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  - Wulfhorst, Helene
A1  - Duwe, Anna-Maria
A1  - Merseburg, Johannes
A1  - Tippkötter, Nils
T1  - Compositional analysis of pretreated (beech) wood using differential scanning calorimetry and multivariate data analysis
JF  - Tetrahedron
N2  - The composition of plant biomass varies depending on the feedstock and pre-treatment conditions and influences its processing in biorefineries. In order to ensure optimal process conditions, the quantitative proportion of the main polymeric components of the pre-treated biomass has to be determined. Current standard procedures for biomass compositional analysis are complex, the measurements are afflicted with errors and therefore often not comparable. Hence, new powerful analytical methods are urgently required to characterize biomass. In this contribution, Differential Scanning Calorimetry (DSC) was applied in combination with multivariate data analysis (MVA) to detect the cellulose content of the plant biomass pretreated by Liquid Hot Water (LHW) and Organosolv processes under various conditions. Unlike conventional techniques, the developed analytic method enables the accurate quantification of monosaccharide content of the plant biomass without any previous sample preparation. It is easy to handle and avoids errors in sample preparation.
Y1  - 2016
U6  - http://dx.doi.org/10.1016/j.tet.2016.04.029
VL  - 72
IS  - 46
SP  - 7329
EP  - 7334
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - CHAP
A1  - Wulfhorst, H.
A1  - Duwe, A.
A1  - Möhring, S.
A1  - Jurca, O.
A1  - Tippkötter, Nils
T1  - Analysis of pretreated biomass by differential scanning 132 calorimetry and multivariate data analysis
T2  - New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany
Y1  - 2016
SP  - 132
PB  - DECHEMA
CY  - Frankfurt am Main
ER  - 
TY  - CHAP
A1  - Wolf, C. Roland
A1  - Kapelyukh, Yury
A1  - Scheer, Nico
A1  - Henderson, Colin J.
ED  - Wilson, Alan G. E.
T1  - Application of Humanised and Other Transgenic Models to Predict Human Responses to Drugs
N2  - The use of transgenic animal models has transformed our knowledge of complex biochemical pathways in vivo. It has allowed disease processes to be modelled and used in the development of new disease prevention and treatment strategies. They can also be used to define cell- and tissue-specific pathways of gene regulation. A further major application is in the area of preclinical development where such models can be used to define pathways of chemical toxicity, and the pathways that regulate drug disposition. One major application of this approach is the humanisation of mice for the proteins that control drug metabolism and disposition. Such models can have numerous applications in the development of drugs and in their more sophisticated use in the clinic.
Y1  - 2015
SN  - 978-1-78262-778-4
U6  - http://dx.doi.org/10.1039/9781782622376-00152
SP  - 152
EP  - 176
PB  - RSC Publ.
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Wissenbach, U.
A1  - Six, S.
A1  - Bongaerts, Johannes
A1  - Ternes, D.
A1  - Steinwachs, S.
A1  - Unden, G.
T1  - A third periplasmic transport system for l-arginine in Escherichia coli: molecular characterization of the artPIQMJ genes, arginine binding and transport
JF  - Molecular microbiology
Y1  - 1995
SN  - 1365-2958 (E-Journal); 0950-382x (Print)
VL  - Vol. 17
IS  - Iss. 4
SP  - 675
EP  - 686
ER  - 
TY  - JOUR
A1  - Winckler, Silvia
A1  - Krueger, Rolf
A1  - Schnitzler, Thomas
A1  - Zang, Werner
A1  - Fischer, Rainer
A1  - Biselli, Manfred
T1  - A sensitive monitoring system for mammalian cell cultivation processes: a PAT approach
JF  - Bioprocess and biosystems engineering
N2  - Biopharmaceuticals such as antibodies are produced in cultivated mammalian cells, which must be monitored to comply with good manufacturing practice. We, therefore, developed a fully automated system comprising a specific exhaust gas analyzer, inline analytics and a corresponding algorithm to precisely determine the oxygen uptake rate, carbon dioxide evolution rate, carbon dioxide transfer rate, transfer quotient and respiratory quotient without interrupting the ongoing cultivation, in order to assess its reproducibility. The system was verified using chemical simulation experiments and was able to measure the respiratory activity of hybridoma cells and DG44 cells (derived from Chinese hamster ovary cells) with satisfactory results at a minimum viable cell density of ~2.0 × 10⁵ cells ml⁻¹. The system was suitable for both batch and fed-batch cultivations in bubble-aerated and membrane-aerated reactors, with and without the control of pH and dissolved oxygen.
