@article{LempiaeinenCouttetBolognanietal.2012,
  author    = {Lempi{\"a}inen, Harri and Couttet, Philippe and Bolognani, Federico and M{\"u}ller, Arne and Dubost, Val{\´e}rie and Luisier, Rapha{\"e}lle and Rio-Espinola, Alberto del and Vitry, Veronique and Unterberger, Elif B. and Thomson, John P. and Treindl, Fridolin and Metzger, Ute and Wrzodek, Clemens and Hahne, Florian and Zollinger, Tulipan and Brasa, Sarah and Kalteis, Magdalena and Marcellin, Magali and Giudicelli, Fanny and Braeuning, Albert and Morawiec, Laurent and Zamurovic, Natasa and L{\"a}ngle, Ulrich and Scheer, Nico and Sch{\"u}beler, Dirk and Goodman, Jay and Chibout, Salah-Dine and Marlowe, Jennifer and Theil, Dietlinde and Heard, David J. and Grenet, Olivier and Zell, Andreas and Templin, Markus F. and Meehan, Richard R. and Wolf, Roland C. and Elcombe, Clifford R. and Schwarz, Michael and Moulin, Pierre and Terranova, R{\´e}mi and Moggs, Jonathan G.},
  title     = {Identification of Dlk1-Dio3 imprinted gene cluster non-coding RNAs as novel candidate biomarkers for liver tumor promotion},
  series = {Toxicological Sciences},
  volume    = {131},
  journal   = {Toxicological Sciences},
  number    = {2},
  publisher = {Oxford University Press},
  address   = {Oxford},
  issn      = {1094-2025},
  doi       = {10.1093/toxsci/kfs303},
  pages     = {375 -- 386},
  year      = {2012},
  abstract  = {The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.},
  language  = {en}
}
@article{RossPlummerRodeetal.2010,
  author    = {Ross, Jillian and Plummer, Simon M. and Rode, Anja and Scheer, Nico and Bower, Conrad C. and Vogel, Ortwin and Henderson, Colin J. and Wolf, C. Roland and Elcombe, Clifford R.},
  title     = {Human constitutive androstane receptor (CAR) and pregnane X receptor (PXR) support the hypertrophic but not the hyperplastic response to the murine nongenotoxic hepatocarcinogens phenobarbital and chlordane in vivo},
  series = {Toxicological Sciences},
  volume    = {116},
  journal   = {Toxicological Sciences},
  number    = {2},
  publisher = {Oxford University Press},
  address   = {Oxford},
  issn      = {1096-0929},
  doi       = {10.1093/toxsci/kfq118},
  pages     = {452 -- 466},
  year      = {2010},
  abstract  = {Mouse nongenotoxic hepatocarcinogens phenobarbital (PB) and chlordane induce hepatomegaly characterized by hypertrophy and hyperplasia. Increased cell proliferation is implicated in the mechanism of tumor induction. The relevance of these tumors to human health is unclear. The xenoreceptors, constitutive androstane receptors (CARs), and pregnane X receptor (PXR) play key roles in these processes. Novel "humanized" and knockout models for both receptors were developed to investigate potential species differences in hepatomegaly. The effects of PB (80 mg/kg/4 days) and chlordane (10 mg/kg/4 days) were investigated in double humanized PXR and CAR (huPXR/huCAR), double knockout PXR and CAR (PXRKO/CARKO), and wild-type (WT) C57BL/6J mice. In WT mice, both compounds caused increased liver weight, hepatocellular hypertrophy, and cell proliferation. Both compounds caused alterations to a number of cell cycle genes consistent with induction of cell proliferation in WT mice. However, these gene expression changes did not occur in PXRKO/CARKO or huPXR/huCAR mice. Liver hypertrophy without hyperplasia was demonstrated in the huPXR/huCAR animals in response to both compounds. Induction of the CAR and PXR target genes, Cyp2b10 and Cyp3a11, was observed in both WT and huPXR/huCAR mouse lines following treatment with PB or chlordane. In the PXRKO/CARKO mice, neither liver growth nor induction of Cyp2b10 and Cyp3a11 was seen following PB or chlordane treatment, indicating that these effects are CAR/PXR dependent. These data suggest that the human receptors are able to support the chemically induced hypertrophic responses but not the hyperplastic (cell proliferation) responses. At this time, we cannot be certain that hCAR and hPXR when expressed in the mouse can function exactly as the genes do when they are expressed in human cells. However, all parameters investigated to date suggest that much of their functionality is maintained.},
  language  = {en}
}
@article{ScheerRossKapelyukhetal.2010,
  author    = {Scheer, Nico and Ross, Jillian and Kapelyukh, Yury and Rode, Anja and Wolf, C. Roland},
  title     = {In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice},
  series = {Drug Metabolism and Disposition},
  volume    = {38},
  journal   = {Drug Metabolism and Disposition},
  number    = {7},
  publisher = {ASPET},
  address   = {Bethesda},
  issn      = {1521-009X},
  doi       = {10.1124/dmd.109.031872},
  pages     = {1046 -- 1053},
  year      = {2010},
  abstract  = {Dexamethasone (DEX) is a potent and widely used anti-inflammatory and immunosuppressant glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a critical role as xenobiotic sensor in mammals to induce the expression of many enzymes, including cytochromes P450 in the CYP3A family. This induction results in its own metabolism. We have used a series of transgenic mouse lines, including a novel, improved humanized PXR line, to compare the induction profile of PXR-regulated drug-metabolizing enzymes after DEX administration, as well as looking at hepatic responses to rifampicin (RIF). The new humanized PXR model has uncovered further intriguing differences between the human and mouse receptors in that RIF only induced Cyp2b10 in the new humanized model. DEX was found to be a much more potent inducer of Cyp3a proteins in wild-type mice than in mice humanized for PXR. To assess whether PXR is involved in the detoxification of DEX in the liver, we analyzed the consequences of high doses of the glucocorticoid on hepatotoxicity on different PXR genetic backgrounds. We also studied these effects in an additional mouse model in which functional mouse Cyp3a genes have been deleted. These strains exhibited different sensitivities to DEX, indicating a protective role of the PXR and CYP3A proteins against the hepatotoxicity of this compound.},
  language  = {en}
}
@article{ScheerRossRodeetal.2008,
  author    = {Scheer, Nico and Ross, Jillian and Rode, Anja and Zevnik, Branko and Niehaves, Sandra and Faust, Nicole and Wolf, C. Roland},
  title     = {A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response},
  series = {Journal of Clinical Investigation},
  volume    = {118},
  journal   = {Journal of Clinical Investigation},
  number    = {9},
  issn      = {1558-8238},
  doi       = {https://doi.org/10.1172/JCI35483},
  pages     = {3228 -- 3239},
  year      = {2008},
  language  = {en}
}
@article{ScheerKapelyukhMcEwanetal.2012,
  author    = {Scheer, Nico and Kapelyukh, Yury and McEwan, Jillian and Beuger, Vincent and Stanley, Lesley A. and Rode, Anja and Wolf, C. Roland},
  title     = {Modeling Human Cytochrome P450 2D6 Metabolism and Drug-drug Interaction by a Novel Panel of Knockout and Humanized Mouse Lines},
  series = {Molecular Pharmacology},
  volume    = {81},
  journal   = {Molecular Pharmacology},
  number    = {1},
