TY - JOUR A1 - Verschitz, Daniel A1 - Butenweg, Christoph T1 - Standsicherheitsnachweis von Behältern für Kleinkläranlagen JF - ACWA aktuell N2 - Die PIA GmbH prüft seit fast 8 Jahren die Standsicherheit von Behältern für Kleinkläranlagen. Diese bestehen in der Regel aus Kunststoff oder Beton und müssen über ihre gesamte Lebensdauer den Beanspruchungen aus Handhabung, Einbau und Betrieb standhalten. Die Standsicherheit kann nach EN 12566 wahlweise durch einen rechnerischen Nachweis oder durch einen praktischen Nachweis wie die Bruchlastprüfung oder die Prüfung in der Grube erfolgen. Y1 - 2014 IS - 12 - 9/2014 SP - 10 PB - RWTH Aachen CY - Aachen ER - TY - JOUR A1 - Haag, S. A1 - Zontar, D. A1 - Schleupen, Josef A1 - Müller, T. A1 - Brecher, C. T1 - Chain of refined perception in self-optimizing assembly of micro-optical systems JF - Journal of sensors and sensor systems N2 - Today, the assembly of laser systems requires a large share of manual operations due to its complexity regarding the optimal alignment of optics. Although the feasibility of automated alignment of laser optics has been shown in research labs, the development effort for the automation of assembly does not meet economic requirements – especially for low-volume laser production. This paper presents a model-based and sensor-integrated assembly execution approach for flexible assembly cells consisting of a macro-positioner covering a large workspace and a compact micromanipulator with camera attached to the positioner. In order to make full use of available models from computer-aided design (CAD) and optical simulation, sensor systems at different levels of accuracy are used for matching perceived information with model data. This approach is named "chain of refined perception", and it allows for automated planning of complex assembly tasks along all major phases of assembly such as collision-free path planning, part feeding, and active and passive alignment. The focus of the paper is put on the in-process image-based metrology and information extraction used for identifying and calibrating local coordinate systems as well as the exploitation of that information for a part feeding process for micro-optics. Results will be presented regarding the processes of automated calibration of the robot camera as well as the local coordinate systems of part feeding area and robot base. Y1 - 2014 U6 - http://dx.doi.org/10.5194/jsss-3-87-2014 SN - 2194-878X VL - 3 IS - 1 SP - 87 EP - 95 PB - Copernicus Publ. CY - Göttingen ER - TY - JOUR A1 - Vos, E. K. A1 - Lagemaat, M. W. A1 - Barentsz, J. O. A1 - Fütterer, J. J. A1 - Zamecnik, P. A1 - Roozen, H. A1 - Orzada, S. A1 - Bitz, Andreas A1 - Maas, M. C. A1 - Scheenen, T. W. J. T1 - Image quality and cancer visibility of T2-weighted Magnetic Resonance Imaging of the prostate at 7 Tesla JF - European Radiology N2 - Objectives To assess the image quality of T2-weighted (T2w) magnetic resonance imaging of the prostate and the visibility of prostate cancer at 7 Tesla (T). Materials & methods Seventeen prostate cancer patients underwent T2w imaging at 7T with only an external transmit/receive array coil. Three radiologists independently scored images for image quality, visibility of anatomical structures, and presence of artefacts. Krippendorff’s alpha and weighted kappa statistics were used to assess inter-observer agreement. Visibility of prostate cancer lesions was assessed by directly linking the T2w images to the confirmed location of prostate cancer on histopathology. Results T2w imaging at 7T was achievable with ‘satisfactory’ (3/5) to ‘good’ (4/5) quality. Visibility of anatomical structures