@misc{CoutoCruzErtanetal.2017,
  author    = {Couto, Rafael C. and Cruz, Vinicius V. and Ertan, Emelie and Eckert, Sebastian and Fondell, Mattis and Dantz, Marcus and Kennedy, Brian and Schmitt, Thorsten and Pietzsch, Annette and Guimar{\~a}es, Freddy F. and {\AA}gren, Hans and Gel'mukhanov, Faris and Odelius, Michael and Kimberg, Victor and F{\"o}hlisch, Alexander},
  title     = {Selective gating to vibrational modes through resonant X-ray scattering},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1124},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-43692},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-436926},
  pages     = {9},
  year      = {2017},
  abstract  = {The dynamics of fragmentation and vibration of molecular systems with a large number of coupled degrees of freedom are key aspects for understanding chemical reactivity and properties. Here we present a resonant inelastic X-ray scattering (RIXS) study to show how it is possible to break down such a complex multidimensional problem into elementary components. Local multimode nuclear wave packets created by X-ray excitation to different core-excited potential energy surfaces (PESs) will act as spatial gates to selectively probe the particular ground-state vibrational modes and, hence, the PES along these modes. We demonstrate this principle by combining ultra-high resolution RIXS measurements for gas-phase water with state-of-the-art simulations.},
  language  = {en}
}
@misc{EckertNorellMiedemaetal.2017,
  author    = {Eckert, Sebastian and Norell, Jesper and Miedema, Piter S. and Beye, Martin and Fondell, Mattis and Quevedo, Wilson and Kennedy, Brian and Hantschmann, Markus and Pietzsch, Annette and van Kuiken, Benjamin E. and Ross, Matthew and Minitti, Michael P. and Moeller, Stefan P. and Schlotter, William F. and Khalil, Munira and Odelius, Michael and F{\"o}hlisch, Alexander},
  title     = {Untersuchung unabh{\"a}ngiger N-H- und N-C-Bindungsverformungen auf ultrakurzen Zeitskalen mit resonanter inelastischer R{\"o}ntgenstreuung},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1121},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-43668},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-436688},
  pages     = {7},
  year      = {2017},
  abstract  = {Die Femtosekundendynamik nach resonanten Photoanregungen mit optischen und R{\"o}ntgenpulsen erm{\"o}glicht eine selektive Verformung von chemischen N-H- und N-C-Bindungen in 2-Thiopyridon in w{\"a}ssriger L{\"o}sung. Die Untersuchung der orbitalspezifischen elektronischen Struktur und ihrer Dynamik auf ultrakurzen Zeitskalen mit resonanter inelastischer R{\"o}ntgenstreuung an der N1s-Resonanz am Synchrotron und dem Freie-Elektronen-Laser LCLS in Kombination mit quantenchemischen Multikonfigurationsberechnungen erbringen den direkten Nachweis dieser kontrollierten photoinduzierten Molek{\"u}lverformungen und ihrer ultrakurzen Zeitskala.},
  language  = {de}
}
@misc{EckertNorellMiedemaetal.2017,
  author    = {Eckert, Sebastian and Norell, Jesper and Miedema, Piter S. and Beye, Martin and Fondell, Mattis and Quevedo, Wilson and Kennedy, Brian and Hantschmann, Markus and Pietzsch, Annette and van Kuiken, Benjamin E. and Ross, Matthew and Minitti, Michael P. and Moeller, Stefan P. and Schlotter, William F. and Khalil, Munira and Odelius, Michael and F{\"o}hlisch, Alexander},
  title     = {Ultrafast Independent N-H and N-C Bond Deformation Investigated with Resonant Inelastic X-Ray Scattering},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1115},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-43687},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-436873},
  pages     = {7},
  year      = {2017},
  abstract  = {The femtosecond excited-state dynamics following resonant photoexcitation enable the selective deformation of N-H and N-C chemical bonds in 2-thiopyridone in aqueous solution with optical or X-ray pulses. In combination with multiconfigurational quantum-chemical calculations, the orbital-specific electronic structure and its ultrafast dynamics accessed with resonant inelastic X-ray scattering at the N 1s level using synchrotron radiation and the soft X-ray free-electron laser LCLS provide direct evidence for this controlled photoinduced molecular deformation and its ultrashort time-scale.},