  publisher = {ASPET},
  address   = {Bethesda, Md.},
  issn      = {1521-0111},
  doi       = {10.1124/mol.111.075192},
  pages     = {63 -- 72},
  year      = {2012},
  abstract  = {The highly polymorphic human cytochrome P450 2D6 enzyme is involved in the metabolism of up to 25\% of all marketed drugs and accounts for significant individual differences in response to CYP2D6 substrates. Because of the differences in the multiplicity and substrate specificity of CYP2D family members among species, it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal studies. To create animal models that reflect the human situation more closely and that allow an in vivo assessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straightforward approach to delete the entire murine Cyp2d gene cluster and replace it with allelic variants of human CYP2D6. By using this approach, we have generated mouse lines expressing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzyme, as well as a Cyp2d cluster knockout mouse. We demonstrate that the various transgenic mouse lines cover a wide spectrum of different human CYP2D6 metabolizer phenotypes. The novel humanization strategy described here provides a robust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug response in the context of personalized medicine.},
  language  = {en}
}
@article{ReugelsBoggettiScheeretal.2006,
  author    = {Reugels, Alexander M. and Boggetti, Barbara and Scheer, Nico and Campos-Ortega, Jos{\´e} A.},
  title     = {Asymmetric localization of Numb:EGFP in dividing neuroepithelial cells during neurulation in Danio rerio},
  series = {Developmental Dynamics},
  volume    = {235},
  journal   = {Developmental Dynamics},
  number    = {4},
  issn      = {1097-0177},
  doi       = {10.1002/dvdy.20699},
  pages     = {934 -- 948},
  year      = {2006},
  language  = {en}
}
@article{HansScheerRiedletal.2004,
  author    = {Hans, Stefan and Scheer, Nico and Riedl, Iris and Weiz{\"a}cker, Elisabeth von and Blader, Patrick and Campos-Ortega, Jos{\´e} A.},
  title     = {her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch signalling},
  series = {Development},
  volume    = {131},
  journal   = {Development},
  number    = {12},
  issn      = {1477-9129},
  doi       = {10.1242/dev.01167},
  pages     = {2957 -- 2969},
  year      = {2004},
  language  = {en}
}
@article{ScheerRiedlWarrenetal.2002,
  author    = {Scheer, Nico and Riedl, Iris and Warren, J.T. and Kuwada, John Y. and Campos-Ortega, Jos{\´e} A.},
  title     = {A quantitative analysis of the kinetics of Gal4 activator and effector gene expression in the zebrafish},
  series = {Mechanism of Development},
  volume    = {112},
  journal   = {Mechanism of Development},
  number    = {1-2},
  issn      = {0925-4773},
  doi       = {10.1016/S0925-4773(01)00621-9},
  pages     = {9 -- 14},
  year      = {2002},
  language  = {en}
}
@article{LawsonScheerPhametal.2001,
  author    = {Lawson, Nathan D. and Scheer, Nico and Pham, Van N. and Kim, Ceol-Hee and Chitnis, Ajay B. and Campos-Ortega, Jos{\´e} A. and Weinstein, Brant M.},
  title     = {Notch signaling is required for arterial-venous differentiation during embryonic vascular development},
  series = {Development},
  volume    = {128},
  journal   = {Development},
  number    = {19},
  issn      = {1477-9129},
  pages     = {3675 -- 3683},
  year      = {2001},
  language  = {en}
}
@article{ScheerGrothHansetal.2001,
  author    = {Scheer, Nico and Groth, Anne and Hans, Stefan and Campos-Ortega, Jos{\´e} A.},
  title     = {An instructive function for Notch in promoting gliogenesis in the zebrafish retina},
  series = {Development},
  volume    = {128},
  journal   = {Development},
  number    = {7},
  issn      = {0950-1991},
  pages     = {1099 -- 1107},
  year      = {2001},
  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{ScheerKapelyukhRodeetal.2015,
  author    = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Oswald, Stefan and Busch, Diana and Mclaughlin, Lesley A. and Lin, De and Henderson, Colin J. and Wolf, C. Roland},
  title     = {Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model},
  series = {Drug Metabolism and Disposition},
  volume    = {43},
  journal   = {Drug Metabolism and Disposition},
  number    = {11},
  publisher = {ASPET},
  address   = {Bethesda},
  issn      = {1521-009x},
  doi       = {10.1124/dmd.115.065656},
  pages     = {1679 -- 1690},
  year      = {2015},
  language  = {en}
}
@article{HoughNalwalkDingetal.2015,
  author    = {Hough, Lindsay B. and Nalwalk, Julia W. and Ding, Xinxin and Scheer, Nico},
  title     = {Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms},
  series = {Drug Metabolism and Disposition},
  volume    = {43},
  journal   = {Drug Metabolism and Disposition},
  number    = {9},
  issn      = {1521-009x},
  doi       = {10.1124/dmd.115.065490},
  pages     = {1326 -- 1330},
  year      = {2015},
  language  = {en}
}
@article{HendersonMclaughlinScheeretal.2015,
  author    = {Henderson, Colin J. and Mclaughlin, Lesley A. and Scheer, Nico and Stanley, Lesley A. and Wolf, C. Roland},
  title     = {Cytochrome b5 Is a Major Determinant of Human Cytochrome P450 CYP2D6 and CYP3A4 Activity In Vivo s},
  series = {Molecular Pharmacology},
  volume    = {87},
  journal   = {Molecular Pharmacology},
  number    = {4},
  publisher = {ASPET},
  address   = {Bethesda},
  issn      = {1521-0111},
  doi       = {10.1124/mol.114.097394},
  pages     = {733 -- 739},
  year      = {2015},
  language  = {en}
}
@article{LuisierLempiaeinenScherbichleretal.2014,
  author    = {Luisier, Rapha{\"e}lle and Lempi{\"a}inen, Harri and Scherbichler, Nina and Braeuning, Albert and Geissler, Miriam and Dubost, Valerie and M{\"u}ller, Arne and Scheer, Nico and Chibout, Salah-Dine and Hara, Hisanori and Picard, Frank and Theil, Diethilde and Couttet, Philippe and Vitobello, Antonio and Grenet, Olivier and Grasl-Kraupp, Bettina and Ellinger-Ziegelbauer, Heidrung and Thomson, John P. and Meehan, Richard R. and Elcombe, Clifford R. and Henderson, Colin J. and Wolf, C. Roland and Schwarz, Michael and Moulin, Pierre and Terranova, Remi and Moggs, Jonathan G.},
  title     = {Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors},
  series = {Toxicological Sciences},
  volume    = {139},
  journal   = {Toxicological Sciences},
  number    = {2},
  publisher = {Oxford University Press},
  address   = {Oxford},
  issn      = {1094-2025},
  doi       = {https://doi.org/10.1093/toxsci/kfu038},
  pages     = {501 -- 511},
  year      = {2014},
  abstract  = {The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.},
  language  = {en}
}
@article{SalpatiChuChenetal.2014,
  author    = {Salpati, Laurent and Chu, Xiaoyan and Chen, Liangfu and Prasad, Bhagwat and Dallas, Shannon and Evers, Raymond and Mamaril-Fishman, Donna and Geier, Ethan G. and Kehler, Jonathan and Kunta, Jeevan and Mezler, Mario and Laplanche, Loic and Pang, Jodie and Soars, Matthew G. and Unadkat, Jashvant D. and van Waterschoot, Robert A.B. and Yabut, Jocelyn and Schinkel, Alfred H. and Scheer, Nico and Rode, Anja},
