@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} } @techreport{DammAnthrakidisFend2016, author = {Damm, Marc Andr{\´e} and Anthrakidis, Anette and Fend, Thomas}, title = {Keramische Porenk{\"o}rpersysteme als SCR-Mischer und Hydrolysekatalysator : BMBF-Projekt: Hydromix : Schlussbericht : Laufzeit: 01.10.2011 bis 31.03.2015}, address = {Aachen}, pages = {30 Seiten : Illustrationen, Diagramme}, year = {2016}, language = {de} } @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} } @techreport{BhattaraiFrotscherDurongetal.2016, author = {Bhattarai, Aroj and Frotscher, Ralf and Durong, Minh Tu{\´a}n and Staat, Manfred}, title = {Schlussbericht zu BINGO. Optimierung des Systems Netzimplantat-Beckenboden zur therapeutischen Gewebeverst{\"a}rkung nach der Integraltheorie.}, address = {Aachen}, pages = {34}, year = {2016}, language = {de} } @misc{HeringUlberTippkoetter2016, author = {Hering, T. and Ulber, Roland and Tippk{\"o}tter, Nils}, title = {Antimikrobielle Oberfl{\"a}chenmodifikation durch Mikropartikel}, series = {Chemie Ingenieur Technik}, volume = {88}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, doi = {10.1002/cite.201650084}, pages = {1302}, year = {2016}, abstract = {Die Ausbildung von Biofilmen in technischen Anlagen, wie z. B. K{\"u}hlkreisl{\"a}ufen, Wasseraufbereitungssystemen und Bioreaktoren, f{\"u}hren zu Materialsch{\"a}den (Biofouling) und stark erh{\"o}htem Energieaufwand. Im Rahmen der aktuellen Forschungsarbeiten erfolgen aktive sowie passive Bio-Modifikationen auf funktionalisierten magnetischen Mikropartikelober-fl{\"a}chen. Um die verschiedenen funktionalisierten magnetischen Mikropartikel zu analysieren und ihre antimikrobielle Wirkung zu testen, wird der Einsatz einer 3D-gedruckten, magnetischen Plattform f{\"u}r ein Fluoreszenz-basiertes Screening-System untersucht. F{\"u}r den Oberfl{\"a}chenschutz wurden verschiedene, antimikrobiell funktionalisierte Partikelkombinationen mit dem Mikroorganismus Escherichia coli GFPmut2 in Bezug auf aktiven Oberfl{\"a}chenschutz verglichen. Um die antimikrobielle Oberfl{\"a}cheneffekte von synergistischen Kombinationen unterschiedlich funktionalisierter Partikel zu bestimmen, werden Oberfl{\"a}chen einem Magnetfeld ausgesetzt, das die Mikropartikel als definierte Schicht auf ihnen zur{\"u}ck h{\"a}lt. Diese modifizierten Oberfl{\"a}chen k{\"o}nnen sowohl durch Fluoreszenzspektroskopie als auch -mikroskopie analysiert werden.}, language = {de} } @misc{EngelTippkoetter2016, author = {Engel, M. and Tippk{\"o}tter, Nils}, title = {Einfluss eines Phenazin-Mediators und elektrischen Potenzials auf die Aceton-Butanol-Ethanol-Fermentation}, series = {Chemie Ingenieur Technik}, volume = {88}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201650105}, pages = {1254}, year = {2016}, abstract = {In den letzten Jahren haben nachhaltige, biotechnologische Prozesse zunehmend an Bedeutung gewonnen. Die Aceton-Butanol-Ethanol-Fermentation (ABE-Fermentation) mit dem anaeroben Bakterium Clostridium acetobutylicum zur Gewinnung von Biobutanol k{\"o}nnte in diesem Zusammenhang eine M{\"o}glichkeit der nachhaltigen Kraftstoffproduktion darstellen. In dieser Arbeit wird der Einfluss zus{\"a}tzlich verf{\"u}gbarer Elektronen durch den Einsatz des Phenazin-Farbstoffs Neutralrot als Redoxmediator sowie das Anlegen eines elektrischen Potenzials w{\"a}hrend der ABE-Fermentation untersucht. Es wird gezeigt, dass das Neutralrot keinen Einfluss auf die Leerlaufspannung von ca. 500 mV vs. Ag/AgCl w{\"a}hrend der Fermentation hat. Der Mediator bewirkt allerdings eine fr{\"u}here Butanolbildung sowie h{\"o}here Butanolkonzentrationen. Wird zudem die Mediatorkonzentration von 125 mM auf 250 mM angehoben, wird dabei auch die maximale Butanolkonzentration um 36 \% ± 1,8 \% innerhalb von28 Stunden gesteigert.