TY  - JOUR
A1  - Öhlschläger, Peter
A1  - Steinberg, Thorsten
A1  - Sehr, Peter
A1  - Osen, Wolfram
T1  - Modification of HPV 16 E7 genes: correlation between the level of protein expression and CTL response after immunization of C57BL/6 mice / Steinberg, Thorsten ; Öhlschläger, Peter ; Sehr, Peter ; Osen, Wolfram ; Gissmann, Lutz
JF  - Vaccine. 23 (2005), H. 9
Y1  - 2005
SN  - 0264-410X
SP  - 1149
EP  - 1157
ER  - 
TY  - JOUR
A1  - Öhlschläger, Peter
A1  - Spies, Elmar
A1  - Alvarez, Gerardo
A1  - Quetting, Michael
A1  - Groettrup, Marcus
T1  - The combination of TLR-9 adjuvantation and electroporation-mediated delivery enhances in vivo antitumor responses after vaccination with HPV-16 E7 encoding DNA
JF  - International Journal of Cancer. 128 (2011), H. 2
Y1  - 2011
SN  - 1097-0215
SP  - 473
EP  - 481
PB  - Wiley
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Öhlschläger, Peter
A1  - Quetting, Michael
A1  - Alvarez, Gerardo
A1  - Dürst, Matthias
A1  - Gissmann, Lutz
A1  - Kaufmann, Andreas M.
T1  - Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants
JF  - International Journal of Cancer
Y1  - 2009
SN  - 1097-0215
VL  - 125
IS  - 1
SP  - 189
EP  - 198
PB  - Wiley
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Öhlschläger, Peter
A1  - Pes, Michaela
A1  - Osen, Wolfram
A1  - Dürst, Matthias
T1  - An improved rearranged Human Papillomavirus Type 16 E7 DNA vaccine candidate (HPV-16 E7SH) induces an E7 wildtype-specific T cell response / Öhlschläger, Peter ; Pes, Michaela ; Osen, Wolfram ; Dürst, Matthias ; Schneider, Achim ; Gissmann, Lutz ; Kaufman
JF  - Vaccine. 24 (2006), H. 15
Y1  - 2006
SN  - 0264-410X
SP  - 2880
EP  - 2893
ER  - 
TY  - JOUR
A1  - Öhlschläger, Peter
A1  - Osen, Wolfram
A1  - Peiler, Tanja
A1  - Caldeira, Sandra
T1  - A DNA vaccine based on a shuffled E7 oncogene of the human papillomavirus type 16 (HPV 16) induces E7-specific cytotoxic T cells but lacks transforming activity / Osen, Wolfram ; Peiler, Tanja ; Öhlschläger, Peter ; Caldeira, Sandra ; Faath, Stefan ; Mich
JF  - Vaccine. 19 (2001), H. 20
Y1  - 2001
SN  - 0264-410X
SP  - 4276
EP  - 4286
ER  - 
TY  - JOUR
A1  - Öhlschläger, Peter
A1  - Osen, Wolfram
A1  - Dell, Kerstin
A1  - Faath, Stefan
T1  - Human papillomavirus type 16 L1 capsomeres induce L1-specific cytotoxic T lymphocytes and tumor regression in C57BL/6 mice / Öhlschläger, Peter ; Osen, Wolfram ; Dell, Kerstin ; Faath, Stefan ; Garcea Robert L: ; Jochmus, Ingrid ; Müller, Martin, Pawlita,
JF  - Journal of Virology. 77 (2003), H. 8
Y1  - 2003
SN  - 1098-5514
SP  - 4635
EP  - 4645
ER  - 
TY  - JOUR
A1  - Öhlschläger, Peter
A1  - Michel, Nico
A1  - Osen, Wolfram
A1  - Freyschmidt, Eva-Jasmin
T1  - T cell response to human papillomavirus 16 E7 in mice: comparison of Cr release assay, intracellular IFN-gamma production, ELISPOT and tetramer staining / Michel, Nico ; Öhlschläger, Peter ; Osen, Wolfram ; Freyschmidt, Eva-Jasmin ; Gutöhrlein, Heidrun ;
JF  - Intervirology. 45 (2002)
Y1  - 2002
SN  - 1423-0100
SP  - 290
EP  - 299
ER  - 
TY  - JOUR
A1  - Öhlschläger, Peter
A1  - Corvinus, Florian M.