  title     = {Evaluation of organic anion transporting polypeptide 1B1 and 1B3 humanized mice as a translational model to study the pharmacokinetics of statins},
  series = {Drug Metabolism and Disposition},
  volume    = {42},
  journal   = {Drug Metabolism and Disposition},
  number    = {8},
  publisher = {ASPET},
  address   = {Bethesda, Md.},
  issn      = {1521-009X},
  doi       = {10.1124/dmd.114.057976},
  pages     = {1301 -- 1313},
  year      = {2014},
  abstract  = {Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization of these models will help to better understand their utility for predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis of these mouse lines by evaluating the compensatory changes in mRNA expression, quantifying the amounts of OATP1B1 and -1B3 protein by liquid chromatography-tandem mass spectrometry, and studying the active uptake in isolated hepatocytes and the pharmacokinetics of some prototypical substrates including statins. Major outcomes from these studies were 1) mostly moderate compensatory changes in only a few genes involved in drug metabolism and disposition, 2) a robust hepatic expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models, and 3) functional activities of the human transporters in hepatocytes isolated from the humanized models with several substrates tested in vitro and with pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized models did not significantly alter liver or plasma concentrations of rosuvastatin and pitavastatin compared with Oatp1a/1b knockout controls under the conditions used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed in vitro and/or in vivo functional activity with some statins, further characterization of these models is required to define their potential use and limitations in the prediction of drug disposition and drug-drug interactions in humans.},
  language  = {en}
}
@article{ScheerHendersonKapelyukhetal.2019,
  author    = {Scheer, Nico and Henderson, Colin James and Kapelyukh, Yury and Rode, Anja and Mclaren, Aileen W. and MacLeod, Alastair Kenneth and Lin, De and Wright, Jayne and Stanley, Lesley and Wolf, C. Roland},
  title     = {An extensively humanised mouse model to predict pathways of drug disposition, drug/drug interactions, and to facilitate the design of clinical trials},
  series = {Drug Metabolism and Disposition},
  journal   = {Drug Metabolism and Disposition},
  number    = {Early view},
  doi       = {10.1124/dmd.119.086397},
  pages     = {69 Seiten},
  year      = {2019},
  language  = {en}
}
@article{HalbachScheer2000,
  author    = {Halbach, Thorsten and Scheer, Nico},
  title     = {Transcriptional activation by the PHD finger is inhibited through an adjacent leucine zipper that binds 14-3-3 proteins},
  series = {Nucleic Acids Research},
  volume    = {28},
  journal   = {Nucleic Acids Research},
  number    = {18},
  issn      = {1362-4962},
  doi       = {10.1093/nar/28.18.3542},
  pages     = {3542 -- 3550},
  year      = {2000},
  language  = {en}
}
@article{ScheerCamposOrtega1999,
  author    = {Scheer, Nico and Campos-Ortega, Jos{\´e} A.},
  title     = {Use of the Gal4-UAS technique for targeted gene expression in the zebrafish},
  series = {Mechanism of Development},
  volume    = {80},
  journal   = {Mechanism of Development},
  number    = {2},
  issn      = {0925-4773},
  doi       = {10.1016/S0925-4773(98)00209-3},
  pages     = {153 -- 158},
  year      = {1999},
  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{ScheerWolf2014,
  author    = {Scheer, Nico and Wolf, C. Roland},
  title     = {Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications},
  series = {Xenobiotica},
  volume    = {44},
  journal   = {Xenobiotica},
  number    = {2},
  publisher = {Taylor \& Francis},
  address   = {Abingdon},
  issn      = {1366-5928},
  doi       = {10.3109/00498254.2013.815831},
  pages     = {96 -- 108},
  year      = {2014},
  abstract  = {1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug-drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described. 2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created. 3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug-drug interactions as well as in human metabolite testing and risk assessment. 4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed.},
  language  = {en}
}
@article{ScheerWolf2013,
  author    = {Scheer, Nico and Wolf, C. Roland},
  title     = {Xenobiotic receptor humanized mice and their utility},
  series = {Drug Metabolism Reviews},
  journal   = {Drug Metabolism Reviews},
  number    = {1},
  publisher = {Taylor \& Francis},
  address   = {London},
  issn      = {1097-9883},
  doi       = {10.3109/03602532.2012.738687},
  pages     = {110 -- 121},
  year      = {2013},
  language  = {en}
}
@article{HendersonScheerWolf2009,
  author    = {Henderson, Colin J. and Scheer, Nico and Wolf, C. Roland},
  title     = {Advances in the generation of mouse models to elucidate the pathways of drug metabolism in rodents and man},
  series = {Expert Review of Clinical Pharmacology},
  volume    = {2},
  journal   = {Expert Review of Clinical Pharmacology},
  number    = {2},
  publisher = {Taylor \& Francis},
  address   = {London},
  issn      = {1751-2441},
  doi       = {10.1586/17512433.2.2.105},
  pages     = {105 -- 109},
  year      = {2009},
  language  = {en}
}
@article{StanleyHorsburghRossetal.2009,
  author    = {Stanley, Lesley A. and Horsburgh, Brian C. and Ross, Jillian and Scheer, Nico and Wolf, C. Roland},
  title     = {Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior},
  series = {Drug Metabolism Reviews},
  volume    = {41},
  journal   = {Drug Metabolism Reviews},
  number    = {1},
  publisher = {Taylor \& Francis},
  address   = {London},
  issn      = {1097-9883},
  doi       = {10.1080/03602530802605040},
  pages     = {27 -- 65},
  year      = {2009},
  language  = {en}
}
@article{StanleyHorsburghRossetal.2006,
  author    = {Stanley, Lesley A. and Horsburgh, Brian C. and Ross, Jillian and Scheer, Nico and Wolf, C. Roland},
  title     = {Nuclear Receptors which play a pivotal role in drug disposition and chemical toxicity},
  series = {Drug Metabolism Reviews},
  volume    = {38},
  journal   = {Drug Metabolism Reviews},
  number    = {3},
  issn      = {1097-9883},
  doi       = {10.1080/03602530600786232},
  pages     = {515 -- 597},
  year      = {2006},
  language  = {en}
}
@article{EngelGemuendeHoltmannetal.2019,
  author    = {Engel, Mareike and Gem{\"u}nde, Andre and Holtmann, Dirk and M{\"u}ller-Renno, Christine and Ziegler, Christiane and Tippk{\"o}tter, Nils and Ulber, Roland},
  title     = {Clostridium acetobutylicum's connecting world: cell appendage formation in bioelectrochemical systems},
  series = {ChemElectroChem},
  volume    = {7},
  journal   = {ChemElectroChem},
  number    = {2},
  publisher = {Wiley},
  address   = {Weinheim},
  issn      = {2196-0216},
  doi       = {10.1002/celc.201901656},
  pages     = {414 -- 420},
  year      = {2019},
