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151. Atrial-like engineered heart tissue: an in vitro model of the human atrium

Author

Lemme, Marta, Ulmer, Bärbel M., Lemoine, Marc D., Zech, Antonia T.L., Flenner, Frederik, Ravens, Ursula, Reichenspurner, Hermann, Rol-Garcia, Miriam, Smith, Godfrey, Hansen, Arne, Christ, Torsten, and Eschenhagen, Thomas

Subjects
cardiovascular system, cardiovascular diseases
Abstract

Cardiomyocytes (CMs) generated from human induced pluripotent stem cells (hiPSCs) are under investigation for their suitability as human models in preclinical drug development. Antiarrhythmic drug development focuses on atrial biology for the treatment of atrial fibrillation. Here we used recent retinoic acid-based protocols to generate atrial CMs from hiPSCs and establish right atrial engineered heart tissue (RA-EHT) as a 3D model of human atrium. EHT from standard protocol-derived hiPSC-CMs (Ctrl-EHT) and intact human muscle strips served as comparators. RA-EHT exhibited higher mRNA and protein concentrations of atrial-selective markers, faster contraction kinetics, lower force generation, shorter action potential duration, and higher repolarization fraction than Ctrl-EHTs. In addition, RA-EHTs but not Ctrl-EHTs responded to pharmacological manipulation of atrial-selective potassium currents. RA- and Ctrl-EHTs’ behavior reflected differences between human atrial and ventricular muscle preparations. Taken together, RA-EHT is a model of human atrium that may be useful in preclinical drug screening.

Published
2018

161. Additional file 1: of Clonal dynamics studied in cultured induced pluripotent stem cells reveal major growth imbalances within a few weeks

Author

Brenière-Letuffe, David, Domke-Shibamiya, Aya, Hansen, Arne, Eschenhagen, Thomas, Fehse, Boris, Riecken, Kristoffer, and Stenzig, Justus

Abstract

Figure S1. Karyotyping. One clone from BJ cell line and two clones from C25-old cells sorted by flow cytometry, cultured for a few passages and karyotype analysed. Karyotyping indicated no chromosomal anomalies in the three sub-clones. Figure S2. Flow cytometry and fluorescence microscopy of RGB-marked cell line 293 T at different time points. Full data for cell line 293 T from Fig. 3. Left to right in each panel: green plotted against blue channel, green against red and blue against red. MOI 4 used to transduce 293 T cells. (A) Clonal dynamics in T75-flask. (B–D) Clonal dynamics in one individual well of a six-well cell culture plate over 25 weeks. (E) Stacked area plots displaying time course of proportion of each possible combination of colours (no colour, red only, green only, blue only, red and green, red and blue, blue and green, all three colours) to sum of all cells. Note similar dent in all plots at week 23 (right panel), probably due to technical reasons. Left panel shows plots with interpolated count at week 23. (F) Fluorescence microscopic images of four cultures in (A)–(D) at week 25. Images taken 3 days after replating. Figure S3. Flow cytometry and fluorescence microscopy of RGB-marked cell line K562 at different time points. Full data for cell line K562 from Fig. 3. Left to right in each panel: green plotted against blue channel, green against red and blue against red. MOI 16 used to transduce K562 cells. (A) Clonal dynamics in T75-flask. (B–D) Clonal dynamics in one individual well of a six-well cell culture plate over 25 weeks. (E) Stacked area plots displaying time course of proportion of each possible combination of colours (no colour, red only, green only, blue only, red and green, red and blue, blue and green, all three colours) to sum of all cells. Note similar dent in all plots at week 23 (right panel), probably due to technical reasons. Left panel shows plot with interpolated count at week 23. (F) Fluorescence microscopic images of the four cultures shown in (A)–(D) at week 25. Images taken 3 days after replating. Figure S4. Flow cytometry and fluorescence microscopic images of RGB-marked primary human dermal fibroblast cultures at different time points. Full data set for primary fibroblasts from Fig. 4. Left to right in each panel: green plotted against blue channel, green against red and blue against red. MOI 1, 2, 3 and 10 used for transduction and four cultures kept separately afterwards. (A) Clonal dynamics analysed by flow cytometry only (p2). (B) Clonal dynamics analysed by flow cytometry and imaged by fluorescence microscopy (further passages). Insets display higher magnification (PDF 24080 kb)

