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Takenaga, Shoko ; Schneider, Benno ; Erbay, E. ; Biselli, Manfred ; Schnitzler, Thomas ; Schöning, Michael Josef ; Wagner, Torsten
A new microfluidic assembly method for semiconductor-based biosensors using 3D-printing technologies was proposed for a rapid and cost-efficient design of new sensor systems. The microfluidic unit is designed and printed by a 3D-printer in just a few hours and assembled on a light-addressable potentiometric sensor (LAPS) chip using a photo resin. The cell growth curves obtained from culturing cells within microfluidics-based LAPS systems were compared with cell growth curves in cell culture flasks to examine biocompatibility of the 3D-printed chips. Furthermore, an optimal cell culturing within microfluidics-based LAPS chips was achieved by adjusting the fetal calf serum concentrations of the cell culture medium, an important factor for the cell proliferation.
Immel, Timo ; Grützke, Martin ; Späte, Anne-Katrin ; Groth, Ulrich ; Öhlschläger, Peter ; Huhn, Thomas
Chelate stabilization of a titanium(IV)–salan alkoxide by ligand exchange with 2,6-pyridinedicarboxylic acid (dipic) resulted in heptacoordinate complex 3 which is not redox-active, stable on silica gel and has increased aqueous stability. 3 is highly toxic in HeLa S3 and Hep G2 and has enhanced antitumor efficacy in a mouse cervical-cancer model.
Henken, F. E. ; Oosterhuis, K. ; Öhlschläger, Peter ; Bosch, L. ; Hooijberg, E. ; Haanen, J. B. A. G. ; Steenbergen, R. D. M.
Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of ‘gene-shuffled’ (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies.
Wiegand, Sandra ; Voigt, Birgit ; Albrecht, Dirk ; Bongaerts, Johannes ; Evers, Stefan ; Hecker, Michael ; Daniel, Rolf ; Liesegang, Heiko
Efficient FACS selection procedure for cells undergoing Flp-mediated site-specific conversions
(1998)
Transcription-promoting genomic sites in mammalia: their elucidation and architectural principles
(1998)
Bode, Jürgen ; Bartsch, Jörg W. ; Boulikas, Toulikas ; Iber, Michaela ; Mielke, Christian ; Schübeler, Dirk ; Seibler, Jost ; Benham, Craig
Feng, Yong-Qing ; Seibler, Jost ; Alami, Raouf ; Eisen, Andrew ; Westerman, Karen A. ; Leboulch, Philippe ; Fiering, Steven ; Bouhassira, Eric E.
The transgeneticist's toolbox: novel methods for the targeted modification of eukaryotic genomes
(2000)
Bode, Jürgen ; Schlake, Thomas ; Iber, Michaela ; Schübeler, Dirk ; Seibler, Jost ; Snezhkov, Evgeney ; Nikolaev, Lev
Cesari, Francesca ; Rennekampff, Verena ; Vintersten, Kristina ; Vuong, Lam Giang ; Seibler, Jost ; Bode, Jürgen ; Wiebel, Franziska F. ; Nordheim, Alfred
Goetze, Sandra ; Baer, Alexandra ; Winkelmann, Silke ; Nehlsen, Kristina ; Seibler, Jost ; Maass, Karin ; Bode, Jürgen
Seibler, Jost ; Zevnik, Branko ; Küter-Luks, Birgit ; Andreas, Susanne ; Kern, Heidrun ; Hennek, Thomas ; Rode, Anja ; Heimann, Cornelia ; Faust, Nicole ; Kauselmann, Gunther ; Schoor, Michael ; Jaenisch, Rudolf ; Rajewsky, Klaus ; Kühn, Ralf ; Schwenk, Frieder
Seibler, Jost ; Küter-Luks, Birgit ; Kern, Heidrun ; Streu, Sandra ; Plum, Leona ; Maurer, Jan ; Kühn, Ralf ; Brüning, Jens C. ; Schwenk, Frieder
Plum, Leona ; Ma, Xiaosong ; Hampel, Brigitte ; Balthasar, Nina ; Coppari, Roberto ; Münzberg, Heike ; Shanabrough, Marya ; Burdakov, Denis ; Rother, Eva ; Janoschek, Ruth ; Alber, Jens ; Belgardt, Bengt F. ; Koch, Linda ; Seibler, Jost ; Schenk, Frieder ; Fekete, Csaba ; Suzuki, Akira ; Mak, Tak W. ; Krone, Wilhelm ; Horvath, Tamas L. ; Ashcroft, Frances M. ; Brüning, Jens C.