  language  = {en}
}
@phdthesis{Bekeraitė2017,
  author    = {Bekeraitė, Simona},
  title     = {Distribution functions of rotating galaxies},
  doi       = {10.25932/publishup-42095},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-420950},
  school      = {Universit{\"a}t Potsdam},
  pages     = {V, 91},
  year      = {2017},
  abstract  = {The work done during the PhD studies has been focused on measurements of distribution functions of rotating galaxies using integral field spectroscopy observations. Throughout the main body of research presented here we have been using CALIFA (Calar Alto Legacy Integral Field Area) survey stellar velocity fields to obtain robust measurements of circular velocities for rotating galaxies of all morphological types. A crucial part of the work was enabled by well-defined CALIFA sample selection criteria: it enabled reconstructing sample-independent distributions of galaxy properties. In Chapter 2, we measure the distribution in absolute magnitude - circular velocity space for a well-defined sample of 199 rotating CALIFA galaxies using their stellar kinematics. Our aim in this analysis is to avoid subjective selection criteria and to take volume and large-scale structure factors into account. Using stellar velocity fields instead of gas emission line kinematics allows including rapidly rotating early type galaxies. Our initial sample contains 277 galaxies with available stellar velocity fields and growth curve r-band photometry. After rejecting 51 velocity fields that could not be modelled due to the low number of bins, foreground contamination or significant interaction we perform Markov Chain Monte Carlo (MCMC) modelling of the velocity fields, obtaining the rotation curve and kinematic parameters and their realistic uncertainties. We perform an extinction correction and calculate the circular velocity v_circ accounting for pressure support a given galaxy has. The resulting galaxy distribution on the M_r - v_circ plane is then modelled as a mixture of two distinct populations, allowing robust and reproducible rejection of outliers, a significant fraction of which are slow rotators. The selection effects are understood well enough that the incompleteness of the sample can be corrected and the 199 galaxies can be weighted by volume and large-scale structure factors enabling us to fit a volume-corrected Tully-Fisher relation (TFR). More importantly, we also provide the volume-corrected distribution of galaxies in the M_r - v_circ plane, which can be compared with cosmological simulations. The joint distribution of the luminosity and circular velocity space densities, representative over the range of -20 > M_r > -22 mag, can place more stringent constraints on the galaxy formation and evolution scenarios than linear TFR fit parameters or the luminosity function alone. In Chapter 3, we measure one of the marginal distributions of the M_r - v_circ distribution: the circular velocity function of rotating galaxies. The velocity function is a fundamental observable statistic of the galaxy population, being of a similar importance as the luminosity function, but much more difficult to measure. We present the first directly measured circular velocity function that is representative between 60 < v_circ < 320 km s^-1 for galaxies of all morphological types at a given rotation velocity. For the low mass galaxy population 60 < v_circ < 170 km s^-1, we use the HIPASS velocity function. For the massive galaxy population 170 < v_circ < 320 km s^-1, we use stellar circular velocities from CALIFA. The CALIFA velocity function includes homogeneous velocity measurements of both late and early-type rotation-supported galaxies. It has the crucial advantage of not missing gas-poor massive ellipticals that HI surveys are blind to. We show that both velocity functions can be combined in a seamless manner, as their ranges of validity overlap. The resulting observed velocity function is compared to velocity functions derived from cosmological simulations of the z = 0 galaxy population. We find that dark matter-only simulations show a strong mismatch with the observed VF. Hydrodynamic Illustris simulations fare better, but still do not fully reproduce observations. In Chapter 4, we present some other work