TY - CHAP A1 - Ulrich, Rainer G. A1 - Schlegel, Matthias A1 - Mertens, Marc A1 - Groschup, Martin H. A1 - Schmidt-Chanasit, Jonas A1 - Plenge-Bönig, Anita A1 - Jacob, Jens A1 - Pelz, Hans-Joachim A1 - Freise, Jona A1 - Wenk, Matthias A1 - Thiel, Jörg A1 - Triebenbacher, Cornelia A1 - Schmolz, Eric A1 - Kurth, Andreas A1 - Krüger, Frank A1 - Rühe, Ferdinand A1 - Kiffner, Christian A1 - Ansorge, Hermann A1 - Gerwin, Werner A1 - Wegener, Wolfgang A1 - Müller, Jörg A1 - Bemmann, Margit A1 - Wolf, Ronny A1 - Otto, Lutz-Florian A1 - Oehme, Rainer A1 - Pfeffer, Martin A1 - Heckel, Gerald A1 - Schex, Susanne A1 - Essbauer, Sandra S. T1 - Netzwerk Nagetier-übertragene Pathogene: Monitoring von Hantavirus-Infektionen in Deutschland T2 - Wildhygiene, Wildtierkrankheiten, Parasiten, Epidemiologie Y1 - 2009 SN - 978-378-88131-2-3 SN - 1436-3895 SP - 229 EP - 250 PB - Ges. für Wildtier- und Jagdforschung CY - Halle/Saale ER - TY - GEN A1 - Lange, Carsten A1 - Schneider, Matthias A1 - Mutz, Michael A1 - Haustein, Martin A1 - Halle, Martin A1 - Seidel, Michael T1 - Model-based design for restoration of a small urban river T2 - Journal of Hydro-environment Research KW - urban river Y1 - 2015 U6 - https://doi.org/10.1016/j.jher.2015.04.003 SN - 1570-6443 VL - 9 IS - 2 SP - 226 EP - 236 ER - TY - GEN A1 - Werner, Jens Martin A1 - Zidek, Martin A1 - Kammerer, Sylvia A1 - Platz Batista da Silva, Natascha A1 - Jung, Friedrich A1 - Schlitt, Hans Jürgen A1 - Hornung, Matthias A1 - Jung, Ernst Michael T1 - Intraoperative contrast-enhanced ultrasound can have a crucial role in surgical decision-making during hepato-pancreatico-biliary surgery –Analysis of impact and input T2 - Clinical Hemorheology and Microcirculation N2 - OBJECTIVE: To assess the impact and procedural input of intraoperative ultrasound (IOUS) with contrast-enhanced ultrasound (CEUS) and ultrasound elastography on surgical decision making during the procedure and consequently the out-come after hepato-pancreatico-biliary (HPB) surgery. MATERIALS AND METHODS: Data of 50 consecutive patients, who underwent HPB surgery from 04/2018 to 07/2018 were prospectively collected for this study. During surgery, IOUS with a high-resolution ultrasound device using CEUS after bolus injection of 2.4–5 ml Sulphur hexafluoride microbubbles using a 6–9 MHz probe and a share wave and strain elastography was performed by an experienced examiner. Process and time analysis were carried out using mobile phone timer. RESULTS: The IOUS with CEUS and elastography correctly identified 42 malignant tumors and 4 benign lesions. In 3 cases, the examination provided false positive result (identifying 3 benign lesions as malignant) and in 1 case a malignant lesion was incorrectly assessed as benign (sensitivity 97,7%, specificity 57,1%, PPV 93,3% and NPV 80%). The specific question by the surgeon could be answered successfully in 98% of the cases. In 76% of the cases, there was a modification (42%) or a fundamental change (34%) of the planned surgical approach due to the information provided by the IOUS. Within the last group, the IOUS had a major impact on therapy outcome. In 7 patients an additional tumor resection was required, in 5 patients the tumor was assessed as inoperable, and in total in 5 patients an intraoperative RFA (4/5) or postoperative RITA (1/5) was required. Regarding procedural input, there was only a slight, but significant difference between the transport and set-up times before the intraoperative use (mean: 14 min 22 s) and the return transport (mean 13 min 6 s), (p = 0,038). The average examination time was 14 