@misc{RothTippkoetter2016,
  author    = {Roth, J. and Tippk{\"o}tter, Nils},
  title     = {New Approach for Enzymatic Hydrolysis of Lignocellulose with Selective Diffusion Separation of the Monosaccharide Products},
  series = {Chemie Ingenieur Technik},
  volume    = {88},
  journal   = {Chemie Ingenieur Technik},
  number    = {9},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {0009-286X},
  doi       = {10.1002/cite.201650301},
  pages     = {1237},
  year      = {2016},
  abstract  = {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 \%.},
  language  = {en}
}
@misc{MoehringWulfhorstCapitainetal.2016,
  author    = {M{\"o}hring, S. and Wulfhorst, H. and Capitain, C. and Roth, J. and Tippk{\"o}tter, Nils},
  title     = {Fractioning of lignocellulosic biomass: Scale-down and automation of thermal pretreatment for parameter optimization},
  series = {Chemie Ingenieur Technik},
  volume    = {88},
  journal   = {Chemie Ingenieur Technik},
  number    = {9},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {0009-286X},
  doi       = {10.1002/cite.201650288},
  pages     = {1229},
  year      = {2016},
  abstract  = {In order to efficiently convert lignocellulose, it is often necessary to conduct a pretreatment. The biomass considered in this study typically comprises of agricultural and horticultural residues, as well as beechwood. A very environmentally friendly method, namely, fungal pretreatment using white-rot fungi, leads to an enhanced enzymatic hydrolysis. In contrast to other processes presented, the energy input is extremely low. However, the fungal growth on the lignocellulosic substrates takes several weeks at least in order to be effective. Thus, the reduction of chemicals and energy for thermal processing is a target of our current research. Liquid hot water (LHW) and solvent-based pretreatment (OrganoSolv) require more complex equipment, as they depend on high temperatures (160 - 180 °C) and enhanced pressure (up to 20 bar). However, they prove to be promising processes in regard to the fractioning of lignocellulose. For optimal lignin recovery the parameters differ from those established in cellulose extraction. A novel screening system scaled down to a reaction volume of 100 mL has been developed and successfully tested for this purpose.},
  language  = {en}
}
@inproceedings{EngelThieringerTippkoetter2016,
  author    = {Engel, Mareike and Thieringer, Julia and Tippk{\"o}tter, Nils},
  title     = {Linking bioprocess engineering and electrochemistry for sustainable biofuel production},
  series = {Young Researchers Symposium, YRS 2016. Proceedings},
  booktitle = {Young Researchers Symposium, YRS 2016. Proceedings},
  publisher = {Fraunhofer Verlag},
  address   = {Karlsruhe},
  pages     = {49 -- 53},
  year      = {2016},
  abstract  = {Electromicrobial engineering is an emerging, highly interdisciplinary research area linking bioprocesses with electrochemistry. In this work, microbial electrosynthesis (MES) of biobutanol is carried out during acetone-butanol-ethanol (ABE) fermentations with Clostridium acetobutylicum. A constant electric potential of -600mV (vs. Ag/AgCl) with simultaneous addition of the soluble redox mediator neutral red is used in order to study the electron transfer between the working electrode and the bacterial cells. The results show an earlier initiation of solvent production for all fermentations with applied potential compared to the conventional ABE fermentation. The f inal butanol concentration can be more than doubled by the application of a negative potential combined with addition of neutral red. Moreover a higher biofilm formation on the working electrode compared to control cultivations has been observed. In contrast to previous studies, our results also indicate that direct electron transfer (DET) might be possible with C. acetobutylicum. The presented results make microbial butanol production economically attractive and therefore support the development of sustainable production processes in the chemical industry aspired by the "Centre for resource-efficient chemistry and raw material change" as well as the the project "NanoKat" working on nanostructured catalysts in Kaiserslautern.},
  language  = {en}
}
@article{HarishWriggersJungketal.2016,
  author    = {Harish, Ajay B. and Wriggers, Peter and Jungk, Juliane and Hojdis, Nils and Recker, Carla},
  title     = {Mesoscale Constitutive Modeling of Non-Crystallizing Filled Elastomers},
  series = {Computational Mechanics},
  volume    = {57},
  journal   = {Computational Mechanics},
  publisher = {Springer},
  address   = {Berlin},
  issn      = {1432-0924},
  doi       = {10.1007/s00466-015-1251-1},
  pages     = {653 -- 677},
  year      = {2016},
  abstract  = {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.},
  language  = {en}
}
@article{SchwabHojdisLacayoetal.2016,
  author    = {Schwab, Lukas and Hojdis, Nils and Lacayo, Jorge and Wilhelm, Manfred},
  title     = {Fourier-Transform Rheology of Unvulcanized, Carbon Black Filled Styrene Butadiene Rubber},
  series = {Macromolecular Materials and Engineering},
  volume    = {301},
  journal   = {Macromolecular Materials and Engineering},
  number    = {4},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1439-2054},
  doi       = {10.1002/mame.201500356},
  pages     = {457 -- 468},
  year      = {2016},
  abstract  = {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.},
  language  = {en}
}
@article{SvaneborgKarimiVarzanehHojdisetal.2016,
  author    = {Svaneborg, Carsten and Karimi-Varzaneh, Hossein Ali and Hojdis, Nils and Fleck, Franz and Everaers, Ralf},
  title     = {Multiscale approach to equilibrating model polymer melts},
  series = {Physical Review E},
  volume    = {94},
  journal   = {Physical Review E},
  number    = {032502},
  publisher = {AIP Publishing},
  address   = {Melville, NY},
  issn      = {2470-0053},
  doi       = {10.1103/PhysRevE.94.032502},
  year      = {2016},
  abstract  = {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.},
  language  = {en}
}
@incollection{ScheerChuSalphatietal.2016,
  author    = {Scheer, Nico and Chu, Xiaoyan and Salphati, Laurent and Zamek-Gliszczynski, Maciej J.},
  title     = {Knockout and humanized animal models to study membrane transporters in drug development},
  series = {Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development},
  booktitle = {Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development},
  editor    = {Nicholls, Glynis},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  isbn      = {978-1-78262-379-3},
  doi       = {10.1039/9781782623793-00298},
  pages     = {298 -- 332},
  year      = {2016},
  language  = {en}
}
@article{ScheerWilson2016,
  author    = {Scheer, Nico and Wilson, Ian D.},
  title     = {A comparison between genetically humanized and chimeric liver humanized mouse models for studies in drug metabolism and toxicity},
  series = {Drug Discovery Today},
  volume    = {21},
  journal   = {Drug Discovery Today},
  number    = {2},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {1359-6446},
  doi       = {10.1016/j.drudis.2015.09.002},
  pages     = {250 -- 263},
  year      = {2016},
  abstract  = {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.},
  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}
}