Y1  - 2014
U6  - http://dx.doi.org/10.1007/s00449-013-1062-8
SN  - 1615-7591 (Print) 1615-7605 (Online)
VL  - 37
IS  - 5
SP  - 901
EP  - 912
PB  - Springer
CY  - Berlin, Heidelberg
ER  - 
TY  - JOUR
A1  - Wilson, Ian D.
A1  - Wilson, Claire E.
A1  - Scheer, Nico
A1  - Dickie, A.P.
A1  - Schreiter, K.
A1  - Wilson, E. M.
A1  - Riley, R. J.
A1  - Wehr, R.
A1  - Bial, J.
T1  - The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice
JF  - Biochemical pharmacology
Y1  - 2017
U6  - http://dx.doi.org/10.1016/j.bcp.2017.03.015
SN  - 1873-2968
VL  - Volume 135
SP  - 139
EP  - 150
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Wilson, C. E.
A1  - Dickie, A. P.
A1  - Schreiter, K.
A1  - Wehr, R.
A1  - Wilson, E. M.
A1  - Bial, J.
A1  - Scheer, Nico
A1  - Wilson, I. D.
A1  - Riley, R. J.
T1  - The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice
JF  - Archives of Toxicology
N2  - The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In addition, the metabolism and excretion were investigated in chimeric liver humanized and murinized FRG mice. Diclofenac reached maximum blood concentrations of 2.43 ± 0.9 µg/mL (n = 3) at 0.25 h post-dose with an AUCinf of 3.67 µg h/mL and an effective half-life of 0.86 h (n = 2). In the murinized animals, maximum blood concentrations were determined as 3.86 ± 2.31 µg/mL at 0.25 h post-dose with an AUCinf of 4.94 ± 2.93 µg h/mL and a half-life of 0.52 ± 0.03 h (n = 3). In C57BL/6J mice, mean peak blood concentrations of 2.31 ± 0.53 µg/mL were seen 0.25 h post-dose with a mean AUCinf of 2.10 ± 0.49 µg h/mL and a half-life of 0.51 ± 0.49 h (n = 3). Analysis of blood indicated only trace quantities of drug-related material in chimeric humanized and murinized FRG mice. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles in humanized mice were different to those of both murinized and wild-type animals, e.g., a higher proportion of the dose was detected in the form of acyl glucuronide metabolites and much reduced amounts as taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57BL/6J mice and humans revealed a greater, though not complete, match between chimeric humanized mice and humans, such that the liver humanized FRG model may represent a model for assessing the biotransformation of such compounds in humans.