  abstract  = {Bacterial cell appendix formation supports cell-cell interaction, cell adhesion and cell movement. Additionally, in bioelectrochemical systems (BES), cell appendages have been shown to participate in extracellular electron transfer. In this work, the cell appendix formation of Clostridium acetobutylicum in biofilms of a BES are imaged and compared with conventional biofilms. Under all observed conditions, the cells possess filamentous appendages with a higher number and density in the BES. Differences in the amount of extracellular polymeric substance in the biofilms of the electrodes lead to the conclusion that the cathode can be used as electron donor and the anode as electron acceptor by C. acetobutylicum. When using conductive atomic force microscopy, a current response of about 15 nA is found for the cell appendages from the BES. This is the first report of conductivity for clostridial cell appendices and represents the basis for further studies on their role for biofilm formation and electron transfer.},
  language  = {en}
}
@article{TippkoetterRoth2020,
  author    = {Tippk{\"o}tter, Nils and Roth, Jasmine},
  title     = {Purified Butanol from Lignocellulose - Solvent-Impregnated Resins for an Integrated Selective Removal},
  series = {Chemie Ingenieur Technik},
  volume    = {92},
  journal   = {Chemie Ingenieur Technik},
  number    = {11},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1522-2640},
  doi       = {10.1002/cite.202000200},
  pages     = {1741 -- 1751},
  year      = {2020},
  abstract  = {In traditional microbial biobutanol production, the solvent must be recovered during fermentation process for a sufficient space-time yield. Thermal separation is not feasible due to the boiling point of n-butanol. As an integrated and selective solid-liquid separation alternative, solvent impregnated resins (SIRs) were applied. Two polymeric resins were evaluated and an extractant screening was conducted. Vacuum application with vapor collection in fixed-bed column as bioreactor bypass was successfully implemented as butanol desorption step. In course of further increasing process economics, fermentation with renewable lignocellulosic substrates was conducted using Clostridium acetobutylicum. Utilization of SIR was shown to be a potential strategy for solvent removal from fermentation broth, while application of a bypass column allows for product removal and recovery at once.},
  language  = {en}
}
@article{ThielMufflerTippkoetteretal.2015,
  author    = {Thiel, Alexander and Muffler, Kai and Tippk{\"o}tter, Nils and Suck, Kirstin and Sohling, Ulrich and Hruschka, Steffen M. and Ulber, Roland},
  title     = {A novel integrated downstream processing approach to recover sinapic acid, phytic acid and proteins from rapeseed meal},
  series = {Journal of Chemical Technology and Biotechnology},
  volume    = {90},
  journal   = {Journal of Chemical Technology and Biotechnology},
  number    = {11},
  publisher = {Wiley},
  address   = {Weinheim},
  doi       = {10.1002/jctb.4664},
  pages     = {1999 -- 2006},
  year      = {2015},
  abstract  = {BACKGROUND Currently, several techniques exist for the downstream processing of protein, phytic acid and sinapic acid from rapeseed and rapeseed meal, but no technique has been developed to separate all of the components in one process. In this work, two new downstream processing strategies focusing on recovering sinapic acid, phytic acid and protein from rapeseed meal were established. RESULTS The sinapic acid content was enhanced by a factor of 4.5 with one method and 5.1 with the other. The isolation of sinapic acid was accomplished using a zeolite-based adsorbent with high adsorptive and optimal desorption characteristics. Phytic acid was isolated using the anion-exchange resin Purolite A200®. In addition, the processes resulted in two separated protein fractions. The ratios of globulin and albumin ratio to the total protein were 59.2\% and 40.1\%, respectively. The steps were then combined in two different ways: (a) a 'sequential process' using the zeolite and A200 in batch processes; and (b) a 'parallel process' using only A200 in a chromatographic system to separate all of the compounds. CONCLUSIONS It can be concluded that isolation of all three components was possible in both processes. These could enhance the added value of current processes using rapeseed meal as a protein source. © 2015 Society of Chemical Industry},
  language  = {en}
}
@article{PasteurTippkoetterKampeisetal.2014,
  author    = {Pasteur, Aline and Tippk{\"o}tter, Nils and Kampeis, Percy and Ulber, Roland},
  title     = {Optimization of high gradient magnetic separation filter units for the purification of fermentation products},
  series = {IEEE TRANSACTIONS ON MAGNETICS},
  volume    = {50},
  journal   = {IEEE TRANSACTIONS ON MAGNETICS},
  number    = {10},
  publisher = {IEEE},
  address   = {New York, NY},
  issn      = {0018-9464},
  doi       = {10.1109/TMAG.2014.2325535},
  pages     = {Artikel 5000607},
  year      = {2014},
  abstract  = {High gradient magnetic separation (HGMS) has been established since the early 1970s. A more recent application of these systems is the use in bioprocesses. To integrate the HGMS in a fermentation process, it is necessary to optimize the separation matrix with regard to the magnetic separation characteristics and permeability of the non-magnetizable components of the fermentation broth. As part of the work presented here, a combined fluidic and magnetic force finite element model simulation was created using the software COMSOL Multiphysics and compared with separation experiments. Finally, as optimal lattice orientation of the separation matrix, a transversal rhombohedral arrangement was defined. The high suitability of the new filter matrix has been verified by separation experiments.},
  language  = {en}
}
@article{TippkoetterWollnySucketal.2014,
  author    = {Tippk{\"o}tter, Nils and Wollny, Steffen and Suck, Kirstin and Sohling, Ulrich and Ruf, Friedrich and Ulber, Roland},
  title     = {Recycling of spent oil bleaching earth as source of glycerol for the anaerobic production of acetone, butanol, and ethanol with Clostridium diolis and lipolytic Clostridium lundense},
  series = {Engineering in Life Sciences},
  volume    = {14},
  journal   = {Engineering in Life Sciences},
  number    = {4},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1618-2863},
  doi       = {10.1002/elsc.201300113},
  pages     = {425 -- 432},
  year      = {2014},
