Browsing by Author "Tovar, Günter (Prof. Dr.)"

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    Experimental and numerical study of turbulence in fusion plasmas using reflectometry synthetic diagnostics
    (2018) Zadvitskiy, Georgiy; Tovar, Günter (Prof. Dr.)
    Anomalous energy and particle transport is closely related to micro-turbulence. Therefore plasma turbulence studies are essential for successful operation of magnetic confinement fusion devices. This thesis deals with the development of interpretative models for Ultra-Fast Swept Reflectometry (USFR), a diagnostic used for the measurement of turbulence radial wave-number spectra in fusion devices. While the interpretation of reflectometry data is quite straightforward for small levels of turbulence, it becomes much trickier for larger levels as the reflectometer answer is no longer linear with the turbulence level. It has been shown for instance that resonances due to probing field trapping can appear in turbulent plasma and produce jumps of the signal phase. In the plasma edge region the turbulence level is usually high and can lead to a non-linear regime of the reflectometer response. The loss of probing beam coherency and beam widening when the probing beam crosses the edge turbulence layer can affect USFR core measurements. Edge turbulence with a long correlation length leads to small beam widening and strong distortion of the probing wave phase. However backscattering effects from turbulence with short correlation lengths are also able to cause reflectometer signal change. To study turbulence wave-number spectra as well as reflectometer signal phase variations, signal amplitude variations can be analized. Unlike signal phase variation, amplitude does not suffer from resonant jumps, and can give more clear qualitative evaluation of turbulence structure. In the case when the turbulence amplitude peaked in the edge region, it can be detected as spectral peak near local Bragg resonance wave-number. USFR with a set of receiving antennas arranged poloidally was proposed to obtain more information on the edge turbulence properties. A displacement of the spectral peak appears when the receiving antenna is misaligned with the emitting one. Peak displacement measurements could provide additional information on probing beam shaping and turbulence properties and help in coherent mode observation as well. A 2D full wave code was applied as a synthetic diagnostic to Gysela gyro-kinetic code data to study Tore-Supra tokamak core turbulence. Radial correlation lengths computed from the amplitude of multi-channel fixed frequency reflectometry signals 5have shown good agreement with the turbulence correlation length directly computed from the simulation. The synthetic diagnostic was then applied to analyse the correlation length and wave-number spectra obtained by USFR in the ASDEX-Upgrade tokamak. A comparison between 1D and 2D results have shown different behaviour. However correlation lengths measured with UFSR signals are in the same order with turbulence ones.
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    Hydrogelsysteme auf Basis UV-polymerisierbarer Biopolymere für den Aufbau von Gewebemimetika mittels Inkjet-Bioprinting am Beispiel von hyalinem Knorpel
    (2014) Hoch, Eva; Tovar, Günter (Prof. Dr.)
    Gegenstand der Arbeit war die Darstellung von Biopolymer-basierten, gewebeähnlichen Hydrogelsystemen und deren Formulierung als Biotinten für das Inkjet-Bioprinting. Dafür wurden zwei Bestandteile der natürlichen extrazellulären Matrix gewählt: Gelatine und Chondroitinsulfat. Beide wurden durch Reaktion mit Methacrylsäureanhydrid derivatisiert. Zur Anpassung der Geleigenschaften an verschiedene native Gewebe durch Variation des Vernetzungsgrades wurden Gelatinederivate mit verschiedenen Methacrylierungsgraden der Aminogruppen erzeugt: Ca. 70 % bis ca. 100 %. Chondroitinsulfat wurde mit einem Methacrylierungsgrad der Disaccharideinheiten von ca. 23 % derivatisiert. Unter Variation des Methacrylierungsgrades sowie des Massenanteiles konnten durch UVA-initiierte Vernetzung in Anwesenheit des Photoinitiators Irgacure® 