Seibler, Jost ; Kleinridders, Andre ; Küter-Luks, Birgit ; Niehaves, Sandra ; Brüning, Jens C. ; Schwenk, Frieder
Investigation of TRPV1 loss-of-function phenotypes in transgenic shRNA expressing and knockout mice
(2008)
Christoph, Thomas ; Bahrenberg, Gregor ; Vry, Jean de ; Englberger, Werner ; Erdmann, Volker A. ; Frech, Moritz ; Kögel, Babette ; Röhl, Thomas ; Schiene, Klaus ; Schröder, Wolfgang ; Seibler, Jost ; Kurreck, Jens
Koch, Linda ; Wunderlich, F. Thomas ; Seibler, Jost ; Könner, A. Christine ; Hampel, Brigitte ; Irlenbusch, Sigrid ; Brabant, Georg ; Kahn, C. Ronald ; Schwenk, Frieder ; Brüning, Jens C.
Kotnik, Katarina ; Popova, Elena ; Todiras, Mihail ; Mori, Marcelo A. ; Alenina, Natalia ; Seibler, Jost ; Bader, Michael
Glaser, Stefan ; Lubitz, Sandra ; Loveland, Kate L. ; Ohbo, Kazu ; Robb, Lorraine ; Schwenk, Frieder ; Seibler, Jost ; Roellig, Daniela ; Kranz, Andrea ; Anastassiadis, Konstantinos ; Stewart, A. Francis
Jordan, Sabine D. ; Krüger, Markus ; Willmes, Diana M. ; Redemann, Nora ; Wunderlich, F. Thomas ; Brönneke, Hella S. ; Merkwirth, Carsten ; Kashkar, Hamid ; Olkkonen, Vesa M. ; Böttger, Thomas ; Braun, Thomas ; Seibler, Jost ; Brüning, Jens C.
The contribution of altered post-transcriptional gene silencing to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. Here, we demonstrate that expression of microRNA (miR)-143 and 145 is upregulated in the liver of genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. Conversely, mice deficient for the miR-143–145 cluster are protected from the development of obesity-associated insulin resistance. Quantitative-mass-spectrometry-based analysis of hepatic protein expression in miR-143-overexpressing mice revealed miR-143-dependent downregulation of oxysterol-binding-protein-related protein (ORP) 8. Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation. Our experiments provide direct evidence that dysregulated post-transcriptional gene silencing contributes to the development of obesity-induced insulin resistance, and characterize the miR-143–ORP8 pathway as a potential target for the treatment of obesity-associated diabetes.
Hasegawa, Maki ; Kapelyukh, Yury ; Tahara, Harunobu ; Seibler, Jost ; Rode, Anja ; Krueger, Sylvia ; Lee, Dongtao N. ; Wolf, C. Roland ; Scheer, Nico
Raab, Monika ; Kappel, Sven ; Krämer, Andrea ; Sanhaji, Mourad ; Matthess, Yves ; Kurunci-Csacsko, Elisabeth ; Calzada-Wack, Julia ; Rathkolb, Birgit ; Rosman, Jan ; Adler, Thure ; Busch, Dirk H. ; Esposito, Irene ; Fuchs, Helmut ; Gailus-Durner, Valérie ; Klingenspor, Martin ; Wolf, Eckhard ; Sänger, Nicole ; Prinz, Florian ; Hrabe de Angelis, Martin ; Seibler, Jost ; Yuan, Juping ; Bergmann, Martin ; Knecht, Rainald ; Kreft, Bertolt ; Strebhardt, Klaus
Meiotic functions of RAD18
(2011)
Inagaki, Akiko ; Sleddens-Linkels, Esther ; Wassenaar, Evelyne ; Ooms, Marja ; Cappellen, Wiggert A. van ; Hoeijmakers, Jan H. J. ; Seibler, Jost ; Vogt, Thomas F. ; Shin, Myung K. ; Grootegoed, J. Anton ; Baarends, Willy M.
Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b
(2013)
Kornfeld, Jan-Wilhelm ; Baitzel, Catherina ; Könner, A. Christine ; Nicholls, Hayley T. ; Vogt, Merly C. ; Herrmanns, Karolin ; Scheja, Ludger ; Haumaitre, Cécile ; Wolf, Anna M. ; Knippschild, Uwe ; Seibler, Jost ; Cereghini, Silvia ; Heeren, Joerg ; Stoffel, Markus ; Brüning, Jens C.
Gebeshuber, Christoph A. ; Kornauth, Christoph ; Dong, Lihua ; Sierig, Ralph ; Seibler, Jost ; Reiss, Martina ; Tauber, Stefanie ; Bilban, Martin ; Wang, Shijun ; Kain, Renate ; Böhmig, Georg A. ; Moeller, Marcus J. ; Gröne, Hermann-Josef ; Englert, Christoph ; Martinez, Javier ; Kerjaschki, Dontscho
Michalak, Ewa Malgorzata ; Nacerddine, Karim ; Pietersen, Alexandra ; Beuger, Vincent ; Pawlitzky, Inka ; Cornelissen-Steijger, Paulien ; Wientjens, Ellen ; Tanger, Ellen ; Seibler, Jost ; Lohuizen, Maarten van ; Jonkers, Jos
A High-Throughput Functional Complementation Assay for Classification of BRCA1 Missense Variants
(2013)
Bouwman, Peter ; Gulden, Hanneke van der ; Heijden, Ingrid van der ; Drost, Rinske ; Klijn, Christiaan N. ; Prasetyanti, Pramudita ; Pieterse, Mark ; Wientjens, Ellen ; Seibler, Jost ; Hogervorst, Frank B. L. ; Jonkers, Jos
In diesem Artikel werden zunächst einleitend der Gasmarkt Deutschland und der sich daraus ergebende Speicherbedarf skizziert. Folgend wird auf verschiedene Speichernutzen aus betriebswirtschaftlicher Perspektive eingegangen und die in diesem Artikel vorgestellten Bewertungsverfahren einleitend beschrieben. In diesem Artikel werden stochastische Optimierungsmethoden aufgegriffen, die sowohl eine Bewertung der Speicher gegenüber einem Spotpreis, als auch gegenüber einer gesamten Forwardcurve ermöglichen. Hierzu werden zunächst Modelle zur Beschreibung der Marktpreise vorgestellt und anhand empirischer Daten kalibriert. Dann wird eine beispielhafte Speicherscheibe zunächst auf Basis der LeastSquareMonteCarloTechnik gegenüber dem stochastischen mehrfaktoriellen Spotpreismodell bewertet. Hieran schließt sich die Vorstellung der Bewertung sowie des Hedgings gegenüber der Forwardcurve an. Abschließend erfolgt eine vergleichende Gegenüberstellung beider Verfahren.
Konstruktion und Raumform im Kirchenbau der Moderne : Die Längsbinderkirchen von Hans Herkommer
(2015)
Breuer, Lars ; Raue, Markus ; Kirschbaum, M. ; Mang, Thomas ; Schöning, Michael Josef ; Thoelen, R. ; Wagner, Torsten
Poly(N-isopropylacrylamide) (PNIPAAm) hydrogel films with incorporated graphene oxide (GO) were developed and tested as light-stimulated actuators. GO dispersions were synthesized via Hummers method and characterized toward their optical properties and photothermal energy conversion. The hydrogels were prepared by means of photopolymerization. In addition, the influence of GO within the hydrogel network on the lower critical solution temperature (LCST) was investigated by differential scanning calorimetry (DSC). The optical absorbance and the response to illumination were determined as a function of GO concentration for thin hydrogel films. A proof of principle for the stimulation with light was performed.