  abstract  = {A major part of edible oil is subjected to bleaching procedures, primarily with minerals applied as adsorbers. Their recycling is currently done either by regaining the oil via organic solvent extraction or by using the spent bleaching earth (SBE) as additive for animal feed, etc. As a new method, the reutilization of the by-product SBE for the microbiologic formation of acetone, butanol, and ethanol (ABE) is presented as proof-of-concept. The SBE was taken from a palm oil cleaning process. The recycling concept is based on the application of lipolytic clostridia strains. Due to considerably long fermentation times, co-fermentation with Candida rugosa and enzymatic hydrolyses of the bound oil with a subsequent clostridia fermentation are shown as alternative routes. Anaerobic fermentations under comparison of different clostridia strains were performed with glycerol media, enzymatically hydrolyzed palm oil and SBE. Solutes, side product compositions and productivities were quantified via HPLC. A successful production of ABE solutes from SBE has been done with a yield of 0.15 g butanol per gram of bound glycerol. Thus, the biotechnological recycling of the waste stream is possible in principle. Inhibition of the substrate suspension has been observed. A chromatographic ion-exchange of substrates increased the biomass concentration.},
  language  = {en}
}
@article{ThielTippkoetterSucketal.2013,
  author    = {Thiel, Alexander and Tippk{\"o}tter, Nils and Suck, Kirstin and Sohling, Ulrich and Ruf, Friedrich and Ulber, Roland},
  title     = {New zeolite adsorbents for downstream processing of polyphenols from renewable resources},
  series = {Engineering in Life Sciences},
  volume    = {13},
  journal   = {Engineering in Life Sciences},
  number    = {3},
  publisher = {Wiley},
  address   = {Weinheim},
  doi       = {10.1002/elsc.201200188},
  pages     = {239 -- 246},
  year      = {2013},
  abstract  = {Commercial materials with polyvinylpolypyrrolidone and polymeric amberlites (XAD7HP, XAD16) are commonly used for the adsorptive downstream processing of polyphenols from renewable resources. In this study, beta-zeolite-based adsorbent systems were examined, and their properties were compared to organic resins. Batch adsorption experiments were conducted with synthetic solutions of major polyphenols. Adsorption isotherms and desorption characteristics of individual adsorbent were determined based on these results. Maximum adsorption capacities were calculated using the Langmuir model. For example, the zeolites had capacities up to 203.2 mg/g for ferulic acid. To extend these results to a complex system, additional experiments were performed on rapeseed meal and wheat seed extracts as representative renewable resources. HPLC analysis showed that with 7.5\% w/v, which is regarded as the optimum amount of zeolites, zeolites A and B could bind 100\% of the major polyphenols as well as release polyphenols at high yields. Additionally, regeneration experiments were performed with isopropyl alcohol at 99°C to evaluate how zeolites regenerate under mild conditions. The results showed only a negligible loss of adsorption capacity and no loss of desorption capacity. In summary, it was concluded that beta-zeolites were promising adsorbents for developing new processes to isolate polyphenols from renewable resources.},
  language  = {en}
}
@article{TippkoetterAlKaidyWollnyetal.2013,
  author    = {Tippk{\"o}tter, Nils and Al-Kaidy, Huschyar and Wollny, Steffen and Ulber, Roland},
  title     = {Functionalized magnetizable particles for downstream processing in single-use systems},
  series = {Chemie Ingenieur Technik},
  volume    = {85},
  journal   = {Chemie Ingenieur Technik},
  number    = {1-2: Special Issue: Single-Use Technology},
  publisher = {Wiley},
  address   = {Weinheim},
  doi       = {10.1002/cite.201200130},
  pages     = {76 -- 86},
  year      = {2013},
  abstract  = {Biotechnological downstream processing is usually an elaborate procedure, requiring a multitude of unit operations to isolate the target component. Besides the disadvantageous space-time yield, the risks of cross-contaminations and product loss grow fast with the complexity of the isolation procedure. A significant reduction of unit operations can be achieved by application of magnetic particles, especially if these are functionalized with affinity ligands. As magnetic susceptible materials are highly uncommon in biotechnological processes, target binding and selective separation of such particles from fermentation or reactions broths can be done in a single step. Since the magnetizable particles can be produced from iron salts and low priced polymers, a single-use implementation of these systems is highly conceivable. In this article, the principles of magnetizable particles, their synthesis and functionalization are explained. Furthermore, applications in the area of reaction engineering, microfluidics and downstream processing are discussed focusing on established single-use technologies and development potential.},
  language  = {en}
}
@article{SiekerNeunerDimitrovaetal.2011,
  author    = {Sieker, Tim and Neuner, Andreas and Dimitrova, Darina and Tippk{\"o}tter, Nils and Muffler, Kai and Bart, Hans-J{\"o}rg and Heinzle, Elmar and Ulber, Roland},
  title     = {Ethanol production from grass silage by simultaneous pretreatment, saccharification and fermentation: First steps in the process development},
  series = {Engineering in Life Sciences},
  volume    = {11},
  journal   = {Engineering in Life Sciences},
  number    = {4},
  publisher = {Wiley},
  address   = {Weinheim},
  doi       = {10.1002/elsc.201000160},
  pages     = {436 -- 442},
  year      = {2011},
  abstract  = {Grass silage provides a great potential as renewable feedstock. Two fractions of the grass silage, a press juice and the fiber fraction, were evaluated for their possible use for bioethanol production. Direct production of ethanol from press juice is not possible due to high concentrations of organic acids. For the fiber fraction, alkaline peroxide or enzymatic pretreatment was used, which removes the phenolic acids in the cell wall. In this study, we demonstrate the possibility to integrate the enzymatic pretreatment with a simultaneous saccharification and fermentation to achieve ethanol production from grass silage in a one-process step. Achieved yields were about 53 g ethanol per kg silage with the alkaline peroxide pretreatment and 91 g/kg with the enzymatic pretreatment at concentrations of 8.5 and 14.6 g/L, respectively. Furthermore, it was shown that additional supplementation of the fermentation medium with vitamins, trace elements and nutrient salts is not necessary when the press juice is directly used in the fermentation step.},
  language  = {en}
}
@article{PothMonzonTippkoetteretal.2011,
  author    = {Poth, Sebastian and Monzon, Magaly and Tippk{\"o}tter, Nils and Ulber, Roland},
  title     = {Lignocellulosic biorefinery: Process integration of hydrolysis and fermentation (SSF process)},
  series = {Holzforschung},
  volume    = {65},
  journal   = {Holzforschung},
  number    = {5},
  publisher = {De Gruyter},
  address   = {Berlin},
  pages     = {633 -- 637},
  year      = {2011},
