@phdthesis{Doriti2017,
  author    = {Doriti, Afroditi},
  title     = {Sustainable bio-based poly-N-glycines and polyesters},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-411286},
  school      = {Universit{\"a}t Potsdam},
  pages     = {vi, 117},
  year      = {2017},
  abstract  = {Nowadays, the need to protect the environment becomes more urgent than ever. In the field of chemistry, this translates to practices such as waste prevention, use of renewable feedstocks, and catalysis; concepts based on the principles of green chemistry. Polymers are an important product in the chemical industry and are also in the focus of these changes. In this thesis, more sustainable approaches to make two classes of polymers, polypeptoids and polyesters, are described. Polypeptoids or poly(alkyl-N-glycines) are isomers of polypeptides and are biocompatible, as well as degradable under biologically relevant conditions. In addition to that, they can have interesting properties such as lower critical solution temperature (LCST) behavior. They are usually synthesized by the ring opening polymerization (ROP) of N-carboxy anhydrides (NCAs), which are produced with the use of toxic compounds (e.g. phosgene) and which are highly sensitive to humidity. In order to avoid the direct synthesis and isolation of the NCAs, N-phenoxycarbonyl-protected N-substituted glycines are prepared, which can yield the NCAs in situ. The conditions for the NCA synthesis and its direct polymerization are investigated and optimized for the simplest N-substituted glycine, sarcosine. The use of a tertiary amine in less than stoichiometric amounts compared to the N-phenoxycarbonyl--sarcosine seems to accelerate drastically the NCA formation and does not affect the efficiency of the polymerization. In fact, well defined polysarcosines that comply to the monomer to initiator ratio can be produced by this method. This approach was also applied to other N-substituted glycines. Dihydroxyacetone is a sustainable diol produced from glycerol, and has already been used for the synthesis of polycarbonates. Here, it was used as a comonomer for the synthesis of polyesters. However, the polymerization of dihydroxyacetone presented difficulties, probably due to the insolubility of the macromolecular chains. To circumvent the problem, the dimethyl acetal protected dihydroxyacetone was polymerized with terephthaloyl chloride to yield a soluble polymer. When the carbonyl was recovered after deprotection, the product was insoluble in all solvents, showing that the carbonyl in the main chain hinders the dissolution of the polymers. The solubility issue can be avoided, when a 1:1 mixture of dihydroxyacetone/ ethylene glycol is used to yield a soluble copolyester.},
  language  = {en}
}
@phdthesis{Dribbisch2017,
  author    = {Dribbisch, Katrin},
  title     = {Translating innovation},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-104719},
  school      = {Universit{\"a}t Potsdam},
  pages     = {VIII, 217},
  year      = {2017},
  abstract  = {This doctoral thesis studies the process of innovation adoption in public administrations, addressing the research question of how an innovation is translated to a local context. The study empirically explores Design Thinking as a new problem-solving approach introduced by a federal government organisation in Singapore. With a focus on user-centeredness, collaboration and iteration Design Thinking seems to offer a new way to engage recipients and other stakeholders of public services as well as to re-think the policy design process from a user's point of view. Pioneered in the private sector, early adopters of the methodology include civil services in Australia, Denmark, the United Kingdom, the United States as well as Singapore. Hitherto, there is not much evidence on how and for which purposes Design Thinking is used in the public sector. For the purpose of this study, innovation adoption is framed in an institutionalist perspective addressing how