TY  - JOUR
A1  - Hough, Lindsay B.
A1  - Nalwalk, Julia W.
A1  - Ding, Xinxin
A1  - Scheer, Nico
T1  - Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms
JF  - Drug Metabolism and Disposition
Y1  - 2015
U6  - https://doi.org/10.1124/dmd.115.065490
SN  - 1521-009x
VL  - 43
IS  - 9
SP  - 1326
EP  - 1330
ER  - 
TY  - JOUR
A1  - Scheer, Nico
A1  - Kapelyukh, Yury
A1  - Rode, Anja
A1  - Oswald, Stefan
A1  - Busch, Diana
A1  - Mclaughlin, Lesley A.
A1  - Lin, De
A1  - Henderson, Colin J.
A1  - Wolf, C. Roland
T1  - Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model
JF  - Drug Metabolism and Disposition
Y1  - 2015
U6  - https://doi.org/10.1124/dmd.115.065656
SN  - 1521-009x
VL  - 43
IS  - 11
SP  - 1679
EP  - 1690
PB  - ASPET
CY  - Bethesda
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  - https://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  - 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  - https://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  - Wilson, Ian D.
A1  - Wilson, Claire E.
A1  - Scheer, Nico
A1  - Dickie, A.P.
A1  - Schreiter, K.
A1  - Wilson, E. M.
A1  - Riley, R. J.
A1  - Wehr, R.
A1  - Bial, J.
T1  - The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice
JF  - Biochemical pharmacology
Y1  - 2017
U6  - https://doi.org/10.1016/j.bcp.2017.03.015
SN  - 1873-2968
VL  - Volume 135
SP  - 139
EP  - 150
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - CHAP
A1  - Mataré, Victor
A1  - Schiffer, Stefan
A1  - Ferrein, Alexander
ED  - Steinbauer, Gerald
ED  - Ferrein, Alexander
T1  - golog++ : An integrative system design
T2  - 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
Y1  - 2019
SN  - 1613-0073
SP  - 29
EP  - 35
ER  - 
TY  - CHAP
A1  - Rütters, René
A1  - Weinheimer, Marius
A1  - Bragard, Michael
T1  - Teaching Control Theory with a Simplified Helicopter Model and a Classroom Fitting Hardware Test-Bench
T2  - 2018 IEEE 59th International Scientific Conference on Power and Electrical Engineering of Riga Technical University (RTUCON)
Y1  - 2018
SN  - 978-1-5386-6903-7
U6  - https://doi.org/10.1109/RTUCON.2018.8659871
ER  - 
TY  - CHAP
A1  - Bragard, Michael
A1  - Hoek, Hauke van
A1  - Hoegen, Anne von
A1  - Doncker, Rik W. De
T1  - Motivation-based Learning: Teaching Fundamentals of Electrical Engineering with an LED Spinning Top
T2  - 2018 IEEE 59th International Scientific Conference on Power and Electrical Engineering of Riga Technical University (RTUCON)
Y1  - 2018
SN  - 978-1-5386-6903-7
U6  - https://doi.org/10.1109/RTUCON.2018.8659810
SP  - 1
EP  - 6
ER  - 
TY  - CHAP
A1  - Bindzus, Manuel
A1  - Bragard, Michael
T1  - Motivating Intuitive Understanding of the Switched Reluctance Machine in the Education of Undergraduate Students
T2  - 2018 IEEE 59th International Scientific Conference on Power and Electrical Engineering of Riga Technical University (RTUCON)
Y1  - 2018
SN  - 978-1-5386-6903-7
U6  - https://doi.org/10.1109/RTUCON.2018.8659870
SP  - 1
EP  - 6
ER  - 
TY  - JOUR
A1  - Leschinger, Tim
A1  - Birgel, Stefan
A1  - Hackl, Michael
A1  - Staat, Manfred
A1  - Müller, Lars Peter
A1  - Wegmann, Kilian
T1  - A musculoskeletal shoulder simulation of moment arms and joint reaction forces after medialization of the supraspinatus footprint in rotator cuff repair
JF  - Computer Methods in Biomechanics and Biomedical Engineering
Y1  - 2019
U6  - https://doi.org/10.1080/10255842.2019.1572749
IS  - Early view
PB  - Taylor & Francis
CY  - London
ER  - 
TY  - JOUR
A1  - Wilson, C. E.
A1  - Dickie, A. P.
A1  - Schreiter, K.
A1  - Wehr, R.
A1  - Wilson, E. M.
A1  - Bial, J.
A1  - Scheer, Nico
A1  - Wilson, I. D.
A1  - Riley, R. J.
T1  - The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice
JF  - Archives of Toxicology
N2  - 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.