  abstract  = {The aim of the present work is the process integration and the optimization of the enzymatic hydrolysis of wood and the following fermentation of the products to ethanol. The substrate is a fiber fraction obtained by organosolv pre-treatment of beech wood. For the ethanol production, a co-fermentation by two different yeasts (Saccharomyces cerevisiae and Pachysolen tannophilus) was carried out to convert glucose as well as xylose. Two approaches has been followed: 1. A two step process, in which the hydrolysis of the fiber fraction and the fermentation to product are separated from each other. 2. A process, in which the hydrolysis and the fermentation are carried out in one single process step as simultaneous saccharification and fermentation (SSF). Following the first approach, a yield of about 0.15 g ethanol per gram substrate can be reached. Based on the SSF, one process step can be saved, and additionally, the gained yield can be raised up to 0.3 g ethanol per gram substrate.},
  language  = {en}
}
@article{TippkoetterRoikaewUlberetal.2010,
  author    = {Tippk{\"o}tter, Nils and Roikaew, Wipa and Ulber, Roland and Hoffmann, Alexander and Denzler, Hans-J{\"o}rg and Buchholz, Heinrich},
  title     = {Paracoccus denitrificans for the effluent recycling during continuous denitrification of liquid food},
  series = {Biotechnology Progress},
  volume    = {26},
  journal   = {Biotechnology Progress},
  number    = {3},
  publisher = {Wiley},
  address   = {Hoboken, NJ},
  issn      = {8756-7938},
  doi       = {10.1002/btpr.384},
  pages     = {756 -- 762},
  year      = {2010},
  abstract  = {Nitrate is an undesirable component of several foods. A typical case of contamination with high nitrate contents is whey concentrate, containing nitrate in concentrations up to 25 l. The microbiological removal of nitrate by Paracoccus denitrificans under formation of harmless nitrogen in combination with a cell retention reactor is described here. Focus lies on the resource-conserving design of a microbal denitrification process. Two methods are compared. The application of polyvinyl alcohol-immobilized cells, which can be applied several times in whey feed, is compared with the implementation of a two step denitrification system. First, the whey concentrate's nitrate is removed by ion exchange and subsequently the eluent regenerated by microorganisms under their retention by crossflow filtration. Nitrite and nitrate concentrations were determined by reflectometric color measurement with a commercially available Reflectoquant® device. Correction factors for these media had to be determined. During the pilot development, bioreactors from 4 to 250 mg·L-1 and crossflow units with membrane areas from 0.02 to 0.80 m2 were examined. Based on the results of the pilot plants, a scaling for the exemplary process of denitrifying 1,000 tons per day is discussed.},
  language  = {en}
}
@article{TippkoetterDeterdingUlber2008,
  author    = {Tippk{\"o}tter, Nils and Deterding, A. and Ulber, Roland},
  title     = {Determination of acetic acid in fermentation broth by gas-diffusion technique},
  series = {Engineering in Life Sciences},
  volume    = {8},
  journal   = {Engineering in Life Sciences},
  number    = {1, Special Issue: Technical Systems for the Use in Life Sciences},
  doi       = {10.1002/elsc.200820227},
  pages     = {62 -- 67},
  year      = {2008},
  abstract  = {Due to the interfering effects of acetic acid in many fermentation processes, a gas-diffusion technique was developed for the online determination of acetic acid. The measurements were accomplished with a flow diffusion analysis (FDA) unit from the TRACE Analytics GmbH, Braunschweig, Germany. The diffusion analysis is based on the UV-absorbance of acetic acid at 205 nm. The measurement was achieved by the separation of an acceptor and a carrier stream (acidified fermentation broth) using a gas permeable polytetrafluoroethylene (PTFE) membrane, whereby broth constituents that would otherwise disturb the UV-measurement of acetic acid, are held back efficiently. Merely, the fermentation by-products, e.g. formic acid, is capable of diffusing through the membrane. While formic acid can disturb the measurement, carbon dioxide does not absorb at 205 nm. The method operates with time-dependent sample enrichment. During the analysis, a small volume of the acceptor stream is stopped for a defined time interval in the acceptor chamber. During this period, the gaseous acetic acid diffuses through the membrane and is enriched in the acceptor chamber. Subsequently after the enrichment, the acceptor stream flows through a UV-detector. The intensity of the signal is proportional to the acetic acid concentration. Online measurements in bioreactors via a sterile filtration probe have been accomplished. A linear calibration in the range of 0.5-5.0 g/L acetic acid with a relative standard deviation of <5 \% was obtained. A sampling rate of 8 samples per hour was possible. The system was applied for the determination of acetic acid in E. coli fermentation broth. The instrument is easy to clean, very user-friendly and does not require any toxic or expensive reagents.},
  language  = {en}
}
@article{KapplerTanudyayaSchmittTippkoetteretal.2007,
  author    = {Kappler-Tanudyaya, Nathalie and Schmitt, Heike and Tippk{\"o}tter, Nils and Meyer, Lina and Lenzen, Sigurd and Ulber, Roland},
  title     = {Combination of biotransformation and chromatography for the isolation and purification of mannoheptulose},
  series = {Biotechnology Journal},
  volume    = {2},
  journal   = {Biotechnology Journal},
  number    = {6},
  issn      = {1860-7314},
  doi       = {10.1002/biot.200700004},
  pages     = {692 -- 699},
  year      = {2007},
  abstract  = {Mannoheptulose is a seven-carbon sugar. It is an inhibitor of glucose-induced insulin secretion due to its ability to selectively inhibit the enzyme glucokinase. An improved procedure for mannoheptulose isolation from avocados is described in this study (based upon the original method by La Forge). The study focuses on the combination of biotransformation and downstream processing (preparative chromatography) as an efficient method to produce a pure extract of mannoheptulose. The experiments were divided into two major phases. In the first phase, several methods and parameters were compared to optimize the mannoheptulose extraction with respect to efficiency and purity. In the second phase, a mass balance of mannoheptulose over the whole extraction process was undertaken to estimate the yield and efficiency of the total extraction process. The combination of biotransformation and preparative chromatography allowed the production of a pure mannoheptulose extract. In a biological test, the sugar inhibited the glucokinase enzyme activity efficiently.},
  language  = {en}
}
@article{RoeschKratzHeringetal.2016,
  author    = {R{\"o}sch, C. and Kratz, F. and Hering, T. and Trautmann, S. and Umanskaya, N. and Tippk{\"o}tter, Nils and M{\"u}ller-Renno, C.M. and Ulber, Roland and Hannig, M. and Ziegler, C.},
  title     = {Albumin-lysozyme interactions: cooperative adsorption on titanium and enzymatic activity},
  series = {Colloids and Surfaces B: Biointerfaces},
  volume    = {149},
  journal   = {Colloids and Surfaces B: Biointerfaces},
  number    = {1},
  publisher = {Elsevier},
  address   = {Amsterdam},
  doi       = {10.1016/j.colsurfb.2016.09.048},
  pages     = {115 -- 121},
  year      = {2016},