minutes, which makes only one third of the overall time demand. CONCLUSION: Combination of IOUS with CEUS and elastography in oncological HPB surgery provides valuable information that affects surgical decision-making. The procedural input of about 45 minutes seems to be a good investment considering the improvement of the surgical procedure and a significant modification of the therapy approach in the majority of the cases. KW - Surgical decision-making KW - hepato-pancreatico-biliary surgery KW - CEUS KW - elastography Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch201031 U6 - https://doi.org/10.3233/CH-201031 VL - 78 IS - 1 SP - 1 EP - 14 ER - TY - GEN A1 - Förster, Stefan A1 - Schenk, Sebastian A1 - Zollner, Eva Maria A1 - Krahn, Oliver A1 - Chiang, Cheng-Tien A1 - Schumann, Florian O. A1 - Bayat, Alireza A1 - Schindler, Karl-Michael A1 - Trautmann, Martin A1 - Hammer, René A1 - Meinel, Klaus A1 - Adeagbo, Waheed A. A1 - Hergert, Wolfram A1 - Flege, Jan Ingo A1 - Falta, Jens A1 - Ellguth, Martin A1 - Tusche, Christian A1 - DeBoissieu, Marc A1 - Muntwiler, Matthias A1 - Gerber, Thomas A1 - Widdra, Wolf T1 - Quasicrystals and their Approximants in 2D Ternary Oxides T2 - Physia Status Solidi B N2 - 2D oxide quasicrystals (OQCs) are recently discovered aperiodic, but well-ordered oxide interfaces. In this topical review, an introduction to these new thin-film systems is given. The concept of quasicrystals and their approximants is explained for BaTiO3 and SrTiO3 derived OQCs and related periodic structures in these 2D oxides. In situ microscopy unravels the high-temperature formation process of OQCs on Pt(111). The dodecagonal structure is discussed regarding tiling statistics and tiling decoration based on the results of atomically resolved scanning tunneling microscopy and various diffraction techniques. In addition, angle-resolved ultraviolet photoemission spectroscopy and X-ray photoelectron spectroscopy results prove a metallic character of the 2D oxide. KW - approximants KW - dodecagonal oxide quasicrystals KW - oxide quasicrystals KW - tiling statistics Y1 - 2020 U6 - https://doi.org/10.1002/pssb.201900624 SN - 0370-1972 SN - 1521-3951 VL - 257 IS - 7 ER - TY - GEN A1 - Boetzl, Fabian A1 - Sponsler, Douglas A1 - Albrecht, Matthias A1 - Batáry, Péter A1 - Birkhofer, Klaus A1 - Knapp, Michal A1 - Krauss, Jochen A1 - Maas, Bea A1 - Martin, Emily A. A1 - Sirami, Clélia A1 - Sutter, Louis A1 - Bertrand, Colette A1 - Baillod, Aliette A1 - Bota, Gerard A1 - Bretagnolle, Vincent A1 - Brotons, Lluís A1 - Frank, Thomas A1 - Fusser, Moritz A1 - Giralt, David A1 - González, Ezequiel A1 - Hof, Anouschka A1 - Luka, Henryk A1 - Marrec, Ronan A1 - Nash, Michael A1 - Ng, Katherina A1 - Plantegenest, Manuel A1 - Poulin, Brigitte A1 - Siriwardena, Gavin A1 - Zubair-Anjum, Muhammad A1 - Entling, Martin A1 - Steffan-Dewenter, Ingolf A1 - Schirmel, Jens T1 - Distance functions of carabids in crop fields depend on functional traits, crop type and adjacent habitat: a synthesis T2 - Proceedings Royal Society. Series B, Biological sciences Y1 - 2024 U6 - https://doi.org/10.1098/rspb.2023.2383 SN - 1471-2954 VL - Vol. 291 SP - 1 EP - 10 ER - TY - CHAP A1 - Warnecke, Martin A1 - Krautz, Hans Joachim A1 - Klatt, Matthias A1 - Aha, Ulrich T1 - Instandhaltungsoptimierung mit genetischen Algorithmen Y1 - 2008 ER - TY - GEN A1 - Koziol, Matthias A1 - Alecke, Björn A1 - Gornik, Martin A1 - Joedicke, Wolfgang A1 - Unstied, Gerhard A1 - Walther, Jörg T1 - Städtebaulicher Investitions- und Förderbedarf 2007 bis 2013 in Deutschland T2 - Raumforschung und Raumordnung