done during the PhD studies, namely, a method that improves the precision of specific angular measurements by combining simultaneous Markov Chain Monte Carlo modelling of ionised gas 2D velocity fields and HI linewidths. To test the method we use a sample of 25 galaxies from the Sydney-AAO Multi-object Integral field (SAMI) survey that had matching ALFALFA HI linewidths. Such a method allows constraining the rotation curve both in the inner regions of a galaxy and in its outskirts, leading to increased precision of specific angular momentum measurements. It could be used to further constrain the observed relation between galaxy mass, specific angular momentum and morphology (Obreschkow \& Glazebrook 2014). Mathematical and computational methods are presented in the appendices.},
  language  = {en}
}
@misc{SchimkaLomadzeRabeetal.2017,
  author    = {Schimka, Selina and Lomadze, Nino and Rabe, Maren and Kopyshev, Alexey and Lehmann, Maren and von Klitzing, Regine and Rumyantsev, Artem M. and Kramarenko, Elena Yu. and Santer, Svetlana},
  title     = {Photosensitive microgels containing azobenzene surfactants of different charges},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {461},
  issn      = {1866-8372},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-413528},
  year      = {2017},
  abstract  = {We report on light sensitive microgel particles that can change their volume reversibly in response to illumination with light of different wavelengths. To make the anionic microgels photosensitive we add surfactants with a positively charged polyamine head group and an azobenzene containing tail. Upon illumination, azobenzene undergoes a reversible photo-isomerization reaction from a trans- to a cis-state accompanied by a change in the hydrophobicity of the surfactant. Depending on the isomerization state, the surfactant molecules are either accommodated within the microgel (trans-state) resulting in its shrinkage or desorbed back into water (cis-isomer) letting the microgel swell. We have studied three surfactants differing in the number of amino groups, so that the number of charges of the surfactant head varies between 1 and 3. We have found experimentally and theoretically that the surfactant concentration needed for microgel compaction increases with decreasing number of charges of the head group. Utilization of polyamine azobenzene containing surfactants for the light triggered remote control of the microgel size opens up a possibility for applications of light responsive microgels as drug carriers in biology and medicine.},
  language  = {en}
}
@phdthesis{Kayser2017,
  author    = {Kayser, Markus},
  title     = {Wechselwirkung der atmosph{\"a}rischen Grenzschicht mit synoptisch-skaligen Prozessen w{\"a}hrend der N-ICE2015 Kampagne},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-411124},
  school      = {Universit{\"a}t Potsdam},
  pages     = {147},
  year      = {2017},
  abstract  = {Die Arktis erw{\"a}rmt sich schneller als der Rest der Erde. Die Auswirkungen manifestieren sich unter Anderem in einer verst{\"a}rkten Erw{\"a}rmung der arktischen Grenzschicht. Diese Arbeit befasst sich mit Wechselwirkungen zwischen synoptischen Zyklonen und der arktischen Atmosph{\"a}re auf lokalen bis {\"u}berregionalen Skalen. Ausgangspunkt daf{\"u}r sind Messdaten und Modellsimulationen f{\"u}r den Zeitraum der N-ICE2015 Expedition, die von Anfang Januar bis Ende Juni 2015 im arktischen Nordatlantiksektor stattgefunden hat. Anhand von Radiosondenmessungen lassen sich Auswirkungen von synoptischen Zyklonen am deutlichsten im Winter erkennen, da sie durch die Advektion warmer und feuchter Luftmassen in die Arktis den Zustand der Atmosph{\"a}re von einem strahlungs-klaren in einen strahlungs-opaken {\"a}ndern. Obwohl dieser scharfe Kontrast nur im Winter existiert, zeigt die Analyse, dass der integrierte Wasserdampf als Indikator f{\"u}r die Advektion von Luftmassen aus niedrigen Breiten in die Arktis auch im Fr{\"u}hjahr geeignet ist. Neben der Advektion von Luftmassen wird der Einfluss der Zyklonen auf die statische Stabilit{\"a}t charakterisiert. Beim Vergleich der N-ICE2015 Beobachtungen mit der SHEBA Kampagne (1997/1998), die {\"u}ber dickerem Eis stattfand, finden sich trotz der unterschiedlichen Meereisregime {\"A}hnlichkeiten