TY - THES A1 - Zhao, Yuhang T1 - Synthesis and surface functionalization on plasmonic nanoparticles for optical applications N2 - This thesis focuses on the synthesis of novel functional materials based on plasmonic nanoparticles. Three systems with targeted surface modification and functionalization have been designed and synthesized, involving modified perylenediimide doped silica-coated silver nanowires, polydopamine or TiO2 coated gold-palladium nanorods and thiolated poly(ethylene glycol) (PEG-SH)/dodecanethiol (DDT) modified silver nanospheres. Their possible applications as plasmonic resonators, chiral sensors as well as photo-catalysts have been studied. In addition, the interaction between silver nanospheres and 2,3,5,6-Tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ) molecules has also been investigated in detail. In the first part of the thesis, surface modification on Ag nanowires (NWs) with optimized silica coating through a modified Stöber method has been firstly conducted, employing sodium hydroxide (NaOH) to replace ammonia solution (NH4OH). The coated silver nanowires with a smooth silica shell have been investigated by single-particle dark-field scattering spectroscopy, transmission electron microscopy and electron-energy loss spectroscopy to characterize the morphologies and structural components. The silica-coated silver nanowires can be further functionalized with fluorescent molecules in the silica shell via a facile one-step coating method. The as-synthesized nanowire is further coupled with a gold nanosphere by spin-coating for the application of the sub-diffractional chiral sensor for the first time. The exciton-plasmon-photon interconversion in the system eases the signal detection in the perfectly matched 1D nanostructure and contributes to the high contrast of the subwavelength chiral sensing for the polarized light. In the second part of the thesis, dumbbell-shaped Au-Pd nanorods coated with a layer of polydopamine (PDA) or titanium dioxide (TiO2) have been constructed. The PDA- and TiO2- coated Au-Pd nanorods show a strong photothermal conversion performance under NIR illumination. Moreover, the catalytic performance of the particles has been investigated using the reduction of 4-nitrophenol (4-NP) as the model reaction. Under light irradiation, the PDA-coated Au-Pd nanorods exhibit a superior catalytic activity by increasing the reaction rate constant of 3 times. The Arrhenius-like behavior of the reaction with similar activation energies in the presence and absence of light irradiation indicates the photoheating effect to be the dominant mechanism of the reaction acceleration. Thus, we attribute the enhanced performance of the catalysis to the strong photothermal effect that is driven by the optical excitation of the gold surface plasmon as well as the synergy with the PDA layer. In the third part, the kinetic study on the adsorption of 2,3,5,6-Tetrafluoro-7,7,8,8-tetracyanoquino-dimethane (F4TCNQ) on the surface of Ag nanoparticles (Ag NPs) in chloroform has been reported in detail. Based on the results obtained from the UV-vis-NIR absorption spectroscopy, cryogenic transmission electron microscopy (cryo-TEM), scanning nano-beam electron diffraction (NBED) and electron energy loss spectroscopy (EELS), a two-step interaction kinetics has been proposed for the Ag NPs and F4TCNQ molecules. It includes the first step of electron transfer from Ag NPs to F4TCNQ indicated by the ionization of F4TCNQ, and the second step of the formation of Ag-F4TCNQ complex. The whole process has been followed via UV-vis-NIR absorption spectroscopy, which reveals distinct kinetics at two stages: the instantaneous ionization and the long-term complex formation. The kinetics and the influence of the molar ratio of Ag NPs/F4TCNQ molecules on the interaction between Ag NPs and F4TCNQ molecules in the organic solution are reported herein for the first time. Furthermore, the control experiment with silica-coated Ag NPs indicates that the charge transfer at the surface between Ag NPs and F4TCNQ molecules has been prohibited by a silica layer of 18 nm. KW - plasmonic nanoparticles KW - silica KW - polydopamine KW - TiO2 KW - chiral sensing KW - catalysis KW - surface interaction Y1 - 2021 ER - TY - THES A1 - Zhao, Xueru T1 - Palaeoclimate and palaeoenvironment evolution from the last glacial maximum into the early holocene (23-8 ka BP) derived from Lago Grande di Monticchio sediment record (S Italy) Y1 - 2021 ER - TY - THES A1 - Zhang, Heshou T1 - Magnetic fields in the universe BT - Diagnostics, turbulent properties, and their implications N2 - The galactic interstellar medium is magnetized and turbulent. The magnetic field and turbulence play important roles in many astrophysical mechanisms, including cosmic ray transport, star formation, etc. Therefore, measurements of magnetic field and turbulence information are crucial for the proper interpretation of astronomical observations. Nonetheless, the magnetic field observation is quite challenging, especially, there is not universal magnetic tracer for diffuse medium. Moreover, the modelling of turbulence can be oversimplified due to the lack of observational tools to diagnose the plasma properties of the turbulence in the galactic interstellar medium. The studies presented in this thesis have addressed these challenges by bridging the theoretical studies of magnetic field and turbulence with numerical simulations and observations. The following research are presented in this thesis. The first observational evidence of the novel magnetic tracer, ground state alignment (GSA), is discovered, revealing the three-dimensional magnetic field as well as 2 orders of magnitude higher precision comparing to previous observational study in the stellar atmosphere of the post-AGB 89 Herculis. Moreover, the application of GSA in the sub-millimeter fine-structure lines is comprehensively studied for different elements and with magnetohydrodynamic simulations. Furthermore, the influence of GSA effect on the spectroscopy is analyzed and it is found that measurable variation will be produced on the spectral line intensity and the line ratio without accounting for the optical pumping process or magnetic field. Additionally, a novel method to measure plasma modes in the interstellar medium, Signatures from Polarization Analysis (SPA), is proposed and applied to real observations. Magneto-sonic modes are discovered in different types of interstellar medium. An explanation is provided for the long-standing mystery, the origin of γ-ray enhanced emission “Cygnus Cocoon”, based on the comparison between the outcome of SPA and multi-waveband observational data. These novel methods have strong potentials for broader observational applications and will play crucial roles in future multi-wavelength astronomy. N2 - Das interstellare Medium ist magnetisiert und turbulent. Das Magnetfeld und die Turbulenz spielen eine wichtige Rolle in vielen astrophysikalischen Prozessen, unter anderem beim Transport kosmischer Strahlung, bei der Entstehung von Sternen usw. Daher sind Messungen des Magnetfelds und der Turbulenz entscheidend bei der korrekten Interpretation astronomischer Beobachtungen. Dennoch ist die Messung des astronomischen Magnetfeldes eine große Herausforderung, besonders da es keinen universellen magnetischen Tracer für diffuse Medien gibt. Außerdem kann es aufgrund des Mangels an geeigneten Beobachtungswerkzeugen für die Plasmaeigenschaften der galaktischen Turbulenz zu übermäßigen Vereinfachungen bei der Turbulenzmodellierung kommen. Die in dieser Arbeit vorgestellten Forschungsergebnisse beschäftigen sich mit diesen Herausforderungen; die Theorien des Magnetfeldes und der Turbulenz werden durch numerische Simulationen und Beobachtungen anwendbar gemacht. Die erste Anwendung eines neuen magnetischen Markers, Ground State Alignment (GSA, deutsch „Grundzustandsausrichtung“), wird vorgestellt. Dabei wird das dreidimensionale Magnetfeld in der Analyse von Beobachtungsdaten aus der stellaren Atmosphäre des post-AGB 89 Herculis um zwei Größenordnungen genauer bestimmt als bei den bisherigen Methoden. Zusätzlich wird die Anwendung von GSA bei der Analyse von sub-millimeter Feinstrukturlinien ausführlich für verschiedene Elemente mit Hilfe von magnetohydrodynamischen Simulationen getestet. Auch der Einfluss von GSA-Effekten auf spektroskopische Analysen wird untersucht; dabei stellt sich heraus, dass messbare Variationen in der Linienbreite und im Verhältnis der Linien verursacht werden, ohne dass optische Pumpprozesse oder das Magnetfeld berücksichtigt werden. Des Weiteren wird die Signatures from Polarization Analysis (SPA, deutsch „Signatur-aus-Polarisationsanalyse“) als neue Messmethode für Plasmamoden im galaktischen Medium vorgestellt und auf reale Beobachtungen angewandt. In verschiedenen galaktischen Medien werden magneto-akustische Moden gefunden. Durch den Vergleich von Ergebnissen der SPA mit Beobachtungsdaten aus verschiedenen elektromagnetischen Frequenzbereichen kann die bisher ungeklärte Herkunft der gammastrahlenverstärkten Emission „Cygnus Cocoon“ erklärt werden. Diese neuen Methoden haben das Potential für eine breitere Anwendung bei der Analyse von Beobachtungen und werden in der Zukunft eine wichtige Rolle in der Multiwellenlängen-Astronomie spielen. KW - magnetic field KW - turbulence KW - polarization KW - interstellar medium KW - cosmic ray propagation Y1 - 2021 ER - TY - THES A1 - Zadorozhnyi, Oleksandr T1 - Contributions to the theoretical analysis of the algorithms with adversarial and dependent data N2 - In this work I present the concentration inequalities of Bernstein's type for the norms of Banach-valued random sums under a general functional weak-dependency assumption (the so-called $\cC-$mixing). The latter is then used to prove, in the asymptotic framework, excess risk upper bounds of the regularised Hilbert valued statistical learning rules under the τ-mixing assumption on the underlying training sample. These results (of the batch statistical setting) are then supplemented with the regret analysis over the classes of Sobolev balls of the type of kernel ridge regression algorithm in the setting of online nonparametric regression with arbitrary data sequences. Here, in particular, a question of robustness of the kernel-based forecaster is investigated. Afterwards, in the framework of sequential learning, the multi-armed bandit problem under $\cC-$mixing assumption on the arm's outputs is considered and the complete regret analysis of a version of Improved UCB algorithm is given. Lastly, probabilistic inequalities of the first part are extended to the case of deviations (both of Azuma-Hoeffding's and of Burkholder's type) to the partial sums of real-valued weakly dependent random fields (under the type of projective dependence condition). KW - Machine learning KW - nonparametric regression KW - kernel methods KW - regularisation KW - concentration inequalities KW - learning rates KW - sequential learning KW - multi-armed bandits KW - Sobolev spaces Y1 - 2021 ER - TY - THES A1 - Yan, Wan T1 - Shape-Memory effects of thermoplatic multiblock copolymers with overlapping thermal transitions Y1 - 2021 ER - TY - THES A1 - Wochatz, Monique T1 - Influence of different loading conditions on scapular movement and scapular muscle activation patterns T1 - Der Einfluss verschiedener Lastsituationen auf Bewegungs- und Aktivitätsmuster des Schulterblatts N2 - The scapula plays a significant role in efficient shoulder movement. Thus, alterations from typical scapular motion during upper limb movements are thought to be associated with shoulder pathologies. However, a clear understanding of the relationship is not yet obtained.. Scapular alterations may only represent physiological variability as their occurrence can appear equally as frequent in individuals with and without shoulder disorders. Evaluation of scapular motion during increased load might be a beneficial approach to detect clinically relevant alterations. However, functional motion adaptations in response to maximum effort upper extremity loading has not been established yet. Therefore, the overall purpose of this research project was to give further insight in physiological adaptations of scapular kinematics and their underlying scapular muscle activity in response to high demanding shoulder movements in healthy asymptomatic individuals. Prior to the investigation of the effect of various load situation, the reproducibility of scapular kinematics and scapular muscle activity were evaluated under maximum effort arm movements. Healthy asymptomatic adults performed unloaded and maximal loaded concentric and eccentric isokinetic shoulder flexion and extension movements in the scapular plane while scapular kinematics and scapular muscle activity were simultaneously assessed. A 3D motion capture system (infra-red cameras & reflective markers) was utilized to track scapular and humerus motion in relation to the thorax. 3D scapular position angles were given for arm raising and lowering between humerus positions of 20° and 120° flexion. To further characterize the scapular pattern, the scapular motion extent and scapulohumeral rhythm (ratio of scapular and humerus motion extent) were determined. Muscle activity of the upper and lower trapezius and the serratus anterior were assessed with surface electromyography. Amplitudes were calculated for the whole ROM and four equidistant movement phases. Reliability was characterized by overall moderate to good reproducibility across the load conditions. Irrespective of applied load, scapular kinematics followed a motion pattern of continuous upward rotation, posterior tilt and external rotation during arm elevation and a continuous downward rotation, anterior tilt and internal rotation during arm lowering. However, kinematics were altered between maximal loaded and unloaded conditions showing increased upward rotation, reduced posterior tilt and external rotation. Further, the scapulohumeral rhythm was decreased and scapular motion extent increased under maximal loaded movements. Muscle activity during maximum effort were of greater magnitude and differed in their pattern in comparison to the continuous increase and decrease of activity during unloaded shoulder flexion and extension. Relationships between scapular kinematics and their underlying scapular muscle activity could only be identified for a few isolated combinations, whereas the majority showed no associations. Scapular kinematics and scapular muscle activity pattern alter according to the applied load. Alterations between the load conditions comply in magnitude and partially in direction with differences seen between symptomatic and asymptomatic individuals. Even though long-term effects of identified adaptations in response to maximum load are so far unclear, deviations from typical scapular motion or muscle activation should not per se be seen as indicators of shoulder impairment. However, evaluation of alterations in scapular motion and activation in response to maximum effort may have the potential to identify individuals that are unable to cope with increased upper limb demands. Findings further challenge the understanding of scapular motion and stabilization by the trapezius and serratus anterior muscles, as clear relationships between the underlying scapular muscle activity and scapular kinematics were neither observed during unloaded nor maximal loaded shoulder movements. N2 - Das Schulterblatt ist entscheidend für die uneingeschränkte Bewegung und Positionierung der oberen Extremität. Atypische Bewegungsmuster des Schulterblatts werden deshalb oft mit Schulterpathologien in Verbindung gebracht, obwohl die zugrundeliegenden Mechanismen noch nicht ausreichend geklärt sind. Abweichungen stellen möglicherweise nur eine Form physiologischer Variabilität dar, da Veränderungen der Schulterblattbewegung sowohl bei Personen mit als auch ohne Schulterbeschwerden auftreten können. Die Beurteilung der Schulterblattbewegung unter erhöhten Lastbedingungen könnte hilfreich bei der Differenzierung von funktionellen und klinisch relevanten Veränderungen sein. Jedoch sind physiologische Anpassungen der Schulterblattkinematik in Reaktion auf maximale Anforderungen während einer Bewegungsaufgabe der oberen Extremität bisher nicht untersucht. Das Ziel dieses Forschungsprojektes war es deshalb weitere Erkenntnisse hinsichtlich physiologischer Anpassungen der Schulterblattkinematik und ihrer zugrundeliegenden Muskelaktivität zu erlangen. Bevor die Effekte verschiedener Belastungssituationen untersucht wurden, erfolgte die Beurteilung der Reproduzierbarkeit der Schulterblattkinematik sowie der Aktivitätslevel schulterblattstabilisierender Muskeln unter maximaler Anstrengung. Gesunde asymptomatische Erwachsene führten isokinetische Schulterbewegungen in Flexion und Extension unter unbelasteten sowie maximal belasteten Bedingungen durch. Zeitgleich wurde die Schulterblattkinematik sowie die Aktivität schulterstabilisierender Muskeln erfasst. Mit Hilfe eines 3D Kamera Systems (Infrarotkameras & reflektierende Marker) wurden Winkelpositionen des Schulterblatts für Humerus-Positionen zwischen 20° und 120° Flexion bestimmt. Zur weiteren Charakterisierung der Schulterblattbewegung wurde das Ausmaß der Schulterblattrotation sowie der skapulohumerale Rhythmus (Verhältnis von Schulterblatt- und Humerus-Bewegung) ermittelt. Während der Schulterbewegungen wurde die Muskelaktivität des oberen und unteren Trapezius sowie des Serratus anterior mit Oberflächen-Elektromyographie erfasst. Aktivitätslevel wurden für das gesamte Bewegungsausmaß sowie für einzelne Bewegungsphasen berechnet. Eine moderate bis gute Reproduzierbarkeit der Winkelpositionen des Schulterblatts sowie der Aktivitätslevel der schulterblattstabilisierenden Muskulatur konnte unter den verschiedenen Lastbedingungen erreicht werden. Unabhängig von der applizierten Last folgte das Schulterblatt einer kontinuierlichen Aufwärtsrotation, Rückwärtsneigung und Außenrotation während der Schulterflexion und einer kontinuierlichen Abwärtsrotation, Vorwärtsneigung und Innenrotation während der Schulterextension. Bei maximalen Belastungen zeigte das Schulterblatt jedoch eine gesteigerte Aufwärtsrotation sowie eine verringerte Rückwärtsneigung und Außenrotation im Vergleich zur unbelasteten Schulterbewegung. Der skapulohumerale Rhythmus verringerte sich und auch das Ausmaß der Schulterblattrotation war unter maximaler Last erhöht. Die Muskelaktivität zeigte sich unter maximaler Anstrengung nicht nur im Ausmaß gesteigert sondern wies auch ein verändertes Aktivitätsmuster im Verlauf der Bewegungen im Vergleich zur kontinuierlichen Zu- und Abnahme der Aktivität während unbelasteter Bedingungen auf. Korrelationen zwischen dem Ausmaß der Schulterblattrotation und dem Aktivitätslevel der Schulterblattmuskulatur konnten nur für einige wenige isolierte Kombinationen identifiziert werden, während die Mehrheit keine Assoziationen zeigte. Die Kinematik des Schulterblatts und die Aktivitätsmuster der Schulterblattmuskulatur ändern sich in Abhängigkeit der Belastung. Veränderungen der Kinematik und Aktivitätsmuster entsprechen dabei im Ausmaß und teilweise in der Ausrichtung den bekannten Unterschieden zwischen symptomatischen und asymptomatischen Populationen. Obwohl die langfristigen Auswirkungen dieser veränderten Schulterblattkinematik unter maximalen Belastungen bislang unklar sind, sollten Abweichungen von der typischen Bewegung des Schulterblatts sowie bekannter Aktivitätsmuster per se nicht als Indikatoren für eine Beeinträchtigung der Schulterfunktion angesehen werden. Dennoch könnten Untersuchungen der Schulterblattkinematik sowie der Aktivität schulterblattrotierender und –stabilisierender Muskeln unter erhöhten Anforderungen Personen identifizieren die aufgrund mangelnder Anpassung die gesteigerten Lasten nicht kompensieren können. Ein klares Zusammenspiel von Schulterblattkinematik und rotierender sowie stabilisierender Schulterblattmuskulatur ließ sich weder unter unbelasteten noch maximal belasteten Bedingungen aufzeigen. KW - scapular kinematics KW - 3D motion analysis KW - scapular muscles KW - electromyography KW - Schulterblattkinematik KW - 3D-Bewegungsanalyse KW - Schulterblattmuskulatur KW - Elektromyografie Y1 - 2021 ER - TY - THES A1 - Wandt, Viktoria Klara Veronika T1 - Trace elements, ageing, and sex BT - impact on genome stability maintenance Y1 - 2021 ER - TY - THES A1 - Verbancic, Jana T1 - Carbon supply and the regulation of primary cell wall synthesis in Arabidopsis thaliana N2 - Cellulose is the most abundant biopolymer on Earth and cell wall (CW) synthesis is one of the major carbon consumers in the plant cell. Structure and several interaction partners of plasma membrane (PM)-bound cellulose synthase (CESA) complexes, CSCs, have been studied extensively, but much less is understood about the signals that activate and translocate CESAs to the PM and how exactly cellulose synthesis is being regulated during the diel cycle. The literature describes CSC regulation possibilities through interactions with accessory proteins upon stress conditions (e.g. CC1), post-translational modifications that regulate CSC speed and their possible anchoring in the PM (e.g. with phosphorylation and S-acylation, respectively). In this thesis, 13CO2 labeling and imaging techniques were employed in the same Arabidopsis seedling growth system to elucidate how and when new carbon is incorporated into cell wall (CW) sugars and UDP-glucose, and to follow CSC behavior during the diel cycle. Additionally, an ubiquitination analysis was performed to investigate a possible mechanism to affect CSC trafficking to and/or from the PM. Carbon is being incorporated into CW glucose at a 3-fold higher rate during the light period in comparison to the night in wild-type seedlings. Furthermore, CSC density at the PM, as an indication of active cellulose synthesizing machinery, is increasing in the light and falling during the night, showing that CW biosynthesis is more active in the light. Therefore, CW synthesis might be regulated by the carbon status of the cell. This regulation is broken in the starchless pgm mutant where light and dark carbon incorporation rates into CW glucose are similar, possibly due to the high soluble sugar content in pgm during the first part of the night. Strikingly, pgm CSC abundance at the PM is constantly low during the whole diel cycle, indicating little or no cellulose synthesis, but can be restored with exogenous sucrose or a longer photoperiod. Ubiquitination was explored as a possible regulating mechanism for translocation of primary CW CSCs from the PM and several potential ubiquitination sites have been identified.. The approach in this thesis enabled to study cellulose/CW synthesis from different angles but in the same growth system, allowing direct comparison of those methodologies, which could help understand the relationship between the amount of available carbon in a plant cell and the cells capacity to synthesize cellulose/CW. Understanding which factors contribute to cellulose synthesis regulation and addressing those fundamental questions can provide essential knowledge to manage the need for increased crop production. KW - cellulose KW - cell wall KW - 13CO2 labeling KW - UDP-glucose KW - ubiquitination Y1 - 2021 ER - TY - THES A1 - Uflewski, Michal T1 - Characterizing the regulation of proton antiport across the thylakoid membrane N2 - Die Energie, die zum Antrieb photochemischer Reaktionen benötigt wird, stammt aus der Ladungstrennung an der Thylakoidmembran. Aufrgrund des Unterschieds in der Protonenkonzentration zwischen dem Stroma der Chloroplasten und dem Thylakoidlumen wird eine Protonenmotorische Kraft (pmf) erzeugt. Die pmf setzt sich aus dem Protonengradienten (ΔpH) und dem Membranpotential (ΔΨ) zusammen, die gemeinsam die ATP-Synthese antreiben. In der Natur schwankt die Energiemenge, die die Photosynthese antreibt, aufgrund häufiger Änderungen der Lichtintensität. Der Thylakoid-Ionentransport kann den Energiefluss durch einen Photosyntheseapparat an die Lichtverfügbarkeit anpassen, indem er die pmf-Zusammensetzung verändert. Die Dissipation von ΔΨ verringert die Ladungsrekombination am Photosystem II, so dass ein Anstieg der ΔpH-Komponente eine Rückkopplung zur Herabregulierung der Photosynthese auslösen kann. Der durch den K+-Austausch-Antiporter 3 (KEA3) gesteuerte K+/H+-Antiport reduziert den ΔpH-Anteil von pmf und dämpft dadurch das nicht-photochemische Quenching (NPQ). Infolgedessen erhöht sich die Photosyntheseeffizienz beim Übergang zu geringerer Lichtintensität. Ziel dieser Arbeit war es, Antworten auf Fragen zur Regulierung der KEA3-Aktivität und ihrer Rolle in der Pflanzenentwicklung zu finden. Die vorgestellten Daten zeigen, dass KEA3 in Pflanzen, denen der Chloroplasten-ATP-Synthase-Assembly-Faktor CGL160 fehlt und die eine verminderte ATP-Synthase-Aktivität aufweisen, eine zentrale Rolle bei der Regulierung der Photosynthese und des Pflanzenwachstums unter stationären Bedingungen spielt. Das Fehlen von KEA3 in der cgl160-Mutante führt zu einer starken Beeinträchtigung des Wachstums, da die Photosynthese aufgrund des erhöhten pH-abhängigen NPQs und des verringerten Elektronenflusses durch den Cytochrom b6f-Komplex eingeschränkt ist. Die Überexpression von KEA3 in der cgl160-Mutante erhöht die Ladungsrekombination im Photosystem II und fördert die Photosynthese. In Zeiten geringer ATP-Synthase-Aktivität profitieren die Pflanzen also von der KEA3-Aktivität. KEA3 unterliegt einer Dimerisierung über seinen regulatorischen C-Terminus (RCT). Der RCT reagiert auf Veränderungen der Lichtintensität, da die Pflanzen, die KEA3 ohne diese Domäne exprimieren, einen reduzierten Lichtschutzmechanismus bei Lichtintensitätsschwankungen aufweisen. Allerdings fixieren diese Pflanzen während der Photosynthese-Induktionsphase mehr Kohlenstoff als Gegenleistung für einen langfristigen Photoprotektor, was die regulierende Rolle von KEA3 in der Pflanzenentwicklung zeigt. Der KEA3-RCT ist dem Thylakoidstroma zugewandt, so dass seine Regulierung von lichtinduzierten Veränderungen in der Stroma-Umgebung abhängt. Die Regulierung der KEA3-Aktivität überschneidet sich mit den pH-Änderungen im Stroma, die bei Lichtschwankungen auftreten. Es hat sich gezeigt, dass ATP und ADP eine Affinität zum heterolog exprimierten KEA3 RCT haben. Eine solche Wechselwirkung verursacht Konformationsänderungen in der RCT-Struktur. Die Faltung der RCT-Liganden-Interaktion hängt vom pH-Wert der Umgebung ab. Mit einer Kombination aus Bioinformatik und In-vitro-Ansatz wurde die ATP-Bindungsstelle am RCT lokalisiert. Das Einfügen einer Punktmutation in der KEA3-RCT Bindungsstelle in planta führte zu einer Deregulierung der Antiporteraktivität beim Übergang zu wenig Licht. Die in dieser Arbeit vorgestellten Daten ermöglichten es uns, die Rolle von KEA3 bei der Anpassung der Photosynthese umfassender zu bewerten und Modelle zur Regulierung der KEA3-Aktivität während des Übergangs zwischen verschiedenen Lichtintensitäten vorzuschlagen. N2 - The energy required to drive photochemical reactions is derived from charge separation across the thylakoid membrane. As the consequence of difference in proton concentration between chloroplasts stroma and thylakoid lumen, a proton motive force (pmf) is generated. The pmf is composed out of the proton gradient (ΔpH) and membrane potential (ΔΨ), and together they drive the ATP synthesis. In nature, the amount of energy fueling photosynthesis varies due to frequent changes in the light intensity. Thylakoid ion transport can adapt the energy flow through a photosynthetic apparatus to the light availability by adjusting the pmf composition. Dissipation of ΔΨ reduces the charge recombination at the photosystem II, allowing for an increase in ΔpH component to trigger a feedback downregulation of photosynthesis. K+ Exchange Antiporter 3 (KEA3) driven K+/H+ antiport reduces the ΔpH fraction of pmf, thereby dampening a non-photochemical quenching (NPQ). As a result, it increases the photosynthesis efficiency during the transition to lower light intensity. This thesis aimed to find the answers for questions concerning KEA3 activity regulation and its role in plant development. Presented data shows that in plants lacking chloroplast ATP synthase assembly factor CGL160 with decreased ATP synthase activity, KEA3 has a pivotal role in photosynthesis regulation and plant growth during steady-state conditions. Lack of KEA3 in cgl160 mutant results in a strong growth impairment, as photosynthesis is limited due to increased pH-dependent NPQ and decreased electron flow through cytochrome b6f complex. Overexpression of KEA3 in cgl160 mutant increases charge recombination at photosystem II, promoting photosynthesis. Thus, during periods of low ATP synthase activity, plants benefit from KEA3 activity. The KEA3 undergoes dimerization via its regulatory C-terminus (RCT). The RCT responds to changes in light intensity as the plants expressing KEA3 without this domain show reduced photo-protective mechanism in light intensity transients. However, those plants fix more carbon during the photosynthesis induction phase as a trade-off for a long-term photoprotection, showing KEA3 regulatory role in plant development. The KEA3 RCT is facing thylakoid stroma, thus its regulation depends on light-induced changes in the stromal environment. KEA3 activity regulation overlaps with the stromal pH changes occurring during light fluctuations. The ATP and ADP has shown to have an affinity towards heterologously expressed KEA3 RCT. Such interaction causes conformational changes in RCT structure. The fold change of RCT-ligand interaction depends on the environmental pH value. With a combination of bioinformatics and in vitro approach, the ATP binding site at RCT was located. Introduction of binding site point mutation in planta KEA3 RCT resulted in antiporter activity deregulation during transition to low light. Together, the data presented in this thesis allowed us to assess more broadly a KEA3 role in photosynthesis adjustment and propose the models of KEA3 activity regulation throughout transition in light intensity. KW - plant KW - photosynthesis KW - thylakoid KW - ion transport KW - fluctuating light KW - Pflanze KW - Photosynthese KW - Thylakoid KW - Ionentransport KW - schwankendes Licht Y1 - 2021 ER - TY - THES A1 - Tung, Wing Tai T1 - Polymeric fibrous scaffold on macro/microscale towards tissue regeneration Y1 - 2021 ER - TY - THES A1 - Topuz, Birol T1 - Social integration and religion BT - a case study on Alevi-Sunni socio-religious groups' relationships in mixed villages in Corum Y1 - 2021 ER - TY - THES A1 - Ting, Michael Kien Yin T1 - Circadian-regulated dynamics of translation in Arabidopsis thaliana Y1 - 2021 ER - TY - THES A1 - Stemmer, Robert T1 - Strategic business model innovation BT - a holistic analysis of strategic business model innovation endeavors within corporate enterpreneurial environments Y1 - 2021 ER - TY - THES A1 - Sonat, Duygu T1 - Institutional change in the Turkish Social Assistance System BT - National Reforms, Street-Lavel Practices Y1 - 2021 ER - TY - THES A1 - Seiberth, Luz Christopher T1 - Intentionality in Sellars BT - a Transcendental Account of Finite Knowledge T2 - Routledge studies in American philosophy N2 - This book argues that Sellars’ theory of intentionality can be understood as an advancement of a transcendental philosophical approach. It shows how Sellars develops his theory of intentionality through his engagement with the theoretical philosophy of Immanuel Kant. The book delivers a provocative reinterpretation of one of the most problematic and controversial concepts of Sellars' philosophy: the picturing-relation. Sellars' theory of intentionality addresses the question of how to reconcile two aspects that seem opposed: the non-relational theory of intellectual and linguistic content and a causal-transcendental theory of representation inspired by the philosophy of the early Wittgenstein. The author explains how both parts cohere in a transcendental account of finite knowledge. He claims that this can only be achieved by reading Sellars as committed to a transcendental methodology inspired by Kant. In a final step, he brings his interpretation to bear on the contemporary metaphilosophical debate on pragmatism and expressivism. Intentionality in Sellars will be of interest to scholars of Sellars and Kant, as well as researchers working in philosophy of mind, epistemology, and the history of nineteenth- and twentieth-century philosophy. Y1 - 2021 SN - 978-1-032-11493-4 SN - 978-1-032-11758-4 SN - 978-1-003-22136-4 U6 - https://doi.org/10.4324/9781003221364 PB - Routledge CY - New York, NY ER - TY - THES A1 - Schindler, Eva Marie T1 - "What we have done is just to put the people in form of a structure" T1 - "Wir haben die Leute einfach strukturiert" BT - The myth of participation and organisation of civil society BT - Der Mythos Partizipation und die Organisierung von Zivilgesellschaft N2 - Participation has become an orthodoxy in the field of development, an essential element of projects and programmes. This book analyses participation in development interventions as an institutionalised expectation – a rationalized myth – and examines how organisations on different levels of government process it. At least two different objectives of participation are appropriate and legitimate for international organisations in the field: the empowerment of local beneficiaries and the achievement of programme goals. Both integrate participatory forums into the organisational logic of development interventions. Local administrations react to the institutionalised expectation with means-ends decoupling, where participatory forums are implemented superficially but de facto remain marginalised in local administrative processes and activities. The book furthermore provides a thick description of the organisationality of participation in development interventions. Participatory forums are shown to be a form of partial organisation. They establish an order in the relationship between administrations and citizens through the introduction of rules and the creation of a defined membership. At the same time, this order is found to be fragile and subject to criticism and negotiation. N2 - Partizipation ist im Feld der Entwicklungszusammenarbeit eine Orthodoxie, ein unentbehrlicher Bestandteil von Projekten und Programmen. Die Arbeit versteht Partizipation in diesem Rahmen als Rationalitätsmythos und analysiert, wie diese institutionalisierte Erwartung von Verwaltungen auf verschiedenen Ebenen bearbeitet wird. Aus der Perspektive internationaler Organisationen existieren im Feld der Entwicklungszusammenarbeit mit dem Empowerment der lokalen Bevölkerung und der Erreichung von Programmzielen zwei angemessene und legitime Zielsetzungen von Partizipation. Beide ermöglichen eine Integration von Partizipation in die Logik von Projekten und Programmen. Lokale Verwaltungen begegnen der institutionalisierten Erwartung mit einer Zweck-Mittel-Entkopplung, bei der Partizipationsforen oberflächlich implementiert, aber in lokalen Verwaltungsprozessen und -aktivitäten de facto marginalisiert werden. Der Organisationsförmigkeit von Partizipation nähert sich die Arbeit durch dichte Beschreibung ihrer Organisationselemente. Die Partizipationsforen werden als eine Form partieller Organisation verstanden, die dem Verhältnis zwischen lokaler Verwaltung und Bürgern eine Ordnung aus Regeln und Mitgliedschaft auferlegt. Gleichzeitig zeigen die Forschungsergebnisse die Fragilität dieser Ordnung auf und legen dar, wie sie hinterfragt und verhandelt wird. KW - participation KW - development interventions KW - organisationality KW - organizational sociology KW - ethnography KW - interpretive research KW - Partizipation KW - Entwicklungszusammenarbeit KW - Organisationsförmigkeit KW - Organisationssoziologie KW - Ethnographie KW - interpretative Forschung Y1 - 2021 ER - TY - THES A1 - Saussenthaler, Sophie T1 - The impact of DNA methylation on susceptibility to typ 2 diabetes in NZO mice N2 - The development of type 2 diabetes (T2D) is driven by genetic as well as life style factors. However, even genetically identical female NZO mice on a high-fat diet show a broad variation in T2D onset. The main objective of this study was to elucidate and investigate early epigenetic determinants of type 2 diabetes. Prior to other experiments, early fat content of the liver (<55.2 HU) in combination with blood glucose concentrations (>8.8 mM) were evaluated as best predictors of diabetes in NZO females. Then, DNA methylome and transcriptome were profiled to identify molecular pathophysiological changes in the liver before diabetes onset. The major finding of this thesis is that alterations in the hepatic DNA methylome precede diabetes onset. Of particular interest were 702 differentially methylated regions (DMRs), of which 506 DMRs had genic localization. These inter-individual DMRs were enriched by fivefold in the KEGG pathway type 2 diabetes mellitus, independent of the level of gene expression, demonstrating an epigenetic predisposition toward diabetes. Interestingly, among the list of hepatic DMRs, eleven DMRs were associated with known imprinted genes in the mouse genome. Thereby, six DMRs (Nap1l5, Mest, Plagl1, Gnas, Grb10 and Slc38a4) localized to imprinting control regions, including five iDMRs that exhibited hypermethylation in livers of diabetes-prone mice. This suggests that gain of DNA methylation in multiple loci of the paternal alleles has unfavourable metabolic consequences for the offspring. Further, the comparative liver transcriptome analysis demonstrated differences in expression levels of 1492 genes related to metabolically relevant pathways, such as citrate cycle and fatty acid metabolism. The integration of hepatic transcriptome and DNA methylome indicated that 449 differentially expressed genes were potentially regulated by DNA methylation, including genes implicated in insulin signaling. In addition, liver transcriptomic profiling of diabetes-resistant and diabetes-prone mice revealed a potential transcriptional dysregulation of 17 hepatokines, in particular Hamp. The hepatic expression of Hamp was decreased by 52% in diabetes-prone mice, on account of an increase in DNA methylation of promoter CpG-118. Hence, HAMP protein levels were lower in mice prone to develop diabetes, which correlated to higher liver triglyceride levels.. In sum, the identified DNA methylation changes appear to collectively favor the initiation and progression of diabetes in female NZO mice. In near future, epigenetic biomarkers are likely to contribute to improved diagnosis for T2D. KW - epigenetics KW - DNA methylation KW - RNAseq KW - fatty liver KW - type 2 diabetes KW - HAMP Y1 - 2021 ER - TY - THES A1 - Salih, Chehab T1 - International Aviation Law for Aerodrome Planning N2 - The objective of this book is to provide ICAO, States, competent authorities and aerodrome operators with a comprehensive overview of legal challenges related to international aerodrome planning. Answers to derived legal questions as well as recommendations thereafter shall help to enhance regulatory systems and to establish a safer aerodrome environment worldwide. Compliant aerodrome planning has an immense impact on the safety of passengers, personnel, aircraft – and of course the airport. Achieving a high safety standard is crucial, as many incidents and accidents in aviation happen at or in the vicinity of airports. Currently, more than 40% of the ICAO Member States do not fully comply with international legal requirements for aerodrome planning. Representatives of ICAO and States, as well as aerodrome and authority personnel, will understand why compliance with the different legal facets of aerodrome planning is challenging and learn how shortcomings can be solved.