Published
2018
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162. Wie viel kosten uns die arbeitsfreien Feiertage? – Zur Einführung eines weiteren Feiertages in den nördlichen Bundesländern

Author

Hansen, Arne and Meyer, Dirk

Subjects
Arbeitszeit, J21, Bruttoinlandsprodukt, Feiertag, ddc:330, Lohnfortzahlung, J20
Abstract

Aktuell wird in Niedersachsen, Bremen, Hamburg und Schleswig-Holstein anlässlich des bundesweit einmalig freien Reformationstages 2017 über die Einführung eines weiteren gesetzlichen Feiertages diskutiert. Arne Hansen und Dirk Meyer, Helmut-Schmidt-Universität, Universität der Bundeswehr, Hamburg, untersuchen die möglichen Auswirkungen eines weiteren arbeitsfreien Tages auf das Bruttoinlandsprodukt. Sie kommen zu dem Ergebnis, dass die Auswirkungen je nach Wirtschaftssektor und kalendarischer Lage eines Feiertages sehr unterschiedlich ausfallen können. Im Regelfall ist ein Produktionsrückgang sowie ein Kosteneffekt spürbar: Der bezahlte Feiertag und Feiertagszuschläge erhöhen die Lohnkosten. Soweit dieses nicht durch Produktivitätssteigerungen kompensiert werden kann, entsteht ein negativer Beschäftigungseffekt, tendenziell steigen die Güterpreise und die Gewinne sinken.

Published
2018

164. Chronic intermittent tachypacing by an optogenetic approach induces arrhythmia vulnerability in human engineered heart tissue

Author

Lemme, Marta, primary, Braren, Ingke, primary, Prondzynski, Maksymilian, primary, Aksehirlioglu, Bülent, primary, Ulmer, Bärbel M, primary, Schulze, Mirja L, primary, Ismaili, Djemail, primary, Meyer, Christian, primary, Hansen, Arne, primary, Christ, Torsten, primary, Lemoine, Marc D, primary, and Eschenhagen, Thomas, primary

Published
2019
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168. Correction: Analysis of Tyrosine Kinase Inhibitor-Mediated Decline in Contractile Force in Rat Engineered Heart Tissue

Author

Jacob, Fabian, primary, Yonis, Amina Y., additional, Cuello, Friederike, additional, Luther, Pradeep, additional, Schulze, Thomas, additional, Eder, Alexandra, additional, Streichert, Thomas, additional, Mannhardt, Ingra, additional, Hirt, Marc N., additional, Schaaf, Sebastian, additional, Stenzig, Justus, additional, Force, Thomas, additional, Eschenhagen, Thomas, additional, and Hansen, Arne, additional

Published
2018
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169. Isogenic Pairs of hiPSC-CMs with Hypertrophic Cardiomyopathy/LVNC-Associated ACTC1 E99K Mutation Unveil Differential Functional Deficits

Author

Smith, James G.W., primary, Owen, Thomas, additional, Bhagwan, Jamie R., additional, Mosqueira, Diogo, additional, Scott, Elizabeth, additional, Mannhardt, Ingra, additional, Patel, Asha, additional, Barriales-Villa, Roberto, additional, Monserrat, Lorenzo, additional, Hansen, Arne, additional, Eschenhagen, Thomas, additional, Harding, Sian E., additional, Marston, Steve, additional, and Denning, Chris, additional

Published
2018
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175. Musclemotion: A versatile open software tool to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo

Author

Medische Fysiologie, Circulatory Health, Sala, Luca, Van Meer, Berend J., Tertoolen, Leon G.J., Bakkers, Jeroen, Bellin, Milena, Davis, Richard P., Denning, Chris, Dieben, Michel A.E., Eschenhagen, Thomas, Giacomelli, Elisa, Grandela, Catarina, Hansen, Arne, Holman, Eduard R., Jongbloed, Monique R.M., Kamel, Sarah M., Koopman, Charlotte D., Lachaud, Quentin, Mannhardt, Ingra, Mol, Mervyn P.H., Mosqueira, Diogo, Orlova, Valeria V., Passier, Robert, Ribeiro, Marcelo C., Saleem, Umber, Smith, Godfrey L., Burton, Francis L., Mummery, Christine L., Medische Fysiologie, Circulatory Health, Sala, Luca, Van Meer, Berend J., Tertoolen, Leon G.J., Bakkers, Jeroen, Bellin, Milena, Davis, Richard P., Denning, Chris, Dieben, Michel A.E., Eschenhagen, Thomas, Giacomelli, Elisa, Grandela, Catarina, Hansen, Arne, Holman, Eduard R., Jongbloed, Monique R.M., Kamel, Sarah M., Koopman, Charlotte D., Lachaud, Quentin, Mannhardt, Ingra, Mol, Mervyn P.H., Mosqueira, Diogo, Orlova, Valeria V., Passier, Robert, Ribeiro, Marcelo C., Saleem, Umber, Smith, Godfrey L., Burton, Francis L., and Mummery, Christine L.