Y1 - 2008 SN - 0034-011 VL - 66 IS - 3 ER - TY - GEN A1 - Kinne, Matthias A1 - Poraj-Kobielska, Marzena A1 - Ullrich, René A1 - Nousiainen, Paula A1 - Sipilä, Jussi A1 - Scheibner, Katrin A1 - Hammel, Kenneth E. A1 - Hofrichter, Martin T1 - Oxidative cleavage of non-phenolic b-O-4 lignin model dimers by an extracellular aromatic peroxygenase T2 - Holzforschung N2 - The extracellular aromatic peroxygenase of the agaric fungus Agrocybe aegerita catalyzed the H2O2-dependent cleavage of non-phenolic arylglycerol-b-aryl ethers (b-O-4 ethers). For instance 1-(3,4-dimethoxyphenyl)-2-(2-methoxy-phenoxy)pro- pane-1,3-diol, a recalcitrant dimeric lignin model compound that represents the major non-phenolic substructure in lignin, was selectively O-demethylated at the para-methoxy group to give formaldehyde and 1-(4-hydroxy-3-methoxyphenyl)- 2-(2-methoxyphenoxy)propane-1,3-diol. The phenol moiety of the latter compound was then enzymatically oxidized into phenoxy radicals and a quinoid cation, which initiated the autocatalytic cleavage of the dimer and the formation of monomers such as 2-methoxy-1,4-benzoquinone and phenoxyl-substituted propionic acid. The introduction of 18O from H218O2 and H218O at different positions into the products provided information about the routes of ether cleavage. Studies with a 14C-labeled lignin model dimer showed that more than 70% of the intermediates formed were further coupled to form polymers with molecular masses above 10 kDa. The results indicate that fungal aromatic peroxyge- nases may be involved in the bioconversion of methoxylated plant ingredients originating from lignin or other sources. KW - Agrocybe aegerita KW - hydroxylation KW - lignin model compound KW - 0-dealkylation KW - peroxidase KW - peroxygenase Y1 - 2011 U6 - https://doi.org/10.1515/HF.2011.057 SN - 1437-434X VL - 65 IS - 5 SP - 673 EP - 679 ER - TY - GEN A1 - Poraj-Kobielska, Marzena A1 - Kinne, Matthias A1 - Ullrich, René A1 - Scheibner, Katrin A1 - Kayser, Gernot A1 - Hammel, Kenneth E. A1 - Hofrichter, Martin T1 - Preparation of human drug metabolites using fungal peroxygenases T2 - Biochemical Pharmacology N2 - The synthesis of hydroxylated and O- or N-dealkylated human drug metabolites (HDMs) via selective monooxygenation remains a challenging task for synthetic organic chemists. Here we report that aromatic peroxygenases (APOs; EC 1.11.2.1) secreted by the agaric fungi Agrocybe aegerita and Coprinellus radians catalyzed the H₂O₂-dependent selective monooxygenation of diverse drugs, including acetanilide, dextrorphan, ibuprofen, naproxen, phenacetin, sildenafil and tolbutamide. Reactions included the hydroxylation of aromatic rings and aliphatic side chains, as well as O- and N-dealkylations and exhibited different regioselectivities depending on the particular APO used. At best, desired HDMs were obtained in yields greater than 80% and with isomeric purities up to 99%. Oxidations of tolbutamide, acetanilide and carbamazepine in the presence of H₂¹⁸O₂ resulted in almost complete incorporation of ¹⁸O into the corresponding products, thus establishing that these reactions are peroxygenations. The deethylation of phenacetin-d₁ showed an observed intramolecular deuterium isotope effect [(k(H)/k(D))(obs)] of 3.1±0.2, which is consistent with the existence of a cytochrome P450-like intermediate in the reaction cycle of APOs. Our results indicate that fungal peroxygenases may be useful biocatalytic tools to prepare pharmacologically relevant drug metabolites. KW - Peroxidase KW - Peroxygenation KW - Hydroxylation KW - O-Dealkylation KW - N-Dealkylation