TY - JOUR A1 - Bialonski, Stephan A1 - Caron, David A. A1 - Schloen, Julia A1 - Feudel, Ulrike A1 - Kantz, Holger A1 - Moorthi, Stefanie D. T1 - Phytoplankton dynamics in the Southern California Bight indicate a complex mixture of transport and biology JF - Journal of Plankton Research N2 - The stimulation and dominance of potentially harmful phytoplankton taxa at a given locale and time are determined by local environmental conditions as well as by transport to or from neighboring regions. The present study investigated the occurrence of common harmful algal bloom (HAB) taxa within the Southern California Bight, using cross-correlation functions to determine potential dependencies between HAB taxa and environmental factors, and potential links to algal transport via local hydrography and currents. A simulation study, in which Lagrangian particles were released, was used to assess travel times due to advection by prevailing ocean currents in the bight. Our results indicate that transport of some taxa may be an important mechanism for the expansion of their distributions into other regions, which was supported by mean travel times derived from our simulation study and other literature on ocean currents in the Southern California Bight. In other cases, however, phytoplankton dynamics were rather linked to local environmental conditions, including coastal upwelling events. Overall, our study shows that complex current patterns in the Southern California Bight may contribute significantly to the formation and expansion of HABs in addition to local environmental factors determining the spatiotemporal dynamics of phytoplankton blooms. Y1 - 2016 U6 - http://dx.doi.org/10.1093/plankt/fbv122 SN - 1464-3774 VL - 38 IS - 4 SP - 1077 EP - 1091 PB - Oxford University Press CY - Oxford ER - TY - CHAP A1 - Bialonski, Stephan T1 - Are interaction clusters in epileptic networks predictive of seizures? T2 - Epilepsy: The Intersection of Neurosciences, Biology, Mathematics, Engineering, and Physics Y1 - 2016 SN - 978-143983886-0 SP - 349 EP - 355 PB - CRC Press ER - TY - JOUR A1 - Becker, Jörg A1 - Delfmann, Patrick A1 - Dietrich, Hanns-Alexander A1 - Steinhorst, Matthias A1 - Eggert, Mathias T1 - Business Process Compliance Checking — Applying and Evaluating a Generic Pattern Matching Approach for Conceptual Models in the Financial Sector JF - Information Systems Frontiers N2 - Given the strong increase in regulatory requirements for business processes the management of business process compliance becomes a more and more regarded field in IS research. Several methods have been developed to support compliance checking of conceptual models. However, their focus on distinct modeling languages and mostly linear (i.e., predecessor-successor related) compliance rules may hinder widespread adoption and application in practice. Furthermore, hardly any of them has been evaluated in a real-world setting. We address this issue by applying a generic pattern matching approach for conceptual models to business process compliance checking in the financial sector. It consists of a model query language, a search algorithm and a corresponding modelling tool prototype. It is (1) applicable for all graph-based conceptual modeling languages and (2) for different kinds of compliance rules. Furthermore, based on an applicability check, we (3) evaluate the approach in a financial industry project setting against its relevance for decision support of audit and compliance management tasks. Y1 - 2016 U6 - http://dx.doi.org/10.1007/s10796-014-9529-y SN - 1572-9419 VL - 18 IS - 2 SP - 359 EP - 405 PB - Springer CY - Berlin 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 - http://dx.doi.org/10.1063/1.4949106 VL - 1734 IS - 1 SP - 050008-1 EP - 050008-7 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 - http://dx.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 - http://dx.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 - Bernecker, Andreas T1 - Divided we reform? Evidence from US welfare policies JF - Journal of Public Economics N2 - Divided government is often thought of as causing legislative deadlock. I investigate the link between divided government and economic reforms using a novel data set on welfare reforms in US states between 1978 and 2010. Panel data regressions show that, under divided government, a US state is around 25% more likely to adopt a welfare reform than under unified government. Several robustness checks confirm this counter-intuitive finding. Case study evidence suggests an explanation based on policy competition between governor, senate, and house. