TY - JOUR A1 - Wiesen, Sebastian A1 - Tippkötter, Nils A1 - Muffler, Kai A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Nils A1 - Ulber, Roland T1 - Adsorptive Vorbehandlung von Rohglycerin für die 1,3-Propandiol Fermentation mit Clostridium diolis JF - Chemie Ingenieur Technik N2 - Bei der Gewinnung von Fettsäuren aus Pflanzenölen, z. B. zur Herstellung von Biopolymeren, oder bei der Biodiesel- und Seifenproduktion, fällt Glycerin als Nebenprodukt an. Bei der Biokonversion dieses Rohstoffes zu 1,3-Propandiol wird der Produktionsorganismus Clostridium diolis durch Verunreinigungen im Rohglycerin gehemmt. Als inhibierende Substanzen konnten freie Fettsäuren identifiziert werden. Mithilfe eines adsorptiven Aufarbeitungsverfahrens ist es gelungen, die Fettsäuren zu entfernen und die Konversionseffizienz zu 1,3-Propandiol zu erhöhen. Y1 - 2014 U6 - https://doi.org/10.1002/cite.201300080 N1 - Englischer Titel: Adsorptive Pretreatment of Crude Glycerol Prior to Fermentation to 1,3-Propanediole by Clostridium Diolis VL - 86 IS - 1-2 SP - 129 EP - 135 PB - Wiley-VCH CY - Weinheim 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 - https://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 - Pasteur, Aline A1 - Tippkötter, Nils A1 - Kampeis, Percy A1 - Ulber, Roland T1 - Optimization of high gradient magnetic separation filter units for the purification of fermentation products JF - IEEE TRANSACTIONS ON MAGNETICS N2 - 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. Y1 - 2014 U6 - https://doi.org/10.1109/TMAG.2014.2325535 SN - 0018-9464 N1 - Article Sequence Number: 5000607 INSPEC Accession Number: 14663042 VL - 50 IS - 10 SP - Artikel 5000607 PB - IEEE CY - New York, NY ER - TY - JOUR A1 - Thiel, Alexander A1 - Muffler, Kai A1 - Tippkötter, Nils A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Friedrich A1 - Ulber, Roland T1 - Aufarbeitung von Polyphenolen aus Weizen mittels Zeolithen am Beispiel der Ferulasäure JF - Chemie IngenieurTechnik N2 - Aufarbeitung von Polyphenolen aus Weizenmittels Zeolithen am Beispiel der Ferulasa¨ ureAlexander Thiel1, Kai Muffler1, Nils Tippko¨ tter1, Kirstin Suck2, Ulrich Sohling2, Friedrich Ruf3und Roland Ulber1,*DOI: 10.1002/cite.201400031Bei der Ferulasa¨ure handelt es sich um einen Wertstoff, der aus Weizen gewonnen und in der Lebensmittel- und Pharma-industrie eingesetzt werden kann. Der Einsatz von Weizen als nachwachsende Rohstoffquelle ist allerdings nur dann wirt-schaftlich durchfu¨hrbar, wenn eine Prozessintegration in die bestehenden industriellen Verfahren gewa¨hrleistet oder einedirekte Konkurrenz zur Mehl- und Sta¨rkeindustrie vermieden werden kann. In diesem Artikel wird ein Verfahren aufge-zeigt, welches hohe Ausbeuten ermo¨glicht und eine Konkurrenz zu bestehenden Verwertungspfaden vermeidet. Y1 - 2015 U6 - https://doi.org/10.1002/cite.201400031 N1 - Englischer Titel: Downstream Processing of Polyphenols from Wheat by Zeolites using the Example of Ferulic Acid VL - 87 IS - 1-2 SP - 128 EP - 136 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Schumann, Christiane A1 - Rogin, Sabine A1 - Schneider, Horst A1 - Tippkötter, Nils A1 - Oster, Jürgen A1 - Kampeis, Percy T1 - Simultane Atline-Quantifizierung von Magnetpartikeln und Mikroorganismen bei einer HGMS-Filtration JF - Chemie Ingenieur Technik N2 - Es wird eine neue Atline-Messmethode vorgestellt, mit der während einer Hochgradienten-Magnetseparation (HGMS)-Filtration eine simultane Quantifizierung von Magnetpartikeln und Mikroorganismen im Filtrat vorgenommen werden kann. Dabei gelingt die Quantifizierung signifikant besser als mit bisher verwendeten Messmethoden. Mit dieser Methode ist es möglich, die Trennleistung einer HGMS-Filtration zu bestimmen und einen Filterdurchbruch durch Konzentrationsanstiege im Bereich einiger µg L−1 von Magnetpartikeln im Filtrat frühzeitig zu detektieren, ohne dass nennenswerte Partikelmengen verloren gehen. Y1 - 2015 U6 - https://doi.org/10.1002/cite.201300158 N1 - Englischer Titel: Simultaneous Atline Quantification of Magnetic Particles and Microorganisms in the HGMS Filtration VL - 87 IS - 1-2 SP - 137 EP - 149 ER - TY - JOUR A1 - Thiel, Alexander A1 - Muffler, Kai A1 - Tippkötter, Nils A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Hruschka, Steffen M. A1 - Ulber, Roland T1 - A novel integrated downstream processing approach to recover sinapic acid, phytic acid and proteins from rapeseed meal JF - Journal of Chemical Technology and Biotechnology N2 - 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 Y1 - 2015 U6 - https://doi.org/10.1002/jctb.4664 VL - 90 IS - 11 SP - 1999 EP - 2006 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Al-Kaidy, Huschyar A1 - Duwe, Anna A1 - Huster, Manuel A1 - Muffler, Kai A1 - Schlegel, Christin A1 - Tim, Sieker A1 - Stadtmüller, Ralf A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Biotechnology and bioprocess engineering – from the first ullmann's article to recent trends JF - ChemBioEng Reviews N2 - 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. Y1 - 2015 U6 - https://doi.org/10.1002/cben.201500008 VL - 2 IS - 3 SP - 175 EP - 184 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Al-Kaidy, Huschyar A1 - Tippkötter, Nils T1 - Superparamagnetic hydrophobic particles as shell material for digital microfluidic droplets and proof-of-principle reaction assessments with immobilized laccase JF - Engineering in Life Sciences N2 - 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. Y1 - 2016 U6 - https://doi.org/10.1002/elsc.201400124 VL - 16 IS - 3 SP - 222 EP - 230 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Roth, Jasmine A1 - Tippkötter, Nils T1 - Evaluation of lignocellulosic material for butanol production using enzymatic hydrolysate medium JF - Cellulose Chemistry and Technology N2 - 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. Y1 - 2016 VL - 50 IS - 3-4 SP - 405 EP - 410 PB - Editura Academiei Romane CY - Bukarest ER - TY - JOUR A1 - Rösch, C. A1 - Kratz, F. A1 - Hering, T. A1 - Trautmann, S. A1 - Umanskaya, N. A1 - Tippkötter, Nils A1 - Müller-Renno, C.M. A1 - Ulber, Roland A1 - Hannig, M. A1 - Ziegler, C. T1 - Albumin-lysozyme interactions: cooperative adsorption on titanium and enzymatic activity JF - Colloids and Surfaces B: Biointerfaces N2 - 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. Y1 - 2016 U6 - https://doi.org/10.1016/j.colsurfb.2016.09.048 VL - 149 IS - 1 SP - 115 EP - 121 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Horbach, Andreas A1 - Duong, Minh Tuan A1 - Staat, Manfred T1 - Modelling of compressible and orthotropic surgical mesh implants based on optical deformation measurement JF - Journal of the mechanical behavior of biomedical materials Y1 - 2017 U6 - https://doi.org/10.1016/j.jmbbm.2017.06.012 SN - 1751-6161 VL - 74 SP - 400 EP - 410 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Michael, Hackl A1 - Mayer, Katharina A1 - Weber, Mareike A1 - Staat, Manfred A1 - van Riet, Roger A1 - Burkhart, Klau Josef A1 - Müller, Lars Peter A1 - Wegmann, Kilian T1 - Plate osteosynthesis of proximal ulna fractures : a biomechanical micromotion analysis JF - The journal of hand surgery Y1 - 2017 U6 - https://doi.org/10.1016/j.jhsa.2017.05.014 SN - 0363-5023 VL - 42 IS - 10 SP - 834.e1 EP - 834.e7 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Pfaff, Raphael A1 - Enning, Manfred T1 - Güterwagen 4.0 - Der Güterwagen für das Internet der Dinge. Teil 2: Ausgewählte technische Aspekte und Prozesse JF - ETR - Eisenbahntechnische Rundschau Y1 - 2017 SN - 0013-2845 VL - 66 IS - 5 SP - 74 EP - 77 PB - DVV Media Group CY - Hamburg ER - TY - JOUR A1 - Pfaff, Raphael A1 - Schmidt, Bernd T1 - Daten in der Cloud - und dann? JF - Deine Bahn N2 - Schienenverkehrssysteme stehen in zunehmendem Wettbewerb, sowohl untereinander als auch mit anderen Verkehrsträgern. Als wichtiger Aspekt zur Steigerung der Kosteneffizienz wird die Digitalisierung des Betriebs und der Fahrzeuge betrachtet. Über eine Prognose der Ausfallwahrscheinlichkeit bzw. Restlebensdauer von Subsystemen können mittels Digitalisierung die Instandhaltungskosten gesenkt werden. Die geringen Fehlerraten im System Bahn machen die Nutzung besonderer Simulationstechniken notwendig. In diesem Beitrag wird gezeigt, wie sich die Subsystemverfügbarkeit aus den