A1  - Orth, Carina
A1  - Moriggl, Richard
T1  - Persistent STAT3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth / Corvinus, Florian, Moriggl, Richard ; Tsareva, Svetlana A. ; Wagner, Stefan ; Pfitzner, Edith B. ; Baus, Daniela ; Kaufmann, Roland : Huber, Luka
JF  - Neoplasia. 7 (2005), H. 6
Y1  - 2005
SN  - 1476-5586
SP  - 545
EP  - 555
ER  - 
TY  - JOUR
A1  - Zientz, Evelyn
A1  - Bongaerts, Johannes
A1  - Unden, Gottfried
T1  - Fumarate regulation of gene expression in Escherichia coli by the DcuSR (dcuSR genes) two-component regulatory system
JF  - Journal of bacteriology
Y1  - 1998
SN  - 1098-5530 (E-Journal); 0021-9193 (Print)
VL  - Vol. 180
IS  - No. 20
SP  - 5421
EP  - 5425
ER  - 
TY  - JOUR
A1  - Zhantlessova, Sirina
A1  - Savitskaya, Irina
A1  - Kistaubayeva, Aida
A1  - Ignatova, Ludmila
A1  - Talipova, Aizhan
A1  - Pogrebnjak, Alexander
A1  - Digel, Ilya
T1  - Advanced “Green” prebiotic composite of bacterial cellulose/pullulan based on synthetic biology-powered microbial coculture strategy
JF  - Polymers
N2  - Bacterial cellulose (BC) is a biopolymer produced by different microorganisms, but in biotechnological practice, Komagataeibacter xylinus is used. The micro- and nanofibrillar structure of BC, which forms many different-sized pores, creates prerequisites for the introduction of other polymers into it, including those synthesized by other microorganisms. The study aims to develop a cocultivation system of BC and prebiotic producers to obtain BC-based composite material with prebiotic activity. In this study, pullulan (PUL) was found to stimulate the growth of the probiotic strain Lactobacillus rhamnosus GG better than the other microbial polysaccharides gellan and xanthan. BC/PUL biocomposite with prebiotic properties was obtained by cocultivation of Komagataeibacter xylinus and Aureobasidium pullulans, BC and PUL producers respectively, on molasses medium. The inclusion of PUL in BC is proved gravimetrically by scanning electron microscopy and by Fourier transformed infrared spectroscopy. Cocultivation demonstrated a composite effect on the aggregation and binding of BC fibers, which led to a significant improvement in mechanical properties. The developed approach for “grafting” of prebiotic activity on BC allows preparation of environmentally friendly composites of better quality.
KW  - coculture
KW  - pullulan
KW  - exopolysaccharides
KW  - prebiotic
KW  - bacterial cellulose
Y1  - 2022
U6  - http://dx.doi.org/10.3390/polym14153224
SN  - 2073-4360
N1  - This article belongs to the Special Issue "Cellulose Based Composites"
VL  - 14
IS  - 15
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Zhang, Jin
A1  - Heimbach, Tycho
A1  - Scheer, Nico
A1  - Barve, Avantika
A1  - Li, Wenkui
A1  - Lin, Wen
A1  - He, Handan
T1  - Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4–Humanized Mouse Studies With PBPK Modeling
JF  - Journal of Pharmaceutical Sciences
N2  - NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir.
Y1  - 2016
U6  - http://dx.doi.org/doi.org/10.1016/j.xphs.2016.01.021
SN  - 0022-3549
VL  - Volume 105
IS  - Issue 4
SP  - 1398
EP  - 1404
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - 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  - 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  - 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  - 
TY  - JOUR
A1  - Wardoyo, Arinto Y.P.
A1  - Noor, Johan A.E.
A1  - Elbers, Gereon
A1  - Schmitz, Sandra
A1  - Flaig, Sascha T.