Published
2018

176. Versatile open software to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo

Author

Sala, Luca, Van Meer, Berend J., Tertoolen, Leon G.J., Bakkers, Jeroen, Bellin, Milena, Davis, Richard P., Denning, Chris, Dieben, Michel A.E., Eschenhagen, Thomas, Giacomelli, Elisa, Grandela, Catarina, Hansen, Arne, Holman, Eduard R., Jongbloed, Monique R.M., Kamel, Sarah M., Koopman, Charlotte D., Lachaud, Quentin, Mannhardt, Ingra, Mol, Mervyn P.H., Orlova, Valeria V., Passier, Robert, Ribeiro, Marcelo C., Saleem, Umber, Smith, Godfrey L., Mummery, Christine L, Burton, Francis L., and Applied Stem Cell Technology

Abstract

Contraction of muscle reflects its physiological state. Methods to quantify contraction are often complex, expensive and tailored to specific models or recording conditions, or require specialist knowledge for data extraction. Here we describe an automated, open-source software tool (MUSCLEMOTION) adaptable for use with standard laboratory and clinical imaging equipment that enables quantitative analysis of normal cardiac contraction, disease phenotypes and pharmacological responses. MUSCLEMOTION allowed rapid and easy measurement of contractility in (i) single cardiomyocytes from primary adult heart and human pluripotent stem cells, (ii) multicellular 2D-cardiomyocyte cultures, 3D engineered heart tissues and cardiac organoids/microtissues in vitro and (iii) intact hearts of zebrafish and humans in vivo. Good correlation was found with conventional measures of contraction in each system. Thus, using a single method for processing video recordings, we obtained reliable pharmacological data and measures of cardiac disease phenotype in experimental cell- and animal models and human echocardiograms.

Published
2017

177. Chronic intermittent tachypacing by an optogenetic approach induces arrhythmia vulnerability in human engineered heart tissue.

Author

Lemme, Marta, Braren, Ingke, Prondzynski, Maksymilian, Aksehirlioglu, Bülent, Ulmer, Bärbel M, Schulze, Mirja L, Ismaili, Djemail, Meyer, Christian, Hansen, Arne, Christ, Torsten, Lemoine, Marc D, and Eschenhagen, Thomas

Abstract

Aims Chronic tachypacing is commonly used in animals to induce cardiac dysfunction and to study mechanisms of heart failure and arrhythmogenesis. Human induced pluripotent stem cells (hiPSC) may replace animal models to overcome species differences and ethical problems. Here, 3D engineered heart tissue (EHT) was used to investigate the effect of chronic tachypacing on hiPSC-cardiomyocytes (hiPSC-CMs). Methods and results To avoid cell toxicity by electrical pacing, we developed an optogenetic approach. EHTs were transduced with lentivirus expressing channelrhodopsin-2 (H134R) and stimulated by 15 s bursts of blue light pulses (0.3 mW/mm2, 30 ms, 3 Hz) separated by 15 s without pacing for 3 weeks. Chronic optical tachypacing did not affect contractile peak force, but induced faster contraction kinetics, shorter action potentials, and shorter effective refractory periods. This electrical remodelling increased vulnerability to tachycardia episodes upon electrical burst pacing. Lower calsequestrin 2 protein levels, faster diastolic depolarization (DD) and efficacy of JTV-519 (46% at 1 µmol/L) to terminate tachycardia indicate alterations of Ca2+ handling being part of the underlying mechanism. However, other antiarrhythmic compounds like flecainide (69% at 1 µmol/L) and E-4031 (100% at 1 µmol/L) were also effective, but not ivabradine (1 µmol/L) or SEA0400 (10 µmol/L). Conclusion We demonstrated a high vulnerability to tachycardia of optically tachypaced hiPSC-CMs in EHT and the effective termination by ryanodine receptor stabilization, sodium or hERG potassium channel inhibition. This new model might serve as a preclinical tool to test antiarrhythmic drugs increasing the insight in treating ventricular tachycardia. [ABSTRACT FROM AUTHOR]