was predominantly scored as ‘satisfactory’ (3/5) and ‘good’ (4/5). If artefacts were present, they were mostly motion artefacts and, to a lesser extent, aliasing artefacts and noise. Krippendorff’s analysis revealed an α = 0.44 between three readers for the overall image quality scores. Clinically significant cancer lesions in both peripheral zone and transition zone were visible at 7T. Conclusion T2w imaging with satisfactory to good quality can be routinely acquired, and cancer lesions were visible in patients with prostate cancer at 7T using only an external transmit/receive body array coil. Y1 - 2014 U6 - http://dx.doi.org/10.1007/s00330-014-3234-6 SN - 1432-1084 VL - 24 IS - 8 SP - 1950 EP - 1958 PB - Springer CY - Cham ER - TY - JOUR A1 - Lagemaat, Miriam W. A1 - Vos, Eline K. A1 - Maas, Marnix C. A1 - Bitz, Andreas A1 - Orzada, Stephan A1 - Uden, Mark J. van A1 - Kobus, Thiele A1 - Heerschap, Arend A1 - Scheenen, Tom W. J. T1 - Phosphorus magnetic resonance spectroscopic imaging at 7 T in patients with prostate cancer JF - Investigative Radiology N2 - Objectives The aim of this study was to identify characteristics of phosphorus (³¹P) spectra of the human prostate and to investigate changes of individual phospholipid metabolites in prostate cancer through in vivo ³¹P magnetic resonance spectroscopic imaging (MRSI) at 7 T. Materials and Methods In this institutional review board–approved study, 15 patients with biopsy-proven prostate cancer underwent T₂-weighted magnetic resonance imaging and 3-dimensional ³¹P MRSI at 7 T. Voxels were selected at the tumor location, in normal-appearing peripheral zone tissue, normal-appearing transition zone tissue, and in the base of the prostate close to the seminal vesicles. Phosphorus metabolite ratios were determined and compared between tissue types. Results Signals of phosphoethanolamine (PE) and phosphocholine (PC) were present and well resolved in most ³¹P spectra in the prostate. Glycerophosphocholine signals were observable in 43% of the voxels in malignant tissue, but in only 10% of the voxels in normal-appearing tissue away from the seminal vesicles. In many spectra, independent of tissue type, 2 peaks resonated in the chemical shift range of inorganic phosphate, possibly representing 2 separate pH compartments. The PC/PE ratio in the seminal vesicles was highly elevated compared with the prostate in 5 patients. A considerable overlap of ³¹P metabolite ratios was found between prostate cancer and normal-appearing prostate tissue, preventing direct discrimination of these tissues. The only 2 patients with high Gleason scores tumors (≥4+5) presented with high PC and glycerophosphocholine levels in their cancer lesions. Conclusions Phosphorus MRSI at 7 T shows distinct features of phospholipid metabolites in the prostate gland and its surrounding structures. In this exploratory study, no differences in ³¹P metabolite ratios were observed between prostate cancer and normal-appearing prostate tissue possibly because of the partial volume effects of small tumor foci in large MRSI voxels. Y1 - 2014 U6 - http://dx.doi.org/10.1097/RLI.0000000000000012 SN - 1536-0210 VL - 49 IS - 5 SP - 363 EP - 372 PB - Lippincott Williams & Wilkins CY - Philadelphia, Pa. ER - TY - JOUR A1 - Pyschny, D. A1 - Döring, Bernd A1 - Feldmann, M. T1 - Ermittlung der thermischen Leistungsfähigkeit des neuartigen multifunktionalen Verbunddeckensystems InaDeck JF - Bauingenieur : die richtungsweisende Zeitschrift im Bauingenieurswesen Y1 - 2014 SN - 0005-6650 N1 - Printausgabe in der Bibliothek Bayernallee vorhanden: 13 Z 049-2014 VL - 89 IS - 3 SP - 116 EP - 124 PB - VDI