in der statischen Stabilit{\"a}t der Atmosph{\"a}re. Die beobachteten Differenzen in der Stabilit{\"a}t lassen sich auf Unterschiede in der synoptischen Aktivit{\"a}t zur{\"u}ckf{\"u}hren. Dies l{\"a}sst vermuten, dass die d{\"u}nnere Eisdecke auf saisonalen Zeitskalen nur einen geringen Einfluss auf die thermodynamische Struktur der arktischen Troposph{\"a}re besitzt, solange eine dicke Schneeschicht sie bedeckt. Ein weiterer Vergleich mit den parallel zur N-ICE2015 Kampagne gestarteten Radiosonden der AWIPEV Station in Ny-{\AA}esund, Spitzbergen, macht deutlich, dass die synoptischen Zyklonen oberhalb der Orographie auf saisonalen Zeitskalen das Wettergeschehen bestimmen. Des Weiteren werden f{\"u}r Februar 2015 die Auswirkungen von in der Vertikalen variiertem Nudging auf die Entwicklung der Zyklonen am Beispiel des hydrostatischen regionalen Klimamodells HIRHAM5 untersucht. Es zeigt sich, dass die Unterschiede zwischen den acht Modellsimulationen mit abnehmender Anzahl der genudgten Level zunehmen. Die gr{\"o}ßten Differenzen resultieren vornehmlich aus dem zeitlichen Versatz der Entwicklung synoptischer Zyklonen. Zur Korrektur des Zeitversatzes der Zykloneninitiierung gen{\"u}gt es bereits, Nudging in den unterstem 250 m der Troposph{\"a}re anzuwenden. Daneben findet sich zwischen den genudgten HIRHAM5-Simulation und den in situ Messungen der gleiche positive Temperaturbias, den auch ERA-Interim besitzt. Das freie HIRHAM hingegen reproduziert das positive Ende der N-ICE2015 Temperaturverteilung gut, besitzt aber einen starken negativen Bias, der sehr wahrscheinlich aus einer Untersch{\"a}tzung des Feuchtegehalts resultiert. An Beispiel einer Zyklone wird gezeigt, dass Nudging Einfluss auf die Lage der H{\"o}hentiefs besitzt, die ihrerseits die Zyklonenentwicklung am Boden beeinflussen. Im Weiteren wird mittels eines f{\"u}r kleine Ensemblegr{\"o}ßen geeigneten Varianzmaßes eine statistische Einsch{\"a}tzung der Wirkung des Nudgings auf die Vertikale getroffen. Es wird festgestellt, dass die {\"A}hnlichkeit der Modellsimulationen in der unteren Troposph{\"a}re generell h{\"o}her ist als dar{\"u}ber und in 500 hPa ein lokales Minimum besitzt. Im letzten Teil der Analyse wird die Wechselwirkung der oberen und unteren Stratosph{\"a}re anhand zuvor betrachteter Zyklonen mit Daten der ERA-Interim Reanalyse untersucht. Lage und Ausrichtung des Polarwirbels erzeugten ab Anfang Februar 2015 eine ungew{\"o}hnlich große Meridionalkomponente des Tropopausenjets, die Zugbahnen in die zentrale Arktis beg{\"u}nstigte. Am Beispiel einer Zyklone wird die {\"U}bereinstimmung der synoptischen Entwicklung mit den theoretischen Annahmen {\"u}ber den abw{\"a}rts gerichteten Einfluss der Stratosph{\"a}re auf die Troposph{\"a}re hervorgehoben. Dabei spielt die nicht-lineare Wechselwirkung zwischen der Orographie Gr{\"o}nlands, einer Intrusion stratosph{\"a}rischer Luft in die Troposph{\"a}re sowie einer in Richtung Arktis propagierender Rossby-Welle eine tragende Rolle. Als Indikator dieser Wechselwirkung werden horizontale Signaturen aus abwechselnd aufsteigender und absinkender Luft innerhalb der Troposph{\"a}re identifiziert.},
  language  = {de}
}
@phdthesis{Schuermann2017,
  author    = {Sch{\"u}rmann, Robin Mathis},
  title     = {Interaction of the potential DNA-radiosensitizer 8-bromoadenine with free and plasmonically generated electrons},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-407017},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xi, 120},
  year      = {2017},
  abstract  = {In Germany more than 200.000 persons die of cancer every year, which makes it the second most common cause of death. Chemotherapy and radiation therapy are often combined to exploit a supra-additive effect, as some chemotherapeutic agents like halogenated nucleobases sensitize the cancerous tissue to radiation. The radiosensitizing action of certain therapeutic agents can be at least partly assigned to their interaction with secondary low energy electrons (LEEs) that are generated along the track of the ionizing radiation. In the therapy of cancer DNA is an important target, as severe DNA damage like double strand breaks induce the cell death. As there is only a limited number of radiosensitizing agents in clinical practice, which are often strongly