Published
2020
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178. Regulation of ICa,L and force by PDEs in human-induced pluripotent stem cell-derived cardiomyocytes.

Author

Saleem, Umber, Ismaili, Djemail, Mannhardt, Ingra, Pinnschmidt, Hans, Schulze, Thomas, Christ, Torsten, Eschenhagen, Thomas, and Hansen, Arne

Subjects
PLURIPOTENT stem cells, PHOSPHODIESTERASES, BIOLOGICAL research, RESEARCH, HETEROCYCLIC compounds, RESEARCH methodology, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, STEM cells, CELLS, ESTERASES
Abstract

Background and Purpose: Phosphodiesterases (PDEs) are important regulators of β-adrenoceptor signalling in the heart. While PDE4 is the most important isoform that regulates ICa,L and force in rodent cardiomyocytes, the dominant isoform in adult human cardiomyocytes is PDE3.Experimental Approach: Given the potential of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for biomedical research, this study characterized the contribution of PDE3 and PDE4 isoforms to the regulation of ICa,L and force in hiPSC-CMs in an engineered heart tissue (EHT) model.Key Results: There was a lower abundance of mRNA for PDE3A and 4A in hiPSC-CM EHT than in non-failing human heart samples. Selective inhibition of PDE3 and 4 with cilostamide and rolipram, respectively, showed that, in hiPSC-CM, PDE4 was the predominant isoform for the regulation of ICa,L (cilostamide: +1.44-fold; rolipram: +1.77-fold). Furthermore, in contrast to cilostamide, rolipram decreased the EC50 of isoprenaline about 15-fold.Conclusion and Implications: The predominance of PDE4 over PDE3 is a peculiarity of hiPSC-CMs and is probably an indicator of immaturity. This finding has implications for the use of hiPSC-CM as pharmacological models to investigate and assess the effects of PDE inhibitors. [ABSTRACT FROM AUTHOR]

Published
2020
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179. ANFA and the Asset Purchase Programmes of the Eurosystem: Non-monetary Policy Operations that Restrict the ECB’s Monetary Policy?

Author

Hansen, Arne and Meyer, Dirk

Subjects
MONETARY policy, CENTRAL banking industry, NET worth, ASSETS (Accounting)
Abstract

Under certain conditions, the Agreement on Net Financial Assets (ANFA) allows the Eurosystem’s national central banks to create central bank money on their own account. The independent position of the European Central bank (ECB) requires transparency and a clear distinction between national additional money and the common money creation of the Eurosystem. The fulfilment of these conditions is critically examined against the background of the asset purchase programmes. The consequences are analysed in the framework of an alternative calculation method for net financial assets. As a result, the independence of the ECB is seen as potentially jeopardised by the restrictions on its leeway to conduct monetary policy. [ABSTRACT FROM AUTHOR]

Published
2020

180. Case Report on: Very Early Afterdepolarizations in HiPSC-Cardiomyocytes—An Artifact by Big Conductance Calcium Activated Potassium Current (Ibk,Ca).

Author

Horváth, András, Christ, Torsten, Koivumäki, Jussi T., Prondzynski, Maksymilian, Zech, Antonia T. L., Spohn, Michael, Saleem, Umber, Mannhardt, Ingra, Ulmer, Bärbel, Girdauskas, Evaldas, Meyer, Christian, Hansen, Arne, Eschenhagen, Thomas, and Lemoine, Marc D.