KW - Cytochrome P450 Y1 - 2011 UR - http://www.sciencedirect.com/science/article/pii/S0006295211004035 U6 - https://doi.org/10.1016/j.bcp.2011.06.020 SN - 1873-2968 VL - 82 IS - 7 SP - 789 EP - 796 ER - TY - GEN A1 - Peng, Lei A1 - Wollenberger, Ulla A1 - Kinne, Matthias A1 - Hofrichter, Martin A1 - Ullrich, René A1 - Scheibner, Katrin A1 - Fischer, Anna A1 - Scheller, Frieder W. T1 - Peroxygenase based sensor for aromatic compounds T2 - Biosensors and Bioelectronics N2 - We report on the redox behaviour of the peroxygenase from Agrocybe aegerita (AaeAPO) which has been electrostatically immobilized in a matrix of chitosan-embedded gold nanoparticles on the surface of a glassy carbon electrode. AaeAPO contains a covalently bound heme-thiolate as the redox active group that exchanges directly electrons with the electrode via the gold nanoparticles. The formal potential E ° ′ of AaeAPO in the gold nanoparticles-chitosan film was estimated to be −(286 ± 9) mV at pH 7.0. The heterogeneous electron transfer rate constant (ks) increases from 3.7 in the scan rate range from 0.2 to 3.0 V s−1 and level off at 63.7 s−1. Furthermore, the peroxide-dependent hydroxylation of aromatic compounds was applied to develop a sensor for naphthalene and nitrophenol. The amperometric measurements of naphthalene are based on the indication of H2O2 consumption. For the chitosan-embedded gold nanoparticle system, the linear range extends from 4 to 40 μM naphthalene with a detection limit of 4.0 μM (S/N = 3) and repeatability of 5.7% for 40 μM naphthalene. KW - Peroxygenase KW - Direct electron transfer KW - Nanoparticles KW - Naphthalene biosensor KW - Bioelectrocatalysis Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?http://www.sciencedirect.com/science/article/pii/S0956566310004501 SN - 1873-4235 VL - 26 IS - 4 SP - 1432 EP - 1436 ER - TY - GEN A1 - Kinne, Matthias A1 - Poraj-Kobielska, Marzena A1 - Aranda, Elisabet A1 - Ullrich, René A1 - Hammel, Kenneth E. A1 - Scheibner, Katrin A1 - Hofrichter, Martin T1 - Regioselective preparation of 5-hydroxypropranolol and 4′-hydroxydiclofenac with a fungal peroxygenase T2 - Bioorganic & Medicinal Chemistry Letters N2 - An extracellular peroxygenase of Agrocybe aegerita catalyzed the H2O2-dependent hydroxylation of the multi-function beta-adrenergic blocker propranolol (1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-ol) and the non-steroidal anti-inflammatory drug diclofenac (2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetic acid) to give the human drug metabolites 5-hydroxypropranolol (5-OHP) and 4′-hydroxydiclofenac (4′-OHD). The reactions proceeded regioselectively with high isomeric purity and gave the desired 5-OHP and 4′-OHD in yields up to 20% and 65%, respectively. 18O-labeling experiments showed that the phenolic hydroxyl groups in 5-OHP and 4′-OHD originated from H2O2, which establishes that the reaction is mechanistically a peroxygenation. Our results raise the possibility that fungal peroxygenases may be useful for versatile, cost-effective, and scalable syntheses of drug metabolites. KW - Peroxidase KW - Peroxygenase KW - Oxygenase KW - Cytochrome P450 KW - Hydroxylation KW - 5-Hydroxypropranolol KW - Propranolol KW - 4′-Hydroxydiclofenac KW - Diclofenac KW - Ascorbic acid Y1 - 2009 UR - http://www.sciencedirect.com/science/article/pii/S0960894X09005071 U6 - https://doi.org/10.1016/j.bmcl.2009.04.015 SN - 1464-3405 VL - 19 IS - 11 SP - 3085 EP - 3087 ER - TY - GEN A1 - Kinne, Matthias A1 - Ullrich, René A1 - Hammel, Kenneth E. A1 - Scheibner, Katrin A1 - Hofrichter, Martin T1 - Regioselective preparation of (R)-2-(4-Hydroxyphenoxy)propionic acid with a fungal peroxygenase T2 - Tetrahedron Letters N2 - The extracellular heme-thiolate peroxygenase of Agrocybe aegerita catalyzed the H2O2-dependent hydroxylation of 2-phenoxypropionic acid (POPA) to give the herbicide precursor 2-(4-hydroxyphenoxy)propionic acid (HPOPA). The reaction proceeded regioselectively with an isomeric purity near 98%, and yielded the desired R-isomer of HPOPA with an enantiomeric excess of 60%. 