concepts are translated to local contexts. The study rejects simplistic views of the innovation adoption process, in which an idea diffuses to another setting without adaptation. The translation perspective is fruitful because it captures the multidimensionality and 'messiness' of innovation adoption. More specifically, the overall research question addressed in this study is: How has Design Thinking been translated to the local context of the public sector organisation under investigation? And from a theoretical point of view: What can we learn from translation theory about innovation adoption processes? Moreover, there are only few empirical studies of organisations adopting Design Thinking and most of them focus on private organisations. We know very little about how Design Thinking is embedded in public sector organisations. This study therefore provides further empirical evidence of how Design Thinking is used in a public sector organisation, especially with regards to its application to policy work which has so far been under-researched. An exploratory single case study approach was chosen to provide an in-depth analysis of the innovation adoption process. Based on a purposive, theory-driven sampling approach, a Singaporean Ministry was selected because it represented an organisational setting in which Design Thinking had been embedded for several years, making it a relevant case with regard to the research question. Following a qualitative research design, 28 semi-structured interviews (45-100 minutes) with employees and managers were conducted. The interview data was triangulated with observations and documents, collected during a field research research stay in Singapore. The empirical study of innovation adoption in a single organisation focused on the intra-organisational perspective, with the aim to capture the variations of translation that occur during the adoption process. In so doing, this study opened the black box often assumed in implementation studies. Second, this research advances translation studies not only by showing variance, but also by deriving explanatory factors. The main differences in the translation of Design Thinking occurred between service delivery and policy divisions, as well as between the first adopter and the rest of the organisation. For the intra-organisational translation of Design Thinking in the Singaporean Ministry the following five factors played a role: task type, mode of adoption, type of expertise, sequence of adoption, and the adoption of similar practices.},
  language  = {en}
}
@phdthesis{Eichler2017,
  author    = {Eichler, Sarah},
  title     = {Multidisziplin{\"a}re kardiologische Rehabilitation bei Patienten nach kathetergest{\"u}tzter Aortenklappenkorrektur},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-406618},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XI, 63, XXXI},
  year      = {2017},
  abstract  = {Hintergrund F{\"u}r Patienten mit hochgradiger Aortenklappenstenose, die aufgrund ihres Alters oder ihrer Multimorbidit{\"a}t ein hohes Operationsrisiko tragen, konnte mit der kathetergest{\"u}tzten Aortenklappenkorrektur (transcatheter aortic valve implantation, TAVI) eine vielversprechende Alternative zum herzchirurgischen Eingriff etabliert werden. Explizite Daten zur multidisziplin{\"a}ren kardiologischen Rehabilitation nach TAVI liegen bislang nicht vor. Ziel vorliegender Arbeit war, den Effekt der kardiologischen Rehabilitation auf die k{\"o}rperliche Leistungsf{\"a}higkeit, den emotionalen Status, die Lebensqualit{\"a}t und die Gebrechlichkeit bei Patienten nach TAVI zu untersuchen sowie Pr{\"a}diktoren f{\"u}r die Ver{\"a}nderung der k{\"o}rperlichen Leistungsf{\"a}higkeit und der Lebensqualit{\"a}t zu identifizieren. Methodik Zwischen 10/2013 und 07/2015 wurden 136 Patienten (80,6 ± 5,0 Jahre, 47,8 \% M{\"a}nner) in Anschlussheilbehandlung nach TAVI in drei kardiologischen Rehabilitationskliniken eingeschlossen. Zur Beurteilung des Effekts der kardiologischen