Fachmedien CY - Düsseldorf ER - TY - JOUR A1 - Maas, Marnix C. A1 - Vos, Eline K. A1 - Lagemaat, Miriam W. A1 - Bitz, Andreas A1 - Orzada, Stephan A1 - Kobus, Thiele A1 - Kraff, Oliver A1 - Maderwald, Stefan A1 - Ladd, Mark E. A1 - Scheenen, Tom W. J. T1 - Feasibility of T₂-weighted turbo spin echo imaging of the human prostate at 7 tesla JF - Magnetic Resonance in Medicine N2 - Purpose To demonstrate that high quality T₂-weighted (T2w) turbo spin-echo (TSE) imaging of the complete prostate can be achieved routinely and within safety limits at 7 T, using an external transceive body array coil only. Methods Nine healthy volunteers and 12 prostate cancer patients were scanned on a 7 T whole-body system. Preparation consisted of B₀ and radiofrequency shimming and localized flip angle calibration. T₁ and T₂ relaxation times were measured and used to define the T2w-TSE protocol. T2w imaging was performed using a TSE sequence (pulse repetition time/echo time 3000–3640/71 ms) with prolonged excitation and refocusing pulses to reduce specific absorption rate. Results High quality T2w TSE imaging was performed in less than 2 min in all subjects. Tumors of patients with gold-standard tumor localization (MR-guided biopsy or prostatectomy) were well visualized on 7 T imaging (n = 3). The number of consecutive slices achievable within a 10-g averaged specific absorption rate limit of 10 W/kg was ≥28 in all subjects, sufficient for full prostate coverage with 3-mm slices in at least one direction. Conclusion High quality T2w TSE prostate imaging can be performed routinely and within specific absorption rate limits at 7 T with an external transceive body array. Y1 - 2014 U6 - http://dx.doi.org/10.1002/mrm.24818 SN - 1522-2594 VL - 71 IS - 5 SP - 1711 EP - 1719 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 - http://dx.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 - 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 - Al-Kaidy, Huschyar A1 - Duwe, Anna A1 - Huster, Manuel A1 - Muffler, Kai A1 - Schlegel, Christin A1 - Sieker, Tim A1 - Stadtmüller, Ralf A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Biotechnologie und Bioverfahrenstechnik – Vom ersten Ullmanns Artikel bis hin zu aktuellen Forschungsthemen JF - Chemie Ingenieur Technik N2 - Biotechnologie und die mit ihr verbundenen technischen Prozesse prägen seit Jahrtausenden die Entwicklung der Menschheit. Ausgehend von empirischen Verfahren, insbesondere zur Herstellung von Lebensmitteln und täglichen Gebrauchsgütern, haben sich diese Disziplinen zu einem der innovativsten Zukunftsfelder entwickelt. Durch das immer detailliertere Verständnis zellulärer Vorgänge können mittlerweile Produktionsstämme gezielt optimiert werden. Im Zusammenspiel mit moderner Prozesstechnik können so eine Vielzahl von Bulk- und Feinchemikalien sowie Pharmazeutika effizient hergestellt werden. In diesem Artikel werden exemplarisch einige der aktuellen Trends vorgestellt. Y1 - 2014 U6 - http://dx.doi.org/10.1002/cite.201400083 SN - 0009-286X VL - 86 IS - 12 SP - 2215 EP - 2225 PB - Wiley-VCH CY - Weinheim ER - 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 - http://dx.