cytotoxic, it would be beneficial to get a deeper understanding of the interaction of less toxic potential radiosensitizers with secondary reactive species like LEEs. Beyond that LEEs can be generated by laser illuminated nanoparticles that are applied in photothermal therapy (PTT) of cancer, which is an attempt to treat cancer by an increase of temperature in the cells. However, the application of halogenated nucleobases in PTT has not been taken into account so far. In this thesis the interaction of the potential radiosensitizer 8-bromoadenine (8BrA) with LEEs was studied. In a first step the dissociative electron attachment (DEA) in the gas phase was studied in a crossed electron-molecular beam setup. The main fragmentation pathway was revealed as the cleavage of the C-Br bond. The formation of a stable parent anion was observed for electron energies around 0 eV. Furthermore, DNA origami nanostructures were used as platformed to determine electron induced strand break cross sections of 8BrA sensitized oligonucleotides and the corresponding nonsensitized sequence as a function of the electron energy. In this way the influence of the DEA resonances observed for the free molecules on the DNA strand breaks was examined. As the surrounding medium influences the DEA, pulsed laser illuminated gold nanoparticles (AuNPs) were used as a nanoscale electron source in an aqueous environment. The dissociation of brominated and native nucleobases was tracked with UV-Vis absorption spectroscopy and the generated fragments were identified with surface enhanced Raman scattering (SERS). Beside the electron induced damage, nucleobase analogues are decomposed in the vicinity of the laser illuminatednanoparticles due to the high temperatures. In order to get a deeper understanding of the different dissociation mechanisms, the thermal decomposition of the nucleobases in these systems was studied and the influence of the adsorption kinetics of the molecules was elucidated. In addition to the pulsed laser experiments, a dissociative electron transfer from plasmonically generated "hot electrons" to 8BrA was observed under low energy continuous wave laser illumination and tracked with SERS. The reaction was studied on AgNPs and AuNPs as a function of the laser intensity and wavelength. On dried samples the dissociation of the molecule was described by fractal like kinetics. In solution, the dissociative electron transfer was observed as well. It turned out that the timescale of the reaction rates were slightly below typical integration times of Raman spectra. In consequence such reactions need to be taken into account in the interpretation of SERS spectra of electrophilic molecules. The findings in this thesis help to understand the interaction of brominated nucleobases with plasmonically generated electrons and free electrons. This might help to evaluate the potential radiosensitizing action of such molecules in cancer radiation therapy and PTT.},
  language  = {en}
}
@phdthesis{Mitzkus2017,
  author    = {Mitzkus, Martin},
  title     = {Spectroscopic surface brightness fluctuations},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-406327},
  school      = {Universit{\"a}t Potsdam},
  pages     = {ix, 89},
  year      = {2017},
  abstract  = {Galaxies evolve on cosmological timescales and to study this evolution we can either study the stellar populations, tracing the star formation and chemical enrichment, or the dynamics, tracing interactions and mergers of galaxies as well as accretion. In the last decades this field has become one of the most active research areas in modern astrophysics and especially the use of integral field spectrographs furthered our understanding. This work is based on data of NGC 5102 obtained with the panoramic integral field spectrograph MUSE. The data are analysed with two separate and complementary approaches: In the first part, standard methods are used to measure the kinematics and than model the gravitational potential using these exceptionally high-quality data. In the second part I develop the new method of surface brightness fluctuation spectroscopy and quantitatively explore its potential to investigate the bright evolved stellar population. Measuring the kinematics of NGC 5102 I discover that this low-luminosity S0 