Rehabilitation wurden jeweils zu Beginn und Ende der Rehabilitation der Frailty (Gebrechlichkeits)-Index (Score bestehend aus Barthel-Index, Instrumental Activities of Daily Living, Mini Mental State Exam, Mini Nutritional Assessment, Timed Up and Go und subjektiver Mobilit{\"a}tsverschlechterung), die Lebensqualit{\"a}t im Short-Form 12 (SF-12) sowie die funktionale k{\"o}rperliche Leistungsf{\"a}higkeit im 6-Minuten Gehtest (6-minute walk test, 6MWT) und die maximale k{\"o}rperliche Leistungsf{\"a}higkeit in der Belastungs-Ergometrie erhoben. Zus{\"a}tzlich wurden soziodemographische Daten (z. B. Alter und Geschlecht), Komorbidit{\"a}ten (z. B. chronisch obstruktive Lungenerkrankung, koronare Herzkrankheit und Karzinom), kardiovaskul{\"a}re Risikofaktoren und die NYHA-Klasse dokumentiert. Pr{\"a}diktoren f{\"u}r die Ver{\"a}nderung der k{\"o}rperlichen Leistungsf{\"a}higkeit und Lebensqualit{\"a}t wurden mit Kovarianzanalysen angepasst. Ergebnisse Die maximale Gehstrecke im 6MWT konnte um 56,3 ± 65,3 m (p < 0,001) und die maximale k{\"o}rperliche Leistungsf{\"a}higkeit in der Belastungs-Ergometrie um 8,0 ± 14,9 Watt (p < 0001) gesteigert werden. Weiterhin konnte eine Verbesserung im SF-12 sowohl in der k{\"o}rperlichen Summenskala um 2,5 ± 8,7 Punkte (p = 0,001) als auch in der psychischen Summenskala um 3,4 ± 10,2 Punkte (p = 0,003) erreicht werden. In der multivariaten Analyse waren ein h{\"o}heres Alter und eine h{\"o}here Bildung signifikant mit einer geringeren Zunahme im 6MWT assoziiert, w{\"a}hrenddessen eine bessere kognitive Leistungsf{\"a}higkeit und Adipositas einen positiven pr{\"a}diktiven Wert aufwiesen. Eine h{\"o}here Selbstst{\"a}ndigkeit und ein besserer Ern{\"a}hrungsstatus beeinflussten die Ver{\"a}nderung in der k{\"o}rperlichen Summenskala des SF-12 positiv, w{\"a}hrenddessen eine bessere kognitive Leistungsf{\"a}higkeit einen Pr{\"a}diktor f{\"u}r eine geringere Ver{\"a}nderung darstellte. Des Weiteren hatten die jeweiligen Ausgangswerte der k{\"o}rperlichen und psychischen Summenskala im SF-12 einen inversen Einfluss auf die Ver{\"a}nderungen in der gleichen Skala. Schlussfolgerung Eine multidisziplin{\"a}re kardiologische Rehabilitation kann sowohl die k{\"o}rperliche Leistungs-f{\"a}higkeit und Lebensqualit{\"a}t verbessern als auch die Gebrechlichkeit von Patienten nach kathetergest{\"u}tzter Aortenklappenkorrektur verringern. Daraus resultierend gilt es, spezifische Assessments f{\"u}r die kardiologische Rehabilitation zu entwickeln. Weiterhin ist es notwendig, individualisierte Therapieprogramme mit besonderem Augenmerk auf kognitive Funktionen und Ern{\"a}hrung zu initiieren, um die Selbstst{\"a}ndigkeit hochbetagter Patienten zu erhalten bzw. wiederherzustellen und um die Pflegebed{\"u}rftigkeit der Patienten hinauszuz{\"o}gern.},
  language  = {de}
}
@phdthesis{Eisold2017,
  author    = {Eisold, Ursula},
  title     = {Cumarin- und DBD-Farbstoffe als Fluoreszenzsonden},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-405833},
  school      = {Universit{\"a}t Potsdam},
  pages     = {109},
  year      = {2017},
  abstract  = {In dieser Arbeit werden drei Themen im Zusammenhang mit den spektroskopischen Eigenschaften von Cumarin- (Cou) und DBD-Farbstoffen ([1,3]Dioxolo[4,5-f][1,3]benzodioxol) behandelt. Der erste Teil zeigt die grundlegende spektroskopische Charakterisierung von 7-Aminocumarinen und ihre potentielle Anwendung als Fluoreszenzsonde f{\"u}r Fluoreszenzimmunassays. Im zweiten Teil werden mit die photophysikalischen Eigenschaften der Cumarine genutzt um Cou- und DBD-funktionalisierte Oligo-Spiro-Ketal-St{\"a}be (OSTK) und ihre Eigenschaften als Membransonden zu untersuchen. Der letzte Teil besch{\"a}ftigt sich mit der Synthese und der Charakterisierung von Cou- und DBD-funktionalisierten Polyprolinen als Referenzsysteme f{\"u}r schwefelfunktionalisierte OSTK-St{\"a}be und ihrer Kopplung an Goldnanopartikel. Immunochemische Analysemethoden sind in der klinischen Diagnostik sehr erfolgreich