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 - 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 - Jörissen, Jörg A1 - Heger, Michael T1 - Zur Wirkung hochschuldidaktisch fundierter und in den Fachbereichen verankerter Lehrveranstaltungsevaluation JF - Qualität in der Wissenschaft (QiW) Y1 - 2014 SN - 1860-3041 VL - 8 IS - 2+3 SP - 70 EP - 80 PB - Universitätsverlag Webler CY - Bielefeld ER - TY - JOUR A1 - Hoehr, Cornelia A1 - Paulßen, Elisabeth A1 - Benard, Francois A1 - Lee, Chris Jaeil A1 - Hou, Xinchi A1 - Badesso, Brian A1 - Ferguson, Simon A1 - Miao, Qing A1 - Yang, Hua A1 - Buckley, Ken A1 - Hanemaayer, Victoire A1 - Zeisler, Stefan A1 - Ruth, Thomas A1 - Celler, Anna A1 - Schaffer, Paul T1 - ⁴⁴ᶢSc production using a water target on a 13 MeV cyclotron JF - Nuclear medicine and biology N2 - Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in development of less common isotopes. Herein, we describe the production of ⁴⁴Sc (t₁⸝₂ = 3.97 h, Eavg,β⁺ = 1.47 MeV, branching ratio = 94.27%) in a solution target and an automated loading system which allows a quick turn-around between different radiometallic isotopes and therefore greatly improves their availability for tracer development. Experimental yields are compared to theoretical calculations. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.nucmedbio.2013.12.016 SN - 1872-9614 VL - 41 IS - 5 SP - 401 EP - 406 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Wilke, Thomas T1 - Gebaute Geschichte in Turin JF - Kunsttexte.de N2 - Städte sind Stein gewordene Geschichte. Ihre realisierte Form ermöglicht Geschichte zu erleben und die Stadtentwicklung nachzuvollziehen. Besonders in Turin ist ablesbar, wie das Haus Savoyen den Ausbau der neuen Hauptstadt zu einer der führenden Barockmetropolen Europas beeinflusste. Y1 - 2014 U6 - http://dx.doi.org/10.18452/7197 SN - 1618-8101 VL - 2014 IS - 1 PB - Humboldt-Universität zu Berlin CY - Berlin ER - TY - JOUR A1 - Lehnertz, Klaus A1 - Ansmann, Gerrit A1 - Bialonski, Stephan A1 - Dickten, Henning A1 - Geier, Christian A1 - Porz, Stephan T1 - Evolving networks in the human epileptic brain JF - Physica D: Nonlinear Phenomena N2 - Network theory provides novel concepts that promise an improved characterization of interacting dynamical systems. Within this framework, evolving networks can be considered as being composed of nodes, representing systems, and of time-varying edges, representing interactions between these systems. This approach is highly attractive to further our understanding of the physiological and pathophysiological dynamics in human brain networks. Indeed, there is growing evidence that the epileptic process can be regarded as a large-scale network phenomenon. We here review methodologies for inferring networks from empirical time series and for a characterization of these evolving networks. We summarize recent findings derived from studies that investigate human epileptic brain networks evolving on timescales ranging from few seconds to weeks. We point to possible pitfalls and open issues, and discuss future perspectives. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.physd.2013.06.009 SN - 0167-2789 VL - 267 SP - 7 EP - 15 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Olbertz, Klaus T1 - Die arbeitsrechtliche Stellung des Prokuristen - Handelsrechtlicher Kompetenzzuwachs mit arbeitsrechtlichen Konsequenzen JF - NWB - Steuer- und Wirtschaftsrecht N2 - Die Beschäftigung von Prokuristen ist gängige betriebliche Praxis. Unternehmen stehen dabei immer wieder vor der Frage, ob und welche Arbeitnehmer sie zu Prokuristen bestellen sollen. Nicht selten bleiben hierbei die arbeitsrechtlichen Konsequenzen, die mit der Bestellung eines Arbeitnehmers zum Prokuristen einhergehen können, unberücksichtigt, wie diverse Gerichtsentscheidungen zeigen. Dieser Beitrag soll einen Überblick über die arbeitsrechtlichen Folgen bei der Beschäftigung von Prokuristen geben und der betrieblichen Praxis somit gleichzeitig als Entscheidungshilfe dienen, wenn es um das Ob und Wie der möglichen Bestellung eines Arbeitnehmers zum Prokuristen geht. Y1 - 2018 SN - 