A1  - Budianto, Arif
T1  - Characterizing volcanic ash elements from the 2015 eruptions of bromo and raung volcanoes, Indonesia
JF  - Polish Journal of Environmental Studies
N2  - The volcanic eruptions of Mt. Bromo and Mt. Raung in East Java, Indonesia, in 2015 perturbed volcanic materials and affected surface-layer air quality at surrounding locations. During the episodes, the volcanic ash from the eruptions influenced visibility, traffic accidents, flight schedules, and human health. In this research, the volcanic ash particles were collected and characterized by relying on the detail of physical observation. We performed an assessment of the volcanic ash elements to characterize the volcanic ash using two different methods which are aqua regia extracts followed by MP-AES and XRF laboratory test of bulk samples. The analysis results showed that the volcanic ash was mixed of many materials, such as Al, Si, P, K, Ca, Ti, V, Cr, Mn, Fe, Ni, and others. Fe, Si, Ca, and Al were found as the major elements, while the others were the trace elements Ba, Cr, Cu, Mn, P, Mn, Ni, Zn, Sb, Sr, and V with the minor concentrations. XRF analyses showed that Fe dominated the elements of the volcanic ash. The XRF analysis showed that Fe was at 35.40% in Bromo and 43.00% in Raung of the detected elements in bulk material. The results of aqua regia extracts analyzed by MP-AES were 1.80% and 1.70% of Fe element for Bromo and Raung volcanoes, respectively.
Y1  - 2020
U6  - http://dx.doi.org/10.15244/pjoes/99101
SN  - 2083-5906
VL  - 29
IS  - 2
SP  - 1899
EP  - 1907
PB  - HARD
CY  - Olsztyn
ER  - 
TY  - JOUR
A1  - Wang, Ren-Qi
A1  - Druckenmüller, Katharina
A1  - Elbers, Gereon
A1  - Guenther, Klaus
A1  - Croué, Jean-Philippe
T1  - Analysis of aquatic-phase natural organic matter by optimized LDI-MS method
JF  - Journal of mass spectrometry
N2  - The composition and physiochemical properties of aquatic-phase natural organic matter (NOM) are most important problems for both environmental studies and water industry. Laser desorption/ionization (LDI) mass spectrometry facilitated successful examinations of NOM, as humic and fulvic acids in NOM are readily ionized by the nitrogen laser. In this study, hydrophobic NOMs (HPO NOMs) from river, reservoir and waste water were characterized by this technique. The effect of analytical variables like concentration, solvent composition and laser energy was investigated. The exact masses of small molecular NOM moieties in the range of 200–1200 m/z were determined in reflectron mode. In addition, spectra of post-source-decay experiments in this range showed that some compounds from different natural NOMs had the same fragmental ions. In the large mass range of 1200–15 000 Da, macromolecules and their aggregates were found in HPO NOMs from natural waters. Highly humic HPO exhibited mass peaks larger than 8000 Da. On the other hand, the waste water and reservoir water mainly had relatively smaller molecules of about 2000 Da. The LDI-MS measurements indicated that highly humic river waters were able to form large aggregates and membrane foulants, while the HPO NOMs from waste water and reservoir water were unlikely to form large aggregates. Copyright © 2014 John Wiley & Sons, Ltd.
Y1  - 2014
U6  - http://dx.doi.org/10.1002/jms.3321
SN  - 1096-9888
VL  - 49
IS  - 2
SP  - 154
EP  - 160
PB  - Wiley
CY  - Bognor Regis
ER  - 
TY  - JOUR
A1  - Waller, Mark P.
A1  - Braun, Heiko
A1  - Hojdis, Nils
A1  - Bühl, Michael
T1  - Geometries of Second-Row Transition-Metal Complexes from Density-Functional Theory
JF  - Journal of Chemical Theory and Computation
Y1  - 2007
U6  - http://dx.doi.org/10.1021/ct700178y
SN  - 1549-9626
VL  - 3
IS  - 6
SP  - 2234
EP  - 2242
ER  - 
TY  - JOUR
A1  - Wagner, Torsten
A1  - Molina, Roberto
A1  - Yoshinobu, Tatsuo
A1  - Kloock, Joachim P.
A1  - Biselli, Manfred
A1  - Canzoneri, Michele
A1  - Schnitzler, Thomas
A1  - Schöning, Michael Josef
T1  - Handheld multi-channel LAPS device as a transducer platform for possible biological and chemical multi-sensor applications
JF  - Electrochimica Acta. 53 (2007), H. 2
Y1  - 2007
SN  - 0013-4686
SP  - 305
EP  - 311
ER  - 
TY  - JOUR
A1  - Wagner, Torsten
A1  - Molina, R.