Y1  - 2018
U6  - https://doi.org/10.1007/s00204-018-2212-1
SN  - 1432-0738
VL  - 92
IS  - 6
SP  - 1953
EP  - 1967
PB  - Springer
ER  - 
TY  - CHAP
A1  - Kazuki, Yasuhiro
A1  - Kobayashi, Kaoru
A1  - Hirabayashi, Masumi
A1  - Abe, Satoshi
A1  - Kajitani, Naoyo
A1  - Kazuki, Kanoko
A1  - Takehara, Shoko
A1  - Takiguchi, Masato
A1  - Satoh, Daisuke
A1  - Kuze, Jiro
A1  - Sakuma, Tetsushi
A1  - Kaneko, Takehito
A1  - Mashimo, Tomoji
A1  - Osamura, Minori
A1  - Hashimoto, Mari
A1  - Wakatsuki, Riko
A1  - Hirashima, Rika
A1  - Fujiwara, Ryoichi
A1  - Deguchi, Tsuneo
A1  - Kurihara, Atsushi
A1  - Tsukazaki, Yasuko
A1  - Senda, Naoto
A1  - Yamamoto, Takashi
A1  - Scheer, Nico
A1  - Oshimura, Mitsuo
T1  - Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism
T2  - PNAS Proceedings of the National Academy of Sciences of the United States of America
Y1  - 2019
U6  - https://doi.org/10.1073/pnas.1808255116
SN  - 1091-6490
VL  - 116
IS  - 8
SP  - 3072
EP  - 3081
ER  - 
TY  - CHAP
A1  - Gierse, Andreas
A1  - Krämer, Stefan
A1  - Daab, Dominique J.
A1  - Hessel, Joana
A1  - Baader, Fabian
A1  - Müller, Brigitte S.
A1  - Wagner, Tobias
A1  - Gdalewitsch, Georg
A1  - Plescher, Engelbert
A1  - Pfützenreuter, Lysan
T1  - Experimental in-flight modal-analysis of a sounding rocket structure
T2  - 21st ESA Symposium on Rocket and Ballon related Research
Y1  - 2013
SN  - 9789290922858
SP  - 341
EP  - 346
ER  - 
TY  - JOUR
A1  - Hüning, Felix
A1  - Hillgärtner, Michael
A1  - Reke, Michael
T1  - Rolling Labs – Teaching Vehicle Electronics from the Beginning
JF  - International Journal of Engineering Pedagogy (iJEP)
Y1  - 2019
U6  - https://doi.org/10.3991/ijep.v9i1.9241
SN  - 2192-4880
VL  - 9
IS  - 1
SP  - 34
EP  - 49
ER  - 
TY  - CHAP
A1  - Kunfermann, Philipp
A1  - Drumm, Christian
T1  - Lifting XML schemas to ontologies - the concept finder algorithm
T2  - MEDIATE 2005 First International Workshop on Mediation in Semantic Web Services    Proceedings of the First International Workshop on Mediation in Semantic Web Services (MEDIATE 2005)
Y1  - 2005
SP  - 113
EP  - 122
ER  - 
TY  - CHAP
A1  - Drumm, Christian
A1  - Lemcke, Jens
A1  - Oberle, Daniel
T1  - Integrating Semantic Web Services and Business Process Management: A Real Use Case
T2  - Proceedings of the ESWC 2006 Workshop Semantics for Business Process Management 2006 (SBPM 2006), June 2006
Y1  - 2006
ER  - 
TY  - CHAP
A1  - Drumm, Christian
A1  - Lemcke, Jens
A1  - Oberle, Daniel
T1  - Business Process Management And Semantic Technologies
T2  - The Semantic Web
Y1  - 2007
SN  - 978-0-387-48531-7
U6  - https://doi.org/10.1007/978-0-387-48531-7_10
SP  - 207
EP  - 239
PB  - Springer
CY  - Boston, MA
ER  - 
TY  - CHAP
A1  - Weber, Ingo
A1  - Markovic, Ivan
A1  - Drumm, Christian
T1  - A conceptual framework for composition in business process management
T2  - Business Information Systems : 10th International Conference, BIS 2007, Poznan, Poland, April 25-27, 2007. Proceedings
Y1  - 2007
SN  - 978-3-540-72035-5
U6  - https://doi.org/10.1007/978-3-540-72035-5_5
SP  - 54
EP  - 66
PB  - Springer
CY  - Berlin, Heidelberg
ER  - 
TY  - CHAP
A1  - Drumm, Christian
A1  - Schmitt, Matthias
A1  - Do, Hong-Hai
A1  - Rahm, Erhard
T1  - Quickmig: automatic schema matching for data migration projects
T2  - Proceedings of the 2007 ACM Conference on Information and Knowledge Management / CIKM'07, Lisboa, Portugal, Nov. 6 - 10, 2007
Y1  - 2007
SN  - 978-1-59593-803-9
U6  - https://doi.org/10.1145/1321440.1321458
SP  - 107
EP  - 116
ER  - 
TY  - JOUR
A1  - Raupp, Sebastian M.
A1  - Schmitt, Marcel
A1  - Walz, Anna-Lena
A1  - Diehm, Ralf
A1  - Hummel, Helga
A1  - Scharfer, Philip
A1  - Schabel, Wilhelm
T1  - Slot die stripe coating of low viscous fluids
JF  - Journal of Coatings Technology and Research
N2  - Slot die coating is applied to deposit thin and homogenous films in roll-to-roll and sheet-to-sheet applications. The critical step in operation is to choose suitable process parameters within the process window. In this work, we investigate an upper limit for stripe coatings. This maximum film thickness is characterized by stripe merging which needs to be avoided in a stable process. It is shown that the upper limit reduces the process window for stripe coatings to a major extent. As a result, stripe coatings at large coating gaps and low viscosities are only possible for relatively thick films. Explaining the upper limit, a theory of balancing the side pressure in the gap region in the cross-web direction has been developed.
Y1  - 2018
U6  - https://doi.org/10.1007/s11998-017-0039-y
SN  - 1935-3804
VL  - 15
IS  - 5
SP  - 899
EP  - 911
PB  - Springer
ER  -