​ KW - Airport planning KW - Airport operation KW - International law and Developing States KW - Amendment of the Chicago Convention KW - Performance-based Regulation KW - Enforcement of international law KW - Integration of international law into domestic law KW - Legal interpretation methods Y1 - 2021 SN - 978-3-030-56841-2 SN - 978-3-030-56842-9 U6 - https://doi.org/10.1007/978-3-030-56842-9 PB - Springer CY - Cham ER - TY - THES A1 - Risch, Lucie T1 - Acute effect of exercise on sonographic detectable achilles tendon blood flow BT - differentiation between physiological and pathological blood flow Y1 - 2021 ER - TY - THES A1 - Rettig, Anja T1 - Learning to read in German BT - eye movements and the perceptual span of German beginning readers and their relation to reading motivation BT - Blickbewegungen und die perzentuelle Lesespanne von deutschsprachigen Leseanfängern und der Zusammenhang zur Lesemotivation N2 - In the present dissertation, the development of eye movement behavior and the perceptual span of German beginning readers was investigated in Grades 1 to 3 (Study 1) and longitudinally within a one-year time interval (Study 2), as well as in relation to intrinsic and extrinsic reading motivation (Study 3). The presented results are intended to fill the gap of only sparse information on young readers’ eye movements and completely missing information on German young readers’ perceptual span and its development. On the other hand, reading motivation data have been scrutinized with respect to reciprocal effects on reading comprehension but not with respect to more immediate, basic cognitive processing (e.g., word decoding) that is indicated by different eye movement measures. Based on a longitudinal study design, children in Grades 1–3 participated in a moving window reading experiment with eye movement recordings in two successive years. All children were participants of a larger longitudinal study on intrapersonal developmental risk factors in childhood and adolescence (PIER study). Motivation data and other psychometric reading data were collected during individual inquiries and tests at school. Data analyses were realized in three separate studies that focused on different but related aspects of reading and perceptual span development. Study 1 presents the first cross-sectional report on the perceptual span of beginning German readers. The focus was on reading rate changes in Grades 1 to 3 and on the issue of the onset of the perceptual span development and its dependence on basic foveal reading processes. Study 2 presents a successor of Study 1 providing first longitudinal data of the perceptual span in elementary school children. It also includes information on the stability of observed and predicted reading rates and perceptual span sizes and introduces a new measure of the perceptual span based on nonlinear mixed-effects models. Another issue addressed in this study is the longitudinal between-group comparison of slower and faster readers which refers to the detection of developmental patterns. Study 3 includes longitudinal reading motivation data and investigates the relation between different eye movement measures including perceptual span and intrinsic as well as extrinsic reading motivation. In Study 1, a decelerated increase in reading rate was observed between Grades 1 to 3. Grade effects were also reported for saccade length, refixation probability, and different fixation duration measures. With higher grade, mean saccade length increased, whereas refixation probability, first-fixation duration, gaze duration, and total reading time decreased. Perceptual span development was indicated by an increase in window size effects with grade level. Grade level differences with respect to window size effects were stronger between Grades 2 and 3 than between Grades 1 and 2. These results were replicated longitudinally in Study 2. Again, perceptual span size significantly changed between Grades 2 and 3, but not between Grades 1 and 2 or Grades 3 and 4. Observed and predicted reading rates were found to be highly stable after first grade, whereas stability of perceptual span was only moderate for all grade levels. Group differences between slower and faster readers in Year 1 remained observable in Year 2 showing a pattern of stable achievement differences rather than a compensatory pattern. Between Grades 2 and 3, between-group differences in reading rate even increased resulting in a Matthew effect. A similar effect was observed for perceptual span development between Grades 3 and 4. Finally, in Study 3, significant relations between beginning readers’ eye movements and their reading motivation were observed. In both years of measurement, higher intrinsic reading motivation was related to more skilled eye movement patterns as indicated by short fixations, longer saccades, and higher reading rates. In Year 2, intrinsic reading motivation was also significantly and negatively correlated with refixation probability. These correlational patterns were confirmed in cross-sectional linear models controlling for grade level and reading amount and including both reading motivation measures, extrinsic and intrinsic motivation. While there were significant positive relations between intrinsic reading motivation and word decoding as indicated by the above stated eye movement measures, extrinsic reading motivation only predicted variance in eye movements in Year 2 (significant for fixation durations and reading rate), with a consistently opposite pattern of effects as compared to intrinsic reading motivation. Finally, longitudinal effects of Year 1 intrinsic reading motivation on Year 2 word decoding were observed for gaze duration, total reading time, refixation probability, and perceptual span within cross-lagged panel models. These effects were reciprocal because all eye movement measures significantly predicted variance in intrinsic reading motivation. Extrinsic reading motivation in Year 1 did not affect any eye movement measure in Year 2, and vice versa, except for a significant, negative relation with perceptual span. Concluding, the present dissertation demonstrates that largest gains in reading development in terms of eye movement changes are observable between Grades 1 and 2. Together with the observed pattern of stable differences between slower and faster readers and a widening achievement gap between Grades 2 and 3 for reading rate, these results underline the importance of the first year(s) of formal reading instruction. The development of the perceptual span lags behind as it is most apparent between Grades 2 and 3. This suggests that efficient parafoveal processing presupposes a certain degree of foveal reading proficiency (e.g., word decoding). Finally, this dissertation demonstrates that intrinsic reading motivation—but not extrinsic motivation—effectively supports the development of skilled reading. N2 - In der vorliegenden Dissertation wurde die Entwicklung der Blickbewegungen und der perzeptuellen Lesespanne von deutschsprachigen Leseanfängern in den Klassenstufen 1–3 im Querschnitt (Studie 1) als auch im Längsschnitt innerhalb eines Jahres (Studie 2) sowie hinsichtlich des Zusammenhangs mit der intrinsischen und der extrinsischen Lesemotivation (Studie 3) untersucht. Die Ergebnisse dieser Arbeit stellen einen bedeutsamen empirischen Beitrag zur ansonsten verhältnismäßig eher spärlichen empirisch-experimentellen Forschung zur frühen Leseentwicklung dar und liefern erste Erkenntnisse über die perzeptuelle Spanne von jungen deutschsprachigen Lesern. Des Weiteren wurde Neuland betreten, indem Blickdaten im Zusammenhang mit Lesemotivationsdaten ausgewertet wurden. Während es umfangreiche Forschungsarbeiten zum reziproken Zusammenhang zwischen Lesemotivation und dem Leserverstehen gibt, ist kaum etwas zu wechselseitigen Lesemotivationseffekten in Bezug auf basale kognitive Prozesse (z.B. die Wort-Dekodierung), wie sie durch verschiedene Blickbewegungsmaße indiziert werden, bekannt. Auf Grundlage eines längsschnittlichen Untersuchungsdesigns nahmen Kinder der Klassenstufen 1–3 in zwei aufeinanderfolgenden Jahren an einem Moving-Window-Leseexperiment mit manipuliertem Text teil. Alle Kinder waren Teilnehmer einer größeren Längsschnittstudie zur Untersuchung von intrapersonellen Risikofaktoren im Kindes- und Jugendalter (PIER-Studie). In individuellen Befragungen und Testungen in den Schulen wurden u.a. auch Lesemotivations- und andere psychometrische Lesedaten erhoben. Die im Labor erfassten Blickdaten wurden zusammen mit diesen psychometrischen Daten im Rahmen von drei separaten Studien ausgewertet, die jeweils verschiedene, jedoch miteinander in Bezug stehende Aspekte der Lese- und Lesespannen-Entwicklung untersuchen. Studie 1 präsentiert einen ersten querschnittlichen Bericht zur perzeptuellen Lesespanne von deutschsprachigen Leseanfängern. Hierbei lag der Fokus auf Veränderungen der Leserate in den Klassenstufen 1–3 und auf der Frage, wann die Entwicklung der perzeptuellen Spanne beginnt und inwiefern diese Entwicklung von basalen fovealen Leseprozessen abhängig ist. Studie 2 stellt eine Folgeuntersuchung dar, die erste Längsschnittdaten zur Entwicklung der perzeptuellen Lesespanne bei Grundschulkindern liefert. Untersucht wurden desweiteren die Stabilität der beobachteten und vorhergesagten Leserate als auch der perzeptuellen Lesespanne. In diesem Zusammenhang wird ein neues Spannenmaß vorgestellt, welches auf nicht-linearen gemischten Modellen basiert. Eine weitere Fragestellung der Studie ist der längsschnittliche Gruppenvergleich von langsameren und schnelleren Lesern, welcher auf die Entdeckung von Entwicklungsmustern abzielt. Studie 3 inkludiert längsschnittliche Lesemotivatonsdaten und untersucht die Beziehung zwischen verschiedenen Blickbewegungsmaßen einschließlich der perzeptuellen Lesespanne und der intrinsischen als auch extrinsischen Lesemotivation unter Berücksichtigung der Lesehäufigkeit. In Hinblick auf die Leseentwicklung in Klassenstufe 1–3 wurde ein zwischen den Klassenstufen abnehmender sukzessiver Anstieg in der Leserate beobachtet. Klassenstufeneffekte wurden außerdem berichtet für die Sakkadenlänge, die Refixationswahrscheinlichkeit und für verschiedene Fixationsdauermaße. Mit höherer Klassenstufe stieg die mittlere Sakkadenlänge, wohingegen die Refixationswahrscheinlichkeit, die Dauer der ersten Fixation auf einem Wort, die Blickdauer im sogenannten First-Pass und die Gesamtlesedauer von Worten abnahmen. Die Entwicklung der perzeptuellen Lesespanne wurde ersichtlich durch einen Anstieg von Fenstergrößen-Effekten mit steigender Klassenstufe. Der Unterschied zwischen den Klassenstufen im Hinblick auf Fenstergrößen-Effekte war größer zwischen Klasse 2 und 3 als zwischen den Klassen 1 und 2. Diese Ergebnisse wurden längsschnittlich repliziert in Studie 2. Wieder zeigte sich ein signifikanter Unterschied in der perzeptuellen Lesespanne zwischen Klassenstufe 2 und 3, jedoch nicht zwischen Klassenstufe 1 und 2 oder Klassenstufe 3 und 4. Die beobachtete und die vorhergesagte Leserate waren hoch stabil jenseits der ersten Klasse, wohingegen für die perzeptuelle Lesespanne für alle Klassenstufen nur eine moderate Stabilität gefunden wurde. Gruppenunterschiede zwischen langsameren und schnelleren Lesern im ersten Untersuchungsjahr wurden auch im zweiten Untersuchungsjahr beobachtet. Dabei zeichnete sich ein Muster eher stabiler anstatt kompensatorischer Leistungsunterschiede ab. Zwischen Klassenstufe 2 und 3 gab es sogar einen Anstieg der Disparität zwischen den Gruppen für die Leserate. Es zeichnete sich also ein sogenannter Matthäus-Effekt ab. Ein ähnlicher Effekt wurde für die perzeptuelle Lesespanne zwischen Klassenstufe 3 und 4 beobachtet. Abschließend wurde in Studie 3 ein signifikanter Zusammenhang zwischen den Blickbewegungen von Leseanfängern und ihrer Lesemotivation gefunden. In beiden Erhebungsjahren, korrelierte eine höhere intrinsische Lesemotivation mit geübteren Blickbewegungsmustern, was sich in kürzeren Fixationen, längeren Sakkaden und höheren Leseraten zeigte sowie im zweiten Erhebungsjahr auch in kleineren Refixationswahrscheinlichkeiten. In querschnittlichen linearen Modellen erwies sich die intrinsiche Lesemotivation als signifikanter Prädiktor für die oben genannten Blickmaße, selbst wenn für Klassenstufe und Lesehäufigkeit kontrolliert wurde und beide Motivationsmaße, die intrinische und die extrinsische Motivation, gleichzeitig ins Modell aufgenommen wurden. Die extrinsische Lesemotivation erwies sich hingegen nur im zweiten Erhebungsjahr als signifikanter Prädiktor der verschiedenen Fixationsdauern und der Leserate, wobei das Effektmuster durchweg entgegengesetzt zu dem für die intrinsische Lesemotivation beobachteten war. Schließlich wurden in kreuzverzögerten Autoregressionsmodellen längsschnittliche Effekte der intrinisichen Lesemotivation auf verschiedene Blickbewegungsmaße (Blickdauer im First-Pass, Gesamtlesezeit, Refixationswahrscheinlichkeit und perzeptuelle Lesespanne) beobachet. Diese Effekte waren reziprok, da alle Blickbewegungsmaße auch signifikant Varianz in der intrinsischen Lesemotivation vorhergesagt haben. Im Gegensatz dazu gab es weder signifikante längsschnittliche Effekte der extrinsichen Lesemotivation auf das Blickverhalten noch in die Gegenrichtung signifikante Effekte von Blickbewegungsmaßen auf die extrinsische Lesemotivation, mit Ausnahme einer signifikanten negativen Beziehung zwischen der extrinsischen Lesemotivation und der Lesespanne. Zusammenfassend lassen sich folgende Erkenntnisse festhalten: Die aktuelle Dissertation zeigt auf, dass der größte Zuwachs bei der Leseentwicklung im Sinne von Blickbewegungsänderungen zwischen den Klassenstufen 1 und 2 zu beobachten ist. Zusammen mit dem beobachteten Muster zeitlich stabiler Gruppenunterschiede zwischen langsameren und schnelleren Lesern und dem größer werdenden Leistungsabstand zwischen Klassenstufe 2 und 3 für das Maß der Leserate unterstreichen die Ergebnisse die Bedeutsamkeit des (der) ersten Jahre(s) formaler Leseinstruktion. Die Entwicklung der perzeptuellen Lesespanne ist verzögert, da sie am deutlichsten zwischen den Klassenstufen 2 und 3 sichtbar wird. Dies legt die Schlussfolgerung nah, dass effiziente parafoveale Verarbeitung einen gewissen Grad an fovealer Lesefertigkeit (d.h. basale Wortdekodierfähigkeiten) erfordert. Schließlich liefert die aktuelle Dissertation auch empirische Belege dafür, dass die intrinsische—aber nicht die extrinsische—Lesemotivation effektiv die Leseentwicklung unterstützt. T2 - Lesen Lernen im Deutschen KW - eye movements KW - perceptual span KW - reading development KW - beginning readers KW - German KW - moving window KW - longitudinal study KW - reading motivation KW - Blickbewegungen KW - perzentuelle Lesespanne KW - Leseentwicklung KW - Leseanfänger KW - Deutsch KW - Moving Window KW - Längsschnittstudie KW - Lesemotivation Y1 - 2021 ER - TY - THES A1 - Reichmann, Robin T1 - Novel applications of machine learning techniques in epidemiology of age-related diseases BT - from multidimensional data modelling to risk prediction Y1 - 2021 ER - TY - THES A1 - Rausch, Ann-Kristin T1 - Development of LC-MS/MS Multi-Methods for the Analysis of Contaminants and Residues N2 - Mycotoxins are secondary metabolites produced by several filamentous fungal species, thus occurring ubiquitously in the environment and food. While the heterogeneous group shows differences in their bioavailability and toxicity, the low-molecular-weight xenobiotics are capable of impacting human and animal health acutely and chronically. Therefore, maximum levels for the major mycotoxins in food and feed are regulated in the current European legislation. Besides free mycotoxins, naturally occurring modified mycotoxins are gaining more attention in recent years. Modified mycotoxins constitute toxins altered by plants, microorganisms, and living organisms in different metabolic pathways or food processing steps. The toxicological relevant compounds often co-occur with their free forms in infested food and feed. Thus, the toxins may contribute to the overall toxicity of mycotoxins, wherefore their presence and toxicity should be considered in risk assessment. Until now, however, there are no regulated limits for modified mycotoxins within the European Union. In this thesis, rapid, sensitive, and robust methods for the analysis of mycotoxins and their modified forms were developed and validated using state-of-the-art high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) systems. Firstly, two analytical methods for determining 38 mycotoxins in cereals and 41 mycotoxins in beer were established since agricultural products count as the primary source of mycotoxin contamination. For the analysis of cereal samples, a QuEChERS- based extraction approach was pursued, while analytes from beer samples were extracted using an acetonitrile precipitation scheme. Validation in cereals, namely wheat, corn, rice, and barley, as well as in beer, demonstrated satisfactory results. To obtain information regarding the natural occurrence of mycotoxins in food products, the developed methods were applied to the analysis of several commercial samples partly produced worldwide. The Fusarium toxins deoxynivalenol and its conjugated metabolite deoxynivalenol-3-glucoside turned out to be the most abundant toxins. None of the other modified mycotoxins were quantified in the samples. However, one cereal sample showed traces of zearalenone- 14-sulfate below the limit of quantification. Moreover, pesticides, plant growth regulators, and tropane alkaloids were investigated in this thesis. Pesticides present biologically highly effective compounds applied in the environment to protect humans from the hazardous effects of pests. While plant growth regulators show similar functions, mainly improving agricultural production, tropane alkaloids are naturally occurring secondary metabolites mainly in the species of Solanaceae that may pose unintended poisoning of humans. The third part of the present thesis aimed to analyze cereal-relevant compounds simultaneously, wherefore a multi-method for the analysis of (modified) mycotoxins, pesticides, plant growth regulators, and tropane alkaloids was established. After processing the samples, this should be done in a single extraction step with subsequent one-time measurements. Various sample preparation procedures were compared, whereby an approach based on an acidified acetonitrile/water extraction, followed by an online clean-up, was finally chosen. The simultaneous determination of more than 350 analytes required an analytical tool that offered an increased resolving power, represented as an enhanced peak capacity, and the possibility of analyzing a broad polarity range. Thus, a two-dimensional LC-MS/MS system based on two different separation mechanisms that performed orthogonal to one another was used for the analysis. Validation of the developed method revealed good performance characteristics for most analytes, while subsequent application showed that 86% of the samples were contaminated with at least one compound. In summary, this thesis provides novel insights into the analysis of food-relevant (modified) mycotoxins. Different sample preparation and LC-MS/MS approaches were introduced, resulting in the development of three new analytical methods. For the first time, such a high number of modified mycotoxins was included in multi-mycotoxin methods and a multi-method ranging both contaminants and residues. Although first steps towards the analysis of modified mycotoxins have been made, further research is needed to elucidate their (co-) occurrence and toxicological behavior in order to understand their relevance to human health in the future. KW - Mycotoxins KW - LC-MS/MS KW - Multi-Methods KW - Cereals KW - Beer Y1 - 2021 ER - TY - THES A1 - Raju, Rajarshi Roy T1 - ‘Smart’ Janus emulsions BT - preparation, characterization, and application as a template for aerogel preparation N2 - Emulsions constitute one of the most prominent and continuously evolving research areas in Colloid Chemistry, which involves the preparation of mixtures or dispersions of immiscible components in a continuous medium. Besides conventional oil-in-water or water-in-oil emulsions, other emulsions of complex droplet morphologies have recently attracted significant research interests. Especially Janus emulsions, in which each droplet is comprised of two distinct sub-regions, have shown versatile potential applications. One of their advantages is the possibility of compartmentalization, which enables to play with two different chemistries in a single droplet. Though microfluidic methods are conventionally used to prepare Janus emulsions, their industrial applications are largely hindered by low throughput and extensive instrumentations. Recently, it has been discovered that simply one-pot moderate/high energy emulsification is also capable of developing Janus morphology, although their preparation and stabilization remain rather substantially challenging. This cumulative doctoral thesis focuses on the preparation and characterization of ‘smart’ Janus emulsions, i.e. Janus emulsions with special stimuli-responsive features. One-step moderate/high energy emulsification of olive and silicone oil in an aqueous medium was carried out. Special consideration was devoted to the interfacial tensions among the components to maintain the criteria of forming characteristic droplet architectures, in addition to avoiding multiple emulsion destabilization phenomena like imminent phase separation or even separated droplet formation. A series of investigations were conducted related to the formation of complexes of charged macromolecules and role of them as stabilizers to achieve stable Janus emulsions for a realistic timeframe (more than 3 months). The correlation between the size of the stabilizer particles and the droplet size of emulsion was established. Furthermore, it was observed that Janus emulsion gels with interesting rheological properties can be fabricated in the presence of suitable polyelectrolyte complexes. Janus emulsions that could be influenced by pH, temperature or magnetic field were successfully produced in presence of characteristic stimuli-responsive stabilizers. Afterwards, the effect of these changes was studied by different characterization techniques. The size and morphology could be tuned easily by changing the pH. The incorporation of iron oxide magnetic nanoparticles (synthesized separately by a co-precipitation method) to one component of the Janus emulsion was carried out so that the movement and orientation of the complex droplets in aqueous media could be controlled by an external magnetic field. Additionally, temperature-triggered instantaneous reversible breakdown of Janus droplets was also accomplished. The responses of the Janus droplets by the stimuli were well-documented and explained. Another goal of the present contribution was to exploit this special morphological feature of emulsions as a template for producing porous materials. This was demonstrated by the preparation of ultralight magnetic responsive aerogels, utilizing Janus emulsion gels. The produced aerogels also showed the capacity to separate toxic dye from water. To the best of our knowledge, this is the first example of investigation towards batch scale production of Janus emulsion with such special stimuli-responsive properties by a simple bulk emulsification method. N2 - Emulsionen bilden eines der bekanntesten und sich ständig weiterentwickelnden Forschungsgebiete in der Kolloidchemie. Dabei werden Gemische oder Dispersionen nicht miteinander mischbarer Komponenten in einem kontinuierlichen Medium hergestellt. Neben den herkömmlichen Öl-in-Wasser- oder Wasser-in-Öl-Emulsionen gewinnen in letzter Zeit andere Emulsionen mit komplexeren Tröpfchenmorphologien zunehmend an Forschungsinteresse. Hier sind vor allem Janus-Emulsionen, zu nennen, die aus zwei nicht mischbaren Ölkomponenten, dispergiert in einem wässerigen Medium, bestehen. Da jedes Tröpfchen aus zwei unterschiedlichen Kompartimenten gebildet wird, besteht hier die Möglichkeit gezielt mit der Chemie der Tröpschenbestandteile zu spielen. Obwohl mikrofluidische Verfahren üblicherweise zur Herstellung von Janus-Emulsionen verwendet werden, finden diese nur begrenzt Anwendung in der Industrie aufgrund des geringen Durchsatzes. Kürzlich wurde entdeckt, dass mit einer einfachen Eintopf-Emulgierung bei mittlerer/hoher Energie auch die Janus-Morphologie erzeugt werden kann. Die Herstellung und Stabilisierung der Emulsionen unter Anwendung dieser Methode bleibt jedoch eine große Herausforderung. Der Fokus dieser kumulativen Doktorarbeit konzentriert sich auf die Herstellung und Charakterisierung von „smarten“ Janus-Emulsionen. Diese sind zum Beispiel Janus-Emulsionen, die auf spezielle Reize/Stimuli reagieren. Eine einstufige Emulgierung mit mittlerer/hoher Energie von Oliven- und Silikonöl wurde im wässrigen Medium durchgeführt. Besonderes Augenmerk wurde auf die Grenzflächenspannungen zwischen den Komponenten gelegt, um die Kriterien für die Bildung charakteristischer Tröpfchenarchitekturen beizubehalten und um mehrfache Emulsionsdestabilisierungsphänomene wie eine Phasentrennung oder sogar eine getrennte Tröpfchenbildung zu vermeiden. Eine Reihe von Untersuchungen bezog sich auf die Bildung von Komplexen geladener Makromoleküle und deren Rolle als Stabilisatoren, um stabile Janus-Emulsionen über einen realistischen Zeitraum (länger als 3 Monate) zu erzielen. Dabei wurde eine Korrelation zwischen der Größe der Komplexe und der Tröpfchengröße festgestellt. Weiterhin konnte gezeigt werden, dass Janus-Emulsionsgele mit interessanten rheologischen Eigenschaften in Gegenwart geeigneter Polyelektrolytkomplexe hergestellt werden können. Temperatur und pH-Wert erwiesen sich als Stimulatoren für ausgewählte polymerstabilisierte Janus Emulsionen. Anschließend wurde die Auswirkung dieser Stimuli durch verschiedene Charakterisierungsmethoden untersucht. Dabei konnten die Größe und die Morphologie durch die Änderung des pH-Wertes eingestellt werden. Durch die Einfügung von magnetischen Eisenoxid-Nanopartikeln in eine der Komponenten der Janus-Emulsion konnten die Orientierung und die Bewegung der Tröpfchen durch ein externes Magnetfeld gesteuert werden. Zusätzlich konnte ein temperaturabhängiger sofortiger reversibler Zusammenfall von Janus-Tröpfchen gezeigt werden.. Ein weiteres Ziel des vorliegenden Arbeit war es, dieses spezielle morphologische Merkmal von Emulsionen als Vorlage für die Herstellung poröser Materialien zu nutzen. Dies wurde durch die Herstellung von ultraleichten magnetischen Aerogelen unter Verwendung von Janus-Emulsionsgelen demonstriert. Die hergestellten Aerogele zeigten die Fähigkeit toxischen Farbstoff von Wasser abzutrennen. Nach unserem besten Wissen ist dies das erste Beispiel für eine Untersuchung zur Herstellung von Janus-Emulsionen im Chargenmaßstab mit solchen speziellen Reiz/Stimuli responsiven Eigenschaften durch ein einfaches Emulgierungsverfahren. KW - janus emulsion KW - emulsion KW - magnetic nanoparticles KW - aerogel KW - stimul-responsive KW - stimul-responsive emulsion KW - pH-responsive KW - temperature-responsive Y1 - 2021 ER - TY - THES A1 - Pingel, Ruta T1 - Well-being effects of proactivity through the lens of self-determination theory N2 - In modern times of evolving globalization and continuous technological developments, organizations are required to respond to ever-changing demands. Therefore, to be successful in today’s highly uncertain environments, organizations need employees to actively search for opportunities, anticipate challenges, and act ahead. In other words, employee proactivity in the workplace represents a highly valuable resource in nowadays organizations. Empirical studies conducted as part of this thesis advance the research on the outcomes of proactivity from the individual perspective. The main contribution of this thesis pertains to revealing several important individual and contextual conditions under which engaging in proactivity will have negative and positive effects on employees’ well-being and their consequent behaviours, as well as shedding light on the unique psychological mechanisms through which these effects unfold. From a practical standpoint, this research underscores the importance of creating work environments that support employees’ autonomous motivation for proactivity and urge organizations and managers to be mindful about the pressures they place on employees to be proactive at work. Besides, this thesis stimulates research efforts aimed at further extending our knowledge of when and how individual proactive behaviours at work will do more good than harm for those who enact them. KW - Proactivity KW - Well-Being KW - Self-Determination Theory KW - Proaktivität KW - Wohlbefinden KW - Selbstbestimmungstheorie Y1 - 2021 ER - TY - THES A1 - Novakovic, Lazar T1 - Investigating DEFECTIVE KERNEL 1 regulation of primary cell wall biosynthesis and mechanical properties during plant growth in Arabidopsis thaliana N2 - Plants possess cell wall, a polysaccharide exoskeleton which encompasses all plant cells. Cell wall gives plant cells mechanical support, defines their shape, enables growth and water transport through a plant. It also has important role in communication with the external environment. Regulation of plant cell wall biosynthesis and cell and organ morphogenesis depends on cell’s ability to detect mechanical signals originating both from the external environment and from internal plant tissues. Thanks to the presence of the cell wall, all living plant cells develop constant internal pressure generated by the active water uptake, known as turgor pressure, which enables them to grow. Thus, actively growing cells in the tissue are exerting mechanical stress to each other. In order to properly coordinate cell growth, tissue morphogenesis and maintain cell-to-cell adhesion, plant cell have to detect these mechanical signals. That is performed by a group of still not well enough characterized plant mechanosensitive proteins. Mechanosensors are proteins capable of detecting changes in mechanical stress patterns and translating them into physiological and developmental outputs. One of plant mechanosensitive proteins, DEFECTIVE KERNEL1 (DEK1) has shown to be a very important in proper plant development. DEK1 bears similarity with animal cysteine proteases of Calpain superfamily. DEK1 is very important for plant development since all null alleles are embryo lethal. During the last 20 years of DEK1 studies, this protein has proven to be a very difficult for different molecular and biochemical manipulations. As a consequence, very little is known about its direct target proteins. Wang and co-workers (2003) and Johnson and co-workers (2008) have given a valuable contribution to biochemical understanding of DEK1 by determining that it functions as Cys-protease in similar way as animal calpains. However, a lot of indirect knowledge was gathered about the effects of disruption and modulation of DEK1 activity. DEK1 is important for proper organ development, epidermal specification, and maintenance. However, some studies have inferred that DEK1 affects expression of different cell wall related genes, and it regulates cell-to-cell adhesion in epidermal cells. This led to two extensive studies (Amanda et al., 2016, 2017) which demonstrated importance of DEK1 in regulation leaf epidermal cell walls in A. thaliana mature leaves and inflorescence stems. These studies demonstrated that DEK1 also influences cell wall thickness and cell-to-cell adhesion and that it could potentially regulate cell growth and expansion. Building up on this research, we decided to try to further characterize molecular and biomechanical aspects of DEK1 mediated cell wall regulation, with special emphasis on regulation of cellulose synthesis. We used two mutant lines, with modulated DEK1 activity, a constitutive overexpressor for DEK1 CALPAIN domain and a point mutant in CALPAIN domain, dek1-4. In Chapter 3 we demonstrated that DEK1 regulates dynamics of Cellulose Synthase Complexes (CSCs). Both lines showed decreased crystalline cellulose contents. This led us to investigate if velocity of CSCs in cotyledons, was affected, since it is known that changes in cellulose contents are often caused by defects in CSC. We found that bothDEK1 modulated lines we used have significantly decreased velocity of CSCs. We have also examined plasma membrane turnover rates of CSCs and found out that after photo-bleaching OE CALPAIN has much faster recovery rates compared to Col-0 wild type, while dek1-4 has lower exocytotic rates of CSCs, and much longer life-time of CSCs inserted into the plasma membrane. These results suggested that DEK1 regulates different aspects of CSC dynamics, possibly through interaction with different regulatory proteins. Decrease in cellulose contents we observed in DEK1 modulated lines, prompted us to investigate how this reflects biomechanics and structural properties of epidermal cotyledon cell walls of DEK1 modulated lines, which is described in Chapter 4. To achieve this, we developed a novel microdissection method for isolation and mechanical and structural characterization of native epidermal cell wall monolayers using atomic force microscopy (AFM). AFM force spectroscopy assays showed that both DEK1 modulated lines had stiffer cell walls compared to Col-0. This was awkward since we initially detected decrease in crystalline cellulose which implied decrease in cell wall stiffness. However, subsequent high-resolution AFM imaging has revealed that DEK1 modulate lines cells walls have their cellulose microfibrils organized in thicker bundles than Col-0. Also, polysaccharide composition analysis has revealed that DEK1 modulated lines have increased abundance of pectins, which could also be responsible for the observed increase in cell wall stiffness. Previous work has shown that different dek1 mutants and modulated lines have defects in cell-to-cell adhesion. This implied that DEK1 may be involved in sensing and/or maintaining cell wall integrity (CWI). We performed several growth assays to determine role of DEK1 in CWI, which is described in Chapter 5. We performed cellulose synthesis perturbation assays with cellulose synthesis inhibitor Isoxaben and obtained very interesting results. While OE CALPAIN plants were hypersensitive to Isoxaben, dek1-4 has shown complete insensitivity. Furthermore, a regular CWI maintenance response, reported in A. thaliana as result of compromised CWI, ectopic lignification in seedlings’ roots was absent in both DEK1 modulated lines we examined. We detected interesting growth response of DEK1 lines to NaCl and mannitol treatments as well. Although these findings are pointing out that DEK1 could be part of CWI signalling pathways, more experiments are necessary to fully elucidate possible role of DEK1 in CWI sensing and/or maintenance pathways, especially to check if DEK1 is interacting with Catharanthus roseus Receptor Like Kinase group of CWI sensors. Studies on 4-month old short day grown DEK1 modulated lines, have shown defects in branching, with development of fasciated stem branches in a DEK1 modulated line overexpressing CALPAIN domain (Amanda et al., 2017). This result pointed out to a possibility that DEK1 may regulate organ morphogenesis and patterning at the level of shoot apical meristem (SAM). Work towards elucidating role of DEK1 in SAM maintenance and organ patterning is detailed in Chapter 6. We determined that OE CALPAIN had significantly larger central zone of SAM as well as larger individual SAM cells in central zone, as well as higher distribution of cell sizes, implying possible cell expansion defects. dek1-4 did not exhibited changes in SAM central zone size or individual stem cell size, but it seemed that it had increased number of stem cells in SAM central zone. Both DEK1 lines had perturbation of phyllotaxis on SAM level, with disturbed divergence angles between floral primordia. Disturbed phyllotaxis was also observed between siliques, in mature plants. In addition to this, OE CALPAIN has exhibited occurrence of multiple (up to four) siliques growing from a single stem node. All this is pointing out that DEK1 might participate in hormone-signalling in the SAM.. DEK1 is a highly intriguing protein. However, since it is a unigene, and in addition to that, a regulatory protease, it probably participates in multiple signalling pathways, which makes understanding its function much more complicated. KW - DEK1 KW - atomic force microscopy KW - cellulose microfibrils KW - shoot apical meristem KW - phyllotaxis KW - biomechanics KW - cellulose synthase complex KW - cell wall Y1 - 2021 ER - TY - THES A1 - Nacak, Selma T1 - Synthesis and Characterization of Upconversion Nanaparticles for Applications in Life Sciences Y1 - 2021 ER - TY - THES A1 - Mogrovejo Arias, Diana Carolina T1 - Assessment of the frequency and relevance of potentially pathogenic phenotypes in microbial isolates from Arctic environments N2 - The Arctic environments constitute rich and dynamic ecosystems, dominated by microorganisms extremely well adapted to survive and function under severe conditions. A range of physiological adaptations allow the microbiota in these habitats to withstand low temperatures, low water and nutrient availability, high levels of UV radiation, etc. In addition, other adaptations of clear competitive nature are directed at not only surviving but thriving in these environments, by disrupting the metabolism of neighboring cells and affecting intermicrobial communication. Since Arctic microbes are bioindicators which amplify climate alterations in the environment, the Arctic region presents the opportunity to study local microbiota and carry out research about interesting, potentially virulent phenotypes that could be dispersed into other habitats around the globe as a consequence of accelerating climate change. In this context, exploration of Arctic habitats as well as descriptions of the microbes inhabiting them are abundant but microbial competitive strategies commonly associated with virulence and pathogens are rarely reported. In this project, environmental samples from the Arctic region were collected and microorganisms (bacteria and fungi) were isolated. The clinical relevance of these microorganisms was assessed by observing the following virulence markers: ability to grow at a range of temperatures, expression of antimicrobial resistance and production of hemolysins. The aim of this project is to determine the frequency and relevance of these characteristics in an effort to understand microbial adaptations in habitats threatened by climate change. The isolates obtained and described here were able to grow at a range of temperatures, in some cases more than 30 °C higher than their original isolation temperature. A considerable number of them consistently expressed compounds capable of lysing sheep and bovine erythrocytes on blood agar at different incubation temperatures. Ethanolic extracts of these bacteria were able to cause rapid and complete lysis of erythrocyte suspensions and might even be hemolytic when assayed on human blood. In silico analyses showed a variety of resistance elements, some of them novel, against natural and synthetic antimicrobial compounds. In vitro experiments against a number of antimicrobial compounds showed resistance phenotypes belonging to wild-type populations and some non-wild type which clearly denote human influence in the acquisition of antimicrobial resistance. The results of this project demonstrate the presence of virulence-associated factors expressed by microorganisms of natural, non-clinical environments. This study contains some of the first reports, to the best of our knowledge, of hemolytic microbes isolated from the Arctic region. In addition, it provides additional information about the presence and expression of intrinsic and acquired antimicrobial resistance in environmental isolates, contributing to the understanding of the evolution of relevant pathogenic species and opportunistic pathogens. Finally, this study highlights some of the potential risks associated with changes in the polar regions (habitat melting and destruction, ecosystem transition and re-colonization) as important indirect consequences of global warming and altered climatic conditions around the planet. N2 - Die Arktis ist ein reiches und dynamisches Ökosystem, welches von Mikroorganismen dominiert wird, die unter extremen Bedingungen überleben und funktionieren können. Eine Reihe physiologischer Anpassungen ermöglichen es der Mikrobiota, in diesem Lebensraum zu überdauern niedrige Temperaturen, geringe Wasser- und Nährstoffverfügbarkeit, hohe UV-Strahlung, usw. standzuhalten. Andere Fähigkeiten zielen darauf ab, sich einen Konkurrenzvorteil zu verschaffen, indem sie mit antimikrobiellen Substanzen benachbarte Mikroorganismen stören und die intermikrobielle Kommunikation beeinflussen. Arktische Mikroorganismen sind Bioindikatoren, die Klimaveränderungen anzeigen können. Die Arktis bietet Möglichkeiten, die lokale Mikrobiota zu untersuchen, um Rückschlüsse auf den Klimawandel zu ziehen. Insbesondere Forschung über potenziell pathogene Phänotypen, die infolge der Beschleunigung des Klimawandels in andere Lebensräume auf der ganzen Welt verteilt werden könnten, ist hier von herausragender Bedeutung. In diesem Zusammenhang gibt es zahlreiche Untersuchungen zur Erforschung arktischer Lebensräume sowie Beschreibungen der in ihnen lebenden Mikroben, während über bakterielle Konkurrenzstrategien, die üblicherweise mit Virulenz und Krankheitserregern verbunden sind, bisher wenig geforscht wurde. In diesem Projekt wurden Umweltproben aus der Arktis entnommen und Bakterien und Pilze isoliert. Die klinische Relevanz dieser Mikroorganismen wurde durch Untersuchung der folgenden Virulenzmarker bewertet: Fähigkeit, in einem bestimmten Temperaturbereich zu wachsen, Expression von Antibiotikaresistenz und Produktion von Hämolysinen. Ziel dieses Projekts war es, das Vorkommen dieser Eigenschaften zu bestimmen, um die mikrobiellen Anpassungen in vom Klimawandel bedrohten Lebensräumen zu verstehen. Die beschriebenen Bakterienisolate konnten in einem relevanten Temperaturbereich wachsen, in einigen Fällen von mehr als 30 °C höher als ihre ursprüngliche Isolationstemperatur. Eine beträchtliche Anzahl der Isolate exprimierte konsistent Verbindungen, die Schaf- und Rindererythrozyten auf Blutagar bei verschiedenen Inkubationstemperaturen lysieren können. Die Extrakte einiger dieser Bakterien konnten eine schnelle und vollständige Lyse von Schaf- und Rindererythrozytensuspensionen verursachen und sind möglicherweise sogar hämolytisch gegenüber humanem Blut. Darüber hinaus zeigten Genomanalysen eine Vielzahl von Resistenzgenen gegen natürliche und synthetische antimikrobielle Verbindungen, einige neuartige. In-vitro-Experimente zeigten, dass einige Resistenzphänotypen zu Wildtyp-Populationen während andere zu Nicht-Wildtyp gehören, was auf einen menschlichen Einfluss auf den Erwerb von Antibiotikaresistenzen in der Umwelt eindeutig hindeutet. Die Ergebnisse dieses Projekts zeigen das Vorhandensein von