TY - CHAP A1 - Jung, Alexander A1 - Staat, Manfred A1 - Müller, Wolfram T1 - Effect of wind on flight style optimisation in ski jumping T2 - 15th International Symposium on Computer Simulation in Biomechanics ; July 9th-11th 2015, Edinburgh, UK Y1 - 2016 SP - 53 EP - 54 PB - The University of Edinburgh ; Loughborough University CY - Edinburgh ER - TY - CHAP A1 - Finger, Felix T1 - Comparative Performance and Benefit Assessment of VTOL and CTOL UAVs T2 - Deutscher Luft- und Raumfahrtkongress (DLRK) 2016, 13.-15.9.2016 Y1 - 2016 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 - 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 - Rösch, C. A1 - Kratz, F. A1 - Hering, T. A1 - Trautmann, S. A1 - Umanskaya, N. A1 - Tippkötter, Nils A1 - Müller-Renno, C.M. A1 - Ulber, Roland A1 - Hannig, M. A1 - Ziegler, C. T1 - Albumin-lysozyme interactions: cooperative adsorption on titanium and enzymatic activity JF - Colloids and Surfaces B: Biointerfaces N2 - The interplay of albumin (BSA) and lysozyme (LYZ) adsorbed simultaneously on titanium was analyzed by gel electrophoresis and BCA assay. It was found that BSA and lysozyme adsorb cooperatively. Additionally, the isoelectric point of the respective protein influences the adsorption. Also, the enzymatic activity of lysozyme and amylase (AMY) in mixtures with BSA was considered with respect to a possible influence of protein-protein interaction on enzyme activity. Indeed, an increase of lysozyme activity in the presence of BSA could be observed. In contrast, BSA does not influence the activity of amylase. Y1 - 2016 U6 - https://doi.org/10.1016/j.colsurfb.2016.09.048 VL - 149 IS - 1 SP - 115 EP - 121 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Wulfhorst, Helene A1 - Duwe, Anna-Maria A1 - Merseburg, Johannes A1 - Tippkötter, Nils T1 - Compositional analysis of pretreated (beech) wood using differential scanning calorimetry and multivariate data analysis JF - Tetrahedron N2 - The composition of plant biomass varies depending on the feedstock and pre-treatment conditions and influences its processing in biorefineries. In order to ensure optimal process conditions, the quantitative proportion of the main polymeric components of the pre-treated biomass has to be determined. Current standard procedures for biomass compositional analysis are complex, the measurements are afflicted with errors and therefore often not comparable. Hence, new powerful analytical methods are urgently required to characterize biomass. In this contribution, Differential Scanning Calorimetry (DSC) was applied in combination with multivariate data analysis (MVA) to detect the cellulose content of the plant biomass pretreated by Liquid Hot Water (LHW) and Organosolv processes under various conditions. Unlike conventional techniques, the developed analytic method enables the accurate quantification of monosaccharide content of the plant biomass without any previous sample preparation. It is easy to handle and avoids errors in sample preparation. Y1 - 2016 U6 - https://doi.org/10.1016/j.tet.2016.04.029 VL - 72 IS - 46 SP - 7329 EP - 7334 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Schopp, Christoph A1 - Doll, Timo A1 - Gräser, Ulrich A1 - Harzheim, Thomas A1 - Heuermann, Holger A1 - Kling, Rainer A1 - Marso, Michael T1 - Capacitively Coupled High-Pressure Lamp Using Coaxial Line Networks JF - IEEE Transactions on Microwave Theory and Techniques N2 - This paper describes the development of a capacitively coupled high-pressure lamp with input power between 20 and 43 W at 2.45 GHz, using a coaxial line network. Compared with other electrodeless lamp systems, no cavity has to be used and a reduction in the input power is achieved. Therefore, this lamp is an alternative to the halogen