1860-9449 IS - 21 SP - 1591 EP - 1596 PB - NWB-Verlag CY - Herne ER - TY - JOUR A1 - Olbertz, Klaus T1 - Der neue gesetzliche Mindestlohn – was gilt und was Unternehmen künftig beachten müssen JF - Gesellschafts- und Wirtschaftsrecht : GWR N2 - Ab dem 1.1.2015 ist es soweit: Deutschland erhält einen flächendeckenden und weitgehend branchenunabhängigen gesetzlichen Mindestlohn. Danach haben grundsätzlich alle abhängig beschäftigten Arbeitnehmer einen Anspruch auf eine Entlohnung von wenigstens 8,50 EUR brutto je Arbeitsstunde. Die Auswirkungen dürften enorm sein. Das Bundesministerium für Arbeit und Soziales geht jedenfalls davon aus, dass aufgrund der Einführung des gesetzlichen Mindestlohns mehrere Millionen Beschäftigte einen höheren Lohn beanspruchen können. Der nachfolgende Beitrag gibt einen Überblick über die wesentlichen Inhalte des gesetzlichen Mindestlohns und Hinweise für Anwendungsprobleme in der betrieblichen Praxis. Y1 - 2018 SN - 1868-1816 SP - 521 EP - 524 ER - TY - JOUR A1 - Olbertz, Klaus T1 - Gestaltung des Anstellungsvertrags - Der Compliance-Beauftragte JF - Arbeit und Arbeitsrecht : AuA N2 - Ein Compliance-Beauftragter soll dafür Sorge tragen, dass aus dem Unternehmen heraus keine Rechtsverletzungen begangen werden. Aber welche rechtlichen Notwendigkeiten und Möglichkeiten resultieren daraus für die Gestaltung des Anstellungsvertrags? Y1 - 2014 SN - 0323-4568 IS - 7 SP - 400 EP - 403 PB - Huss Medien CY - Berlin ER - TY - JOUR A1 - Tran, Duc Hung T1 - Multiple corporate governance attributes and the cost of capital – Evidence from Germany JF - The British Accounting Review N2 - This paper investigates the extent to which corporate governance affects the cost of debt and equity capital of German exchange-listed companies. I examine corporate governance along three dimensions: financial information quality, ownership structure and board structure. The results suggest that firms with high levels of financial transparency and bonus compensations face lower cost of equity. In addition, block ownership is negatively related to firms' cost of equity when the blockholders are other firms, managers or founding-family members. Consistent with the conjecture that agency costs increase with firm size, I find significant cost of debt effects only in the largest German companies. Here, the creditors demand lower cost of debt from firms with block ownerships held by corporations or banks. My findings demonstrate that a uniform set of governance attributes is unlikely to satisfy suppliers of debt and equity capital equally. Y1 - 2018 U6 - http://dx.doi.org/https://doi.org/10.1016/j.bar.2014.02.003 SN - 0890-8389 VL - 46 IS - 2 SP - 179 EP - 197 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Luisier, Raphaëlle A1 - Lempiäinen, Harri A1 - Scherbichler, Nina A1 - Braeuning, Albert A1 - Geissler, Miriam A1 - Dubost, Valerie A1 - Müller, Arne A1 - Scheer, Nico A1 - Chibout, Salah-Dine A1 - Hara, Hisanori A1 - Picard, Frank A1 - Theil, Diethilde A1 - Couttet, Philippe A1 - Vitobello, Antonio A1 - Grenet, Olivier A1 - Grasl-Kraupp, Bettina A1 - Ellinger-Ziegelbauer, Heidrung A1 - Thomson, John P. A1 - Meehan, Richard R. A1 - Elcombe, Clifford R. A1 - Henderson, Colin J. A1 - Wolf, C. Roland A1 - Schwarz, Michael A1 - Moulin, Pierre A1 - Terranova, Remi A1 - Moggs, Jonathan G. T1 - Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors JF - Toxicological Sciences N2 - The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB. Y1 - 2014 U6 - http://dx.doi.org/https://doi.org/10.1093/toxsci/kfu038 SN - 1094-2025 VL - 139 IS - 2 SP - 501 EP - 511 PB - Oxford University Press CY - Oxford ER -