@article{HoughNalwalkDingetal.2015, author = {Hough, Lindsay B. and Nalwalk, Julia W. and Ding, Xinxin and Scheer, Nico}, title = {Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms}, series = {Drug Metabolism and Disposition}, volume = {43}, journal = {Drug Metabolism and Disposition}, number = {9}, issn = {1521-009x}, doi = {10.1124/dmd.115.065490}, pages = {1326 -- 1330}, year = {2015}, language = {en} } @article{ScheerKapelyukhRodeetal.2015, author = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Oswald, Stefan and Busch, Diana and Mclaughlin, Lesley A. and Lin, De and Henderson, Colin J. and Wolf, C. Roland}, title = {Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model}, series = {Drug Metabolism and Disposition}, volume = {43}, journal = {Drug Metabolism and Disposition}, number = {11}, publisher = {ASPET}, address = {Bethesda}, issn = {1521-009x}, doi = {10.1124/dmd.115.065656}, pages = {1679 -- 1690}, year = {2015}, language = {en} } @article{DallasSalphatiGomezZepedaetal.2016, author = {Dallas, Shannon and Salphati, Laurent and Gomez-Zepeda, David and Wanek, Thomas and Chen, Liangfu and Chu, Xiaoyan and Kunta, Jeevan and Mezler, Mario and Menet, Marie-Claude and Chasseigneaux, Stephanie and Decl{\`e}ves, Xavier and Langer, Oliver and Pierre, Esaie and DiLoreto, Karen and Hoft, Carolin and Laplanche, Loic and Pang, Jodie and Pereira, Tony and Andonian, Clara and Simic, Damir and Rode, Anja and Yabut, Jocelyn and Zhang, Xiaolin and Scheer, Nico}, title = {Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model}, series = {Molecular Pharmacology}, volume = {89}, journal = {Molecular Pharmacology}, number = {5}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.115.102079}, pages = {492 -- 504}, year = {2016}, abstract = {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.}, 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} } @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} }