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.jpubeco.2016.08.003 SN - 0047-2727 VL - 142 SP - 24 EP - 38 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Rieper, Harald A1 - Gebhardt, Andreas A1 - Stucker, Brent T1 - Process parameters for Selective Laser Melting of AgCu7 T2 - DDMC, Fraunhofer Direct Digital Manufacturing Conference, 3 Y1 - 2016 SN - 978-3-8396-1001-5 N1 - DDMC, 2016, Fraunhofer Direct Digital Manufacturing Conference, 3rd, Berlin, DE, 2016-03-16 - 2016-03-17 SP - 171 EP - 176 PB - Fraunhofer-Verlag CY - Stuttgart ER - TY - JOUR A1 - Aimenova, Zh. E. A1 - Digel, Ilya A1 - Eshibaev, А. А. T1 - Dynamics of accumulation of lagochirzin in Lagochilus setulosus phytomass during the growing season and also features of its cultivation in the conditions of a typical sierozem JF - KazNU Bulletin. Biology series N2 - L.setulosus is offered for creation of biopreparation «Setulin», possesing he- mostatic action, the basic reactant of biopreparation is diterpen – lagochirzin. Results under the maintenance and dynamics of diterpen lagochirzin accumula- tion in various parts of L.setulosus are presented: in roots, stalks, leaves, flowers and calyx lobes during the growing season, and also results on conditions of cultivation L.setulosus in the conditions of a typical sierozem are resulted. From the obtained data is visible, that the given species of a plant is endemic. It is established, that dynamics of accumulation of lagochirzin in phytomass accrues from the beginning to the middle of the growing season. The chemical analysis of L.setulosus on a localization of lagochirzin in various organs of a plant, has shown, that the greatest quantity of lagochirzin collects in calyx lobes of the plants. Also it is established, that L.setulosus can be cultivated in the conditions of the typical sierozem, a mineral food is necessary for the given species of plants of Lagochilus genus, except nitric fertilizers. Comparative studying of wild-growing and cultural forms of L.setulosus has shown, that in the cultivated phytomass of plants the maintenance of lagochirzin on 17-20 % higher than in the wild-growing species. Y1 - 2016 SN - 1563-0218 N1 - Original in russischer Sprache VL - 69 IS - 4 SP - 4 EP - 11 PB - Al-Farabi Kazakh National University CY - Almaty ER - TY - CHAP A1 - Matcha, Heike ED - Herneoja, Aulikki ED - Österlund, Toni ED - Markkanen, Piia T1 - From Designing Buildings from Systems to Designing Systems for Buildings T2 - Complexity & Simplicity - Proceedings of the 34th eCAADe Conference - Volume 1 N2 - We study the novel possibilities computer aided design and production open up for the design of building systems. Such systems today can, via individualized mass production, consist of a larger number and more complex parts than previously and therefore be assembled into more complex wholes. This opens up the possibility of designing specialized systems specifically for single buildings. The common order of starting with a building system and designing a building using this system can be reversed to designing a building first and then developing a system specifically for that building. We present and discuss research that incorporates students design projects into research work and fosters links between research and teaching. KW - Building Systems KW - Parametric Design KW - Parametric Modelling KW - Structuralist Architecture Y1 - 2016 U6 - http://dx.doi.org/10.52842/conf.ecaade.2016.1.237 N1 - Proceedings of the 34th eCAADe Conference, University of Oulu, Oulu, Finland, 22-26 August 2016. SP - 237 EP - 240 PB - ECAADe CY - Oulu, Finland ER - TY - THES A1 - Frotscher, Ralf T1 - Electromechanical modeling and simulation of thin cardiac tissue constructs - smoothed FEM applied to a biomechanical plate problem Y1 - 2016 N1 - Duisburg, Essen, Universität Duisburg-Essen, Diss., 2016 ER - TY - JOUR A1 - Scheer, Nico A1 - Wilson, Ian D. T1 - A comparison between genetically humanized and chimeric liver humanized mouse models for studies in drug metabolism and toxicity JF - Drug Discovery Today N2 - Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug–drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.drudis.2015.09.002 SN - 1359-6446 VL - 21 IS - 2 SP - 250 EP - 263 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Scheer, Nico A1 - Chu, Xiaoyan A1 - Salphati, Laurent A1 - Zamek-Gliszczynski, Maciej J. ED - Nicholls, Glynis T1 - Knockout and humanized animal models to study membrane transporters in drug development T2 - Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development