galaxy hosts two counter rotating discs. The more central stellar component co-rotates with the large amount of HI gas. Investigating the populations I find strong central age and metallicity gradients with a younger and more metal rich central population. The spectral resolution of MUSE does not allow to connect these population gradients with the two counter rotating discs. The kinematic measurements are modelled with Jeans anisotropic models to infer the gravitational potential of NGC 5102. Under the self-consistent mass-follows-light assumption none of the Jeans models is able to reproduce the observed kinematics. To my knowledge this is the strongest evidence evidence for a dark matter dominated system obtained with this approach so far. Including a Navarro, Frenk \& White dark matter halo immediately solves the discrepancies. A very robust result is the logarithmic slope of the total matter density. For this low-mass galaxy I find a value of -1.75 +- 0.04, shallower than an isothermal halo and even shallower than published values for more massive galaxies. This confirms a tentative relation between total mass slope and stellar mass of galaxies. The Surface Brightness Fluctuation (SBF) method is a well established distance measure, but due to its sensitive to bright stars also used to study evolved stars in unresolved stellar populations. The wide-field spectrograph MUSE offers the possibility to apply this technique for the first time to spectroscopic data. In this thesis I develop the spectroscopic SBF technique and measure the first SBF spectrum of any galaxy. I discuss the challenges for measuring SBF spectra that rise due to the complexity of integral field spectrographs compared to imaging instruments. Since decades, stellar population models indicate that SBFs in intermediate-to-old stellar systems are dominated by red giant branch and asymptotic giant branch stars. Especially the later carry significant model uncertainties, making these stars a scientifically interesting target. Comparing the NGC 5102 SBF spectrum with stellar spectra I show for the first time that M-type giants cause the fluctuations. Stellar evolution models suggest that also carbon rich thermally pulsating asymptotic giant branch stars should leave a detectable signal in the SBF spectrum. I cannot detect a significant contribution from these stars in the NGC 5102 SBF spectrum. I have written a stellar population synthesis tool that predicts for the first time SBF spectra. I compute two sets of population models: based on observed and on theoretical stellar spectra. In comparing the two models I find that the models based on observed spectra predict weaker molecular features. The comparison with the NGC 5102 spectrum reveals that these models are in better agreement with the data.},
  language  = {en}
}
@phdthesis{Leonhardt2017,
  author    = {Leonhardt, Helmar},
  title     = {Chemotaxis, shape and adhesion dynamics of amoeboid cells studied by impedance fluctuations in open and confined spaces},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-405016},
  school      = {Universit{\"a}t Potsdam},
  pages     = {98},
  year      = {2017},
  abstract  = {Die vorliegende Arbeit befasst sich mit elektrischen Impedanzmessungen von ameoboiden Zellen auf Mikroelektroden. Der Modellorganismus Dictyostelium discoideum zeigt unter der Bedingung des Nahrungsentzugs einen {\"U}bergang zum kollektiven Verhalten, bei dem sich chemotaktische Zellen zu einem multizellul{\"a}ren Aggregat zusammenschliessen. Wir zeigen wie Impedanzaufnahmen {\"u}ber die Dynamik der Zell-substrat Adh{\"a}sion ein pr{\"a}zises Bild der Phasen der Aggregation liefern. Dar{\"u}berhinaus zeigen wir zum ersten mal systematische Einzelzellmessungen von Wildtyp-Zellen und vier Mutanten, die sich in der St{\"a}rke der Substratadh {\"a}sion unterscheiden. Wir zeichneten die projizierte Zellfl{\"a}che durch Zeitverlaufsmikroskopie auf und fanden eine Korrelation zwischen den quasi-periodischen Oszillationen in der Kinetik der projizierten Fl{\"a}che - der Zellform-Oszillation - und dem Langzeittrend des Impedanzsignals. Amoeboidale Motilit{\"a}t offenbart sich typischerweise durch einen Zyklus von Membranausst{\"u}lpung, Substratadh{\"a}sion, Vorw{\"a}rtsziehen des Zellk{\"o}rpers und Einziehen