incandescent lamp for domestic lighting. To serve the demands of domestic lighting, the filling of the lamp is optimized over all other resulting requirements, such as high efficacy at low induced powers and fast startups. A workflow to develop RF-driven plasma applications is presented, which makes use of the hot S-parameter technique. Descriptions of the fitting process inside a circuit and FEM simulator are given. Results of the combined ignition and operation network from simulations and measurements are compared. An initial prototype is built and measurements of the lamp's lighting properties are presented along with an investigation of the efficacy optimizations using large signal amplitude modulation. With this lamp, an efficacy of 135 lmW -1 is achieved. Y1 - 2016 U6 - https://doi.org/10.1109/TMTT.2016.2600326 SN - 0018-9480 VL - 64 IS - 10 SP - 3363 EP - 3368 PB - IEEE CY - New York, NY ER - TY - JOUR A1 - Levers, A. A1 - Staat, Manfred A1 - Laack, Walter van T1 - Analysis of the long-term effect of the MBST® nuclear magnetic resonance therapy on gonarthrosis JF - Orthopedic Practice Y1 - 2016 VL - 47 IS - 11 SP - 521 EP - 528 ER - TY - CHAP A1 - Bhattarai, Aroj A1 - Staat, Manfred ED - Erni, Daniel T1 - Female pelvic floor dysfunction: progress weakening of the support system T2 - 1st YRA MedTech Symposium 2016 : April 8th / 2016 / University of Duisburg-Essen N2 - The structure of the female pelvic floor (PF) is an inter-related system of bony pelvis,muscles, pelvic organs, fascias, ligaments, and nerves with multiple functions. Mechanically, thepelvic organ support system are of two types: (I) supporting system of the levator ani (LA) muscle,and (II) the suspension system of the endopelvic fascia condensation [1], [2]. Significantdenervation injury to the pelvic musculature, depolimerization of the collagen fibrils of the softvaginal hammock, cervical ring and ligaments during pregnancy and vaginal delivery weakens thenormal functions of the pelvic floor. Pelvic organ prolapse, incontinence, sexual dysfunction aresome of the dysfunctions which increases progressively with age and menopause due toweakened support system according to the Integral theory [3]. An improved 3D finite elementmodel of the female pelvic floor as shown in Fig. 1 is constructed that: (I) considers the realisticsupport of the organs to the pelvic side walls, (II) employs the improvement of our previous FEmodel [4], [5] along with the patient based geometries, (III) incorporates the realistic anatomy andboundary conditions of the endopelvic (pubocervical and rectovaginal) fascia, and (IV) considersvarying stiffness of the endopelvic fascia in the craniocaudal direction [3]. Several computationsare carried out on the presented computational model with healthy and damaged supportingtissues, and comparisons are made to understand the physiopathology of the female PF disorders. Y1 - 2016 U6 - https://doi.org/10.17185/duepublico/40821 SP - 11 EP - 12 PB - Universität Duisburg-Essen CY - Duisburg ER - TY - CHAP A1 - Kahmann, Stephanie A1 - Hackl, Michael A1 - Wegmann, Kilian A1 - Müller, Lars-Peter A1 - Staat, Manfred ED - Erni, Daniel T1 - Impact of a proximal radial shortening osteotomy on the distribution of forces and the stability of the elbow T2 - 1st YRA MedTech Symposium 2016 : April 8th / 2016 / University of Duisburg-Essen N2 - The human arm consists of the humerus (upper arm), the medial ulna and the lateral radius (forearm). The joint between the humerus and the ulna is called humeroulnar joint and the joint between the humerus and the radius is called humeroradial joint. Lateral and medial collateral ligaments stabilize the elbow. Statistically, 2.5 out of 10,000 people suffer from radial head fractures [1]. In these