCON)}, isbn = {978-1-5386-6903-7}, doi = {10.1109/RTUCON.2018.8659871}, year = {2018}, language = {en} } @inproceedings{BragardHoekHoegenetal.2018, author = {Bragard, Michael and Hoek, Hauke van and Hoegen, Anne von and Doncker, Rik W. De}, title = {Motivation-based Learning: Teaching Fundamentals of Electrical Engineering with an LED Spinning Top}, series = {2018 IEEE 59th International Scientific Conference on Power and Electrical Engineering of Riga Technical University (RTUCON)}, booktitle = {2018 IEEE 59th International Scientific Conference on Power and Electrical Engineering of Riga Technical University (RTUCON)}, isbn = {978-1-5386-6903-7}, doi = {10.1109/RTUCON.2018.8659810}, pages = {1 -- 6}, year = {2018}, language = {en} } @inproceedings{BindzusBragard2018, author = {Bindzus, Manuel and Bragard, Michael}, title = {Motivating Intuitive Understanding of the Switched Reluctance Machine in the Education of Undergraduate Students}, series = {2018 IEEE 59th International Scientific Conference on Power and Electrical Engineering of Riga Technical University (RTUCON)}, booktitle = {2018 IEEE 59th International Scientific Conference on Power and Electrical Engineering of Riga Technical University (RTUCON)}, isbn = {978-1-5386-6903-7}, doi = {10.1109/RTUCON.2018.8659870}, pages = {1 -- 6}, year = {2018}, language = {en} } @article{LeschingerBirgelHackletal.2019, author = {Leschinger, Tim and Birgel, Stefan and Hackl, Michael and Staat, Manfred and M{\"u}ller, Lars Peter and Wegmann, Kilian}, title = {A musculoskeletal shoulder simulation of moment arms and joint reaction forces after medialization of the supraspinatus footprint in rotator cuff repair}, series = {Computer Methods in Biomechanics and Biomedical Engineering}, journal = {Computer Methods in Biomechanics and Biomedical Engineering}, number = {Early view}, publisher = {Taylor \& Francis}, address = {London}, doi = {10.1080/10255842.2019.1572749}, year = {2019}, language = {en} } @article{WilsonDickieSchreiteretal.2018, author = {Wilson, C. E. and Dickie, A. P. and Schreiter, K. and Wehr, R. and Wilson, E. M. and Bial, J. and Scheer, Nico and Wilson, I. D. and Riley, R. J.}, title = {The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice}, series = {Archives of Toxicology}, volume = {92}, journal = {Archives of Toxicology}, number = {6}, publisher = {Springer}, issn = {1432-0738}, doi = {10.1007/s00204-018-2212-1}, pages = {1953 -- 1967}, year = {2018}, abstract = {The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In addition, the metabolism and excretion were investigated in chimeric liver humanized and murinized FRG mice. Diclofenac reached maximum blood concentrations of 2.43 ± 0.9 µg/mL (n = 3) at 0.25 h post-dose with an AUCinf of 3.67 µg h/mL and an effective half-life of 0.86 h (n = 2). In the murinized animals, maximum blood concentrations were determined as 3.86 ± 2.31 µg/mL at 0.25 h post-dose with an AUCinf of 4.94 ± 2.93 µg h/mL and a half-life of 0.52 ± 0.03 h (n = 3). In C57BL/6J mice, mean peak blood concentrations of 2.31 ± 0.53 µg/mL were seen 0.25 h post-dose with a mean AUCinf of 2.10 ± 0.49 µg h/mL and a half-life of 0.51 ± 0.49 h (n = 3). Analysis of blood indicated only trace quantities of drug-related material in chimeric humanized and murinized FRG mice. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles in humanized mice were different to those of both murinized and wild-type animals, e.g., a higher proportion of the dose was detected in the form of acyl glucuronide metabolites and much reduced amounts as taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57BL/6J mice and humans revealed a greater, though not complete, match between chimeric humanized mice and humans, such that the liver humanized FRG model may represent a model for assessing the biotransformation of such compounds in humans.}, language = {en} } @inproceedings{KazukiKobayashiHirabayashietal.2019, author = {Kazuki, Yasuhiro and Kobayashi, Kaoru and Hirabayashi, Masumi and Abe, Satoshi and Kajitani, Naoyo and Kazuki, Kanoko and Takehara, Shoko and Takiguchi, Masato and Satoh, Daisuke and Kuze, Jiro and Sakuma, Tetsushi and Kaneko, Takehito and Mashimo, Tomoji and Osamura, Minori and Hashimoto, Mari and Wakatsuki, Riko and Hirashima, Rika and Fujiwara, Ryoichi and Deguchi, Tsuneo and Kurihara, Atsushi and Tsukazaki, Yasuko and Senda, Naoto and Yamamoto, Takashi and Scheer, Nico and Oshimura, Mitsuo}, title = {Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism}, series = {PNAS Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, booktitle = {PNAS Proceedings of the National Academy of Sciences of the United States of America}, number = {8}, issn = {1091-6490}, doi = {10.1073/pnas.1808255116}, pages = {3072 -- 3081}, year = {2019}, language = {en} } @inproceedings{BaaderReiswichBartschetal.2018, author = {Baader, Fabian and Reiswich, M. and Bartsch, M. and Keller, D. and Tiede, E. and Keck, G. and Demircian, A. and Friedrich, M. and Dachwald, Bernd and Sch{\"u}ller, K. and Lehmann, Raphael and Chojetzki, R. and Durand, C. and Rapp, L. and Kowalski, Julia and F{\"o}rstner, R.}, title = {VIPER - Student research on extraterrestrical ice penetration technology}, series = {Proceedings of the 2nd Symposium on Space Educational Activities}, booktitle = {Proceedings of the 2nd Symposium on Space Educational Activities}, pages = {1 -- 6}, year = {2018}, abstract = {Recent analysis of scientific data from Cassini and earth-based observations gave evidence for a global ocean under a surrounding solid ice shell on Saturn's moon Enceladus. Images of Enceladus' South Pole showed several fissures in the ice shell with plumes constantly exhausting frozen water particles, building up the E-Ring, one of the outer rings of Saturn. In this southern region of Enceladus, the ice shell is considered to be as thin as 2 km, about an order of magnitude thinner than on the rest of the moon. Under the ice shell, there is a global ocean consisting of liquid water. Scientists are discussing different approaches the possibilities of taking samples of water, i.e. by melting through the ice using a melting probe. FH Aachen UAS developed a prototype of maneuverable melting probe which can navigate through the ice that has already been tested successfully in a terrestrial environment. This means no atmosphere and or ambient pressure, low ice temperatures of around 100 to 150K (near the South Pole) and a very low gravity of 0,114 m/s^2 or 1100 μg. Two of these influencing measures are about to be investigated at FH Aachen UAS in 2017, low ice temperature and low ambient pressure below the triple point of water. Low gravity cannot be easily simulated inside a large experiment chamber, though. Numerical simulations of the melting process at RWTH Aachen however are showing a gravity dependence of melting behavior. Considering this aspect, VIPER provides a link between large-scale experimental simulations at FH Aachen UAS and numerical simulations at RWTH Aachen. To analyze the melting process, about 90 seconds of experiment time in reduced gravity and low ambient pressure is provided by the REXUS rocket. In this time frame, the melting speed and contact force between ice and probes are measured, as well as heating power and a two-dimensional array of ice temperatures. Additionally, visual and infrared cameras are used to observe the melting process.}, language = {en} }