und werden heute auch f{\"u}r die Nahrungsmittelkontrolle und {\"U}berwachung von Umweltfragen mit einbezogen. Dadurch sind sie von großem Interesse f{\"u}r weitere Forschungen. Unter den verschiedenen Immunassays zeichnen sich lumineszenzbasierte Formate durch ihre herausragende Sensitivit{\"a}t aus, die dieses Format f{\"u}r zuk{\"u}nftige Anwendungen besonders attraktiv macht. Die Notwendigkeit von Multiparameterdetektionsm{\"o}glichkeiten erfordert einen Werkzeugkasten mit Farbstoffen, um die biochemische Reaktion in ein optisch detektierbares Signal umzuwandeln. Hier wird bei einem Multiparameteransatz jeder Analyt durch einen anderen Farbstoff mit einer einzigartigen Emissionsfarbe, die den blauen bis roten Spektralbereich abdecken, oder eine einzigartige Abklingzeit detektiert. Im Falle eines kompetitiven Immunassayformats w{\"a}re f{\"u}r jeden der verschiedenen Farbstoffe ein einzelner Antik{\"o}rper erforderlich. In der vorliegenden Arbeit wird ein leicht modifizierter Ansatz unter Verwendung einer Cumarineinheit, gegen die hochspezifische monoklonale Antik{\"o}rper (mAb) erzeugt wurden, als grundlegendes Antigen pr{\"a}sentiert. Durch eine Modifikation der Stammcumarineinheit an einer Position des Molek{\"u}ls, die f{\"u}r die Erkennung durch den Antik{\"o}rper nicht relevant ist, kann auf den vollen Spektralbereich von blau bis tiefrot zugegriffen werden. In dieser Arbeit wird die photophysikalische Charakterisierung der verschiedenen Cumarinderivate und ihrer entsprechenden Immunkomplexe mit zwei verschiedenen, aber dennoch hochspezifischen, Antik{\"o}rpern pr{\"a}sentiert. Die Cumarinfarbstoffe und ihre Immunkomplexe wurden durch station{\"a}re und zeitaufgel{\"o}ste Absorptions- sowie Fluoreszenzemissionsspektroskopie charakterisiert. Dar{\"u}ber hinaus wurden Fluoreszenzdepolarisationsmessungen durchgef{\"u}hrt, um die Daten zu vervollst{\"a}ndigen, die die verschiedenen Bindungsmodi der beiden Antik{\"o}rper betonten. Im Gegensatz zu h{\"a}ufig eingesetzten Nachweissystemen wurde eine massive Fluoreszenzverst{\"a}rkung bei der Bildung des Antik{\"o}rper-Farbstoffkomplexes bis zu einem Faktor von 50 gefunden. Wegen der leichten Emissionsfarben{\"a}nderung durch das Anpassen der Cumarinsubstitution in der f{\"u}r die Antigenbindung nicht relevanten Position des Elternmolek{\"u}ls, ist eine Farbstoff-Toolbox vorhanden, die bei der Konstruktion von kompetitiven Multiparameterfluoreszenzverst{\"a}rkungsimmunassays verwendet werden kann. Oligo-Spiro-Thio-Ketal-St{\"a}be werden aufgrund ihres hydrophoben R{\"u}ckgrats leicht in Doppellipidschichten eingebaut und deshalb als optische Membransonde verwendet. Wegen ihres geringen Durchmessers wird nur eine minimale St{\"o}rung der Doppellipidschicht verursacht. Durch die Markierung mit Fluoreszenzfarbstoffen sind neuartige F{\"o}rster-Resonanz-Energietransfersonden mit hoch definierten relativen Orientierungen der {\"U}bergangsdipolmomente der Donor- und Akzeptorfarbstoffe zug{\"a}nglich und macht die Klasse der OSTK-Sonden zu einem leistungsstarken, flexiblen Werkzeugkasten f{\"u}r optische Biosensoranwendungen. Mit Hilfe von station{\"a}ren und zeitaufgel{\"o}sten Fluoreszenzexperimenten wurde der Einbau von Cumarin- und DBD markierten OSTK-St{\"a}ben in großen unilamellaren Vesikeln untersucht und die Ergebnisse durch Fluoreszenzdepolarisationsmessungen untermauert. Der letzte Teil dieser Arbeit besch{\"a}ftigt sich mit der Synthese und Charakterisierung von Cou- und DBD-funktionalisierten Polyprolinen und ihrer Kopplung an Goldnanopartikel. Die farbstoffmarkierten Polyproline konnten erfolgreich hergestellt werden. Es zeigten sich deutlich Einfl{\"u}sse auf die spektroskopischen Eigenschaften der Farbstoffe durch die Bindung an die Polyprolinhelix. Die Kopplung an die 5 nm großen AuNP konnte erfolgreich durchgef{\"u}hrt werden. Die Erfahrungen, die durch die Kopplung der Polyproline an die AuNP, gewonnen wurde, ist die Basis f{\"u}r eine Einzelmolek{\"u}l-AFM-FRET-Nanoskopie mit OSTK-St{\"a}ben.},