Virulenz-assoziierten Faktoren, die von Mikroorganismen natürlicher, nicht klinischer Umgebungen exprimiert werden. Diese Studie enthält nach unserem besten Wissen einige der ersten Berichte über hämolytische Mikroben, die aus der Arktis isoliert wurden. Darüber hinaus liefert es zusätzliche Informationen über das Vorhandensein und die Expression von intrinsischer und erworbener antimikrobieller Resistenz in Umweltisolaten und trägt zum Verständnis der Entwicklung relevanter pathogener Spezies und opportunistischer Pathogene bei. Schließlich beleuchtet diese Studie einige der potenziellen Risiken, die mit Veränderungen in den Polarregionen (Schmelzen und Zerstörung des Lebensraums, Übergang des Ökosystems und Wiederbesiedlung) als wichtige indirekte Folgen der globalen Erwärmung und veränderter klimatischer Bedingungen auf dem Planeten verbunden sind. KW - Arctic KW - pathogens KW - virulence KW - hemolysis KW - antimicrobial resistance KW - climate change KW - bacteria KW - fungi KW - thermotolerance KW - antibiotic resistance KW - Arktis KW - Krankheitserreger KW - Virulenz KW - Hämolyse KW - Antibiotikaresistenz KW - Klimawandel KW - Bakterien KW - Pilze KW - Thermotoleranz Y1 - 2021 N1 - The author would like to acknowledge that the project leading to this doctoral dissertation has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 675546, research project “Microorganisms in Warming Arctic Environments - MicroArctic”. ER - TY - THES A1 - Mancini, Carola T1 - Analysis of the effects of age-related changes of metabolic flux on brown adipocyte formation and function N2 - Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis, thereby allowing mammals to maintain a constant body temperature in a cold environment. Thermogenic capacity of this tissue is due to a high mitochondrial density and expression of uncoupling protein 1 (UCP1), a unique brown adipocyte marker which dissipates the mitochondrial proton gradient to produce heat instead of ATP. BAT is actively involved in whole-body metabolic homeostasis and during aging there is a loss of classical brown adipose tissue with concomitantly reduced browning capacity of white adipose tissue. Therefore, an age-dependent decrease of BAT-related energy expenditure capacity may exacerbate the development of metabolic diseases, including obesity and type 2 diabetes mellitus. Given that direct effects of age-related changes of BAT-metabolic flux have yet to be unraveled, the aim of the current thesis is to investigate potential metabolic mechanisms involved in BAT-dysfunction during aging and to identify suitable metabolic candidates as functional biomarkers of BAT-aging. To this aim, integration of transcriptomic, metabolomic and proteomic data analyses of BAT from young and aged mice was performed, and a group of candidates with age-related changes was revealed. Metabolomic analysis showed age-dependent alterations of metabolic intermediates involved in energy, nucleotide and vitamin metabolism, with major alterations regarding the purine nucleotide pool. These data suggest a potential role of nucleotide intermediates in age-related BAT defects. In addition, the screening of transcriptomic and proteomic data sets from BAT of young and aged mice allowed identification of a 60-kDa lysophospholipase, also known as L-asparaginase (Aspg), whose expression declines during BAT-aging. Involvement of Aspg in brown adipocyte thermogenic function was subsequently analyzed at the molecular level using in vitro approaches and animal models. The findings revealed sensitivity of Aspg expression to β3-adrenergic activation via different metabolic cues, including cold exposure and treatment with β3-adrenergic agonist CL. To further examine ASPG function in BAT, an over-expression model of Aspg in a brown adipocyte cell line was established and showed that these cells were metabolically more active compared to controls, revealing increased expression of the main brown-adipocyte specific marker UCP1, as well as higher lipolysis rates. An in vitro loss-of-function model of Aspg was also functionally analyzed, revealing reduced brown adipogenic characteristics and an impaired lipolysis, thus confirming physiological relevance of Aspg in brown adipocyte function. Characterization of a transgenic mouse model with whole-body inactivation of the Aspg gene (Aspg-KO) allowed investigation of the role of ASPG under in vivo conditions, indicating a mild obesogenic phenotype, hypertrophic white adipocytes, impairment of the early thermogenic response upon cold-stimulation and dysfunctional insulin sensitivity. Taken together, these data show that ASPG may represent a new functional biomarker of BAT-aging that regulates thermogenesis and therefore a potential target for the treatment of age-related metabolic disease. KW - adipose tissue KW - aging KW - nutrients KW - metabolism KW - Fettgewebe KW - Alterung KW - Stoffwechsel KW - Nährstoffe Y1 - 2021 U6 - https://doi.org/10.25932/publishup-51266 ER - TY - THES A1 - Malmedie, Lydia T1 - Translating and organzing a wicked problem BT - making sense of the EU promoting human rights for LGBTI persons in Uganda Y1 - 2021 ER - TY - THES A1 - Makowski, Silvia T1 - Discriminative Models for Biometric Identification using Micro- and Macro-Movements of the Eyes N2 - Human visual perception is an active process. Eye movements either alternate between fixations and saccades or follow a smooth pursuit movement in case of moving targets. Besides these macroscopic gaze patterns, the eyes perform involuntary micro-movements during fixations which are commonly categorized into micro-saccades, drift and tremor. Eye movements are frequently studied in cognitive psychology, because they reflect a complex interplay of perception, attention and oculomotor control. A common insight of psychological research is that macro-movements are highly individual. Inspired by this finding, there has been a considerable amount of prior research on oculomotoric biometric identification. However, the accuracy of known approaches is too low and the time needed for identification is too long for any practical application. This thesis explores discriminative models for the task of biometric identification. Discriminative models optimize a quality measure of the predictions and are usually superior to generative approaches in discriminative tasks. However, using discriminative models requires to select a suitable form of data representation for sequential eye gaze data; i.e., by engineering features or constructing a sequence kernel and the performance of the classification model strongly depends on the data representation. We study two fundamentally different ways of representing eye gaze within a discriminative framework. In the first part of this thesis, we explore the integration of data and psychological background knowledge in the form of generative models to construct representations. To this end, we first develop generative statistical models of gaze behavior during reading and scene viewing that account for viewer-specific distributional properties of gaze patterns. In a second step, we develop a discriminative identification model by deriving Fisher kernel functions from these and several baseline models. We find that an SVM with Fisher kernel is able to reliably identify users based on their eye gaze during reading and scene viewing. However, since the generative models are constrained to use low-frequency macro-movements, they discard a significant amount of information contained in the raw eye tracking signal at a high cost: identification requires about one minute of input recording, which makes it inapplicable for real world biometric systems. In the second part of this thesis, we study a purely data-driven modeling approach. Here, we aim at automatically discovering the individual pattern hidden in the raw eye tracking signal. To this end, we develop a deep convolutional neural network DeepEyedentification that processes yaw and pitch gaze velocities and learns a representation end-to-end. Compared to prior work, this model increases the identification accuracy by one order of magnitude and the time to identification decreases to only seconds. The DeepEyedentificationLive model further improves upon the identification performance by processing binocular input and it also detects presentation-attacks. We find that by learning a representation, the performance of oculomotoric identification and presentation-attack detection can be driven close to practical relevance for biometric applications. Eye tracking devices with high sampling frequency and precision are expensive and the applicability of eye movement as a biometric feature heavily depends on cost of recording devices. In the last part of this thesis, we therefore study the requirements on data quality by evaluating the performance of the DeepEyedentificationLive network under reduced spatial and temporal resolution. We find that the method still attains a high identification accuracy at a temporal resolution of only 250 Hz and a precision of 0.03 degrees. Reducing both does not have an additive deteriorating effect. KW - Machine Learning Y1 - 2021 ER - TY - THES A1 - Liu, Yue T1 - Polymeric objects switchable between two shapes N2 - As the ongoing trend of developing smart materials that can reversibly switch geometry stimulated by environmental control addressed increasing attention in many research fields, especially for biomedical or soft robotic applications. Shape-memory polymers (SMPs), which can change shape, stiffness, size, and structure when exposed to an external stimulus, are intensively explored as encouraging material candidates for achieving multifunctionality, and for miniaturizing into micro-components to expand the applications. Besides, the geometrical design has gained growing attention for creating engineering applications, such as bi-stable mechanisms, and has the potential to be explored by implementing SMP for new functions. In this context, this thesis aimed to develop smart micro-/nano-objects based on SMP and explore new functions by geometrical design using SMP. Here, two types of stimuli-responsive objects capable of one-way temperature-memory effect (TME) or free-standing reversible actuation e.g., micro/nanofibers (i) and microcuboids (ii) at different aspects were explored. At first, it was hypothesized that the advanced atomic force microscopy (AFM) platform can be established to study individual polymeric micro-/nanofibers (i) in terms of incorporation and characterization of a reversible shape-memory actuation capability. Crystallizable material was chosen for preparing the fibers and the molecular alignment within the fibers among different diameters will influence the crystallization-induced elongation during cooling that determined the reversible effect. For the second type, microcuboids (ii), it was hypothesized that a programming and quantification approach can be developed to enable the realization and characterization of a one-way micro-TME and micro-shape-memory polymer actuation (SMPA) in microcuboids. The responsive temperature of one-way shape transformation can be tuned by programming temperature (Tp) and the separation temperature (Tsep) for post-programming can influence the actuation. Finally, a geometrical design with bi-stability was combined with SME to create new functions of shape actuation. It was hypothesized that the predicted bi-stable or mono-stable structures can be achieved with the aid of digital fabrication methods. Using shape-memory effect (SME), the alteration of bi-stable and mono-stable can initiate shape transformation with a larger magnitude and higher energy output. In the first part, the method to quantify the reversible SMPA of a single micro/nano crystallizable fiber with geometry change during the actuation was explored. Electrospinning was used to prepare poly (ε-caprolactone) (PCL) micro/nanofiber with different diameters, which were fixed by UV glue and crosslinked on the structured silicon wafer. Using AFM, the programming, as well as the observation of recovery and reversible displacement of the fiber, were performed by vertical three-point bending at the free suspended part. A plateau tip was chosen to achieve stable contact and longer working distance for performing larger deformation, enabling intensified reversible SMPA of single fibers. In this way, programming strains of 39 ± 1% or 46 ± 1% were realized for fiber with a diameter of 1 ± 0.2 µm and 300 ± 50 nm, which were bent at 80 °C and fixed at 10 °C. Values for the reversible elongation of εrev = 3.4 ± 0.1% and 10.5 ± 0.1% were obtained for a single micro and nanofiber respectively between 10 and 60 °C. The higher actuation effect observed for nanofiber demonstrated that the highly compact and oriented crystallites in nanofibers, which determined the pronounced εrev compared to the thick microfibers. Besides, a stable reversible actuation of a nanofiber can be tracked by AFM tip up to 10 cycles, indicating a sustainable application can be achieved on the fiber actuators. The findings obtained for cPCL micro-/nano-fibers will help design and evaluate the next generation polymeric microactuators or micromanipulators. The second part of the thesis studies the shape-memory effect (SME) of a single individual SMP micro-object by controlling deformation temperatures during programming and actuation temperatures during reversible change. In this work, microcuboids of crosslinked poly[ethylene-co-(vinyl acetate)] (cPEVA) elastomers with 18 wt% vinyl acetate (VA) contents were successfully prepared by template-based replication from polydimethylsiloxane (PDMS) mold. The micro-TME and micro-SMPA were observed and studied based on micro-geometry change using optical microscopy (OM) and AFM. Different switching temperatures of shape recovery were achieved from 55 °C to 86 °C by tuning Tp from 55 °C to 100 °C, indicating a successful implementation of micro-TME on individual microcuboid. For micro-SMPA functionalization, microcuboids were deformed by compression at 100 °C and the change in single particle height was monitored during cyclic heating and cooling between various Tseps from 60 °C to 85 °C and 20 °C. The micro-SMPA on a single microcuboid was achieved with a reversible strain in the range of 2 to 7%, whereby higher compression ratio CR and Tsep induced prominent reversible strain. The results achieved in this work demonstrated the successful functionalization of microcuboids with different SMEs by controlling temperatures during programming and actuation processes. Based on these achievements, such micro-objects can be further designed as on demand switchable microactuators or release systems with adjustable working temperatures. In the last part of the work, a new function of shape-memory polymeric bi-stable 3D structured film was designed and fabricated. The SME and geometrical design of compliant mechanics were merged to enable switching between bi-stable and mono-stable states, which generate snap movement that mimics the Venus flytrap. A truncated tetrahedron structure with a slope angle as a tunable parameter to alter the bi-stability was chosen for the study to combine with SME. It was anticipated that the structured film designed with a slope angle of 30° exhibited mono-stable behavior, and such a structure with a slope angle of 45° exhibited bi-stable behavior. Then the structured SMP film of designed mono-stable shape was successfully fabricated using soft lithography based on 3D printed master molds supported from digital manufacturing. The structured mold was also used in programming the SMP film into the structure with a higher slope angle to attain bi-stability. Finally, the switching between bi-stable and mono-stable states was successfully realized using SME, which introduces snapping movement triggered by heat. The implementation of compliant mechanisms by the SME increased the magnitude of thermally induced reconfiguration without additional external force. To sum up, the results of the thesis support the development of smart objects capable of one-way micro-TME, free-standing reversible actuation, or bi-stability mediated shape-memory reconfiguration. Electrospinning and template-based method were used for fabrication with good control of geometry and low size dispersity. Microscopy methods especially the AFM platform with decent sensitivity was developed for implementation as well as characterization of SME on individual micro-/nanoobjects. Implementation of bi-stability improves the shape transformation amplitude of thermally triggered SMP. These findings can give novel insights for designing polymer-based actuators or soft robotics. KW - shape-memory polymer KW - compliant mechanism KW - atomic force microscopy Y1 - 2021 ER - TY - THES A1 - Liu, Sisi T1 - The history of plant diversity change and community assemply a high-altitude and high-latitude ecosystems inferred from sedimentary (ancient) DNA and pollen Y1 - 2021 ER - TY - THES A1 - Krause, Michael T1 - Digital surveillance fiction BT - dataveillance in contemporary science fiction Y1 - 2021 SN - 978-3-86938-154-1 PB - AVINUS CY - Hamburg ER - TY - THES A1 - Knox-Brown, Patrick Frank T1 - Towards understanding the sequence-structure-function relationship of intrinsically disordered LEA_4 proteins from Arabidopsis thaliana N2 - Water-deficits can cause lethal damage to organisms, which is rooted in cellular dehydration. Many plant species, but also other organisms have developed mechanisms to tolerate such stresses, such as the expression of LEA proteins. Many studies report on physiological protective functions of LEA proteins but lack information about their precise mechanisms on a molecular level. Most LEA proteins are intrinsically disordered in dilute solution but may adopt a distinct secondary structure upon changes in solvent conditions. Understanding the molecular mechanism of how LEA proteins contribute to the counteraction of cellular damage during water-deficits may in the long-term pave the way for breeding crops that are resistant to the effects of global warming. The objective of the work at hand is to improve the biophysical understanding of the sequencestructure-function relationship of LEA proteins as membrane stabilizers, based on the LEA_4 family of the model plant A. thaliana. This is pursued by using a combination of spectroscopic and scattering techniques, supported by bioinformatics and computational analyses. Eight out of the 18 LEA_4 proteins are experimentally assessed revealing that a coil-helix transition in response to water-deficit is a common feature, as predicted for the entire family. In addition, they all stabilize simple membrane models during a freeze/ thaw cycle. Three-dimensional structure prediction of representative members suggests that their completely folded states are represented by a sequential arrangement of alpha-helical segments connected by unstructured linkers, which is experimentally verified for the LEA_4 protein COR15A. The unstructured linker region of COR15A represents a conserved motif among its closest homologs and is, therefore, of particular interest. Facilitating a set of seven designed and investigated COR15A mutants uncovers a complex interplay of transient interactions between the amphipathic alpha-helical segments, mediated by the linker, which fine-tunes folding transitions and structural ensembles upon reduced water-availability. Finally, alpha-helicity is also induced in COR15A upon temperature decrease, which is enhanced in the presence of osmolytes. In addition, high solution osmolarity induced secondary structure is followed by oligomerization of COR15A. Interestingly, the functionality of COR15A, in terms of liposome stabilization, strongly correlates with its alpha-helix ratio in the folded state. The present work significantly improves the understanding of the sequence-structure-function relationship for LEA_4 proteins and offers novel findings on folding mechanisms and oligomerization of COR15A. N2 - Wasserdefizite können zu letalem Schaden von Organismen führen, der letztendlich aus zellulärer Dehydrierung resultiert. Viele Pflanzen, aber auch andere Organismen haben Mechanismen entwickelt, um solche Stressfaktoren zu tolerieren, z.B. die Expression von LEAProteinen. Diverse Studien beschreiben deren physiologische Schutzfunktionen, es fehlen jedoch Informationen ihrer präzisen Mechanismen auf molekularer Ebene. Die meisten LEA-Proteine sind in wässriger Lösung intrinsisch unstrukturiert, können jedoch in Reaktion auf veränderte Lösungsmittelbedingungen geordnete Strukturen ausbilden. Ein solides Verständnis ihrer molekularen Mechanismen führt daher über die Entschlüsselung ihrer Sequenz-StrukturFunktions-Beziehungen, welche langfristig den Weg zur Entwicklung von Pflanzen