18O-labeling experiments showed that the phenolic hydroxyl in HPOPA originated from H2O2, which establishes that the reaction is mechanistically a peroxygenation. Our results raise the possibility that fungal peroxygenases may be useful for a variety of organic oxidations. KW - Peroxidase KW - Peroxygenase KW - Oxygenase KW - Cytochrome P450 KW - Hydroxylation KW - 2-(4-Hydroxyphenoxy)propionic acid KW - Ascorbic acid Y1 - 2008 UR - http://www.sciencedirect.com/science/article/pii/S0040403908014421 U6 - https://doi.org/10.1016/j.tetlet.2008.07.152 SN - 1873-3581 VL - 49 IS - 41 SP - 5950 EP - 5953 ER - TY - GEN A1 - Poraj-Kobielska, Marzena A1 - Kinne, Matthias A1 - Ullrich, René A1 - Scheibner, Katrin A1 - Hofrichter, Martin T1 - A spectrophotometric assay for the detection of fungal peroxygenases T2 - Analytical Biochemistry N2 - Rapid and simple spectrophotometric methods are required for the unambiguous detection of recently discovered fungal peroxygenases in vivo and in vitro. This paper describes a peroxygenase-specific assay using 5-nitro-1,3-benzodioxole as substrate. The product, 4-nitrocatechol, produces a yellow color at pH 7, which can be followed over time at 425 nm (ε425 = 9,700 M−1 cm−1), and a red color when adjusted to pH >12, which can be measured in form of an end-point determination at 514 nm (ε514 = 11,400 M−1 cm−1). The assay is suitable for detecting peroxygenase activities in complex growth media and environmental samples as well as for high-throughput screenings. KW - Monooxygenase KW - Peroxidase KW - Heme-thiolate KW - P450 KW - Chloroperoxidase KW - 5-Nitro-1,3-benzodioxole Y1 - 2012 UR - http://www.sciencedirect.com/science/article/pii/S0003269711006610 UR - 1096-0309 U6 - https://doi.org/10.1016/j.ab.2011.10.009 VL - 421 IS - 1 SP - 327 EP - 329 ER - TY - GEN A1 - Jäckle, Sara A1 - Liebhaber, Martin A1 - Niederhausen, Jens A1 - Büchele, Matthias A1 - Duarte, Roberto Felix A1 - Wilks, Regan G. A1 - Bär, Marcus A1 - Lips, Klaus A1 - Christiansen, Silke T1 - Unveiling the Hybrid n-Si/PEDOT:PSS Interface T2 - ACS Applied Materials & Interfaces Y1 - 2016 U6 - https://doi.org/10.1021/acsami.6b01596 SN - 1944-8244 SN - 1944-8252 VL - 8 IS - 13 SP - 8841 EP - 8848 ER - TY - CHAP A1 - Haberl, Matthias A1 - Sanftl, Benedikt A1 - Trautmann, Martin A1 - Weigel, Robert A1 - Kölpin, Alexander T1 - A Direct RF-to-Baseband Quadrature Subsampling Receiver Using a Low Cost ADC T2 - IEEE Radio and Wireless Symposium (RWS 2017), Phoenix, Arizona, USA, 15-18 January 2017 Y1 - 2017 SN - 978-1-5090-3446-8 U6 - https://doi.org/10.1109/RWS.2017.7885970 SP - 144 EP - 146 PB - IEEE CY - Piscataway, NJ ER - TY - GEN A1 - Frank, Martin A1 - Reißland, Torsten A1 - Lurz, Fabian A1 - Völkel, Matthias A1 - Lambrecht, Franziska A1 - Kiefl, Stefan A1 - Ghesquiere, Pol A1 - Ng, Herman Jalli A1 - Kissinger, Dietmar A1 - Weigel, Robert A1 - Kölpin, Alexander T1 - Antenna and Package Design for 61 GHz and 122 GHz Radar Sensors in Embedded Wafer-Level Ball Grid Array Technology T2 - IEEE Transactions on Microwave Theory and Techniques Y1 - 2018 U6 - https://doi.org/10.1109/TMTT.2018.2873368 