des hinteren Teils der Zelle. Dieser Motilit{\"a}tszyklus resultiert in quasi-periodischen Oszillationen der projizierten Zellfl{\"a}che und der Impedanz. In allen gemessenen Zelllinien wurden f{\"u}r diesen Zyklus {\"a}hnliche Periodendauern beobachtet trotz der Unterschiede in der Anhaftungsst{\"a}rke. Wir beobachteten, dass die St{\"a}rke der Zell-substrat Anhaftung die Impedanz stark beeinflusst, indem die Abweichungen vom Mittelwert (die Gr{\"o}sse der Fluktuationen) vergr{\"o}ssert sind bei Zellen, die die vom Zytoskelett generierten Kr{\"a}fte effektiv auf das Substrat {\"u}bertragen. Zum Beispiel sind bei talA- Zellen, in welchen das Actin verankernde Protein Talin fehlt, die Fluktuationen stark reduziert. Einzelzellkraft-Spektroskopie und Ergebnisse eines Abl{\"o}sungsassays, bei dem Adh{\"a}sionskraft gemessen wird indem Zellen einer Scherspannung ausgesetzt werden, best{\"a}tigen, dass die Gr{\"o}sse der Impedanz-fluktuationen ein korrektes Mass f{\"u}r die St{\"a}rke der Substratadh{\"a}sion ist. Schliesslich haben wir uns auch mit dem Einbau von Zell-substrat-Impedanz-Sensoren in mikro-fluidische Apparaturen befasst. Ein chip-basierter elektrischer Chemotaxis Assay wurde entwickelt, der die Geschwindigkeit chemotaktischer Zellen misst, welche entlang eines chemischen Konzentrationsgradienten {\"u}ber Mikroelektroden wandern.},
  language  = {en}
}
@phdthesis{Paul2017,
  author    = {Paul, Fabian},
  title     = {Markov state modeling of binding and conformational changes of proteins},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-404273},
  school      = {Universit{\"a}t Potsdam},
  pages     = {X, 112},
  year      = {2017},
  abstract  = {Proteins are molecules that are essential for life and carry out an enormous number of functions in organisms. To this end, they change their conformation and bind to other molecules. However, the interplay between conformational change and binding is not fully understood. In this work, this interplay is investigated with molecular dynamics (MD) simulations of the protein-peptide system Mdm2-PMI and by analysis of data from relaxation experiments. The central task it to uncover the binding mechanism, which is described by the sequence of (partial) binding events and conformational change events including their probabilities. In the simplest case, the binding mechanism is described by a two-step model: binding followed by conformational change or conformational change followed by binding. In the general case, longer sequences with multiple conformational changes and partial binding events are possible as well as parallel pathways that differ in their sequences of events. The theory of Markov state models (MSMs) provides the theoretical framework in which all these cases can be modeled. For this purpose, MSMs are estimated in this work from MD data, and rate equation models, which are related to MSMs, are inferred from experimental relaxation data. The MD simulation and Markov modeling of the PMI-Mdm2 system shows that PMI and Mdm2 can bind via multiple pathways. A main result of this work is a dissociation rate on the order of one event per second, which was calculated using Markov modeling and is in agreement with experiment. So far, dissociation rates and transition rates of this magnitude have only been calculated with methods that speed up transitions by acting with time-dependent, external forces on the binding partners. The simulation technique developed in this work, in contrast, allows the estimation of dissociation rates from the combination of free energy calculation and direct MD simulation of the fast binding process. Two new statistical estimators TRAM and TRAMMBAR are developed to estimate a MSM from the joint data of both simulation types. In addition, a new analysis technique for time-series data from chemical relaxation experiments is developed in this work. It allows to identify one of the above-mentioned two-step mechanisms as the mechanism that underlays the data. The new method is valid for a broader range of concentrations than previous methods and therefore allows to choose the concentrations such that the mechanism can be uniquely identified. It is successfully tested with data for the binding of recoverin to a rhodopsin kinase peptide.},
  language  = {en}
}