Y1 - 2016 SN - 978-1-78262-379-3 U6 - http://dx.doi.org/10.1039/9781782623793-00298 SP - 298 EP - 332 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Weber, Tobias A1 - Arent, Jan-Christoph A1 - Münch, Lukas A1 - Duhovic, Miro A1 - Balvers, Johannes M. T1 - A fast method for the generation of boundary conditions for thermal autoclave simulation JF - Composites Part A N2 - Manufacturing process simulation enables the evaluation and improvement of autoclave mold concepts early in the design phase. To achieve a high part quality at low cycle times, the thermal behavior of the autoclave mold can be investigated by means of simulations. Most challenging for such a simulation is the generation of necessary boundary conditions. Heat-up and temperature distribution in an autoclave mold are governed by flow phenomena, tooling material and shape, position within the autoclave, and the chosen autoclave cycle. This paper identifies and summarizes the most important factors influencing mold heat-up and how they can be introduced into a thermal simulation. Thermal measurements are used to quantify the impact of the various parameters. Finally, the gained knowledge is applied to develop a semi-empirical approach for boundary condition estimation that enables a simple and fast thermal simulation of the autoclave curing process with reasonably high accuracy for tooling optimization. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.compositesa.2016.05.036 SN - 1359-835X VL - 88 SP - 216 EP - 225 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Svaneborg, Carsten A1 - Karimi-Varzaneh, Hossein Ali A1 - Hojdis, Nils A1 - Fleck, Franz A1 - Everaers, Ralf T1 - Multiscale approach to equilibrating model polymer melts JF - Physical Review E N2 - We present an effective and simple multiscale method for equilibrating Kremer Grest model polymer melts of varying stiffness. In our approach, we progressively equilibrate the melt structure above the tube scale, inside the tube and finally at the monomeric scale. We make use of models designed to be computationally effective at each scale. Density fluctuations in the melt structure above the tube scale are minimized through a Monte Carlo simulated annealing of a lattice polymer model. Subsequently the melt structure below the tube scale is equilibrated via the Rouse dynamics of a force-capped Kremer-Grest model that allows chains to partially interpenetrate. Finally the Kremer-Grest force field is introduced to freeze the topological state and enforce correct monomer packing. We generate 15 melts of 500 chains of 10.000 beads for varying chain stiffness as well as a number of melts with 1.000 chains of 15.000 monomers. To validate the equilibration process we study the time evolution of bulk, collective, and single-chain observables at the monomeric, mesoscopic, and macroscopic length scales. Extension of the present method to longer, branched, or polydisperse chains, and/or larger system sizes is straightforward. Y1 - 2016 U6 - http://dx.doi.org/10.1103/PhysRevE.94.032502 SN - 2470-0053 VL - 94 IS - 032502 PB - AIP Publishing CY - Melville, NY ER - TY - JOUR A1 - Schwab, Lukas A1 - Hojdis, Nils A1 - Lacayo, Jorge A1 - Wilhelm, Manfred T1 - Fourier-Transform Rheology of Unvulcanized, Carbon Black Filled Styrene Butadiene Rubber JF - Macromolecular Materials and Engineering N2 - Rubber materials filled with reinforcing fillers display nonlinear rheological behavior at small strain amplitudes below γ0 < 0.1. Nevertheless, rheological data are analyzed mostly in terms of linear parameters, such as shear moduli (G′, G″), which loose their physical meaning in the nonlinear regime. In this work styrene butadiene rubber filled with carbon black (CB) under large amplitude oscillatory shear (LAOS) is analyzed in terms of the nonlinear parameter I3/1. Three different CB grades are used and the filler load is varied between 0 and 70 phr. It is found that I3/1(φ) is most sensitive to changes of the total accessible filler surface area at low strain amplitudes (γ0 = 0.32). The addition of up to 70 phr CB leads to an increase of I3/1(φ) by a factor of more than ten. The influence of the measurement temperature on I3/1 is pronounced for CB levels above the percolation threshold. Y1 - 2016 U6 - http://dx.doi.org/10.1002/mame.201500356 SN - 1439-2054 VL - 301 IS - 4 SP - 457 EP - 468 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Harish, Ajay B. A1 - Wriggers, Peter A1 - Jungk, Juliane A1 - Hojdis, Nils A1 - Recker, Carla T1 - Mesoscale Constitutive Modeling of Non-Crystallizing Filled Elastomers