Subjects
PLURIPOTENT stem cells, ION channels, POTASSIUM, CALCIUM, LONG QT syndrome
Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent an unlimited source of human CMs that could be a standard tool in drug research. However, there is concern whether hiPSC-CMs express all cardiac ion channels at physiological level and whether they might express non-cardiac ion channels. In a control hiPSC line, we found large, “noisy” outward K+ currents, when we measured outward potassium currents in isolated hiPSC-CMs. Currents were sensitive to iberiotoxin, the selective blocker of big conductance Ca2+-activated K+ current (IBK,Ca). Seven of 16 individual differentiation batches showed a strong initial repolarization in the action potentials (AP) recorded from engineered heart tissue (EHT) followed by very early afterdepolarizations, sometimes even with consecutive oscillations. Iberiotoxin stopped oscillations and normalized AP shape, but had no effect in other EHTs without oscillations or in human left ventricular tissue (LV). Expression levels of the alpha-subunit (KCa1.1) of the BKCa correlated with the presence of oscillations in hiPSC-CMs and was not detectable in LV. Taken together, individual batches of hiPSC-CMs can express sarcolemmal ion channels that are otherwise not found in the human heart, resulting in oscillating afterdepolarizations in the AP. HiPSC-CMs should be screened for expression of non-cardiac ion channels before being applied to drug research. [ABSTRACT FROM AUTHOR]

Published
2020
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183. Human Induced Pluripotent Stem Cell–Derived Engineered Heart Tissue as a Sensitive Test System for QT Prolongation and Arrhythmic Triggers

Author

Lemoine, Marc D., primary, Krause, Tobias, additional, Koivumäki, Jussi T., additional, Prondzynski, Maksymilian, additional, Schulze, Mirja L., additional, Girdauskas, Evaldas, additional, Willems, Stephan, additional, Hansen, Arne, additional, Eschenhagen, Thomas, additional, and Christ, Torsten, additional

Published
2018
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185. CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy

Author

Mosqueira, Diogo, primary, Mannhardt, Ingra, additional, Bhagwan, Jamie R, additional, Lis-Slimak, Katarzyna, additional, Katili, Puspita, additional, Scott, Elizabeth, additional, Hassan, Mustafa, additional, Prondzynski, Maksymilian, additional, Harmer, Stephen C, additional, Tinker, Andrew, additional, Smith, James G W, additional, Carrier, Lucie, additional, Williams, Philip M, additional, Gaffney, Daniel, additional, Eschenhagen, Thomas, additional, Hansen, Arne, additional, and Denning, Chris, additional

Published
2018
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187. Low Resting Membrane Potential and Low Inward Rectifier Potassium Currents Are Not Inherent Features of hiPSC-Derived Cardiomyocytes

Author

Horváth, András, primary, Lemoine, Marc D., additional, Löser, Alexandra, additional, Mannhardt, Ingra, additional, Flenner, Frederik, additional, Uzun, Ahmet Umur, additional, Neuber, Christiane, additional, Breckwoldt, Kaja, additional, Hansen, Arne, additional, Girdauskas, Evaldas, additional, Reichenspurner, Hermann, additional, Willems, Stephan, additional, Jost, Norbert, additional, Wettwer, Erich, additional, Eschenhagen, Thomas, additional, and Christ, Torsten, additional

Published
2018
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188. MUSCLEMOTION

Author

Sala, Luca, primary, van Meer, Berend J., additional, Tertoolen, Leon G.J., additional, Bakkers, Jeroen, additional, Bellin, Milena, additional, Davis, Richard P., additional, Denning, Chris, additional, Dieben, Michel A.E., additional, Eschenhagen, Thomas, additional, Giacomelli, Elisa, additional, Grandela, Catarina, additional, Hansen, Arne, additional, Holman, Eduard R., additional, Jongbloed, Monique R.M., additional, Kamel, Sarah M., additional, Koopman, Charlotte D., additional, Lachaud, Quentin, additional, Mannhardt, Ingra, additional, Mol, Mervyn P.H., additional, Mosqueira, Diogo, additional, Orlova, Valeria V., additional, Passier, Robert, additional, Ribeiro, Marcelo C., additional, Saleem, Umber, additional, Smith, Godfrey L., additional, Burton, Francis L., additional, and Mummery, Christine L., additional

Published
2018
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189. Vasopressin stimulates the proliferation and differentiation of red blood cell precursors and improves recovery from anemia