An enzyme-based multi-parameter biosensor is developed for monitoring the concentration of formate, d-lactate, and l-lactate in biological samples. The sensor is based on the specific dehydrogenation by an oxidized β-nicotinamide adenine dinucleotide (NAD+)-dependent dehydrogenase (formate dehydrogenase, d-lactic dehydrogenase, and l-lactic dehydrogenase, respectively) in combination with a diaphorase from Clostridium kluyveri (EC 1.8.1.4). The enzymes are immobilized on a platinum working electrode by cross-linking with glutaraldehyde (GA). The principle of the determination scheme in case of l-lactate is as follows: l-lactic dehydrogenase (l-LDH) converts l-lactate into pyruvate by reaction with NAD+. In the presence of hexacyanoferrate(III), the resulting reduced β-nicotinamide adenine dinucleotide (NADH) is then regenerated enzymatically by diaphorase. The electrochemical detection is based on the current generated by oxidation of hexacyanoferrate(II) at an applied potential of +0.3 V vs. an Ag/AgCl reference electrode. The biosensor will be electrochemically characterized in terms of linear working range and sensitivity. Additionally, the successful practical application of the sensor is demonstrated in an extract from maize silage.
Dersch, Jürgen ; Geyer, Michael ; Herrmann, Ulf ; Jones, Scott A. ; Kelly, Bruce ; Kistner, Rainer ; Ortmanns, Winfried ; Pitz-Paal, Robert ; Price, Henry
Kearney, David W. ; Kelly, Bruce ; Herrmann, Ulf ; Cable, R. ; Pacheco, J. ; Mahoney, R. ; Price, Henry ; Blake, D. ; Nava, P. ; Potrovitza, N.
Simulating the electromagnetic‐thermal treatment of thin aluminium layers for adhesion improvement
(2015)
A composite layer material used in packaging industry is made from joining layers of different materials using an adhesive. An important processing step in the production of aluminium-containing composites is the surface treatment and consequent coating of adhesive material on the aluminium surface. To increase adhesion strength between aluminium layer and the adhesive material, the foil is heat treated. For efficient heating, induction heating was considered as state-of-the-art treatment process. Due to the complexity of the heating process and the unpredictable nature of the heating source, the control of the process is not yet optimised. In this work, a finite element analysis of the process was established and various process parameters were studied. The process was simplified and modelled in 3D. The numerical model contains an air domain, an aluminium layer and a copper coil fitted with a magnetic field concentrating material. The effect of changing the speed of the aluminium foil (or rolling speed) was studied with the change of the coil current. Statistical analysis was used for generating a general control equation of coil current with changing rolling speed.
Huck, Christina ; Poghossian, Arshak ; Bäcker, Matthias ; Reisert, Steffen ; Kramer, Friederike ; Begoyan, Vardges K. ; Buniatyan, Vahe Vazgen ; Schöning, Michael Josef
High-k perovskite oxide of barium strontium titanate (BST) represents a very attractive multi-functional transducer material for the development of (bio-)chemical sensors. In this work, a Si-based sensor chip containing Pt interdigitated electrodes covered with a thin BST layer (485 nm) has been developed for multi-parameter chemical sensing. The chip has been applied for the contactless measurement of the electrolyte conductivity, the detection of adsorbed charged macromolecules (positively charged polyelectrolytes of polyethylenimine) and the concentration of hydrogen peroxide (H2O2) vapor. The experimental results of functional testing of individual sensors are presented. The mechanism of the BST sensitivity to charged polyelectrolytes and H2O2 vapor has been proposed and discussed.