beobachteten Fehlerraten der Teilfunktionen vorhersagen lässt. Y1 - 2016 SN - 0948-7263 IS - 6 SP - 50 EP - 55 PB - Bahn-Fachverlag CY - Berlin ER - TY - JOUR A1 - Schneider, Wilhelm A1 - Schneider, Bettina A1 - Kinder, Stephanie A1 - Meinhardt, Kerstin T1 - Grundbegriffe der Abgabenordnung JF - Das Wirtschaftsstudium : wisu ; Zeitschrift für Ausbildung, Examen, Berufseinstieg und Fortbildung Y1 - 2017 SN - 0340-3084 N1 - Printausgabe in der Bibliothek Eupener Str. unter der Signatur 43 Z 568 VL - 46 IS - 5 SP - 575 EP - 581 PB - Lange CY - Düsseldorf ER - TY - JOUR A1 - Yoshinobu, Tatsuo A1 - Miyamoto, Ko-ichiro A1 - Werner, Frederik A1 - Poghossian, Arshak A1 - Wagner, Torsten A1 - Schöning, Michael Josef T1 - Light-addressable potentiometric sensors for quantitative spatial imaging of chemical species JF - Annual Review of Analytical Chemistry N2 - A light-addressable potentiometric sensor (LAPS) is a semiconductor-based chemical sensor, in which a measurement site on the sensing surface is defined by illumination. This light addressability can be applied to visualize the spatial distribution of pH or the concentration of a specific chemical species, with potential applications in the fields of chemistry, materials science, biology, and medicine. In this review, the features of this chemical imaging sensor technology are compared with those of other technologies. Instrumentation, principles of operation, and various measurement modes of chemical imaging sensor systems are described. The review discusses and summarizes state-of-the-art technologies, especially with regard to the spatial resolution and measurement speed; for example, a high spatial resolution in a submicron range and a readout speed in the range of several tens of thousands of pixels per second have been achieved with the LAPS. The possibility of combining this technology with microfluidic devices and other potential future developments are discussed. Y1 - 2017 U6 - https://doi.org/10.1146/annurev-anchem-061516-045158 SN - 1936-1327 VL - 10 SP - 225 EP - 246 PB - Annual Reviews CY - Palo Alto, Calif. ER - TY - JOUR A1 - Sousa, Marcos A. M. A1 - Siqueira, Jose R. Jr. A1 - Vercik, Andres A1 - Schöning, Michael Josef A1 - Oliveira, Osvaldo N. Jr. T1 - Determining the optimized layer-by-layer film architecture with dendrimer/carbon nanotubes for field-effect sensors JF - IEEE Sensors Journal N2 - The capacitive electrolyte–insulator–semiconductor (EIS) structure is a typical device based on a field-effect sensor platform. With a simple silicon-based structure, EIS have been useful for several sensing applications, especially with incorporation of nanostructured films to modulate the ionic transport and the flat-band potential. In this paper, we report on ion transport and changes in flat-band potential in EIS sensors made with layer-by-layer films containing poly(amidoamine) (PAMAM) dendrimer and single-walled carbon nanotubes (SWNTs) adsorbed on p-Si/SiO 2 /Ta 2 O 5 chips with an Al ohmic contact. The impedance spectra were fitted using an equivalent circuit model, from which we could determine parameters such as the double-layer capacitance. This capacitance decreased with the number of bilayers owing to space charge accumulated at the electrolyte–insulator interface, up to three PAMAM/SWNTs bilayers, after which it stabilized. The charge-transfer resistance was also minimum for three bilayers, thus indicating that this is the ideal architecture for an optimized EIS performance. The understanding of the influence of nanostructures and the fine control of operation parameters pave the way for optimizing the design and performance of new EIS sensors. Y1 - 2017 U6 - https://doi.org/10.1109/JSEN.2017.2653238 SN - 1558-1748 VL - 17 IS - 6 SP - 1735 EP - 1740 PB - IEEE CY - New York ER - TY - JOUR A1 - Gamella, Maria A1 - Zakharchenko, Andrey A1 - Guz, Nataliia A1 - Masi, Madeline A1 - Minko, Sergiy A1 - Kolpashchikov, Dmitry M. A1 - Iken, Heiko A1 - Poghossian, Arshak A1 - Schöning, Michael Josef A1 - Katz, Evgeny T1 - DNA computing system activated by electrochemically triggered DNA realease from a polymer-brush-modified electrode