Y1  - 2018
U6  - http://dx.doi.org/10.1007/s00204-018-2212-1
SN  - 1432-0738
VL  - 92
IS  - 6
SP  - 1953
EP  - 1967
PB  - Springer
ER  - 
TY  - JOUR
A1  - Wilming, Anja
A1  - Begemann, Jens
A1  - Kuhne, Stefan
A1  - Regestein, Lars
A1  - Bongaerts, Johannes
A1  - Evers, Stefan
A1  - Maurer, Karl-Heinz
A1  - Büchs, Jochen
T1  - Metabolic studies of γ-polyglutamic acid production in Bacillus licheniformis by small-scale continuous cultivations
JF  - Biochemical engineering journal
Y1  - 2013
SN  - 1873-295X (E-Journal); 1369-703X (Print)
VL  - Vol. 73
SP  - 29
EP  - 37
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Wiesen, Sebastian
A1  - Tippkötter, Nils
A1  - Muffler, Kai
A1  - Suck, Kirstin
A1  - Sohling, Ulrich
A1  - Ruf, Friedrich
A1  - Ulber, Roland
T1  - Adsorption of fatty acids to layered double hydroxides in aqueous systems
JF  - Adsorption
N2  - Due to their anion exchange characteristics, layered double hydroxides (LDHs) are suitable for the detoxification of aqueous, fatty acid containing fermentation substrates. The aim of this study is to examine the adsorption mechanism, using crude glycerol from plant oil esterification as a model system. Changes in the intercalation structure in relation to the amount of fatty acids adsorbed are monitored by X-ray diffraction and infra-red spectroscopy. Additionally, calcination of LDH is investigated in order to increase the binding capacity for fatty acids. Our data propose that, at ambient temperature, fatty acids can be bound to the hydrotalcite by adsorption or in addition by intercalation, depending on fatty acid concentration. The adsorption of fatty acids from crude glycerol shows a BET-like behavior. Above a fatty acid concentration of 3.5 g L−1, intercalation of fatty acids can be shown by the appearance of an increased interlayer spacing. This observation suggests a two phase adsorption process. Calcination of LDHs allows increasing the binding capacity for fatty acids by more than six times, mainly by reduction of structural CO32−.
Y1  - 2015
VL  - 21
IS  - 6-7
SP  - 459
EP  - 466
PB  - Springer
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Wiegand, Sandra
A1  - Voigt, Birgit
A1  - Albrecht, Dirk
A1  - Bongaerts, Johannes
A1  - Evers, Stefan
A1  - Hecker, Michael
A1  - Daniel, Rolf
A1  - Liesegang, Heiko
T1  - Fermentation stage-dependent adaptations of Bacillus licheniformis during enzyme production
JF  - Microbial Cell Factories
Y1  - 2013
U6  - http://dx.doi.org/10.1186/1475-2859-12-120
SN  - 1475-2859
VL  - 12
SP  - 120
PB  - Biomed Central
CY  - London
ER  - 
TY  - JOUR
A1  - Wiegand, Sandra
A1  - Dietrich, Sascha
A1  - Hertel, Robert
A1  - Bongaerts, Johannes
A1  - Evers, Stefan
A1  - Volland, Sonja
A1  - Daniel, Rolf
A1  - Liesegang, Heiko
T1  - RNA-Seq of Bacillus licheniformis: active regulatory RNA features expressed within a productive fermentation
JF  - BMC genomics
Y1  - 2013
SN  - 1471-2164
VL  - Vol. 14
SP  - 667
PB  - BioMed Central
CY  - London
ER  - 
TY  - JOUR
A1  - Whitehead, Mark
A1  - Öhlschläger, Peter
A1  - Almajhdi, Fahad N.
A1  - Alloza, Leonor
A1  - Marzábal, Pablo
A1  - Meyers, Ann E.
A1  - Hitzeroth, Inga I.
A1  - Rybicki, Edward P.
T1  - Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice
JF  - BMC cancer
Y1  - 2014
U6  - http://dx.doi.org/10.1186/1471-2407-14-367
SN  - 1471-2407
IS  - 14:367
SP  - 1
EP  - 15
PB  - BioMed Central
CY  - London
ER  - 
TY  - JOUR
A1  - Werner, Frederik
A1  - Krumbe, Christoph
A1  - Schumacher, Katharina
A1  - Groebel, Simone
A1  - Spelthahn, Heiko
A1  - Stellberg, Michael
A1  - Wagner, Torsten
A1  - Yoshinobu, Tatsuo
A1  - Selmer, Thorsten
A1  - Keusgen, Michael
A1  - Baumann, Marcus
A1  - Schöning, Michael Josef
T1  - Determination of the extracellular acidification of Escherichia coli by a light-addressable potentiometric sensor
JF  - Physica status solidi (a) : applications and material science. 208 (2011), H. 6
Y1  - 2011
SN  - 1862-6319
SP  - 1340
EP  - 1344
PB  - Wiley
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Werner, Frederik
A1  - Groebel, Simone
A1  - Krumbe, Christoph
A1  - Wagner, Torsten
A1  - Selmer, Thorsten
A1  - Yoshinobu, Tatsuo
A1  - Baumann, Marcus
A1  - Schöning, Michael Josef
T1  - Nutrient concentration-sensitive microorganism-based biosensor
JF  - Physica Status Solidi (a)
Y1  - 2012
U6  - http://dx.doi.org/10.1002/pssa.201100801
SN  - 1862-6319
VL  - 209
IS  - 5
SP  - 900
EP  - 904
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Werkhausen, Amelie
A1  - Albracht, Kirsten
A1  - Cronin, Neil J.