ebnen, die Resistenzen gegen die Auswirkungen der globalen Erwärmung aufweisen.. Ziel der vorliegenden Arbeit ist, das Verständnis der Sequenz-Struktur-Funktions-Beziehung der LEA_4-Familie aus der Modellpflanze A. thaliana zu verbessern. Dazu wird eine Kombination von Spektroskopie- und Streutechniken (unterstützt durch prädiktive Computeranalysen) verwendet. Alle acht experimentell untersuchten der insgesamt 18 LEA_4-Proteine zeigen einen Coil-Helix-Übergang in Reaktion auf Wasserdefizit als gemeinsames Merkmal und stabilisieren einfache Membranmodelle während eines Gefrier-/ Tau-Vorgang. Die dreidimensionale Strukturvorhersage repräsentativer LEA_4-Proteine deutet an, dass der gefaltete Zustand einer Abfolge alpha-helikaler Segmente unterbrochen durch unstrukturierte Domänen entspricht, was für das LEA_4-Protein COR15A experimentell belegt wird. Der unstrukturierte Linker, der die beiden alpha-helikalen Segmente von COR15A verbindet, stellt ein Motiv dar, das innerhalb der nächsten Homologen konserviert ist und ist daher von besonderem Interesse. Mithilfe von sieben entworfenen und untersuchten COR15A-Mutanten kann der komplexe Zusammenhang transienter Wechselwirkungen zwischen den amphipathischen, alpha-helikalen Segmenten, vermittelt durch den Linker, gezeigt werden. Dieser spielt eine zentrale Rolle in der Feinabstimmung von Faltungsübergängen und strukturellen Ensembles bei verringerter Wasserverfügbarkeit. Ferner wird gezeigt, dass alpha-helikale Struktur auch durch Temperaturerniedrigung induziert werden kann, was in Gegenwart von Osmolyten stärker ausgeprägt ist. Hohe Osmolaritäten induzieren außerdem eine Oligomerisierung von COR15A. Interessanterweise korreliert die Funktionalität von COR15A (die Stabilisierung von Liposomen) stark mit dem relativen alpha-Helix-Anteil im gefalteten Zustand. Die vorliegende Arbeit verbessert erheblich das Verständnis für eine Sequenz-StrukturFunktions-Beziehung für LEA_4-Proteine und bietet neue Erkenntnisse zu Faltungsmechanismen und Oligomerisierung von COR15A. KW - IDPs KW - alpha-helix KW - coil-helix KW - linker KW - structure-function KW - protein-folding KW - LEA Y1 - 2021 ER - TY - THES A1 - Keles, Engin T1 - Atmospheric properties and dynamics of gaseous exoplanets inferred from high-resolution alkali line transmission spectroscopy N2 - The characterization of exoplanets applying high-resolution transmission spectroscopy ini- tiated a new era making it possible to trace atmospheric signature at high altitudes in exoplanet atmospheres and to determine atmospheric properties which enrich our under- standing of the formation and evolution of the solar system. In contrast to what is observed in our solar system, where gaseous planets orbit at wide orbits, Jupiter type exoplanets were detected in foreign stellar systems surrounding their host stars within few days, in close orbits, the so called hot- and ultra-hot Jupiters. The most well studied ones are HD209458b and HD189733b, which are the first exoplanets where absorption is detected in their atmospheres, namely from the alkali line sodium. For hot Jupiters, the resonant alkali lines are the atmospheric species with one of the strongest absorption signatures, due to their large absorption cross-section. However, al- though the alkali lines sodium and potassium were detected in low-resolution observations for various giant exoplanets, potassium was absent in different high-resolution investiga- tions in contrast to sodium. The reason for this is quite puzzling, since both alkalis have very similar physical and chemical properties (e.g. condensation and ionization proper- ties). Obtaining high-resolution transit observations of HD189733b and HD209458b, we were able to detect potassium on HD189733b (Manuscript 1), which was the first high-resolution detection of potassium on an exoplanet. The absence of potassium on HD209458b could be reasoned by depletion processes, such as condensation or photo-ionization or high-altitude clouds. In a further study (Manuscript II), we resolved the potassium line and compared this to a previously detected sodium absorption on this planet. The comparison showed, that the potassium lines are either tracing different altitudes and temperatures compared to the sodium lines, or are depleted so that the planetary Na/K- ratio is way larger than the stellar one. A comparison of the alkali lines with synthetic line profiles showed that the sodium lines were much broader than the potassium lines, probably being induced by winds. To investigate this, the effect of zonal streaming winds on the sodium lines on Jupiter-type planets is investigated in a further study (Manuscript III), showing that such winds can significantly broaden the Na- lines and that high-resolution observations can trace such winds with different properties. Furthermore, investigating the Na-line observations for different exoplanets, I showed that the Na-line broadening follows a trend with cooler planets showing stronger line broadening and so hinting on stronger winds, matching well into theoretical predictions. Each presented manuscript depends on the re- sults published within the previous manuscript, yielding a unitary study of the exoplanet HD189733b. The investigation of the potassium absorption required to account for different effects: The telluric lines removal and the effect of center-to-limb variation (see Manuscript I), the residual Rossiter-Mc-Laughlin effect (see Manuscript II) and the broadening of spectral lines on a translucent atmospheric ring by zonal jet streams (see Manuscript III). This thesis shows that high-resolution transmission spectroscopy is a powerful tool to probe sharp alkali line absorption on giant exoplanet atmospheres and to investigate on the properties and dynamics of hot Jupiter type atmospheres. KW - planets and satellites: atmospheres KW - planets and satellites: composition KW - planets and satellites: gaseous planets KW - exoplanets Y1 - 2021 ER - TY - THES A1 - Kaptur, Joanna Alexandra T1 - The LEUNIG regulatory complex BT - how does it control shoot apical meristem formation and its postembryonic activity? N2 - Patterning along the apical-basal (A-B) axis is a crucial step during the early stages of plant embryogenesis and leads to the establishment of two poles of which each will develop their own stem cell niches. The activity of these meristems is responsible for post-embryonic growth, with the shoot apical meristem (SAM) generating the above-ground organs and the root apical meristem (RAM) producing the subterranean structures of the plant. While several transcriptional regulators governing A-B patterning have been identified, precisely how their regulatory function is orchestrated remains elusive. This study focuses on transcriptional co-regulators LEUNIG (LUG) and closely related LEUNIG_HOMOLOG (LUH) and their role in the formation of A-B patterning during embryogenesis as well as their post-embryonic maintenance. A link between the LUG regulatory complex and SAM formation and maintenance comes from the observation that lug mutants heterozygous for the luh allele (lug luh+/-) often have enlarged SAMs resulting from misregulated cell divisions. A more severe phenotype is observed in lug luh double mutants which are embryonically lethal. In this study, a detailed characterisation of lug luh embryo phenotype reveals that these mutants display aberrant cell divisions along the A-B axis, which correlates with defects in auxin distribution, complete loss of apical identity, and altered expression of transcription factors determining basal fate. Like other co-regulators, LUG and LUH lack intrinsic DNA-binding domains and instead must interact with DNA-binding cofactors to ensure recruitment to regulatory elements of target genes. This either involves direct contact between the co-regulators and transcription factors (TFs) or the formation of higher-order complexes with adaptor proteins such as SEUSS (SEU) or related SEUSS-LIKEs (SLKs), which facilitate binding to specific TFs. Results presented in this study provide insight into the molecular framework for the LUG regulatory complex activity during embryogenesis. Both yeast and in planta assays showed that LUG/LUH and SEU/SLKs physically associate with a variety of WUSCHEL-RELATED HOMEOBOX (WOX) TFs including members of the WOX2-module. Furthermore, genetic interactions between members of the WOX2-module and the LUG regulatory complex, support their mutual action during embryogenesis. Based on the reduced activity of HOMEODOMAIN LEUCINE-ZIPPER CLASS III (HD-ZIPIII) promoters in lug luh embryos, a model is proposed in which the LUG regulatory complex functions together with WOX2-module to promote apical identity and subsequent SAM initiation through regulation of the HD-ZIPIIIs. The activity of the LUG complex in promoting basal embryo identity through positive regulation of microRNA165/166 suggests that this complex also has functions that are independent of the WOX2-module. Preliminary work reported in this study further uncovered the role of the LUG regulatory complex in post-embryonic development. While the fasciated inflorescence meristems of lug luh+/- plants displayed defects in auxin transport and altered activity of stem cell markers, embryonically rescued lug luh mutants formed flat and differentiated SAMs. In addition, rescued lug luh mutants exhibited severely disorganised RAM and defects in quiescent center (QC) specification, supporting the involvement of the LUG complex in post-embryonic RAM maintenance. KW - LEUNIG LEUNIG_HOMOLOG SEUSS SEUSS-LIKEs Arabidopsis embryogenesis WOX2-module HD-ZIPIII Y1 - 2021 ER - TY - THES A1 - Hébert, Raphaёl T1 - Investigation of vegetation and terrestrial climate variablity during the holocene BT - bridging the gap from annual to millennial timescales Y1 - 2021 ER - TY - THES A1 - Huang, Sichao T1 - Past and present biodiversity in northeastern Siberia inferred from sedimentary DNA metabarcoding N2 - The arctic-boreal treeline is a transition zone from taiga to tundra covering a vast area in Siberia. It often features large environmental gradients and reacts sensitively to changes in the environment. For example, the expansion of shrubs and a northward movement of the treeline are observable in Siberia as a response to the warming climate. The changes in vegetation across the treeline are known to influence the water chemistry in the lakes. This causes further alteration to the composition and diversity of sensitive aquatic organisms such as diatoms and macrophytes. Despite the rising awareness of the complex climate-feedback mechanisms of terrestrial plants, the understanding of their assembly rules and about responses of aquatic biomes in the surrounding treeline lakes is still limited. The goal of this thesis is to examine the previous and present biodiversity of terrestrial and freshwater biomes from the Siberian treeline ecotone, as well as their reactions to environmental changes. In particular, this thesis attempts to examine the performance of applying sedimentary DNA metabarcoding in terrestrial plants, aquatic macrophytes and diatoms, their spatial patterns along the environmental gradients and their temporal patterns throughout the climate transition from the late Pleistocene to Holocene. Sedimentary DNA metabarcoding combined with next-generation sequencing is applied as a primary tool to explore the composition and diversity of terrestrial plants, diatoms and aquatic macrophytes. The main study area is located in Chukotka of northeastern Siberia in the Arctic, a biodiversity hotspot due to its continental location and the diverse habitats of the glacial refugium. The modern diatom diversity was assessed with a specific diatom metabarcoding marker and morphological identification. Both approaches agree to a dominance of Fragilariaceae and Aulacoseiraceae, as well as on the environmental influential indicators of the diatom community. The high diversity of Fragilariaceae identified in the thermokarst lakes is found to follow the vegetation gradient along the treeline, suggesting that diatom metabarcoding can decipher relationships between diatom assemblage shifts and the relevant environmental changes. In particular, the metabarcoding approach detects diversification of fragilarioids in glacial lakes which is not visible using morphology. Sedimentary ancient DNA records indicate a vegetation mosaic of forb-dominated steppe-tundra during 28-19 ka, followed by a shift to dwarf-shrub tundra during 19-14 ka. During the most recent 14 thousand years, the vegetation consists of deciduous shrublands, then a change to boreal forest is observed. Investigations on the alpha diversity of the vegetation show that species richness is unexpectedly highest during pre-LGM, which is likely related to the extensive area that allows for more taxa. The optimum Holocene warming during 9-6 ka is not accompanied by a high richness as widely believed, but with an evenly distributed community by the fulfilment of erect shrubs. Furthermore, changes in taxonomic and phylogenetic diversity show complementary results in understanding community diversity. The composition and richness in the modern macrophytes community from Siberian Arctic and Chinese alpine are best co-influenced by July temperature and electrical conductivity.. Past macrophyte turnover during the late Pleistocene-Holocene is less noticeable in Siberia, whereas a pronounced community change from emergent to submerged plants is detected from Chinese alpine regions at about 14 ka due to increasing temperature and varying water conductivity. Finally, sedimentary DNA metabarcoding is a cost-effective and powerful proxy for ecological application, whereas completeness of the reference library, coverage and resolution of the metabarcoding marker are the major limitations of sedimentary DNA based diversity monitoring. The composition and richness in modern vegetation and macrophytes across broad spatial gradients is constrained by environmental variables, suggesting a potential usage for environmental monitoring. Diatom distributions are driven by different water variables along the treeline. Past records indicate that the shrub coverage has a noticeable influence on the assemblies of both terrestrial plants and aquatic macrophytes, though the shift in macrophyte community is relatively minor in the past 28 thousand years. In the long-term, the shrub expansion may eventually result in a genetically more diverse vegetation community but reduced species richness. When exceeding the optimal temperatures, further warming may lead to a decrease and putative loss of macrophytes and diatoms. N2 - Die arktisch-boreale Baumgrenze ist eine Übergangszone von Taiga zu Tundra, die ein weites Gebiet in Sibirien abdeckt. Es weist häufig große Umweltgradienten auf und reagiert empfindlich auf Änderungen in der Umwelt. Beispielsweise sind in Sibirien als Reaktion auf das sich erwärmende Klima die Ausdehnung von Sträuchern und eine Bewegung der Baumgrenze nach Norden zu beobachten. Es ist bekannt, dass die Veränderungen der Vegetation entlang der Baumgrenze die Wasserchemie in den Seen beeinflussen. Dies führt zu einer weiteren Veränderung der Zusammensetzung und Vielfalt empfindlicher Wasserorganismen wie Kieselalgen und Makrophyten. Trotz des zunehmenden Bewusstseins für die komplexen Klimarückkopplungsmechanismen von Landpflanzen ist das Verständnis ihrer Zusammensetzung und der Reaktionen aquatischer Biome in den umliegenden Baumseen immer noch begrenzt. Ziel dieser Arbeit ist es, die bisherige und gegenwärtige Artenvielfalt von Land- und Süßwasserbiomen aus dem sibirischen Baumlinien-Ökoton sowie deren Reaktionen auf Umweltveränderungen zu untersuchen. In dieser Arbeit wird insbesondere versucht, die Leistung der Anwendung der sedimentären DNA-Metabarkodierung in Landpflanzen, aquatischen Makrophyten und Kieselalgen, ihre räumlichen Muster entlang der Umweltgradienten und ihre zeitlichen Muster während des Klimaübergangs vom späten Pleistozän zum Holozän zu untersuchen. Die metabolische DNA-Metabarkodierung in Kombination mit der “Next generation Sequencing” wird als primäres Instrument zur Untersuchung der Zusammensetzung und Vielfalt von Landpflanzen, Kieselalgen und aquatischen Makrophyten eingesetzt. Das Hauptuntersuchungsgebiet befindet sich in Chukotka im Nordosten Sibiriens in der Arktis, einem Hotspot für Artenvielfalt aufgrund seiner kontinentalen Lage und der vielfältigen Lebensräume des Gletscher-Refugiums. Die moderne Diatomeendiversität wurde mit einem spezifischen Diatom-Metabarcoding Marker und einer morphologischen Identifizierung bewertet. Beide Ansätze stimmen mit einer Dominanz von Fragilariaceae und Aulacoseiraceae sowie mit den umweltbeeinflussenden Indikatoren der Kieselalgengemeinschaft überein. Die hohe Vielfalt der in den Thermokarstseen identifizierten Fragilariaceae folgt dem Vegetationsgradienten entlang der Baumgrenze, was darauf hindeutet, dass die Metabarkodierung von Kieselalgen Beziehungen zwischen Verschiebungen der Kieselalgenassemblage und den relevanten Umweltveränderungen entschlüsseln kann. Insbesondere erkennt der Metabarcoding-Ansatz eine Diversifikation von Fragilarioiden in Gletscherseen, die unter Verwendung der Morphologie nicht sichtbar ist. Sedimentäre alte DNA-Aufzeichnungen weisen auf ein Vegetationsmosaik der von Forb dominierten Steppentundra zwischen 28 und 19 ka hin, gefolgt von einer Verschiebung in die Zwergstrauch-Tundra zwischen 19 und 14 ka. In den letzten 14.000 Jahren besteht die Vegetation aus Laubbäumen, dann wird eine Veränderung des borealen Waldes beobachtet. Untersuchungen zur Alpha-Diversität der Vegetation zeigen, dass der Artenreichtum vor der LGM unerwartet am höchsten ist, was wahrscheinlich mit dem ausgedehnten Gebiet zusammenhängt, das mehr Taxa zulässt. Die optimale Erwärmung des Holozäns während 9-6 ka geht nicht mit einem hohen Reichtum einher, wie allgemein angenommen wird, sondern mit einer gleichmäßig verteilten Gemeinschaft durch die Erfüllung aufrecht stehender Sträucher. Darüber hinaus zeigen Änderungen der taxonomischen und phylogenetischen Vielfalt komplementäre Ergebnisse für das Verständnis der Vielfalt in der Gemeinschaft. Die Zusammensetzung und der Reichtum der modernen Makrophytengemeinschaft aus der sibirischen Arktis und den chinesischen Alpen werden am besten von der Temperatur im Juli und der elektrischen Leitfähigkeit beeinflusst. Der vergangene Makrophytenumsatz während des späten Pleistozän-Holozäns ist in Sibirien weniger auffällig, während in chinesischen Alpenregionen bei etwa 14 ka aufgrund der steigenden Temperatur und der unterschiedlichen Wasserleitfähigkeit ein ausgeprägter Wechsel der Gemeinschaft von emergenten zu untergetauchten Pflanzen festgestellt wird. Schließlich ist die Sediment-DNA-Metabarkodierung ein kostengünstiger und leistungsfähiger Proxy für die ökologische Anwendung, während die Vollständigkeit der Referenzbibliothek, die Abdeckung und die Auflösung des Metabarkodierungsmarkers die Hauptbeschränkungen der auf Sediment-DNA basierenden Diversitätsüberwachung darstellen. Die Zusammensetzung und der Reichtum an moderner Vegetation und Makrophyten über breite räumliche Gradienten hinweg werden durch Umgebungsvariablen eingeschränkt, was auf eine mögliche Verwendung für die Umweltüberwachung hindeutet. Die Verteilung der Kieselalgen wird durch verschiedene Wasservariablen entlang der Baumgrenze gesteuert. Frühere Aufzeichnungen zeigen, dass die Strauchbedeckung einen spürbaren Einfluss auf die Ansammlungen von Landpflanzen und Wassermakrophyten hat, obwohl die Verschiebung der Makrophytengemeinschaft in den letzten 28.000 Jahren relativ gering ist. Langfristig kann die Strauchausdehnung letztendlich zu einer genetisch vielfältigeren Vegetationsgemeinschaft führen, die jedoch den Artenreichtum verringert. Wenn die optimalen Temperaturen überschritten werden, kann eine weitere Erwärmung zu einer Abnahme und einem mutmaßlichen Verlust von Makrophyten und Kieselalgen führen. KW - metabarcoding KW - plant diversity KW - iatom diversity KW - phylogenetic diversity KW - ancient DNA Y1 - 2021 ER - TY - THES A1 - Hoffmann, Julia T1 - Influence of artificial light at night on the behavior of small mammals T1 - Der Einfluss von künstlicher nächtlicher Beleuchtung auf das Verhalten von Kleinsäugern N2 - Artificial light at night (ALAN), one form of human-induced rapid environmental change, is continuously spreading in space and time and increasing in intensity as part of the ongoing urbanization. A vast range of animals is known to be affected by ALAN as, among other things, it can mask natural light cues and change both the perceived as well as the actual predation risk. Since ALAN per se is restricted to the night, the majority of studies so far have focused on nocturnal species or