A1  - Biselli, Manfred
A1  - Canzoneri, Michele
A1  - Schnitzler, Thomas
A1  - Yoshinobu, Tatsuo
A1  - Schöning, Michael Josef
T1  - A light-addressable potentiometric sensor system for fast, simultaneous and spatial detection of the metabolic activity of biological cells
JF  - Transducers '07 Eurosensors XXI : digest of technical papers ; the14th International Conference on Solid-State Sensors, Actuators and Microsystems, June 10-14, 2007, Lyon, France / Gilles Delapierre (Ed.)
Y1  - 2007
SN  - 1-4244-0841-5
N1  - Eurosensors 21, 2007, Lyon ; International Conference on Solid-State Sensors, Actuators and Microsystems 14, 2007, Lyon
SP  - 1107
EP  - 1110
PB  - IEEE
CY  - Piscataway
ER  - 
TY  - JOUR
A1  - Wackwitz, B.
A1  - Bongaerts, Johannes
A1  - Goodman, S. D.
A1  - Unden, Gottfried
T1  - Growth phase-dependent regulation of nuoA-N expression in Escherichia coli K-12 by the Fis protein: upstream binding sites and bioenergetic significance
JF  - Molecular and general genetics : MGG
Y1  - 1999
SN  - 1617-4623 (E-Journal); 1617-4615 (Print)
VL  - Vol. 262
IS  - Iss. 4 - 5
SP  - 876
EP  - 883
ER  - 
TY  - JOUR
A1  - Voigt, Birgit
A1  - Schroeter, Rebecca
A1  - Jürgen, Britta
A1  - Albrecht, Dirk
A1  - Evers, Stefan
A1  - Bongaerts, Johannes
A1  - Maurer, Karl-Heinz
A1  - Schweder, Thomas
A1  - Hecker, Michael
T1  - The response of Bacillus licheniformis to heat and ethanol stress and the role of the SigB regulon
JF  - Proteomics
Y1  - 2013
SN  - 1615-9861 (E-Journal); 1615-9853 (Print)
VL  - Vol. 13
IS  - Iss. 14
SP  - 2140
EP  - 2146
PB  - Wiley
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Voigt, Birgit
A1  - Albrecht, Dirk
A1  - Sievers, Susanne
A1  - Becher, Dörte
A1  - Bongaerts, Johannes
A1  - Evers, Stefan
A1  - Schweder, Thomas
A1  - Maurer, Karl-Heinz
A1  - Hecker, Michael
T1  - High-resolution proteome maps of Bacillus licheniformis cells growing in minimal medium
JF  - Proteomics
Y1  - 2015
U6  - http://dx.doi.org/10.1002/pmic.201400504
SN  - 1615-9861
VL  - 15
IS  - 15
SP  - 2629
EP  - 2633
PB  - Wiley
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Unden, Gottfried
A1  - Bongaerts, Johannes
T1  - Alternative respiratory pathways of Escherichia coli: energetics and transcriptional regulation in response to electron acceptors
JF  - Biochimica et biophysica acta (BBA) - Bioenergetics
Y1  - 1997
SN  - 1879-2650 (E-Journal); 0005-2728 (Print)
VL  - Vol. 1320
IS  - Iss. 3
SP  - 217
EP  - 234
ER  - 
TY  - JOUR
A1  - Unden, G.
A1  - Becker, S.
A1  - Bongaerts, Johannes
A1  - Schirawski, J.
A1  - Six, S.
T1  - Oxygen regulated gene expression in facultatively anaerobic bacteria
JF  - Antonie van Leeuwenhoek
Y1  - 1994
SN  - 0003-6072 (Print) ; 1572-9699 (online)
VL  - Vol. 66
IS  - Iss. 1-3
SP  - 3
EP  - 22
ER  - 
TY  - JOUR
A1  - Unden, G.
A1  - Becker, S.
A1  - Bongaerts, Johannes
A1  - Holighaus, G.
A1  - Schirawski, J.
A1  - Six, S.