A1  - Meier, Rahel
A1  - Mojsen-Moeller, Jens
A1  - Seynnes, Olivier R.
T1  - Modulation of muscle-tendon interaction in the human triceps surae during an energy dissipation task
JF  - Journal of Experimental Biology
Y1  - 2017
U6  - http://dx.doi.org/10.1242/jeb.164111
SN  - 0022-0949
VL  - 220
IS  - 22
SP  - 4141
EP  - 4149
ER  - 
TY  - CHAP
A1  - Wendorff, Marion
A1  - Eggert, Thorsten
A1  - Pohl, Martina
A1  - Dresen, Carola
A1  - Müller, Michael
A1  - Jaeger, Karl-Erich
A1  - Sprenger, Georg A.
A1  - Schürmann, Melanie
A1  - Schürmann, Martin
A1  - Johnen, Sandra
A1  - Sprenger, Gerda
A1  - Sahm, Hermann
A1  - Inoue, Tomoyuki
A1  - Schörken, Ulrich
A1  - Breittaupt, Holger
A1  - Frölich, Bettina
A1  - Heim, Petra
A1  - Iding, Hans
A1  - Juchem, Bettina
A1  - Siegert, Petra
A1  - Kula, Maria-Regina
A1  - Weckbecker, Andrea
A1  - Hummel, Werner
A1  - Fessner, Wolf-Dieter
A1  - Elling, Lothar
A1  - Wolberg, Michael
A1  - Bode, Silke
A1  - Feldmann, Ralf
A1  - Geilenkirchen, Petra
A1  - Schubert, Thomas
A1  - Walter, Lydia
A1  - Dünnwald, Thomas
A1  - Demir, Ayhan S.
A1  - Kolter-Jung, Doris
A1  - Nitsche, Adam
A1  - Dünkelmann, Pascal
A1  - Cosp, Annabel
A1  - Lingen, Bettina
T1  - Catalytic asymmetric synthesis : section 2.2
T2  - Asymmetric synthesis with chemical and biological methods / ed. by Dieter Enders ...
Y1  - 2007
SN  - 978-3-527-31473-7
SP  - 298
EP  - 413
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Welden, Rene
A1  - Jablonski, Melanie
A1  - Wege, Christina
A1  - Keusgen, Michael
A1  - Wagner, Patrick Hermann
A1  - Wagner, Torsten
A1  - Schöning, Michael Josef
T1  - Light-Addressable Actuator-Sensor Platform for Monitoring and Manipulation of pH Gradients in Microfluidics: A Case Study with the Enzyme Penicillinase
JF  - Biosensors
N2  - The feasibility of light-addressed detection and manipulation of pH gradients inside an electrochemical microfluidic cell was studied. Local pH changes, induced by a light-addressable electrode (LAE), were detected using a light-addressable potentiometric sensor (LAPS) with different measurement modes representing an actuator-sensor system. Biosensor functionality was examined depending on locally induced pH gradients with the help of the model enzyme penicillinase, which had been immobilized in the microfluidic channel. The surface morphology of the LAE and enzyme-functionalized LAPS was studied by scanning electron microscopy. Furthermore, the penicillin sensitivity of the LAPS inside the microfluidic channel was determined with regard to the analyte’s pH influence on the enzymatic reaction rate. In a final experiment, the LAE-controlled pH inhibition of the enzyme activity was monitored by the LAPS.