2959 chemisch stabile Gelatinehydrogele mit großer Variationsbreite ihrer Quellbarkeit (ca. 370 % bis 965 %) und mechanischen Festigkeit (ca. 5 kPa bis 370 kPa) erzeugt werden. Die erreichten Quellbarkeiten und mechanischen Festigkeiten lagen im Bereich verschiedener nativer Weichgewebe. Die Vernetzung mithilfe eines hoch intensiven, fokussierten Laserstrahles im Sinne der Zweiphotonenpolymerisation ermöglichte außerdem die Erzeugung von mikrostrukturierten Gelatinehydrogelen. Gelenkknorpel (hyaliner Knorpel), welcher in der vorliegenden Arbeit als Modellgewebe gewählt wurde, besitzt herausragende Eigenschaften bezüglich seiner Festigkeit und Quellbarkeit. Durch die Integration von Chondroitinsulfat in die Gelatinehydrogele konnten die Geleigenschaften im Hinblick auf die Beschaffenheit von nativem Gelenkknorpel verbessert werden, indem die Quellbarkeit bei gleichbleibender Festigkeit signifikant erhöht wurde. So wiesen beispielsweise 10 Gew.-%-ige Gelatinehydrogele (Methacrylierungsgrad ca. 85 %) einen Speichermodul von ca. 9,8 kPa und eine Quellbarkeit von ca. 660 % auf. Vergleichbare Hybrid-Hydrogele mit Chondroitinsulfat besaßen mit ca. 10,7 kPa einen nahezu unveränderten Speichermodul, wohingegen die Quellbarkeit mit ca. 830 % signifikant höher war. Die physikalischen Eigenschaften der Hybrid-Hydrogele aus Gelatine und Chondroitinsulfat waren damit nativem Gelenkknorpel ähnlicher als die reiner Gelatinehydrogele. Bei der Verkapselung von Chondrozyten in dreidimensionale Gelatine- und Gelatine-Chondroitinsulfat-Hydrogele zeigte sich ein deutlicher Einfluss der Gelzusammensetzung auf die Morphologie und das Proliferationsverhalten der Zellen. Chondrozyten in Chondroitinsulfat-haltigen Gelen wiesen eine zellarttypische kugelige Morphologie und eine geringe proliferative Aktivität auf. Chondrozyten in reinen Gelatinegelen besaßen vorwiegend eine Fibroblasten-artige Morphologie und eine höhere Proliferationsrate, wie es für dedifferenzierte Chondrozyten typisch ist. Dies deutet darauf hin, dass die dargestellten Chondroitinsulfat-haltigen Hydrogele den Chondrozyten-spezifischen Differenzierungszustand stabilisierten, während reine Gelatinehydrogele dies nicht taten. Im Hinblick auf die Verarbeitung der dargestellten Materialsysteme mittels Inkjet-Druckverfahren wurde die Viskosität der Hydrogelprecursorlösungen untersucht. Lösungen unmodifizierter und niedrig methacrylierter Gelatine mit Massenanteilen >= 10 Gew.-% gelierten bei 25 °C und besaßen selbst bei 37 °C Viskositäten > 10 mPa s, die für kommerzielle Inkjet-Druckköpfe zu hoch sind. Dahingegen wiesen Lösungen hoch methacrylierter Gelatine bei 37 °C und 25 °C bis zu Konzentrationen von 15 Gew.-% Inkjet-druckbare Viskositäten < 10 mPa s auf. Die zusätzliche Acetylierung der Gelatinederivate mit niedrigem Methacrylierungsgrad bewirkte eine Maskierung noch vorhandener freier Aminogruppen, ohne dass sich der Gehalt an vernetzbaren Methacrylgruppen änderte. Durch die daraus resultierende Reduktion der inter- und intramolekularen Wechselwirkungen der Gelatinemakromonomere konnten auch diese Lösungen zu Inkjet-druckbaren Biotinten formuliert werden. Die Doppelfunktionalisierung mit Acetyl- und Methacrylgruppen ermöglichte damit die Formulierung von Gelatine-basierten Inkjet-Biotinten mit einer großen Bandbreite der Quellbarkeit und der Festigkeit der resultierenden Hydrogele. Die dargestellten Materialsysteme wurden als Biotinten mit einem piezoelektrischen Mikrodosiersystem verarbeitet. Dabei konnte bei einer Drucktemperatur von 25 °C ein stabiler Druckprozess etabliert werden. Weiterhin wurde gezeigt, dass eine solche Verarbeitung für Chondrozyten zytokompatibel ist. In der vorliegenden Arbeit gelang damit die Formulierung von Biopolymer-basierten Biotinten für das Inkjet-Bioprinting mit lebenden Säugerzellen. Diese Biotinten können zu Hydrogelen vernetzt werden, deren mechanische Eigenschaften verschiedenen nativen Geweben entsprechen. Die dargestellten Materialsysteme besitzen damit ein hohes Potenzial für den Aufbau funktionaler Gewebemodelle, wie zum Beispiel hyaliner Knorpel, mit biomimetischer Kompartimentierung und Mikrostruktur.