behavioral changes during the night. How polyphasic species respond to ALAN has been largely overlooked, although they can possibly carry over effects of nighttime illumination into the day. Additionally, individuals within a species are known to consistently differ in their personality which includes risk-taking behavior. While this implies that ALAN can lead to varying anti-predatory responses in animals within a population, knowledge on this topic is still very limited. This thesis aims at investigating what initial behavioral reaction is caused by ALAN in polyphasic small mammals while also incorporating an animal’s personality. Nighttime and daytime activity, movement and foraging behavior of the bank vole (Myodes glareolus) were investigated in regards to effects of different light intensities and partial illumination in the laboratory. Additionally, changes in intra- and interspecific interactions of bank voles and striped field mice (Apodemus agrarius) subjected to ALAN were studied in experimental populations in semi-natural outdoor enclosures. Chapter I explores whether behavioral responses to ALAN of varying intensity are related to animal personality. Results showed that bank voles reduced movement and foraging already under dim light and that bold animals generally moved and foraged more than shy animals. Exclusively under bright illumination did bold animals exploit the food patches more than shy animals. The results demonstrate that bank voles are affected by light intensities prevalent in urban habitats. Additionally, certain light scenarios might lead to an advantage of and a shift towards certain personality types. Chapter II focusses on the effects of partial ALAN on foraging behavior of animals with varying animal personalities while extending the view towards possible carry-over effects of ALAN into the daytime. While bank voles reduced foraging behavior in illuminated areas at night, they increased foraging behavior in those areas at the subsequent day. Bold individuals generally had lower giving-up densities than shy individuals but this difference was especially pronounced during daytime at formerly illuminated food patches. Thus, ALAN can have carry-over effects into the daytime in polyphasic animals and thus has the potential to affect daytime intra- and interspecific interactions. Chapter III broadens the view from the individual to the population level. Experimental populations consisting of bank voles and striped field mice were established in large outdoor enclosures successively experienced natural and artificial light conditions at night. VHF telemetry data revealed that animals were predominantly active during the day under natural conditions. This difference between day and night vanished under ALAN. Additionally, conspecifics reduced home range overlap, proximity and activity synchrony while boldness was not associated with behavioral changed due to ALAN. The results suggest that ALAN has the potential to alter intraspecific interactions and thus can have fitness consequences on the population level. Overall, the present thesis shows that ALAN can affect nighttime and daytime behavior as well as intraspecific interactions of polyphasic small mammals. Differences in risk- taking behavior of individuals may vary in importance depending on other environmental variables. Thus, this thesis hopefully triggers broadening the view regarding the role of an animal’s personality in coping with ALAN and the effects on daytime behavior and diurnal species. N2 - Künstliche Beleuchtung bei Nacht ist eine Form schnell eintretender Umweltveränderung, die durch den Menschen verursacht wird. Sie breitet sich in Raum und Zeit kontinuierlich aus und nimmt, als Teil der fortschreitenden Urbanisierung, stetig an Intensität zu. Ein breites Spektrum an Tieren wird von künstlicher Beleuchtung beeinflusst, da sie unter anderem natürliche Lichtsignale maskieren und sowohl das wahrgenommene als auch das reale Prädationsrisiko verändern kann. Da künstliche Beleuchtung an sich auf die Nacht beschränkt ist, hat sich ein Großteil der bisher durchgeführten Studien auf ihre Effekte auf nachtaktive Tierarten bzw. nächtliche Verhaltensweisen beschränkt. Jedoch wurde bisher kaum untersucht, auf welche Weise Tiere mit einem polyphasischen Aktivitätsrhythmus auf künstliche Beleuchtung reagieren, obwohl sie möglicherweise Effekte von künstlicher Beleuchtung bei Nacht auf den Tag übertragen können. Zusätzlich ist bekannt, dass sich Individuen einer Art konsistent in ihrer Tierpersönlichkeit unterscheiden, welche ihr Risikoverhalten einschließt. Während dies darauf hindeutet, dass künstliche Beleuchtung bei Nacht unterschiedliche antiprädatorische Verhaltensanpassungen bei Tieren innerhalb einer Population hervorrufen kann, sind die Kenntnisse über diesen Themenkomplex bisher sehr gering. Diese Doktorarbeit hat zum Ziel, die anfänglichen Verhaltensänderungen von polyphasischen Kleinsäugern, welche durch künstliche Beleuchtung bei Nacht hervorgerufen werden, zu untersuchen. Zusätzlich wird die Persönlichkeit der Tiere berücksichtigt. Es wurden Aktivität, Bewegungsmuster und Nahrungssuchverhalten in der Nacht und am Tag von Rötelmäusen (Myodes glareolus) in Bezug auf die Effekte verschiedener Lichtintensitäten und partieller Beleuchtung bei Nacht untersucht. Während diese Versuche im Labor stattfanden, wurde zusätzlich ein Versuch in semi- natürlichen Außengehegen durchgeführt. In diesem lag der Fokus auf Veränderungen in intra- und interspezifischen Interaktionen innerhalb künstlicher Populationen bestehend aus Rötelmäusen und Brandmäusen (Apodemus agrarius), welche bei Nacht künstlicher Beleuchtung ausgesetzt waren. Kapitel I untersucht inwiefern Verhaltensänderungen aufgrund künstlicher Beleuchtung bei Nacht mit der Persönlichkeit der Tiere in Verbindung stehen. Die Ergebnisse zeigen, dass Rötelmäuse ihre Bewegung und die Nahrungssuche bereits unter schwacher nächtlicher Beleuchtung reduzierten. Risikofreudigere Tiere bewegten sich mehr und suchten häufiger nach Nahrung als weniger risikofreudige Tiere. Diese Resultate verdeutlichen, dass Rötelmäuse durch solche Lichtintensitäten beeinträchtigt werden, wie sie für urbane Habitate typisch sind. Bestimmte Lichtszenarien könnten zudem zu einem Vorteil für und eine Selektion auf bestimmte Persönlichkeitstypen führen. Kapitel II konzentriert sich auf die Effekte, welche eine partielle Beleuchtung auf das Nahrungssuchverhalten von Tieren haben kann, welche sich hinsichtlich ihrer Persönlichkeit unterscheiden. Zusätzlich wird untersucht, inwiefern künstliche Beleuchtung bei Nacht auch am Tag zu Verhaltensveränderungen führen kann. Während die Rötelmäuse bei Nacht ihre Nahrungssuche in beleuchteten Bereichen einschränkten, zeigten sie dort eine gesteigerte Nahrungssuche am folgenden Tag. Risikofreudigere Tiere beuteten die Futterstellen stärker aus als weniger risikofreudige Tiere, wobei dieser Unterschied am Tag in den ehemals beleuchteten Futterstellen besonders stark war. Somit kann künstliche Beleuchtung in der Nacht auch Effekte auf das Verhalten von polyphasischen Tieren am Tag haben. Sie hat somit das Potential am Tag vorkommende intra- und interspezifische Interaktionen zu beeinflussen. Kapitel III weitet schließlich den Blickwinkel von der Individuen- hin zur Populationsebene. Es wurden experimentelle Populationen bestehend aus Rötelmäusen und Brandmäusen in großen Außengehegen etabliert, welche zuerst natürliche Lichtbedingungen und anschließend künstliche Beleuchtung bei Nacht erfuhren. Durch die Nutzung von UKW-Telemetriedaten konnte gezeigt werden, dass die Tiere unter natürlichen Lichtbedingungen vorwiegend tagaktiv waren. Dieser Unterschied in der Aktivität zwischen Tag und Nacht verschwand bei künstlicher Beleuchtung bei Nacht. Zusätzlich reduzierten Artgenossen die Überlappung ihrer Aktionsräume, ihre Nähe zueinander und die Synchronität ihrer Aktivitätszeiten. Risikobereitschaft beeinflusste die gezeigten Verhaltensveränderungen unter künstlicher Beleuchtung bei Nacht nicht. Die Resultate deuten darauf hin, dass künstliche Beleuchtung bei Nacht intraspezifische Interaktionen beeinflussen kann und somit potentiell Konsequenzen für die Fitness auf der Populationsebene haben kann. Zusammenfassend kann diese Doktorarbeit zeigen, dass künstliche Beleuchtung bei Nacht sowohl das Verhalten bei Nacht und bei Tag als auch intraspezifische Interaktionen von polyphasischen Kleinsäugern beeinflussen kann. Wie stark Unterschiede im Risikoverhalten von Individuen eine Rolle spielen, könnte von anderen Umweltfaktoren abhängen, welche mit der künstlichen Beleuchtung interagieren. Diese Arbeit bewirkt so hoffentlich eine Erweiterung des Blickwinkels, indem zukünftig die Rolle von Tierpersönlichkeiten im Umgang mit künstlicher Beleuchtung bei Nacht und die Effekte dieser Beleuchtung auf das Verhalten am Tag sowie tagaktive Arten berücksichtigt werden. KW - light pollution KW - human-induced rapid environmental change KW - urbanization KW - movement KW - activity KW - Lichtverschmutzung KW - anthropogene Umweltveränderungen KW - Urbanisation KW - Fortbewegung KW - Aktivität Y1 - 2021 ER - TY - THES A1 - Heywood Jones, David T1 - Moses Hirschel and Enlightenment Breslau BT - A City and its Jews in the Late Eighteenth Century N2 - Breslau has been almost entirely forgotten in the Anglophone sphere as a place of Enlightenment. Moreover, in the context of the Jewish Enlightenment, Breslau has never been discussed as a place of intercultural exchange between German-speaking Jewish, Protestant and Catholic intellectuals. The story of Moses Hirschel offers us an excellent case-study to investigate the complex reciprocal relationship between Jewish and non-Jewish enlighteners in a prosperous and influential Central European city on the cusp of the 18th century. KW - Haskalah KW - Moses Hirschel KW - Breslau KW - enlightenment KW - Mendelssohn Y1 - 2021 SN - 978-3-030-46234-5 SN - 978-3-030-46235-2 U6 - https://doi.org/10.1007/978-3-030-46235-2 PB - Palgrave Macmillan CY - Cham ER - TY - THES A1 - Herpich, Catrin T1 - Fibroblast growth factor 21 and its association with nutritional stimuli in older age N2 - Fibroblast growth differentiation factor 21 (FGF21) is known as a pivotal regulator of the glucose and lipid metabolism. As such, it is considered beneficial and has even been labelled a longevity hormone. Nevertheless, recent observational studies have shown that FGF21 is increased in higher age with possible negative effects such as loss of lean and bone mass as well as decreased survival. Hepatic FGF21 secretion can be induced by various nutritional stimuli such as starvation, high carbohydrate and fat intake as well as protein deficiency.. So far it is still unclear whether the FGF21 response to different macronutrients is altered in older age. An altered response would potentially contribute to explain the higher FGF21 concentrations found in older age. In this publication-based doctoral dissertation, a cross-sectional study as well as a dietary challenge were conducted to investigate the influence of nutrition on FGF21 concentrations and response in older age. In a cross-sectional study, FGF21 concentrations were assessed in older patients with and without cachexia anorexia syndrome anorexia syndrome compared to an older community-dwelling control group. Cachexia anorexia syndrome is a multifactorial syndrome frequently occurring in old age or in the context of an underlying disease. It is characterized by a severe involuntary weight loss, loss of appetite (anorexia) and reduced food intake, therefore representing a state of severe nutrient deficiency, in some aspects similar to starvation. The highest FGF21 concentrations were found in patients with cachexia anorexia syndrome. Moreover, FGF21 was positively correlated with weight loss and loss of appetite. In addition, cachexia anorexia syndrome itself was associated with FGF21 independent of sex, age and body mass index. As cachectic patients presumably exhibit protein malnutrition and FGF21 has been proposed a marker for protein insufficiency, the higher levels of FGF21 in patients with cachexia anorexia syndrome might be partly explained by insufficient protein intake. In order to investigate the acute response of FGF21 to different nutritional stimuli, a dietary challenge with a parallel group design was conducted. Here, healthy older (65-85 years) and younger (18-35 years) adults were randomized to one of four test meals: a dextrose drink, a high carbohydrate, high fat or high protein meal. Over the course of four hours, postprandial FGF21 concentrations (dynamics) were assessed and the FGF21 response (incremental area under the curve) to each test meal was examined.. In a sub-group of older and younger women, also the adiponectin response was investigated, as adiponectin is a known mediator of FGF21 effects on glucose and lipid metabolism. The dietary meal challenge revealed that dextrose and high carbohydrate intake result in higher FGF21 concentrations after four hours in older adults. This was partly explained by higher postprandial glucose concentrations in the old. For high fat ingestion no age differences were found. For the first time, acute FGF21 response to high protein intake was shown. Here, protein ingestion resulted in lower FGF21 concentrations in younger compared to older adults. Furthermore, sufficient protein intake, according to age-dependent recommendations, of the previous day, was associated with lower FGF21 concentrations in both age groups. The higher FGF21 response to dextrose ingestion resulted in a higher adiponectin response in older women, independent of fat mass, insulin resistance, triglyceride concentrations, inflammation and oxidative stress. Following the high fat meal, adiponectin concentrations declined in older women. Adiponectin response was not affected by meal composition in younger women. In summary, this thesis showed a positive association of FGF21 and cachexia anorexia syndrome with concomitant anorexia in older patients. Regarding the acute FGF21 response, a higher response following dextrose and carbohydrate ingestion was found in older compared with younger subjects. This might be attributed to a higher glucose response in older age. Furthermore, it was shown that the higher FGF21 response after dextrose ingestion possibly contributes to a higher adiponectin response in older women, independent of potential metabolic and inflammatory confounders. Acute protein ingestion resulted in a significant decrease in FGF21 concentrations. Moreover, protein intake of the previous day was inversely associated with fasting FGF21 concentrations. This might explain why FGF21 concentrations are higher in cachexia anorexia syndrome. These results therefore support the role of FGF21 as a sensor of protein restriction. N2 - Der Fibroblasten Wachstumsfaktor 21 (FGF21) gilt als wichtiger Regulator des Glukose- und Fettstoffwechsels. Es werden ihm verschiedene förderliche Eigenschaften zugeschrieben und er wurde darüber hinaus als Langlebigkeitshormon bezeichnet. Nichtsdestotrotz konnten Beobachtungsstudien zeigen, dass FGF21 Konzentration im Alter erhöht sind und möglicherweise mit negativen Auswirkungen, wie dem Verlust von Muskel- und Knochenmasse sowie einer geringeren Überlebenswahrscheinlichkeit, verbunden sind. FGF21 Sekretion in der Leber kann durch Hungern und verschiedene Makronährstoffe, wie hohe Kohlenhydrat- und Fettaufnahme, sowie einem Proteinmangel, induziert werden. Bisher ist jedoch unklar, ob sich die FGF21 Response auf verschiedene Makronährstoffe zwischen älteren und jüngeren Erwachsenen unterscheidet. Eine veränderte Response, könnte dazu beitragen die höheren FGF21 Konzentrationen im Alter zu erklären. In dieser vorliegenden kumulativen Dissertation wurden eine Querschnittsstudie sowie ein experimenteller Mahlzeitentest durchgeführt, um den Einfluss von Ernährung auf FGF21 Konzentrationen und die FGF21 Response im Alter zu untersuchen. In der Querschnittsstudie wurden FGF21 Konzentration von älteren PatientInnen mit und ohne Kachexie-Anorexie Syndrom sowie einer älteren Kontrollgruppe verglichen. Kachexie-Anorexie Syndrom ist ein multifaktorielles Syndrom, welches häufig im Alter und im Rahmen verschiedener Erkrankungen auftritt. Charakteristisch hierfür ist ein starker ungewollter Gewichtsverlust, Appetitverlust (Anorexie) sowie eine verminderte Nahrungsaufnahme. Daher repräsentiert das Kachexie-Anorexie Syndrom einen Zustand des schwerwiegenden Nährstoffmangels, der mit Unterernährung bei langanhaltenden Hungerphasen vergleichbar ist. Die höchsten FGF21 Konzentrationen wiesen PatientInnen mit Kachexie-Anorexie Syndrom auf. Des Weiteren korrelierte FGF21 positiv mit Gewichts- und Appetitverlust. Zusätzlich war das Kachexie-Anorexie Syndrom unabhängig von Alter, Geschlecht und BMI mit FGF21 assoziiert. Es ist davon auszugehen, dass PatientInnen mit Kachexie-Anorexie Syndrom eine unzureichende Proteinzufuhr aufweisen. Da FGF21 als Marker für Proteinrestriktion gilt, könnten die hohen FGF21 Konzentrationen bei Kachexie-Anorexie Syndrom teilweise durch eine zu geringe Proteinzufuhr erklärt werden. Um die akute Response von FGF21 auf verschiedene Makronährstoffe zu untersuchen, wurde ein Mahlzeitentest mit parallelen Gruppen durchgeführt. Hierfür erhielten ältere (65-85 Jahre) und jüngere (18-35 Jahre) Erwachsene eine von vier verschiedenen Testmahlzeiten (Dextrose Getränk, Kohlenhydrat-, Fett- und Proteinreiche Mahlzeit). Über vier Stunden wurden postprandiale FGF21 Konzentrationen (Dynamik) bestimmt und die FGF21 Response (inkrementelle Fläche unter der Kurve) auf jede Testmahlzeit untersucht. In einer Subgruppe von älteren und jüngeren Frauen wurde außerdem die Adiponektin Response bestimmt, da Adiponektin bekanntermaßen die Effekte von FGF21 auf den Glukose- und Fettstoffwechsel mediiert. Der Mahlzeitentest konnte zeigen, dass Dextrose und die kohlenhydratreiche Mahlzeit bei älteren Erwachsenen zu höheren FGF21 Konzentrationen nach vier Stunden führten. Dies könnte durch die höheren postprandialen Glukose Konzentrationen der Älteren erklärt werden. Die FGF21 Response auf die fettreiche Mahlzeit wies keine Altersunterschiede auf. Zum ersten Mal konnte die akute FGF21 Response auf eine proteinreiche Mahlzeit gezeigt werden. Hierbei führte die Mahlzeit bei jüngeren im Vergleich zu älteren Erwachsenen zu niedrigeren FGF21 Konzentration nach vier Stunden. Des Weiteren, war das Erreichen der altersspezifischen Proteinzufuhr des Vortrags bei beiden Altersgruppen mit niedrigeren nüchtern FGF21 Konzentrationen assoziiert. Bei älteren Frauen führte die höhere FGF21 Response nach Dextrose Aufnahme zu einer höheren Adiponektin Response, unabhängig von Fettmasse, Insulinresistenz, Triglyzeride Konzentrationen, Inflammation und oxidativem Stress. Nach Einnahme der fettreichen Mahlzeit sanken die Adiponektin Konzentrationen bei älteren Frauen, während bei jüngeren Frauen die Adiponektin Response nicht durch die Zusammensetzung der Mahlzeit beeinflusst wurde. Zusammenfassend konnte diese Dissertation eine positive Assoziation von FGF21 mit Kachexie-Anorexie Syndrom bei gleichzeitiger Anorexie bei älteren PatientInnen zeigen. Bezüglich der akuten Response von FGF21 zeigte sich eine höhere Response auf Dextrose und Kohlenhydrat-Aufnahme bei älteren im Vergleich zu jüngeren ProbandInnen. Dies ist vermutlich auf die erhöhte Glukose Response im Alter zurückzuführen. Des Weiteren konnte gezeigt werden, dass eine höhere FGF21 Response auf Dextrose bei älteren Frauen mit einer veränderten Adiponektin Response einhergingen, unabhängig von potentiellen metabolischen und inflammatorischen Einflussfaktoren. Eine akute hohe Proteinaufnahme führte zu einem deutlichen Abfall der postprandialen FGF21 Konzentrationen. Zudem bestand eine inverse Assoziation zwischen FGF21 Nüchternkonzentrationen und der Proteinzufuhr des Vortags. Dies könnte zum Teil erklären, warum FGF21 Konzentrationen bei Kachexie-Anorexie Syndrom erhöht sind. Demnach unterstützen diese Ergebnisse auch die Rolle von FGF21 als Sensor für Proteinrestriktion. KW - Ageing KW - FGF21 KW - protein KW - postprandial response Y1 - 2021 ER - TY - THES A1 - Heinzel, Mirko Noa T1 - World Bank staff and project implementation BT - the importance of country-specific knowledge Y1 - 2021 ER - TY - THES A1 - Hebisch, Benjamin T1 - Power in supply chain negotiations: a two-stage approach T2 - Schriftenreihe zum Verhandlungsmanagement ; Band 15 N2 - Negotiations between buyers and suppliers directly influence a company’s costs, revenue, and consequently its profits. The outcome of these negotiations relies heavily on the companies’ as well as the negotiators’ power position. Across three empirical articles the author demonstrates how the own power position can first be identified as well as