T1  - O2-sensing and O2-dependent gene regulation in facultatively anaerobic bacteria
JF  - Archives of microbiology
Y1  - 1995
SN  - 1432-072X (E-Journal); 0003-9276 (Print); 0302-8933 (Print)
VL  - Vol. 164
IS  - Iss. 2
SP  - 81
EP  - 90
ER  - 
TY  - JOUR
A1  - Tüg, Helmut
A1  - Baumann, Marcus
T1  - Problems of UV-B radiation measurements in biological research : critical remarks on current techniques and suggestions for improvements
JF  - Geophysical research letters
Y1  - 1994
SN  - 1944-8007 (E-Journal); 0094-8276 (Print)
VL  - Vol. 21
IS  - Iss. 8
SP  - 689
EP  - 692
ER  - 
TY  - JOUR
A1  - Tüg, Helmut
A1  - Baumann, Marcus
T1  - Reply to the comments by R.L. McKenzie and P.V. Johnston on our paper “Problems of UV-B radiation measurements in biological research: Critical Remarks on current techniques and suggestions for improvements”
JF  - Geophysical research letters
Y1  - 1995
SN  - 1944-8007 (E-Journal); 0094-8276 (Print)
VL  - Vol. 22
IS  - Iss. 9
SP  - 1159
EP  - 1160
ER  - 
TY  - JOUR
A1  - Turek, Monika
A1  - Ketterer, Lothar
A1  - Claßen, Melanie
A1  - Berndt, Heinz
A1  - Elbers, Gereon
A1  - Krüger, Peter
A1  - Keusgen, Michael
A1  - Schöning, Michael Josef
T1  - Development and Electrochemical Investigations of an EIS-(Electrolyte-Insulator-Semiconductor) based Biosensor for Cyanide Detection
JF  - Sensors
Y1  - 2007
SN  - 1424-8220
VL  - 7
IS  - 8
SP  - 1415
EP  - 1426
ER  - 
TY  - JOUR
A1  - Trapp, Svenja
A1  - Lammers, Tom
A1  - Engudar, Gokce
A1  - Hoehr, Cornelia
A1  - Denkova, Antonia G.
A1  - Paulßen, Elisabeth
A1  - de Kruijff, Robin M.
T1  - Membrane-based microfluidic solvent extraction of Ga-68 from aqueous Zn solutions: towards an automated cyclotron production loop
JF  - EJNMMI Radiopharmacy and Chemistry
KW  - Microfluidic solvent extraction
KW  - Ga-68
KW  - Cyclotron production
KW  - Medical radionuclide production
KW  - Metal contaminants
Y1  - 2023
U6  - http://dx.doi.org/10.1186/s41181-023-00195-2
SN  - 2365-421X
VL  - 2023
IS  - 8, Article number: 9
SP  - 1
EP  - 14
PB  - Springer Nature
ER  - 
TY  - JOUR
A1  - Tran, Quang Hon
A1  - Bongaerts, Johannes
A1  - Vlad, Dorina
A1  - Unden, Gottfried
T1  - Requirement for the proton-pumping NADH dehydrogenase I of Escherichia coli in respiration of NADH to fumarate and its bioenergetic implications
JF  - European journal of biochemistry
Y1  - 1997
SN  - 0014-2956
VL  - Vol. 244
IS  - Iss. 1
SP  - 155
EP  - 160
ER  - 
TY  - JOUR
A1  - Tippkötter, Nils
A1  - Wollny, Steffen
A1  - Suck, Kirstin
A1  - Sohling, Ulrich
A1  - Ruf, Friedrich
A1  - Ulber, Roland
T1  - 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
JF  - Engineering in Life Sciences
N2  - 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.
Y1  - 2014
U6  - http://dx.doi.org/10.1002/elsc.201300113
SN  - 1618-2863
VL  - 14
IS  - 4
SP  - 425
EP  - 432
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Tippkötter, Nils
A1  - Stückmann, Henning
A1  - Kroll, Stephen
A1  - Winkelmann, Gunda
A1  - Noack, Udo
A1  - Scheper, Thomas
A1  - Ulber, Roland
T1  - A semi-quantitative dipstick assay for microcystin
JF  - Analytical and Bioanalytical Chemistry
N2  - An immunochromatographic lateral flow dipstick assay for the fast detection of microcystin-LR was developed. Colloid gold particles with diameters of 40 nm were used as red-colored antibody labels for the visual detection of the antigen. The new dipstick sensor is capable of detecting down to 5 µg·l−1 (ppb; total inversion of the color signal) or 1 ppb (observation of color grading) of microcystin-LR. The course of the labeling reaction was observed via spectrometric wave shifts caused by the change of particle size during the binding of antibodies. Different stabilizing reagents showed that especially bovine serum albumin (BSA) and casein increase the assays sensitivity and the conjugate stability. Performance of the dipsticks was quantified by pattern processing of capture zone CCD images. Storage stability of dipsticks and conjugate suspensions over 115 days under different conditions were monitored. The ready-to-use dipsticks were successfully tested with microcystin-LR-spiked samples of outdoor drinking- and salt water and applied to the tissue of microcystin-fed mussels.