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    Identification and production of cardio-inductive extracellular matrix proteins for applications in regenerative medicine
    (2014) Holeiter, Monika; Tovar, Günter (Prof. Dr.)
    Cardiovascular disease (CVD) remains one of the leading causes of death in the world, despite significant advances that have been made in cardiology and cardiac surgery in order to change this fact. The most common cause of acute damage to the heart is a myocardial infarction (MI) event. Oxygen depletion during MI leads to a rapid loss of cardiomyocytes at the site of injury, which drastically and permanently impairs the heart’s contractile force and the patients’ quality of life. Unlike in the highly organized extracellular matrix (ECM) microenvironment in healthy myocardium, this remodeling process is characterized by an imbalanced turnover of ECM proteins and interstitial fibrosis. To address this major health problem, the regeneration of functional cardiac tissue and restoration of heart function is the driving goal for researchers worldwide. In early human development, wounds heal rapidly and without the formation of a scar. Fetal wound healing has the potential to not only close the wound, but to regenerate functional tissue and therefore be a blueprint for ideal tissue repair. These findings provided the basis for the hypothesis of this work, which describes how a specific cardiovascular ECM at the onset of human cardiogenesis could contain key ECM proteins to promote cardioinduction and increase the heart’s potential for functional tissue regeneration. In order to identify specific ECM proteins that provide cardiovascular microenvironmental cues during human embryogenesis, we used embryoid bodies (EBs) generated from human embryonic stem cell (hESC) line H9 as a model for early human development. The results of this work show that an efficient cardiovascular differentiation protocol could be designed that generates a high number of spontaneously beating EBs. The expression patterns of the non-fibrillar ECM proteins decorin and nidogen-1 in the beating EBs were identified by real-time polymerase chain reaction (qPCR) analysis. Decorin and nidogen-1 expression is significantly increased during cardiovascular differentiation of hESCs in EBs, suggesting an important role of these proteins in early cardiac development. This result is supported by semi-quantitative analysis of immunofluorescence (IF) images. In order to test the potential of these proteins to support cardiovascular differentiation in vitro or to serve as potential therapeutic candidates, stable clones for the recombinant expression of active human decorin and nidogen-1 were generated. The production clones that provided the highest yields were adapted to suspension culture and serum depletion, followed by production up-scaling and protein purification using fast protein liquid chromatography (FPLC)-controlled methods. The identity and purity of the decorin and nidogen-1 concentrates was verified with specific antibodies. Glycosylation status and activity of these purified ECM proteins could be confirmed utilizing deglycosylation enzymes and Co-Immunoprecipitation (Co-IP) with known interaction partners. The hypothesis of this work was tested in vitro, using the purified decorin and nidogen-1 as coatings on cell culture dishes. A cardio-inductive effect of nidogen-1 on hESC-derived EBs could be shown for the first time, as identified by a significant increase of cardiovascular differentiation efficiency on the coating containing nidogen-1. The effect of decorin and nidogen-1 injections were tested in vivo in a mouse MI and reperfusion (MI/R) model. Echocardiography revealed a significant increase of the ejection fraction (EF), an important physiological parameter for heart function, in the mice that received nidogen-1 injections compared to the control mice four weeks post MI/R. This effect resulted in a remarkable difference of 14.5% EF to the control mice. Qualitative histological analyses revealed that the cardiac morphology was better preserved and showed less pathological remodeling due to the nidogen-1 treatment compared to controls. The results presented in this thesis include the identification of the potentially cardio-inductive hESC-derived cardiovascular ECM proteins decorin and nidogen-1, their recombinant production in CHO cells and the establishment of an in vitro hESC-based test system, with which we showed for the first time a cardio-inductive effect of nidogen-1. In addition, utilization of a small animal MI/R model revealed a significantly improved heart function and qualitative histological analyses showed a better preservation of cardiac morphology and lower degree of pathological remodeling after peri-infarct injections of nidogen-1 compared to controls. These results provide a direct reference towards the development of an early-stage nidogen-1-based therapy for the prevention of heart failure.