Author

Mayer, Balázs, primary, Németh, Krisztián, additional, Krepuska, Miklós, additional, Myneni, Vamsee D., additional, Maric, Dragan, additional, Tisdale, John F., additional, Hsieh, Matthew M., additional, Uchida, Naoya, additional, Lee, Heon-Jin, additional, Nemeth, Michael J., additional, Holmbeck, Kenn, additional, Noguchi, Constance Tom, additional, Rogers, Heather, additional, Dey, Soumyadeep, additional, Hansen, Arne, additional, Hong, Jeffrey, additional, Chow, Ian, additional, Key, Sharon, additional, Szalayova, Ildikó, additional, Pagani, Jerome, additional, Markó, Károly, additional, McClain-Caldwell, Ian, additional, Vitale-Cross, Lynn, additional, Young, W. Scott, additional, Brownstein, Michael J., additional, and Mezey, Éva, additional

Published
2017
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190. InPulse CrackIT Challenge: Development of An In Vitro Platform Using Physiologically Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes to Screen for Drug-Induced Effects on Cardiac Contractility

Author

Harris, Kate, primary, Rossman, Eric, additional, Xu, Xiaoping, additional, Clements, Peter, additional, Mannhardt, Ingra, additional, Hansen, Arne, additional, Saleem, Umber, additional, Eschenhagen, Thomas, additional, Hortigon, Maria, additional, Rodriguez, Victor Zamora, additional, Smith, Godfrey, additional, van Meer, Berend, additional, Tertoolen, Leon, additional, Mummery, Christine, additional, Ribeiro, Marcelo, additional, Passier, Robert, additional, de Korte, Tessa, additional, Vlaming, Marijn, additional, Braam, Stefan, additional, Vickers, Cathy, additional, Mosqueira, Diogo, additional, Firth, Karl, additional, Prodanov, Ljupcho, additional, George, Vinoj, additional, and Denning, Chris, additional

Published
2017
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191. The measurement problem is the measurement problem is the measurement problem

Author

Baumann, Veronika, Hansen, Arne, and Wolf, Stefan

Subjects
Quantum Physics, FOS: Physical sciences, Quantum Physics (quant-ph)
Abstract

Recently, it has been stated that single-world interpretations of quantum theory are logically inconsistent. The claim is derived from contradicting statements of agents in a setup combining two Wigner's-friend experiments. Those statements stem from applying the measurement-update rule subjectively, i.e., only for the respective agent's own measurement. We argue that the contradiction expresses the incompatibility of collapse and unitarity - resulting in different formal descriptions of a measurement - and does not allow to dismiss any specific interpretation of quantum theory.

Published
2016
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192. Ein Schuldenerlass als Ende mit Schrecken?

Author

Hansen, Arne and Meyer, Dirk

Abstract

The rising debt-to-GDP ratios of the eurozone member states result not least from the coronavirus crisis. Without external support, especially with regard to Italy, but also for other Mediterranean states, access to the capital market could be seriously threatened in the medium run. The recovery fund ‘Next Generation EU’ likely directs the fundamental structures of the European Union (EU) towards a fiscal union with considerable transfer elements, while the Pandemic Emergency Purchase Programme (PEPP), which is declared as a monetary policy instrument, is even discussed as a violation of the prohibition of monetary financing. As an alternative, this contribution analyses a debt relief by the European System of Central Banks (ESCB), implemented via an EU debt agency. This construction would avoid a negative equity position of the central banks and also enable a legal integration into the EU system. The question remains: What would be the consequences of such a non-recurring step?

Published
2021
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194. Commentary on Winzeler et al 'Low arginine vasopressin levels in patients with diabetes insipidus are not associated with anaemia'.

Author

Mayer, Balázs, Németh, Krisztián, Krepuska, Miklós, Myneni, Vamsee D., Maric, Dragan, Tisdale, John F., Hsieh, Matthew M., Uchida, Naoya, Lee, Heon‐Jin, Nemeth, Michael J., Holmbeck, Kenn, Noguchi, Constance Tom, Rogers, Heather, Dey, Soumyadeep, Hansen, Arne, Hong, Jeffrey, Chow, Ian, Key, Sharon, Szalayova, Ildikó, and Pagani, Jerome

Subjects
VASOPRESSIN, DIABETES insipidus, PEOPLE with diabetes, ERYTHROPOIETIN receptors, ANEMIA, BLOOD cell count
Abstract