  abstract  = {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.},
  language  = {en}
}
@article{RothTippkoetter2016,
  author    = {Roth, Jasmine and Tippk{\"o}tter, Nils},
  title     = {Evaluation of lignocellulosic material for butanol production using enzymatic hydrolysate medium},
  series = {Cellulose Chemistry and Technology},
  volume    = {50},
  journal   = {Cellulose Chemistry and Technology},
  number    = {3-4},
  publisher = {Editura Academiei Romane},
  address   = {Bukarest},
  pages     = {405 -- 410},
  year      = {2016},
  abstract  = {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.},
  language  = {en}
}
@article{AlKaidyTippkoetter2016,
  author    = {Al-Kaidy, Huschyar and Tippk{\"o}tter, Nils},
  title     = {Superparamagnetic hydrophobic particles as shell material for digital microfluidic droplets and proof-of-principle reaction assessments with immobilized laccase},
  series = {Engineering in Life Sciences},
  volume    = {16},
  journal   = {Engineering in Life Sciences},
  number    = {3},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  doi       = {10.1002/elsc.201400124},
  pages     = {222 -- 230},
  year      = {2016},
  abstract  = {In the field of biotechnology and molecular biology, the use of small liquid volumes has significant advantages. In particular, screening and optimization runs with acceptable amounts of expensive and hardly available catalysts, reagents, or biomolecules are feasible with microfluidic technologies. The presented new microfluidic system is based on the inclusion of small liquid volumes by a protective shell of magnetizable microparticles. Hereby, discrete aqueous microreactor drops with volumes of 1-30 μL can be formed on a simple planar surface. A digital movement and manipulation of the microreactor is performed by overlapping magnetic forces. The magnetic forces are generated by an electrical coil matrix positioned below a glass plate. With the new platform technology, several discrete reaction compartments can be moved simultaneously on one surface. Due to the magnetic fields, the reactors can even be merged to initiate reactions by mixing or positioned above surface-immobilized catalysts and then opened by magnetic force. Comparative synthesis routes of the magnetizable shell particles and superhydrophobic glass slides including their performance and stability with the reaction platform are described. The influence of diffusive mass transport during the catalyzed reaction is discussed by evaluation finite element model of the microreactor. Furthermore, a first model dye reaction of the enzyme laccase has been established.},
  language  = {en}
}
@article{AlKaidyDuweHusteretal.2015,
  author    = {Al-Kaidy, Huschyar and Duwe, Anna and Huster, Manuel and Muffler, Kai and Schlegel, Christin and Tim, Sieker and Stadtm{\"u}ller, Ralf and Tippk{\"o}tter, Nils and Ulber, Roland},
  title     = {Biotechnology and bioprocess engineering - from the first ullmann's article to recent trends},
  series = {ChemBioEng Reviews},
  volume    = {2},
  journal   = {ChemBioEng Reviews},
  number    = {3},
  publisher = {Wiley},
  address   = {Weinheim},
  doi       = {10.1002/cben.201500008},
  pages     = {175 -- 184},
  year      = {2015},
  abstract  = {For several thousand years, biotechnology and its associated technical processes have had a great impact on the development of mankind. Based on empirical methods, in particular for the production of foodstuffs and daily commodities, these disciplines have become one of the most innovative future issues. Due to the increasing detailed understanding of cellular processes, production strains can now be optimized. In combination with modern bioprocesses, a variety of bulk and fine chemicals as well as pharmaceuticals can be produced efficiently. In this article, some of the current trends in biotechnology are discussed.},
  language  = {en}
}
@article{AlKaidyKuthanHeringetal.2016,
  author    = {Al-Kaidy, Huschyar and Kuthan, Kai and Hering, Thomas and Tippk{\"o}tter, Nils},
  title     = {Aqueous droplets used as enzymatic microreactors and their electromagnetic actuation},
  series = {Journal of Visualized Experiments},
  journal   = {Journal of Visualized Experiments},
  number    = {Issue 126},
  issn      = {1940-087X},
  doi       = {10.3791/54643},
  year      = {2016},
  abstract  = {For the successful implementation of microfluidic reaction systems, such as PCR and electrophoresis, the movement of small liquid volumes is essential. In conventional lab-on-a-chip-platforms, solvents and samples are passed through defined microfluidic channels with complex flow control installations. The droplet actuation platform presented here is a promising alternative. With it, it is possible to move a liquid drop (microreactor) on a planar surface of a reaction platform (lab-in-a-drop). The actuation of microreactors on the hydrophobic surface of the platform is based on the use of magnetic forces acting on the outer shell of the liquid drops which is made of a thin layer of superhydrophobic magnetite particles. The hydrophobic surface of the platform is needed to avoid any contact between the liquid core and the surface to allow a smooth movement of the microreactor. On the platform, one or more microreactors with volumes of 10 µL can be positioned and moved simultaneously. The platform itself consists of a 3 x 3 matrix of electrical double coils which accommodate either neodymium or iron cores. The magnetic field gradients are automatically controlled. By variation of the magnetic field gradients, the microreactors' magnetic hydrophobic shell can be manipulated automatically to move the microreactor or open the shell reversibly. Reactions of substrates and corresponding enzymes can be initiated by merging the microreactors or bringing them into contact with surface immobilized catalysts.},
  language  = {en}
}
@article{BrabandPaulssenAbram2006,
  author    = {Braband, Henrik and Paulßen, Elisabeth and Abram, Ulrich},
  title     = {Nitridorhenium(V) Complexes with 1,3-Dialkyl-4,5-dimethylimidazole-2-ylidenes},
  series = {Zeitschrift f{\"u}r anorganische und allgemeine Chemie : ZAAC = Journal of inorganic and general chemistry},
  volume    = {632},
  journal   = {Zeitschrift f{\"u}r anorganische und allgemeine Chemie : ZAAC = Journal of inorganic and general chemistry},
  number    = {6},
  issn      = {1521-3749},
  doi       = {10.1002/zaac.200600002},
  pages     = {1051 -- 1056},
  year      = {2006},
  language  = {en}
}
@article{PaulssenSchweighoeferAbram2010,
  author    = {Paulßen, Elisabeth and Schweigh{\"o}fer, Philip V. and Abram, Ulrich},
  title     = {Reactions of [ReOX3(PPh3)2] Complexes (X = Cl, Br) with Phenylacetylene and the Structures of the Products},
  series = {Zeitschrift f{\"u}r anorganische und allgemeine Chemie : ZAAC = Journal of inorganic and general chemistry},
  volume    = {636},
  journal   = {Zeitschrift f{\"u}r anorganische und allgemeine Chemie : ZAAC = Journal of inorganic and general chemistry},
  number    = {5},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1521-3749},