KW  - microfluidics
KW  - enzyme kinetics
KW  - actuator-sensor system
KW  - light-addressable electrode
KW  - light-addressable potentiometric sensor
Y1  - 2021
U6  - http://dx.doi.org/10.3390/bios11060171
SN  - 2079-6374
N1  - This article belongs to the Special Issue "Selected Papers from the 1st International Electronic Conference on Biosensors (IECB 2020)"
VL  - 11
IS  - 6
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Welden, Melanie
A1  - Severins, Robin
A1  - Poghossian, Arshak
A1  - Wege, Christina
A1  - Bongaerts, Johannes
A1  - Siegert, Petra
A1  - Keusgen, Michael
A1  - Schöning, Michael Josef
T1  - Detection of acetoin and diacetyl by a tobacco mosaic virus-assisted field-effect biosensor
JF  - Chemosensors
N2  - Acetoin and diacetyl have a major impact on the flavor of alcoholic beverages such as wine or beer. Therefore, their measurement is important during the fermentation process. Until now, gas chromatographic techniques have typically been applied; however, these require expensive laboratory equipment and trained staff, and do not allow for online monitoring. In this work, a capacitive electrolyte–insulator–semiconductor sensor modified with tobacco mosaic virus (TMV) particles as enzyme nanocarriers for the detection of acetoin and diacetyl is presented. The enzyme acetoin reductase from Alkalihalobacillus clausii DSM 8716ᵀ is immobilized via biotin–streptavidin affinity, binding to the surface of the TMV particles. The TMV-assisted biosensor is electrochemically characterized by means of leakage–current, capacitance–voltage, and constant capacitance measurements. In this paper, the novel biosensor is studied regarding its sensitivity and long-term stability in buffer solution. Moreover, the TMV-assisted capacitive field-effect sensor is applied for the detection of diacetyl for the first time. The measurement of acetoin and diacetyl with the same sensor setup is demonstrated. Finally, the successive detection of acetoin and diacetyl in buffer and in diluted beer is studied by tuning the sensitivity of the biosensor using the pH value of the measurement solution.
Y1  - 2022
U6  - http://dx.doi.org/10.3390/chemosensors10060218
SN  - 2227-9040
N1  - This article belongs to the Special Issue "Nanostructured Devices for Biochemical Sensing"
VL  - 10
IS  - 6
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Welden, Melanie
A1  - Poghossian, Arshak
A1  - Vahidpour, Farnoosh
A1  - Wendlandt, Tim
A1  - Keusgen, Michael
A1  - Wege, Christina
A1  - Schöning, Michael Josef
T1  - Towards multi-analyte detection with field-effect capacitors modified with tobacco mosaic virus bioparticles as enzyme nanocarriers
JF  - Biosensors
N2  - Utilizing an appropriate enzyme immobilization strategy is crucial for designing enzyme-based biosensors. Plant virus-like particles represent ideal nanoscaffolds for an extremely dense and precise immobilization of enzymes, due to their regular shape, high surface-to-volume ratio and high density of surface binding sites. In the present work, tobacco mosaic virus (TMV) particles were applied for the co-immobilization of penicillinase and urease onto the gate surface of a field-effect electrolyte-insulator-semiconductor capacitor (EISCAP) with a p-Si-SiO₂-Ta₂O₅ layer structure for the sequential detection of penicillin and urea. The TMV-assisted bi-enzyme EISCAP biosensor exhibited a high urea and penicillin sensitivity of 54 and 85 mV/dec, respectively, in the concentration range of 0.1–3 mM. For comparison, the characteristics of single-enzyme EISCAP biosensors modified with TMV particles immobilized with either penicillinase or urease were also investigated. The surface morphology of the TMV-modified Ta₂O₅-gate was analyzed by scanning electron microscopy. Additionally, the bi-enzyme EISCAP was applied to mimic an XOR (Exclusive OR) enzyme logic gate.
KW  - urease
KW  - enzyme-logic gate
KW  - bi-enzyme biosensor
KW  - capacitive field-effect sensor
KW  - tobacco mosaic virus (TMV)
KW  - penicillinase
Y1  - 2022
U6  - http://dx.doi.org/10.3390/bios12010043
SN  - 2079-6374
N1  - This article belongs to the Special Issue "Biosensors: 10th Anniversary Feature Papers"
VL  - 12
IS  - 1
PB  - MDPI
CY  - Basel
ER  -