Oberländer, Jan ; Bromm, Alexander ; Wendeler, Luisa ; Iken, Heiko ; Palomar Duran, Marlena ; Greeff, Anton ; Kirchner, Patrick ; Keusgen, Michael ; Schöning, Michael Josef
Sterilisation processes are compulsory in medicine, pharmacy, and food industries to prevent infections of consumers and microbiological contaminations of products. Monitoring the sterilisation by conventional microbiological methods is time- and lab-consuming. To overcome this problem, in this work a novel biosensor has been proposed. The sensor enables a fast method to evaluate sterilisation processes. By means of thin-film technology the sensor's transducer structures in form of IDEs (interdigitated electrodes) have been fabricated on a silicon substrate. Physical characterisation of the developed sensor was done by AFM, SEM, and profilometry. Impedance analyses were conducted for the electrical characterisation. As microbiological layer spores of B. atrophaeus have been immobilised on the sensing structure; spores of this type are a well-known sterilisation test organism. Impedance measurements at a fixed frequency over time were performed to monitor the immobilisation process. A sterilisation process according to aseptic filling machines was applied to demonstrate the sensor functionality. After both, immobilisation and sterilisation, a change in impedance could successfully be detected.
Simulation model for the transient process behaviour of solar aluminium recycling in a rotary kiln
(2015)
Huber, M. ; Streblow, R. ; Müller, D. ; Lange, S. ; Joneleit, R. ; Sefker, T. ; Rau, Sebastian ; Wollert, Jörg F.
The radio-based wireless data communication has made the realization of new technical solutions possible in many fields of the automation technology (AT). For about ten years, a constant disproportionate growth of wireless technologies can be observed in the automation technology.
However, it shows that especially for the AT, conventional technologies of office automation are unsuitable and/or not manageable. The employment of mobile services in the industrial automation technology has the potential of significant cost and time savings. This leads to an increased productivity in various fields of the AT, for example in the factory and process automation or in production logistics. In this paper technologies and solutions for an automation-suited supply of mobile wireless services will be introduced under the criteria of real time suitability, IT-security and service orientation.
Emphasis will be put on the investigation and development of wireless convergence layers for different radio technologies, on the central provision of support services for an easy-to-use, central, backup enabled management of combined wired / wireless networks and on the study on integrability in a Profinet real-time Ethernet network.
Auswirkungen des Forderungsverzichtes – Steuerliche Belastung und Beeinflussung der Steuerquote
(2009)
Latente Steuern stellen eine Schnittstelle zwischen handelsrechtlicher Rechnungslegung und Steuerrecht dar. Das Verhältnis von Handels- und Steuerrecht ist dabei keinesfalls stetig; vielmehr fordert die Dynamik des deutschen Steuerrechts in vielen Bereichen regelmäßige Anpassungen in der Bilanzierung in Handels- und Steuerbilanz. Dies gilt insbesondere für die Bilanzierung latenter Steuern im handelsrechtlichen Jahresabschluss, welche durch das BilMoG deutlich an Bedeutung gewonnen hat. Neben latenten Steuern auf temporäre Differenzen ist es nunmehr erforderlich, Verlustvorträge und die Folgen der Zinsschranke bei der Berechnung latenter Steuern zu berücksichtigen. Der nachfolgende Beitrag geht auf die Berücksichtigung von Verlust- und Zinsvorträgen und die Berücksichtigungsfähigkeit von EBITDA-Vorträgen bei der Berechnung latenter Steuern ein und beleuchtet dabei insbesondere auch praktische Fragestellungen.
In den letzten drei bis vier Jahren unterlag der Bereich der Bilanzierung und Offenlegung von unsicheren Steuerpositionen im IFRS- und US-GAAP-Abschluss einem stetigen Wandel. Sowohl nach US-GAAP als auch nach IFRS nehmen die Anforderungen an die Bilanzierung und Offenlegung beständig zu. Schon allein dies zeigt die Bedeutung, die dem Themenbereich der Steuerrisiken beigemessen wird. Aber nicht nur im Rahmen der Berichterstattung im Jahresabschluss stehen Steuerrisiken oben auf der Agenda, auch der amerikanische Internal Revenue Service (IRS) verfolgt das Thema sehr konsequent und plant, bestimmte Unternehmen zu Angaben von Steuerrisiken im Rahmen der Steuererklärungen zu verpflichten.
Der Aufsatz befasst sich mit den neueren Entwicklungen im Bereich der Bilanzierung und Offenlegung von unsicheren Steuerpositionen in der Rechnungslegung nach IFRS, US-GAAP und HGB und der Offenlegung von Steuerrisiken im Rahmen der Steuererklärung.