The observations that haematopoietic stem cells (HSCs) express vasopressin receptors and that patients with cDI were intermittently anaemic convinced us to study the effect of vasopressin on HSCs in vitro and in vivo. Dear Editor, We found Winzeler et al's paper1 on the effect of arginine vasopressin (AVP) in patients suffering from central diabetes insipidus (cDI) and primary polydipsia (PP) quite interesting. [Extracted from the article]

Published
2021
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195. Die Zuordnung von Wirtschaftsguetern zu Betriebstaetten im Recht der Doppelbesteuerungsabkommen : Ein funktionaler Ansatz unter Beruecksichtigung der Fiktion der uneingeschraenkten Selbstaendigkeit der Betriebstaette

Author

Hansen, Arne F. and Hansen, Arne F.

Subjects
International business enterprises--Taxation--Law and legislation
Abstract

Die Betriebstätte als Teil eines grenzüberschreitend ansässigen Einheitsunternehmens ist zivilrechtlich unselbständig. Im Recht der Doppelbesteuerungsabkommen hingegen gilt für die Betriebstätte die Fiktion der steuerrechtlich uneingeschränkten Selbstständigkeit, wodurch sie zum Besteuerungssubjekt wird. Die Studie widmet sich der Abgrenzung der Besteuerungsrechte am Gewinn eines grenzüberschreitend tätigen Einheitsunternehmens und entwickelt einen funktionalen Ansatz zur Zuordnung der Wirtschaftsgüter zu Betriebstätten.

Published
2014

196. Human iPSC-derived cardiomyocytes cultured in 3D engineered heart tissue show physiological upstroke velocity and sodium current density

Author

Lemoine, Marc D., primary, Mannhardt, Ingra, additional, Breckwoldt, Kaja, additional, Prondzynski, Maksymilian, additional, Flenner, Frederik, additional, Ulmer, Bärbel, additional, Hirt, Marc N., additional, Neuber, Christiane, additional, Horváth, András, additional, Kloth, Benjamin, additional, Reichenspurner, Hermann, additional, Willems, Stephan, additional, Hansen, Arne, additional, Eschenhagen, Thomas, additional, and Christ, Torsten, additional

Published
2017
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198. Evaluation of MYBPC3 trans -Splicing and Gene Replacement as Therapeutic Options in Human iPSC-Derived Cardiomyocytes

Author

Prondzynski, Maksymilian, primary, Krämer, Elisabeth, additional, Laufer, Sandra D., additional, Shibamiya, Aya, additional, Pless, Ole, additional, Flenner, Frederik, additional, Müller, Oliver J., additional, Münch, Julia, additional, Redwood, Charles, additional, Hansen, Arne, additional, Patten, Monica, additional, Eschenhagen, Thomas, additional, Mearini, Giulia, additional, and Carrier, Lucie, additional

Published
2017
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199. Differentiation of cardiomyocytes and generation of human engineered heart tissue

Author

Breckwoldt, Kaja, primary, Letuffe-Brenière, David, additional, Mannhardt, Ingra, additional, Schulze, Thomas, additional, Ulmer, Bärbel, additional, Werner, Tessa, additional, Benzin, Anika, additional, Klampe, Birgit, additional, Reinsch, Marina C, additional, Laufer, Sandra, additional, Shibamiya, Aya, additional, Prondzynski, Maksymilian, additional, Mearini, Giulia, additional, Schade, Dennis, additional, Fuchs, Sigrid, additional, Neuber, Christiane, additional, Krämer, Elisabeth, additional, Saleem, Umber, additional, Schulze, Mirja L, additional, Rodriguez, Marita L, additional, Eschenhagen, Thomas, additional, and Hansen, Arne, additional

Published
2017
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200. Blinded Contractility Analysis in hiPSC-Cardiomyocytes in Engineered Heart Tissue Format: Comparison With Human Atrial Trabeculae

Author

Mannhardt, Ingra, primary, Eder, Alexandra, additional, Dumotier, Berengere, additional, Prondzynski, Maksymilian, additional, Krämer, Elisabeth, additional, Traebert, Martin, additional, Söhren, Klaus-Dieter, additional, Flenner, Frederik, additional, Stathopoulou, Konstantina, additional, Lemoine, Marc D., additional, Carrier, Lucie, additional, Christ, Torsten, additional, Eschenhagen, Thomas, additional, and Hansen, Arne, additional

Published
2017
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