  doi       = {10.1002/zaac.200900478},
  pages     = {779 -- 783},
  year      = {2010},
  abstract  = {Oxorhenium(V) complexes [ReOX3(PPh3)2] (X = Cl, Br) react with phenylacetylene under formation of complexes with ylide-type ligands. Compounds of the compositions [ReOCl3(PPh3){C(Ph)C(H)(PPh3)}] (1), [ReOBr3(OPPh3){C(Ph)C(H)(PPh3)}] (2), and [ReOBr3(OPPh3){C(H)C(Ph)(PPh3)}] (3) were isolated and characterized by X-ray diffraction. They contain a ligand, which was formed by a nucleophilic attack of released PPh3 at coordinated phenylacetylene. The structures of the products show that there is no preferable position for this attack. Cleavage of the Re-C bond in 3 and dimerization of the organic ligand resulted in the formation of the [{(PPh3)(H)CC(Ph)}2]2+ cation, which crystallized as its [(ReOBr4)(OReO3)]2- salt.},
  language  = {en}
}
@article{PaulssenKueckmannAbram2007,
  author    = {Paulßen, Elisabeth and K{\"u}ckmann, Theresa and Abram, Ulrich},
  title     = {Silver(I) Complexes of 1,3-Dialkyl-4,5-dimethylimidazol-2-ylidenes and their Use as Precursors for the Synthesis of Rhenium(V) NHC Complexes},
  series = {Zeitschrift f{\"u}r anorganische und allgemeine Chemie : ZAAC = Journal of inorganic and general chemistry},
  volume    = {633},
  journal   = {Zeitschrift f{\"u}r anorganische und allgemeine Chemie : ZAAC = Journal of inorganic and general chemistry},
  number    = {5-6},
  issn      = {1521-3749},
  doi       = {10.1002/zaac.200700021},
  pages     = {830 -- 834},
  year      = {2007},
  language  = {en}
}
@article{BrabandYegenPaulssenetal.2005,
  author    = {Braband, Henrik and Yegen, Eda and Paulßen, Elisabeth and Abram, Ulrich},
  title     = {[{ReN(PMe2Ph)3}{ReO3N}]2 - Structural Evidence for the Nitridotrioxorhenate(VII) Anion, [ReO3N]2-},
  series = {Zeitschrift f{\"u}r anorganische und allgemeine Chemie : ZAAC = Journal of inorganic and general chemistry},
  volume    = {631},
  journal   = {Zeitschrift f{\"u}r anorganische und allgemeine Chemie : ZAAC = Journal of inorganic and general chemistry},
  number    = {12},
  issn      = {1521-3749},
  doi       = {10.1002/zaac.200500240},
  pages     = {2408 -- 2410},
  year      = {2005},
  language  = {en}
}
@article{PaulssenAlbertoAbram2010,
  author    = {Paulßen, Elisabeth and Alberto, Roger and Abram, Ulrich},
  title     = {Synthesis, Characterization, and Structures of R3EOTcO3 Complexes (E = C, Si, Ge, Sn, Pb) and Related Compounds},
  series = {Inorganic Chemistry},
  volume    = {49},
  journal   = {Inorganic Chemistry},
  number    = {7},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {1520-510X},
  doi       = {10.1021/ic1001094},
  pages     = {3525 -- 3530},
  year      = {2010},
  abstract  = {AgTcO4 reacts with R3ECl compounds (E = C, Si, Ge, Sn, Pb; R = Me, iPr, tBu, Ph), tBu2SnCl2, or PhMgCl under formation of novel trioxotechnetium(VII) derivatives. The carbon and silicon derivatives readily undergo decomposition, which was proven by 99Tc NMR spectroscopy and the isolation of decomposition products such as [TcOCl3(THF)(OH2)]. Compounds [Ph3GeOTcO3], [(THF)Ph3SnOTcO3], [(O3TcO)SntBu2(OH)]2, and [(THF)4Mg(OTcO3)2] are more stable and were isolated in crystalline form and characterized by X-ray diffraction.},
  language  = {en}
}
@article{PaulssenKongArciszewskietal.2012,
  author    = {Paulßen, Elisabeth and Kong, Shushu and Arciszewski, Pawel and Wielbalck, Swantje and Abram, Ulrich},
  title     = {Aryl and NHC Compounds of Technetium and Rhenium},
  series = {Journal of the American Chemical Society},
  volume    = {134},
  journal   = {Journal of the American Chemical Society},
  number    = {22},
  publisher = {ACS Publications},
  address   = {Washington, DC},
  issn      = {1520-5126},
  doi       = {10.1021/ja3033718},
  pages     = {9118 -- 9121},
  year      = {2012},
  abstract  = {Air- and water-stable phenyl complexes with nitridotechnetium(V) cores can be prepared by straightforward procedures. [TcNPh2(PPh3)2] is formed by the reaction of [TcNCl2(PPh3)2] with PhLi. The analogous N-heterocyclic carbene (NHC) compound [TcNPh2(HLPh)2], where HLPh is 1,3,4-triphenyl-1,2,4-triazol-5-ylidene, is available from (NBu4)[TcNCl4] and HLPh or its methoxo-protected form. The latter compound allows the comparison of different Tc-C bonds within one compound. Surprisingly, the Tc chemistry with such NHCs does not resemble that of corresponding Re complexes, where CH activation and orthometalation dominate.},
  language  = {en}
}
@article{BarbazanHagenbachPaulssenetal.2010,
  author    = {Barbaz{\´a}n, Paula and Hagenbach, Adelheid and Paulßen, Elisabeth and Abram, Ulrich and Carballo, Rosa and Rodriguez-Hermida, Sabina and V{\´a}zquez-L{\´o}pez, Ezequiel M.},
  title     = {Tricarbonyl Rhenium(I) and Technetium(I) Complexes with Hydrazones Derived from 4,5-Diazafluoren-9-one and 1,10-Phenanthroline-5,6-dione},
  series = {European Journal of Inorganic Chemistry},
  journal   = {European Journal of Inorganic Chemistry},
  number    = {29},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1099-0682},
  doi       = {10.1002/ejic.201000522},
  pages     = {4622 -- 4630},
  year      = {2010},
  abstract  = {Tricarbonylrhenium(I) and -technetium(I) halide (halide = Cl and Br) complexes of ligands derived from 4,5-diazafluoren-9-one (df) and 1,10-phenanthroline-5,6-dione (phen) derivatives of benzoic and 2-hydroxybenzoic acid hydrazides have been prepared. The complexes have been characterized by elemental analysis, MS, IR, 1H NMR and absorption and emission UV/Vis spectroscopic methods. The metal centres (ReI and TcI) are coordinated through the nitrogen imine atoms and establish five-membered chelate rings, whereas the hydrazone groups stand uncoordinated. The 1H NMR spectra suggest the same behaviour in solution on the basis of only marginal variations in the chemical shifts of the hydrazine protons.},
  language  = {en}
}
@article{PaulssenNgyugenKahlckeetal.2012,
  author    = {Paulßen, Elisabeth and Ngyugen, Hung Huy and Kahlcke, Nils and Deflon, Victor M. and Abram, Ulrich},
  title     = {Tricarbonyltechnetium(I) and -rhenium(I) complexes with N′-thiocarbamoylpicolylbenzamidines},
  series = {Polyhedron},
  volume    = {40},
  journal   = {Polyhedron},
  number    = {1},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0277-5387},
  doi       = {10.1016/j.poly.2012.04.008},
  pages     = {153 -- 158},
  year      = {2012},
  abstract  = {N,N-Dialkylamino(thiocarbonyl)-N′-picolylbenzamidines react with (NEt4)2[M(CO)3X3] (M = Re, X = Br; M = Tc, X = Cl) under formation of neutral [M(CO)3L] complexes in high yields. The monoanionic NNS ligands bind in a facial coordination mode and can readily be modified at the (CS)NR1R2 moiety. The complexes [99Tc(CO)3(LPyMor)] and [Re(CO)3(L)] (L = LPyMor, LPyEt) were characterized by X-ray diffraction. Reactions of [99mTc(CO)3(H2O)3]+ with the N′-thiocarbamoylpicolylbenzamidines give the corresponding 99mTc complexes. The ester group in HLPyCOOEt allows linkage between biomolecules and the metal core.},
  language  = {en}
}