}, language = {de} } @inproceedings{StephanHeuermannPrantner2016, author = {Stephan, Achim and Heuermann, Holger and Prantner, Michael}, title = {Cutting human tissue with novel atmospheric-pressure microwave plasma jet}, series = {46th European Microwave Conference (EuMC)}, booktitle = {46th European Microwave Conference (EuMC)}, publisher = {IEEE}, isbn = {978-2-87487-043-9}, doi = {10.1109/EuMC.2016.7824490}, pages = {902 -- 905}, year = {2016}, language = {en} } @incollection{Streit2016, author = {Streit, Wilfried}, title = {Kalkulation}, series = {Zahlentafeln f{\"u}r den Baubetrieb}, booktitle = {Zahlentafeln f{\"u}r den Baubetrieb}, edition = {9., {\"u}berarb. und aktual. Aufl.}, publisher = {Springer Vieweg}, address = {Wiesbaden}, isbn = {978-3-658-02838-1 (Online)}, doi = {10.1007/978-3-658-02838-1_13}, pages = {1391 -- 1501}, year = {2016}, abstract = {Das Kapitel behandelt die Kosten- und Preisermittlung, die Kostenvorgabe und Kostenkontrolle. Der Angebotspreis wird aufgeschl{\"u}sselt in die Einzelkosten der Teilleistungen, die Baustellengemeinkosten, die Allgemeinen Gesch{\"a}ftskosten und einen Zuschlag f{\"u}r Wagnis und Gewinn. Auf der Basis der Angebotskalkulation werden die Vorgaben f{\"u}r die Kostenkontrolle entwickelt.}, language = {de} } @article{GossmannFrotscherLinderetal.2016, author = {Goßmann, Matthias and Frotscher, Ralf and Linder, Peter and Bayer, Robin and Epple, U. and Staat, Manfred and Temiz Artmann, Ayseg{\"u}l and Artmann, Gerhard}, title = {Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells}, series = {Cellular physiology and biochemistry}, volume = {38}, journal = {Cellular physiology and biochemistry}, number = {3}, publisher = {Karger}, address = {Basel}, issn = {1421-9778 (Online)}, doi = {10.1159/000443124}, pages = {1182 -- 1198}, year = {2016}, abstract = {Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.}, language = {en} } @misc{WulfhorstMerseburgTippkoetter2016, author = {Wulfhorst, H. and Merseburg, J. and Tippk{\"o}tter, Nils}, title = {Batteriekomponenten aus nachwachsenden Rohstoffen}, series = {Chemie Ingenieur Technik}, volume = {88}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201650333}, pages = {1234 -- 1235}, year = {2016}, abstract = {In diesem Beitrag geht es um die Integration von Stoffstr{\"o}men einer Lignocellulose-Bioraffinerie in Verfahren zur Batterieherstellung. Pflanzliche Reststoffe aus der Biokraftstoffherstellung wie Lignin sollen zur Herstellung neuer Batteriematerialien verwendet werden. Hierbei wird das Lignin als Matrix f{\"u}r die vorgraphitischen C-haltigen Einlagerungsverbindungen in den Elektroden genutzt. Die Si-C-Komposite werden durch das Einbetten von Si in eine Ligninmatrix mit anschließender Carbonisierung hergestellt. Das Lignin hierf{\"u}r wird durch die sequentielle hydrothermale Vorbehandlung von Buchenholz bei variablen Bedingungen gewonnen und mit Si-Nanopartikel sowie als Referenz ohne Si-Nanopartikel gef{\"a}llt. Die Ergebnisse zeigen, dass die sequenzielle Vorbehandlung h{\"o}here Ausbeuten im Vergleich zum LHW- oder Organosolv-Aufschluss liefert. Um eine Anode herzustellen, wurde das resultierende Si-C-Kompositmaterial carbonisiert, auf einen Stromsammler aufgetragen und elektro-chemisch charakterisiert. Der Einfluss der Vorbehandlungsschritte auf den Herstellungsprozess und die {\"o}konomische Bewertung des untersuchten Bioraffinerie-Prozesses wurde mithilfe eines Stoffstrommodells analysiert.}, language = {de} }