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    The influence of flow shear on drift-wave interactions in the stellarator TJ-K
    (2021) Ullmann, Til; Tovar, Günter (Prof. Dr.)
    The investigation of the interaction between shear flows and turbulence in magnetically confined fusion plasmas is motivated by the fact that shear flows can lead to a reduction or even suppression of the turbulent transport to the vessel wall. Thus they can significantly improve the performance of future nuclear fusion power plants. Therefore, in this thesis the influence of stationary background shear and time-dependent zonal flows on the wave interactions was investigated. The turbulence-generated zonal flows not only have the character of a shear flow, but in turn extract energy from the turbulence, while they themselves do not contribute to the transport of particles to the outside. Due to this special property, the dependence of this energy transfer on the background shearing rate was investigated experimentally. Because of its low-temperature plasmas, the stellarator experiment TJ-K offers the possibility of measuring the dynamics even within the confinement area by invasive diagnostics, such as Langmuir probes. This way, the tilting of turbulent eddy structures could be related to the background shear. The Reynolds stress, as a measure for the tilting, is linearly dependent on the shearing rate. Since the energy transfer between zonal flows and turbulence is composed of the product of the Reynolds stress and the background shear, a quadratic dependence of the energy transfer on the shearing rate was expected and here experimentally confirmed. In addition, the energy transfer between turbulence and zonal flows also led to a redistribution of the spectral power in favor of the zonal flows from ≈ 5% up to ≈ 40% of the total power for increasing shearing rate. In the picture of drift-wave turbulence, the non-linearity of the dynamics is reflected in three-wave interaction. The drift waves follow resonance conditions in the wavenumber and frequency space, which in turn are linked by the dispersion relation so that not all couplings are allowed. This defined coupling space is also called the resonant manifold. Theoretical considerations by Gürcan assumed that shear flows cause the coupling space of the nonlinear three-wave interaction to contract. Experimentally, this behavior could now be demonstrated on the basis of the shear-character of time-dependent zonal flows using the method of time-resolved wavenumber-frequency bicoherence. Here, it was shown that the effective coupling space actually shrinks with the occurrence of the shear flow and expands again with the decay of the zonal flow. The results in this thesis show that E×B background shear flows, as they occur during the transition from low to highly confined fusion plasmas, can trigger turbulence-driven zonal flows, whose Reynolds stress drive was initiated by a mean tilt of the vortex structure. At the same time, shear flows can restrict the coupling space of drift waves and thus increase the importance of large-scale structures, in particular e.g. zonal flows that do not contribute to turbulent transport, as possible energy sinks. If the shear flows are zonal flows themselves, self-amplification can become effective.
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    Investigation of geodesic acoustic mode flow oscillations using Doppler reflectometry in ASDEX Upgrade
    (2017) Simon, Patrick; Tovar, Günter (Prof. Dr.)
    Magnetic confinement fusion is a promising candidate for a future energy source. Its efficiency is limited by particle and heat transport due to plasma turbulence. A thorough understanding of the turbulence and turbulence moderation mechanisms, is therefore needed. The geodesic acoustic mode (GAM) is a radially localised plasma flow oscillation which contributes to the reduction of turbulent transport through velocity shearing. This thesis investigates the fundamental behaviour of the GAM through a systematic experimental study of its properties in the ASDEX Upgrade tokamak. In particular, the role of the plasma geometry on the scaling of the GAM frequency and amplitude, as well as the GAM radial structure are investigated in detail. The experimental data was obtained with the aid of the microwave Doppler reflectometry diagnostic. The GAM frequency scaling is compared with multiple models which reproduce the expected fundamental scaling behaviour, but do not give a satisfyingly accurate prediction. The GAM amplitude is studied in connection with damping rates predicted by models for collisional and collisionless Landau damping processes. It is found that finite orbit width effects need to be considered and that collisional damping effects cannot be neglected. In studying the GAM radial structure, three distinct states are identified for different plasma conditions. Transitions between these states are observed under variations of the plasma geometry.
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