fractures the cartilage is often affected. Caused by the injured cartilage, degenerative diseases like posttraumatic arthrosis may occur. The resulting pain and reduced range of motion have an impact on the patient’s quality of life. Until now, there has not been a treatment which allows typical loads in daily life activities and offers good long-term results. A new surgical approach was developed with the motivation to reduce the progress of the posttraumatic arthrosis. Here, the radius is shortened by 3 mm in the proximal part [2]. By this means, the load of the radius is intended to be reduced due to a load shift to the ulna. Since the radius is the most important stabilizer of the elbow it has to be confirmed that the stability is not affected. In the first test (Fig. 1 left), pressure distributions within the humeroulnar and humeroradial joints a native and a shortened radius were measured using resistive pressure sensors (I5076 and I5027, Tekscan, USA). The humerus was loaded axially in a tension testing machine (Z010, Zwick Roell, Germany) in 50 N steps up to 400 N. From the humerus the load is transmitted through both the radius and the ulna into the hand which is fixed on the ground. In the second test (Fig. 1 right), the joint stability was investigated using a digital image correlation system to measure the displacement of the ulna. Here, the humerus is fixed with a desired flexion angle and the unconstrained forearm lies on the ground. A rope connects the load actuator with a hook fixed in the ulna. A guide roller is used so that the rope pulls the ulna horizontally when a tensile load is applied. This creates a moment about the elbow joint with a maximum value of 7.5 Nm. Measurements were performed with varying flexion angles (0°, 30°, 60°, 90°, 120°). For both tests and each measurement, seven specimens were used. Student ́s t-test was employed to determine whether the mean values of the measurements in native specimen and operated specimens differ significantly. Y1 - 2016 U6 - https://doi.org/10.17185/duepublico/40821 SP - 7 EP - 8 PB - Universität Duisburg-Essen CY - Duisburg ER - TY - CHAP A1 - Teixeira Boura, Cristiano José A1 - Niederwestberg, Stefan A1 - McLeod, Jacqueline A1 - Herrmann, Ulf A1 - Hoffschmidt, Bernhard T1 - Development of heat exchanger for high temperature energy storage with bulk materials T2 - AIP Conference Proceedings Y1 - 2016 U6 - https://doi.org/10.1063/1.4949106 VL - 1734 IS - 1 SP - 050008-1 EP - 050008-7 ER - TY - CHAP A1 - Stollenwerk, Dominik A1 - Rieke, Christian A1 - Dahmen, Markus A1 - Pieper, Martin T1 - Biogas Production Modelling : A Control System Engineering Approach T2 - IOP Conference Series: Earth and Environmental Science. Bd. 32 Y1 - 2016 U6 - https://doi.org/10.1088/1755-1315/32/1/012008 SN - 1755-1315 N1 - ICARET 2016, International Conference on Advances in Renewable Energy and Technologies, Putrajaya, MY, Feb 23-25, 2016 SP - 012008/1 EP - 012008/4 ER - TY - CHAP A1 - König, Johannes Alexander A1 - Wolf, Martin R. ED - Stephanidis, C. T1 - The pyramid assessment framework for ‘competence developing games’ T2 - Communications in Computer and Information Science Y1 - 2016 SN - 978-331940541-4 U6 - https://doi.org/10.1007/978-3-319-40542-1_37 SN - 1865-0929 N1 - 18th International Conference on Posters’ Extended Abstracts, HCI International 2016; Toronto; Canada; 17 July 2016 through 22 July 2016 VL - 618 SP - 232 EP - 237 PB - Springer ER - TY - JOUR A1 - Roth, Jasmine A1 - Tippkötter, Nils T1 - Evaluation of lignocellulosic material for butanol production using enzymatic hydrolysate medium JF - Cellulose Chemistry and Technology N2 - Butanol is a promising gasoline additive and platform chemical that can be readily produced via acetone-butanolethanol (ABE) fermentation from pretreated lignocellulosic materials. This article examines lignocellulosic material from beech wood for ABE fermentation, using Clostridium acetobutylicum. First, the utilization of both C₅₋ (xylose) and C₆₋ (glucose) sugars as sole carbon source was investigated in static cultivation, using serum bottles and synthetic medium. The utilization of pentose sugar resulted in a solvent yield of 0.231 g·g_sugar⁻¹, compared to 0.262 g·g_sugar⁻¹ using hexose. Then, the Organosolv pretreated crude cellulose fibers (CF) were enzymatically decomposed, and the resulting hydrolysate medium was analyzed for inhibiting compounds (furans, organic acids, phenolics) and treated with ionexchangers for detoxification. Batch fermentation in a bioreactor using CF hydrolysate medium resulted in a total solvent yield of 0.20 gABE·g_sugar⁻¹. Y1 - 2016 VL - 50 IS - 3-4 SP - 405 EP - 410 PB - Editura Academiei Romane CY - Bukarest ER - TY - JOUR A1 - Steinbauer, Gerald A1 - Ferrein, Alexander T1 - 20 Years of RoboCup JF - KI - Künstliche Intelligenz Y1 - 2016 U6 - https://doi.org/10.1007/s13218-016-0442-z SN - 1610-1987 VL - 30 IS - 3-4 SP - 221 EP - 224 PB - Springer CY - Berlin ER - TY - CHAP A1 - Stephan, Achim A1 - Heuermann, Holger A1 - Prantner, Michael T1 - Cutting human tissue with novel atmospheric-pressure microwave plasma jet T2 - 46th European Microwave Conference (EuMC) Y1 - 2016 SN - 978-2-87487-043-9 U6 - https://doi.org/10.1109/EuMC.2016.7824490 SP - 902 EP - 905 PB - IEEE ER - TY - JOUR A1 - Goßmann, Matthias A1 - Frotscher, Ralf A1 - Linder, Peter A1 - Bayer, Robin A1 - Epple, U. A1 - Staat, Manfred A1 - Temiz Artmann, Aysegül A1 - Artmann, Gerhard T1 - Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells JF - Cellular physiology and biochemistry N2 - 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. KW - Inotropic compounds KW - Pharmacology KW - Ion channels KW - CellDrum KW - Heart tissue culture KW - Induced pluripotent stem cells KW - Cardiac myocytes Y1 - 2016 U6 - https://doi.org/10.1159/000443124 SN - 1421-9778 (Online) SN - 1015-8987 (Print) VL - 38 IS - 3 SP - 1182 EP - 1198 PB - Karger CY - Basel ER - TY - GEN A1 - Roth, J. A1 - Tippkötter, Nils T1 - New Approach for Enzymatic Hydrolysis of Lignocellulose with Selective Diffusion Separation of the Monosaccharide Products T2 - Chemie Ingenieur Technik N2 - Enzymatic hydrolysis of lignocellulosic material plays an important role in the classical biorefinery approach. Apart from the pretreatment of the raw material, hydrolysis is the basis for the conversion of the cellulose and hemicellulose fraction into fermentable sugars. After hydrolysis, usually a solid-liquid separation takes place, in order to separate the residual plant material from the sugar-rich fraction, which can be subsequently used in a fermentation step. In order to factor out the separation step, the usage of in alginate immobilized crude cellulose fiber beads (CFBs) were evaluated. Pretreated cellulose fibers are incorporated in an alginate matrix together with the relevant enzymes. In doing so, sugars diffuse trough the alginate matrix, allowing a simplified delivery into the surrounding fluid. This again reduces product inhibition of the glucose on the enzyme catalysts. By means of standardized bead production the hydrolysis in lab scale was possible. First results show that liberation of glucose and xylose is possible, allowing a maximum total sugar yield of 75 %. Y1 - 2016 U6 - https://doi.org/10.1002/cite.201650301 SN - 0009-286X SN - 1522-2640 (eISSN) N1 - ProcessNet-Jahrestagung 2016 und 32. DECHEMA-Jahrestagung der Biotechnologen 2016, 12. - 15. September 2016, Eurogress Aachen VL - 88 IS - 9 SP - 1237 PB - Wiley-VCH CY - Weinheim ER -