SN - 0018-9480 SN - 1557-9670 SP - 1 EP - 13 ER - TY - RPRT A1 - Klatt, Matthias A1 - Pfeiffer, Klaus A1 - Bendig, Martin A1 - Platta, Kristian A1 - Matzekat, David T1 - Betrachtungen zur Mindesterzeugung von Braunkohlekraftwerken im Kontext des Netzbetriebs Y1 - 2018 UR - https://mwe.brandenburg.de/media/bb1.a.3814.de/Studie_konventionelle_Mindesterzeugung_Endbericht.pdf PB - Brandenburgische Technische Universität, Fachgebiet Dezentrale Energiesysteme [u.a.] CY - Cottbus ; Senftenberg ER - TY - GEN A1 - Noack, Martin A1 - Kühhorn, Arnold A1 - Kober, Markus A1 - Firl, Matthias T1 - A new stress-based topology optimization approach for finding flexible structures T2 - Structural and Multidisciplinary Optimization N2 - This paper presents a new FE-based stress-related topology optimization approach for finding bending governed flexible designs. Thereby, the knowledge about an output displacement or force as well as the detailed mounting position is not necessary for the application. The newly developed objective function makes use of the varying stress distribution in the cross section of flexible structures. Hence, each element of the design space must be evaluated with respect to its stress state. Therefore, the method prefers elements experiencing a bending or shear load over elements which are mainly subjected to membrane stresses. In order to determine the stress state of the elements, we use the principal stresses at the Gauss points. For demonstrating the feasibility of the new topology optimization approach, three academic examples are presented and discussed. As a result, the developed sensitivity-based algorithm is able to find usable flexible design concepts with a nearly discrete 0 − 1 density distribution for these examples. KW - Topology optimization KW - Flexible structure KW - Stress-based KW - SIMP KW - Conceptual design Y1 - 2021 U6 - https://doi.org/10.1007/s00158-021-02960-w SN - 1615-147X SN - 1615-1488 VL - 64 IS - 4 SP - 1997 EP - 2007 ER - TY - GEN A1 - Kraljevski, Ivan A1 - Duckhorn, Frank A1 - Barth, Martin A1 - Tschöpe, Constanze A1 - Schubert, Frank A1 - Wolff, Matthias T1 - Autoencoder-based Ultrasonic NDT of Adhesive Bonds T2 - IEEE SENSORS 2021, Conference Proceedings, Oct 31- Nov 4, Sydney, Australia N2 - We present an approach for ultrasonic non-destructive testing of adhesive bonding employing unsupervised machine learning with autoencoders.The models are trained exclusively on the features derived from pulse-echo ultrasonic signals on a specimen with good adhesive bonding and tested on another specimen with artificially added defects.The resulting pseudo-probabilities indicating anomalies are visualized and presented along to the C-scan of the same specimen. As a result, we achieved improved representation of the defects, allowing their automatic and reliable detection. Y1 - 2021 SN - 978-1-7281-9501-8 U6 - https://doi.org/10.1109/SENSORS47087.2021.9639864 PB - IEEE ER - TY - GEN A1 - Tolksdorf, Johann Friedrich A1 - Kaiser, Knut A1 - Petr, Libor A1 - Herbig, Christoph A1 - Kočár, Petr A1 - Heinrich, Susann A1 - Wilke, Franziska D.H. A1 - Theuerkauf, Martin A1 - Fülling, Alexander A1 - Schubert, Matthias A1 - Schröder, Frank A1 - Křivánek, Roman A1 - Schulz, Lars A1 - Bonhage, Alexander A1 - Hemker, Christiane T1 - Past human impact in a mountain forest: geoarchaeology of a medieval glass production and charcoal hearth site in the Erzgebirge, Germany T2 - Regional Environmental Change Y1 - 2020 U6 - https://doi.org/10.1007/s10113-020-01638-1 SN - 1436-378X SN - 1436-3798 VL - 20 IS - 3 ER -