improved and subsequently used to maximize profits in negotiations between sellers and buyers. In the first paper the sources underlying buyer and supplier power are identified and weighted. The results of the first paper show the impact of each single sources on the buyer and supplier power. The number of suppliers available for one product is by far the most important source of power for both sides. The results indicate that a higher number of suppliers leads to a better power position of the buyer and simultaneously to an inferior power position of a single supplier. The second paper aims to examine the impact of the number of suppliers on the outcome of buyer-seller-negotiations thereby considering the innovation level of the products purchased. The results of the second study which are based on real negotiation data from a German car manufacturer indicate that the number of available suppliers has a stronger impact on the negotiation outcome for innovative than for functional, less innovative products. The third paper analyzes how the ability to take the counterpart’s perspective (perspective taking ability) influences the negotiation outcome. This relationship is examined for different power positions. The results indicate that a negotiator’s high perspective taking ability leads to a more unfavorable negotiation outcome compared to low perspective taking ability. Simultaneously, high perspective taking ability causes a more positive perception of the conducted negotiation than low perspective taking ability. This contradictory effect of perspective taking ability bears the risk for buyers and suppliers to assess an unfavorable outcome as positive. Finally, the results of the papers are summarized and discussed. The dissertation concludes with implications for practice, limitations of the work, and approaches for future research. N2 - Verhandlungen zwischen Einkäufern und Zulieferern haben einen unmittelbaren Einfluss auf die Kosten und den Umsatz eines Unternehmens und sind dementsprechend ein wichtiger Faktor für deren Gewinn. Das Ergebnis dieser Verhandlungen hängt maßgeblich von der Machtposition der Unternehmen und damit auch der Verhandler ab. In dieser Studie wird in den drei empirischen Artikeln gezeigt, wie die Machtposition zunächst identifiziert sowie verbessert und anschließend gewinnmaximierend in Verhandlungen zwischen Verkäufern und Einkäufern eingesetzt werden kann. Im ersten Paper werden die der Macht von Einkäufern und Lieferanten zu Grunde liegenden Ursachen identifiziert und gewichtet. Die Ergebnisse des ersten Papers zeigen, wie stark die einzelnen identifizierten Faktoren die Macht des Einkäufers und des Vertriebs beeinflussen. Die Anzahl der für ein Produkt zur Verfügung stehenden Lieferanten ist für beide Seiten die mit Abstand wichtigste Ursache für Macht. Es wird herausgestellt, dass eine höhere Anzahl an Lieferanten zu einer besseren Machtposition des Einkäufers und gleichzeitig zu einer schlechteren Machtposition des Verkäufers führt. Das Ziel des zweiten Papers ist es, den Einfluss der Anzahl der Lieferanten auf das Ergebnis von Verhandlungen zwischen Einkäufern und Verkäufern zu untersuchen. Dabei werden die verschiedenen Innovationsgrade der zu beschaffenden Produkte berücksichtigt. Auf Basis realer Verhandlungsdaten eines deutschen Automobilerstellers wird gezeigt, dass die Anzahl der für ein Produkt zur Verfügung stehenden Lieferanten bei innovativen Produkten einen stärkeren Einfluss auf das Verhandlungsergebnis hat als bei funktionalen, weniger innovativen Produkten. Das dritte Paper ermittelt, wie die Fähigkeit, die Perspektive der Gegenseite einzunehmen (Perspective Taking Ability) das Verhandlungsergebnis beeinflusst. Dieser Zusammenhang wird für verschiedene Machtpositionen untersucht. Die Ergebnisse lassen darauf schließen, dass hohe Perspective Taking Ability eines Verhandlungsführerenden in der besseren Machtposition zu einem schlechteren Ergebnis führt als niedrige Perspective Taking Ability. Gleichzeitig führt eine hohe Ausprägung der Fähigkeit zu einer positiveren Wahrnehmung der geführten Verhandlung als eine niedrige Ausprägung. Dieser gegensätzliche Effekt von Perspective Taking Ability birgt für Einkäufer und Verkäufer in einer überlegenen Machtposition das Risiko, ein schlechteres Verhandlungsergebnis positiv zu bewerten. Die Ergebnisse der Studien werden am Ende der Dissertation zusammengefasst und diskutiert. Es werden Implikationen für die Praxis abgeleitet sowie Limitationen und Ansätze zukünftiger Forschung aufgezeigt. KW - Automotive KW - Business-to-Business KW - Experiment KW - Expertenbefragung KW - Negotiation KW - Supply Chain Management KW - Verhandlungsmanagement Y1 - 2021 SN - 978-3-339-12400-5 SN - 978-3-339-12401-2 PB - Kovac CY - Hamburg ER - TY - THES A1 - Hadad, Yemima T1 - History of Forgetfulness BT - Dialogue and Hasidism in Martin Buber's Theopolitics Y1 - 2021 ER - TY - THES A1 - Grum, Marcus T1 - Construction of a concept of neuronal modeling N2 - The business problem of having inefficient processes, imprecise process analyses, and simulations as well as non-transparent artificial neuronal network models can be overcome by an easy-to-use modeling concept. With the aim of developing a flexible and efficient approach to modeling, simulating, and optimizing processes, this paper proposes a flexible Concept of Neuronal Modeling (CoNM). The modeling concept, which is described by the modeling language designed and its mathematical formulation and is connected to a technical substantiation, is based on a collection of novel sub-artifacts. As these have been implemented as a computational model, the set of CoNM tools carries out novel kinds of Neuronal Process Modeling (NPM), Neuronal Process Simulations (NPS), and Neuronal Process Optimizations (NPO). The efficacy of the designed artifacts was demonstrated rigorously by means of six experiments and a simulator of real industrial production processes. N2 - Die vorliegende Arbeit addressiert das Geschäftsproblem von ineffizienten Prozessen, unpräzisen Prozessanalysen und -simulationen sowie untransparenten künstlichen neuronalen Netzwerken, indem ein Modellierungskonzept zum Neuronalen Modellieren konstruiert wird. Dieses neuartige Konzept des Neuronalen Modellierens (CoNM) fungiert als flexibler und effizienter Ansatz zum Modellieren, Simulieren und Optimieren von Prozessen mit Hilfe von neuronalen Netzwerken und wird mittels einer Modellierungssprache, dessen mathematischen Formalisierung und technischen Substanziierung sowie einer Sammlung von neuartigen Subartefakten beschrieben. In der Verwendung derer Implementierung als CoNM-Werkzeuge können somit neue Arten einer Neuronalen-Prozess-Modellierung (NPM), Neuronalen-Prozess-Simulation (NPS) sowie Neuronalen-Prozess-Optimierung (NPO) realisiert werden. Die Wirksamkeit der erstellten Artefakte wurde anhand von sechs Experimenten demonstriert sowie in einem Simulator in realen Produktionsprozessen gezeigt. T2 - Konzept des Neuronalen Modellierens KW - Deep Learning KW - Artificial Neuronal Network KW - Explainability KW - Interpretability KW - Business Process KW - Simulation KW - Optimization KW - Knowledge Management KW - Process Management KW - Modeling KW - Process KW - Knowledge KW - Learning KW - Enterprise Architecture KW - Industry 4.0 KW - Künstliche Neuronale Netzwerke KW - Erklärbarkeit KW - Interpretierbarkeit KW - Geschäftsprozess KW - Simulation KW - Optimierung KW - Wissensmanagement KW - Prozessmanagement KW - Modellierung KW - Prozess KW - Wissen KW - Lernen KW - Enterprise Architecture KW - Industrie 4.0 Y1 - 2021 ER - TY - THES A1 - Förster, Desiree T1 - Aesthetic experience of metabolic processes N2 - Simultaneously speculative and inspired by everyday experiences, this volume develops an aesthetics of metabolism that offers a new perspective on the human-environment relation, one that is processual, relational, and not dependent on conscious thought. In art installations, design prototypes, and researchcreation projects that utilize air, light, or temperature to impact subjective experience the author finds aesthetic milieus that shift our awareness to the role of different sense modalities in aesthetic experience. Metabolic and atmospheric processes allow for an aesthetics besides and beyond the usually dominant visual sense. Y1 - 2021 SN - 978-3-95796-180-8 SN - 978-3-95796-181-5 SN - 978-3-95796-182-2 PB - meson press CY - Lüneburg ER - TY - THES A1 - Engel, Anika T1 - Endocrine effects of plasticizers and the development of a breast cell-based toxicity screening system N2 - Humans are frequently exposed to a variety of endocrine disrupting chemicals (EDCs), which can cause harmful effects, e.g. disturbance of growth, development and reproduction, and cancer (UBA, 2016). EDCs are often components of synthetically manufactured products. Materials made of plastics, building materials, electronic items, textiles or cosmetic products can be particularly contaminated (Ain et al., 2021). One group of EDCs that has gained increased interest in recent years is phthalates. They are used as plasticizers in plastic materials to which people are daily exposed to. Phthalate plasticizers exert their harmful effects among others via activation of the estrogen receptor α (ERα), the estrogen receptor β (ERβ) and via inhibition of the androgen receptor (AR). Some phthalates have already been classified by the EU as Cancerogenic-, Mutagenic-, Reprotoxic- (CMR) substances and their use in industry has been restricted. After oral ingestion, phthalates are metabolized and are finally excreted with the urine. Numerous toxicological studies exist on phthalates, but mainly with the parent substances, not with their primary and secondary metabolites. In the course of the restriction of phthalates by the EU, the phthalate-free plasticizer di-isononylcyclohexane-1,2-dicarboxylate (DINCH®), was introduced to the market. So far, almost no toxicologically relevant properties have been identified for DINCH®. However, the effects of DINCH® have only been studied in animal experiments and, as with phthalates, almost exclusively with the parent substance. However, toxic effects of a particular compound may be induced by its metabolites and not by the parent compound itself. Therefore, potential endocrine effects of 15 phthalates, 19 phthalate metabolites, DINCH®, and five of its metabolites were investigated using reporter gene assays on the ERα, ERβ, and the AR. In addition, studies of the influence of some selected plasticizers on peroxisome proliferator-activated receptor α (PPARα) and peroxisome proliferator-activated receptor γ (PPARγ) activity were performed. Furthermore, a H295R steroidogenesis assay was performed to determine the influence of DINCH® and its metabolites on estradiol or testosterone synthesis. Analysis of the experiments shows that the phthalates either stimulated or inhibited ERα and ERβ activity and inhibited AR activity, whereas the phthalate metabolites did not affect the activity of these human hormone receptors. In contrast, metabolites of di-(2-ethylhexyl) phthalate (DEHP) stimulated transactivation of the human PPARα and PPARγ in analogous reporter gene assays, although DEHP itself did not activate these nuclear receptors. Therefore, primary and secondary phthalate metabolites appear to exert different effects at the molecular level compared to the parent compounds. Similarly, the results showed that the phthalate-free plasticizer DINCH® itself did not affect the activity of ERα, ERβ, AR, PPARα and PPARγ, while the DINCH® metabolites were shown to activate all these receptors. In the case of AR, DINCH® metabolites mainly enhanced AR activity stimulated by dihydrotestosterone (DHT). In the H295R steroidogenesis assay, neither DINCH® nor any of its metabolites affected estradiol or testosterone synthesis. Primary and secondary metabolites of DINCH® thus exert different effects at the molecular level than DINCH® itself. However, all these in vitro effects of DINCH® metabolites were observed only at high concentrations, which were about three orders of magnitude higher than the reported DINCH® metabolite concentrations in human urine. Therefore, the in vitro data does not support the assumption that DINCH® or any of the metabolites studied could have significant endocrine effects in vivo at relevant exposure levels in humans. Following the demonstration of direct and indirect endocrine effects of the studied plasticizers, a new effect-based in vitro 3D screening tool for toxicity assays of non-genotoxic carcinogens was developed using estrogen receptor-negative (ER-) MCF10-A cells and estrogen receptor-positive (ER+) MCF-12A cells. This arose from the background that breast cancer is the most common cancer occurring in women and estrogenic substances, such as phthalates, can probably influence the disease. The human mammary epithelial cell lines MCF-10A and MCF-12A form well-differentiated acini-like structures when cultured in three-dimensional Matrigel culture for a period of 20 days. The model should make it possible to detect substance effects on cell differentiation and growth, on mammary cell acini, and to differentiate between estrogenic and non-estrogenic effects at the same time. In the present study, both cell lines were tested for their suitability as an effect-based in vitro assay system for non-genotoxic carcinogens. An Automated Acinus Detection And Morphological Evaluation (ADAME) software solution has been developed for automatic acquisition of acinus images and determination of morphological parameters such as acinus size, lumen size, and acinus roundness. Several test substances were tested for their ability to affect acinus formation and cellular differentiation. Human epithelial growth factor (EGF) stimulated acinus growth for both cell lines, while all trans retinoic acid (RA) inhibited acinar growth. The potent estrogen 17β-estradiol had no effect on acinus formation of MCF-10A cells but resulted in larger MCF-12A acini. Thus, the parallel use of both cell lines together with the developed high content screening and evaluation tool allows the rapid identification of the estrogenic and cancerogenic properties of a given test compound. The morphogenesis of the acini was only slightly affected by the test substances. On the one hand, this suggests a robust test system, on the other hand, it probably cannot detect low-potent estrogenic compounds such as phthalates or DINCH®. The advantage of the robustness of the system, however, may be that vast numbers of "positive" results with questionable biological relevance could be avoided, such as those observed in sensitive reporter gene assays. N2 - Der Mensch ist häufig einer Vielzahl von endokrin wirksamen Chemikalien (EDCs) ausgesetzt, die schädliche Auswirkungen haben können, z. B. Störungen von Wachstum, Entwicklung und Fortpflanzung sowie Krebs (UBA, 2016). Eine Gruppe von EDCs, die in den letzten Jahren vermehrt an Interesse gewonnen hat, sind die Phthalate. Diese werden als Weichmacher in Kunststoffen verwendet. Einige Phthalate wurden bereits von der EU als Kanzerogene-, Mutagene-, Reproduktionstoxische- (CMR) Stoffe klassifiziert und ihre Verwendung in der Industrie beschränkt. Nach der oralen Aufnahme werden Phthalate metabolisiert und schließlich mit dem Urin ausgeschieden. Für die Phthalate existieren zwar zahlreiche toxikologische Studien, allerdings vorwiegend mit den Ausgangssubstanzen, nicht mit ihren primären und sekundären Metaboliten. Im Zuge der Beschränkung der Phthalate durch die EU wurde der phthalatfreie Weichmacher Diisononylcyclohexan-1,2-dicarboxylat (DINCH®), auf den Markt gebracht. DINCH® werden bisher kaum toxikologisch relevante Eigenschaften zugeordnet. Bislang wurden die Auswirkungen von DINCH® jedoch lediglich in Tierexperimenten untersucht und fast ausschließlich mit der Stamm-Substanz. Aus diesem Grund wurden potentiell endokrine Effekte von 15 Phthalaten, 19 Phthalat-Metaboliten, DINCH® und fünf seiner Metabolite unter Verwendung von Reportergen-Assays auf den ERα, ERβ und den AR untersucht. Zusätzlich wurden Untersuchungen des Einflusses einiger ausgewählter Substanzen auf die Aktivität des Peroxisom-Proliferator-aktivierten Rezeptor α (PPARα) und des Peroxisom-Proliferator-aktivierten Rezeptor γ (PPARγ) durchgeführt. Weiterhin wurde ein H295R-Steroidogenese-Assay durchgeführt, um den Einfluss von DINCH® und seinen Metaboliten auf die Estradiol- oder Testosteronsynthese zu bestimmen. Die Auswertung der Experimente zeigt, dass die Phthalate entweder die ERα- und ERβ-Aktivität stimulierten oder hemmten und die AR-Aktivität hemmten, während die Phthalatmetaboliten keinen Einfluss auf die Aktivität dieser menschlichen Hormonrezeptoren hatten. Im Gegensatz dazu stimulierten die Metaboliten von Di-(2-ethylhexyl) phthalat (DEHP) die Transaktivierung des humanen PPARα und PPARγ in analogen Reportergen-Assays, obwohl DEHP selbst diese Kernrezeptoren nicht aktivierte. Daher scheinen primäre und sekundäre Phthalatmetaboliten im Vergleich zu den Ausgangsverbindungen unterschiedliche Wirkungen auf molekularer Ebene auszuüben. Ebenso zeigten die Ergebnisse, dass der phthaltfreie Weichmacher DINCH® selbst keinen Einfluss auf die Aktivität von ERα, ERβ, AR, PPARα und PPARγ hatte, während die DINCH®-Metaboliten nachweislich alle diese Rezeptoren aktivierten. Im Falle des AR verstärkten die DINCH®-Metaboliten vor allem die durch Dihydrotestosteron (DHT) stimulierte AR-Aktivität. Im H295R-Steroidogenese-Assay beeinflusste weder DINCH® noch einer seiner Metaboliten die Estradiol- oder Testosteronsynthese. Primäre und sekundäre Metabolite von DINCH® üben demnach auf molekularer Ebene andere Effekte aus als DINCH® selbst. Die hier gewonnenen in vitro-Daten unterstützen die Annahme nicht, dass DINCH® oder einer der untersuchten Metaboliten erhebliche endokrine Wirkungen in vivo bei relevanten Expositionsmengen beim Menschen haben könnten. Nachdem endokrine Wirkungen der untersuchten Weichmacher nachgewiesen werden konnten, wurde ein neues wirkungsbasiertes in vitro 3D-Screening-Tool für Toxizitäts-Tests nicht genotoxischer Karzinogene mit östrogenrezeptor-negativen (ER-) MCF10-A-Zellen und östrogenrezeptor-positiven (ER+) MCF-12A-Zellen entwickelt. Dies geschah aus dem Hintergrund, dass Brustkrebs die häufigste Krebsart bei Frauen ist und östrogene Stoffe wie Phthalate die Krankheit vermutlich beeinflussen können. Die humanen Brustepithelzelllinien MCF-10A und MCF-12A bilden gut differenzierte azinusartige Strukturen, wenn sie in dreidimensionaler Matrigel-Kultur über einen Zeitraum von 20 Tagen kultiviert werden. Das Modell sollte es ermöglichen Substanzeffekte auf die Zelldifferenzierung und das Zellwachstum der Brustzell-Azini zu detektieren und dabei gleichzeitig zwischen östrogenen und nicht östrogenen Effekten differenzieren. Eine Softwarelösung zur automatisierten Acinus Detection And Morphological Evaluation (ADAME) wurde zur automatischen Erfassung von Acinus-Bildern und zur Bestimmung morphologischer Parameter wie Azinus-Größe, Lumengröße und Azinus-Rundheit entwickelt. Eine Reihe von Testsubstanzen wurde auf ihre Fähigkeit getestet, die Azinusbildung und die zelluläre Differenzierung zu beeinflussen. Der humane epitheliale Wachstumsfaktor (EGF) stimulierte das Azinuswachstum für beide Zelllinien, während all-trans-Retinsäure (RA) das Azinuswachstum hemmte. Das starke Östrogen 17β-Östradiol hatte keinen Einfluss auf die Azinusbildung von MCF-10A-Azini, führte aber zu größeren MCF-12A-Azini. Die parallele Verwendung beider Zelllinien zusammen mit dem hierbei entwickelten High-Content-Screening- und Evaluierungstool ermöglicht somit die schnelle Identifizierung der östrogenen oder kanzerogenen Eigenschaften einer gegebenen Testverbindung. Die Morphogenese der Azini wurde durch die Testsubstanzen nur geringfügig beeinflusst. Dies spricht einerseits für ein robustes Testsystem, andererseits kann es wahrscheinlich keine niedrigpotenten östrogenen Verbindungen wie Phthalate oder DINCH® erkennen. Der Vorteil der Robustheit des Systems kann jedoch darin liegen, dass eine große Zahl "positiver" Ergebnisse mit fragwürdiger biologischer Relevanz vermieden werden könnte, wie sie bei empfindlichen Reportergen-Assays zu beobachten sind. KW - phthalates KW - 3D breast cell model KW - endocrine disruption Y1 - 2021 U6 - https://doi.org/10.25932/publishup-53117 ER - TY - THES A1 - Dineva, Ekaterina Ivanova T1 - Sun-as-a-star Spectroscopy with PEPSI BT - tracing solar activity in strongchromospheric absorption lines Y1 - 2021 ER - TY - THES A1 - Czapka, Sophia T1 - The bilingual advantage in executive functions and its influence on spelling Y1 - 2021 ER - TY - THES A1 - Brunacci, Nadia T1 - Oligodepsipeptides as matrix for drug delivery systems and submicron particulate carriers Y1 - 2021 ER -