JF - Computational Mechanics N2 - Elastomers are exceptional materials owing to their ability to undergo large deformations before failure. However, due to their very low stiffness, they are not always suitable for industrial applications. Addition of filler particles provides reinforcing effects and thus enhances the material properties that render them more versatile for applications like tyres etc. However, deformation behavior of filled polymers is accompanied by several nonlinear effects like Mullins and Payne effect. To this day, the physical and chemical changes resulting in such nonlinear effect remain an active area of research. In this work, we develop a heterogeneous (or multiphase) constitutive model at the mesoscale explicitly considering filler particle aggregates, elastomeric matrix and their mechanical interaction through an approximate interface layer. The developed constitutive model is used to demonstrate cluster breakage, also, as one of the possible sources for Mullins effect observed in non-crystallizing filled elastomers. Y1 - 2016 U6 - http://dx.doi.org/10.1007/s00466-015-1251-1 SN - 1432-0924 VL - 57 SP - 653 EP - 677 PB - Springer CY - Berlin ER - TY - BOOK A1 - Altherr, Lena T1 - Algorithmic System Design under Consideration of Dynamic Processes N2 - Nach Stand von Wissenschaft und Technik werden Komponenten hinsichtlich ihrer Eigenschaften, wie Lebensdauer oder Energieeffizienz, optimiert. Allerdings können selbst hervorragende Komponenten zu ineffizienten oder instabilen Systemen führen, wenn ihr Zusammenspiel nur unzureichend berücksichtigt wird. Eine Systembetrachtung schafft ein größeres Optimierungspotential - dem erhöhten Potential steht jedoch auch ein erhöhter Komplexitätsgrad gegenüber. Die vorliegende Arbeit ist im Rahmen des Sonderforschungsbereichs 805 entstanden, dessen Ziel die Beherrschung von Unsicherheit in Systemen des Maschinenbaus ist. Die Arbeit zeigt anhand eines realen Systems aus dem Bereich der Hydraulik, wie Unsicherheit in der Entwicklungsphase beherrscht werden kann. Hierbei ist neu, dass die durch den späteren Betrieb zu erwartende Systemdegradation eines jeden möglichen Systemvorschlags antizipiert werden kann. Dadurch können Betriebs- und Wartungskosten vorausgesagt und minimiert werden und durch eine optimale Betriebs- und Wartungsstrategie die Verfügbarkeit des Systems garantiert werden. Wesentliche Fragen bei der optimalen Auslegung des betrachteten hydrostatischen Getriebes sind dessen physikalische Modellierung, die Darstellung des Optimierungsproblems als gemischt-ganzzahliges lineares Programm, und dessen algorithmische Behandlung zur Lösungsfindung. Hierzu werden Heuristiken zum schnelleren Auffinden sinnvoller Systemtopologien vorgestellt und mittels mathematischer Dekomposition eine Bewertung des dynamischen Verschleiß- und Wartungsverlaufs möglicher Systemvorschläge vorgenommen. Die Arbeit stellt die Optimierung technischer Systeme an der Schnittstelle von Mathematik, Informatik und Ingenieurwesen sowohl gründlich als auch anschaulich und nachvollziehbar dar. KW - Mixed Integer Programming KW - Technical Operations Research KW - Optimization KW - System Design Y1 - 2016 SN - 978-3-8440-4848-3 PB - Shaker CY - Aachen ER - TY - CHAP A1 - Altherr, Lena A1 - Ederer, Thorsten A1 - Lorenz, Ulf A1 - Pelz, Peter F. A1 - Pöttgen, Philipp ED - Lübbecke, Marco E. ED - Koster, Arie ED - Letmathe, Peter ED - Madlener, Reihard ED - Preis, Britta ED - Walther, Grit T1 - Designing a feedback control system via mixed-integer programming T2 - Operations Research Proceedings 2014: Selected Papers of the Annual International Conference of the German Operations Research N2 - Pure analytical or experimental methods can only find a control strategy for technical systems with a fixed setup. In former contributions we presented an approach that simultaneously finds the optimal topology and the optimal open-loop control of a system via Mixed Integer Linear Programming (MILP). In order to extend this approach by a closed-loop control we present a Mixed Integer Program for a time discretized tank level control. This model is the basis for an extension by combinatorial decisions and thus for the variation of the network topology. Furthermore, one is able to appraise feasible solutions using the global optimality gap. KW - Optimal Topology KW - Controller Parameter KW - Level Control System KW - Technical Operation Research KW - Optimal Closed Loop Y1 - 2016 SN - 978-3-319-28695-2 U6 - http://dx.doi.org/10.1007/978-3-319-28697-6_18 SP - 121 EP - 127 PB - Springer CY - Cham ER -