array JF - Electroanalysis N2 - An array of four independently wired indium tin oxide (ITO) electrodes was used for electrochemically stimulated DNA release and activation of DNA-based Identity, AND and XOR logic gates. Single-stranded DNA molecules were loaded on the mixed poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA)/poly(methacrylic acid) (PMAA) brush covalently attached to the ITO electrodes. The DNA deposition was performed at pH 5.0 when the polymer brush is positively charged due to protonation of tertiary amino groups in PDMAEMA, thus resulting in electrostatic attraction of the negatively charged DNA. By applying electrolysis at −1.0 V(vs. Ag/AgCl reference) electrochemical oxygen reduction resulted in the consumption of hydrogen ions and local pH increase near the electrode surface. The process resulted in recharging the polymer brush to the negative state due to dissociation of carboxylic groups of PMAA, thus repulsing the negatively charged DNA and releasing it from the electrode surface. The DNA release was performed in various combinations from different electrodes in the array assembly. The released DNA operated as input signals for activation of the Boolean logic gates. The developed system represents a step forward in DNA computing, combining for the first time DNA chemical processes with electronic input signals. Y1 - 2017 U6 - https://doi.org/10.1002/elan.201600389 SN - 1521-4109 VL - 29 IS - 2 SP - 398 EP - 408 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Bronder, Thomas A1 - Poghossian, Arshak A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Label-free detection of double-stranded DNA molecules with polyelectrolyte-modified capacitive field-effect sensors T1 - Markierungsfreie Detektion doppelsträngiger DNA Moleküle mit Hilfe von Polyelektrolyt-modifizierten kapazitiven Feldeffekt-Sensoren JF - tm - Technisches Messen N2 - In this study, polyelectrolyte-modified field-effect-based electrolyte-insulator-semiconductor (EIS) devices have been used for the label-free electrical detection of double-stranded deoxyribonucleic acid (dsDNA)molecules. The sensor-chip functionalization with a positively charged polyelectrolyte layer provides the possibility of direct adsorptive binding of negatively charged target DNA oligonucleotides onto theSiO2-chip surface.EIS sensors can be utilized as a tool to detect surface-charge changes; the electrostatic adsorption of oligonucleotides onto the polyelectrolyte layer leads to a measureable surface-potential change. Signals of 39mV have been recorded after the incubation with the oligonucleotide solution. Besides the electrochemical experiments, the successful adsorption of dsDNA onto the polyelectrolyte layer has been verified via fluorescence microscopy. The presented results demonstrate that the signal recording of EISchips, which are modified with a polyelectrolyte layer, canbe used as a favorable approach for a fast, cheap and simple detection method for dsDNA. Y1 - 2017 U6 - https://doi.org/10.1515/teme-2017-0015 VL - 84 IS - 10 SP - 628 EP - 634 PB - De Gruyter CY - Oldenbourg ER - TY - JOUR A1 - Arreola, Julio A1 - Oberländer, Jan A1 - Mätzkow, M. A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Surface functionalization for spore-based biosensors with organosilanes JF - Electrochimica Acta N2 - In the present work, surface functionalization of different sensor materials was studied. Organosilanes are well known to serve as coupling agent for biomolecules or cells on inorganic materials. 3-aminopropyltriethoxysilane (APTES) was used to attach microbiological spores time to an interdigitated sensor surface. The functionality and physical properties of APTES were studied on isolated sensor materials, namely silicon dioxide (SiO2) and platinum (Pt) as well as the combined material on sensor level. A predominant immobilization of spores could be demonstrated on SiO2 surfaces. Additionally, the impedance signal of APTES-functionalized biosensor chips has been investigated. Y1 - 2017 U6 - https://doi.org/10.1016/j.electacta.2017.04.157 SN - 0013-4686 VL - 241 SP - 237 EP - 243 PB - Elsevier CY - Amsterdam ER -