@phdthesis{Gerner2019, author = {Gerner, Frank}, title = {Functional analysis of polarization and podosome formation of murine and human megakaryocytes}, doi = {10.25972/OPUS-16050}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-160508}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {In mammals, blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MK) that extend polarized cell protrusions (proplateles) into BM sinusoids. Proplatelet formation (PPF) requires substantial cytoskeletal rearrangements that have been shown to involve the formation of podosomes, filamentous actin (F-actin) and integrin-rich structures. However, the exact molecular mechanisms regulating MK podosome formation, polarization and migration within the BM are poorly defined. According to current knowledge obtained from studies with other cell types, these processes are regulated by Rho GTPase proteins like RhoA and Cdc42. In this thesis, polarization and podosome formation were investigated in MKs from genetically modified mice, as well as the cell lines K562 and Meg01 by pharmacological modulation of signaling pathways. The first part of this thesis describes establishment of the basic assays for investigation of MK polarization. Initial data on polarization of the MK-like erythroleukemia cell line K562 revealed first insights into actin and tubulin dynamics of wild type (WT) and RhoA knock-out (RhoA-/-) K562 cells. Phorbol 12-myristate 13-acetate (PMA)-induction of K562 cells led to the expected MK-receptor upregulation but also RhoA depletion and altered polarization patterns. The second part of this thesis focuses on podosome formation of MKs. RhoA is shown to be dispensable for podosome formation. Cdc42 is revealed as an important, but not essential regulator of MK spreading and podosome formation. Studies of signaling pathways of podosome formation reveal the importance of the tyrosine kinases Src, Syk, as well as glycoprotein (GP)VI in MK spreading and podosome formation. This thesis provides novel insights into the mechanisms underlying polarization and podosome formation of MKs and reveals new, important information about cytoskeletal dynamics of MKs and potentially also platelets.}, subject = {Megakaryozyt}, language = {en} } @phdthesis{Selle2007, author = {Selle, Reimer Andreas}, title = {Adaptive Polarization Pulse Shaping and Modeling of Light-Matter Interactions with Neural Networks}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-25596}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2007}, abstract = {The technique of ultrafast polarization shaping is applied to a model quantum system, the potassium dimer. The polarization dependence of the multiphoton ionization dynamics in this molecule is first investigated in pump-probe experiments, and it is then more generally addressed and exploited in an adaptive quantum control experiment utilizing near-IR polarization-shaped laser pulses. The extension of these polarization shaping techniques to the UV spectral range is presented, and methods for the generation and characterization of polarization-shaped laser pulses in the UV are introduced. Systematic scans of double-pulse sequences are introduced for the investigation and interpretation of control mechanisms. This concept is first introduced and illustrated for an optical demonstration experiment, and it is then applied for the analysis of the intrapulse dumping mechanism that is observed in the excitation of a large dye molecule in solution with ultrashort laser pulses. Shaped laser pulses are employed as a means for obtaining copious amounts of data on light-matter interactions. Neural networks are introduced as a novel tool for generating computer-based models for these interactions from the accumulated data. The viability of this approach is first tested for second harmonic generation (SHG) and molecular fluorescence processes. Neural networks are then utilized for modeling the far more complex coherent strong-field dynamics of potassium atoms.}, subject = {Lasertechnologie}, language = {en} }