Y1  - 2009
U6  - http://dx.doi.org/10.1007/s00216-009-2750-8
SN  - 1618-2650
VL  - 394
IS  - 3
SP  - 863
EP  - 869
PB  - springer
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Tippkötter, Nils
A1  - Roth, Jasmine
T1  - Purified Butanol from Lignocellulose – Solvent‐Impregnated Resins for an Integrated Selective Removal
JF  - Chemie Ingenieur Technik
N2  - 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.
KW  - Biofuel
KW  - Biorefinery
KW  - Butanol
KW  - Clostridium acetobutylicum
KW  - Lignocellulose
Y1  - 2020
U6  - http://dx.doi.org/10.1002/cite.202000200
SN  - 1522-2640
VL  - 92
IS  - 11
SP  - 1741
EP  - 1751
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Tippkötter, Nils
A1  - Roikaew, Wipa
A1  - Ulber, Roland
A1  - Hoffmann, Alexander
A1  - Denzler, Hans-Jörg
A1  - Buchholz, Heinrich
T1  - Paracoccus denitrificans for the effluent recycling during continuous denitrification of liquid food
JF  - Biotechnology Progress
N2  - 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.
Y1  - 2010
U6  - http://dx.doi.org/10.1002/btpr.384
SN  - 8756-7938
VL  - 26
IS  - 3
SP  - 756
EP  - 762
PB  - Wiley
CY  - Hoboken, NJ
ER  - 
TY  - JOUR
A1  - Tippkötter, Nils
A1  - Roikaew, W.
A1  - Ulber, R.
T1  - Nitrate removal from whey concentrate with biotechnological regeneration of the waste water
JF  - European dairy magazine : EDM
Y1  - 2008
SN  - 0936-6318
IS  - 1
SP  - 30
EP  - 32
ER  - 
TY  - JOUR
A1  - Tippkötter, Nils
A1  - Duwe, Anna-Maria
A1  - Wiesen, Sebastian
A1  - Sieker, Tim
A1  - Ulber, Roland
T1  - Enzymatic hydrolysis of beech wood lignocellulose at high solid contents and its utilization as substrate for the production of biobutanol and dicarboxylic acids
JF  - Bioresource Technology
N2  - The development of a cost-effective hydrolysis for crude cellulose is an essential part of biorefinery developments. To establish such high solid hydrolysis, a new solid state reactor with static mixing is used. However, concentrations >10% (w/w) cause a rate and yield reduction of enzymatic hydrolysis. By optimizing the synergetic activity of cellulolytic enzymes at solid concentrations of 9%, 17% and 23% (w/w) of crude Organosolv cellulose, glucose concentrations of 57, 113 and 152 g L⁻¹ are reached. However, the glucose yield decreases from 0.81 to 0.72gg⁻¹ at 17% (w/w). Optimal conditions for hydrolysis scale-up under minimal enzyme addition are identified. As result, at 23% (w/w) crude cellulose the glucose yield increases from 0.29 to 0.49gg⁻¹. As proof of its applicability, biobutanol, succinic and itaconic acid are produced with the crude hydrolysate. The potential of the substrate is proven e.g. by a high butanol yield of 0.33gg⁻¹.
Y1  - 2014
U6  - http://dx.doi.org/10.1016/j.biortech.2014.06.052
VL  - 167
SP  - 447
EP  - 455
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Tippkötter, Nils
A1  - Deterding, A.
A1  - Ulber, Roland
T1  - Determination of acetic acid in fermentation broth by gas-diffusion technique
JF  - Engineering in Life Sciences
N2  - 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.
Y1  - 2008
U6  - http://dx.doi.org/10.1002/elsc.200820227
VL  - 8
IS  - 1, Special Issue: Technical Systems for the Use in Life Sciences
SP  - 62
EP  - 67
ER  -