  language  = {de}
}
@phdthesis{Fischbach2017,
  author    = {Fischbach, Jens},
  title     = {Isothermale Amplifikationsmethoden f{\"u}r den DNA- und Pyrophosphat-abh{\"a}ngigen Pathogennachweis},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-406072},
  school      = {Universit{\"a}t Potsdam},
  pages     = {viii, 125},
  year      = {2017},
  abstract  = {Hintergrund: Etablierte Protein- und Nukleins{\"a}ure-basierte Methoden f{\"u}r den spezifischen Pathogennachweis sind nur unter standardisierten Laborbedingungen von geschultem Personal durchf{\"u}hrbar und daher mit einem hohen Zeit- und Kostenaufwand verbunden. In der Nukleins{\"a}ure-basierten Diagnostik kann durch die Einf{\"u}hrung der isothermalen Amplifikation eine schnelle und kosteng{\"u}nstige Alternative zur Polymerase-Kettenreaktion (PCR) verwendet werden. Die Loop-mediated isothermal amplification (LAMP) bietet aufgrund der hohen Amplifikationseffizienz vielf{\"a}ltige Detektionsm{\"o}glichkeiten, die sowohl f{\"u}r Schnelltest- als auch f{\"u}r Monitoring-Anwendungen geeignet sind. Ein wesentliches Ziel dieser Arbeit war die Verbesserung der Anwendbarkeit der LAMP und die Entwicklung einer neuen Methode f{\"u}r den einfachen, schnellen und g{\"u}nstigen Nachweis von Pathogenen mittels alternativer DNA- oder Pyrophosphat-abh{\"a}ngiger Detektionsverfahren. Hier wurden zun{\"a}chst direkte und indirekte Detektionsmethoden untersucht und darauf aufbauend ein Verfahren entwickelt, mit dem neue Metallionen-abh{\"a}ngige Fluoreszenzfarbstoffe f{\"u}r die selektive Detektion von Pyrophosphat in der LAMP und anderen enzymatischen Reaktionen identifiziert werden k{\"o}nnen. Als Alternative f{\"u}r die DNA-basierte Detektion in der digitalen LAMP sollten die zuvor etablierten Farbstoffe f{\"u}r den Pyrophosphatnachweis in einer Emulsion getestet werden. Abschließend wurde ein neuer Reaktionsmechanismus f{\"u}r die effiziente Generierung hochmolekularer DNA unter isothermalen Bedingungen als Alternative zur LAMP entwickelt. Ergebnisse: F{\"u}r den Nachweis RNA- und DNA-basierter Phythopathogene konnte die Echtzeit- und Endpunktdetektion mit verschiedenen Farbstoffen in einem geschlossenen System etabliert werden. Hier wurde Berberin als DNA-interkalierender Fluoreszenzfarbstoff mit vergleichbarer Sensitivit{\"a}t zu SYBR Green und EvaGreen erfolgreich in der LAMP mit Echtzeitdetektion eingesetzt. Ein Vorteil von Berberin gegen{\"u}ber den anderen Farbstoffen ist die Toleranz der DNA-Polymerase auch bei hohen Farbstoffkonzentrationen. Berberin kann daher auch in der geschlossenen LAMP-Reaktion ohne zus{\"a}tzliche Anpassung der Reaktionsbedingungen f{\"u}r die Endpunktdetektion verwendet werden. Dar{\"u}ber hinaus konnte Hydroxynaphtholblau (HNB), das f{\"u}r den kolorimetrischen Endpunktnachweis bekannt ist, erstmals auch f{\"u}r die fluorimetrische Detektion der LAMP in Echtzeit eingesetzt werden. Zus{\"a}tzlich konnten in der Arbeit weitere Metallionen-abh{\"a}ngige Farbstoffe zur indirekten Detektion der LAMP {\"u}ber das Pyrophosphat identifiziert werden. Daf{\"u}r wurde eine iterative Methode entwickelt, mit der potenzielle Farbstoffe hinsichtlich ihrer Enzymkompatibilit{\"a}t und ihrer spektralen Eigenschaften bei An- oder Abwesenheit von Manganionen selektiert werden k{\"o}nnen. Mithilfe eines kombinatorischen Screenings im Mikrotiterplattenformat konnte die komplexe Konzentrationsabh{\"a}ngigkeit zwischen den einzelnen Komponenten f{\"u}r einen fluorimetrischen Verdr{\"a}ngungsnachweis untersucht werden. Durch die Visualisierung des Signal-Rausch-Verh{\"a}ltnis' als Intensit{\"a}tsmatrix (heatmap) konnten zun{\"a}chst Alizarinrot S und Tetrazyklin unter simulierten Reaktionsbedingungen selektiert werden. In der anschließenden enzymatischen LAMP-Reaktion konnte insbesondere Alizarinrot S als g{\"u}nstiger, nicht-toxischer und robuster Fluoreszenzfarbstoff identifiziert werden und zeigte eine Pyrophosphat-abh{\"a}ngige Zunahme der Fluoreszenzintensit{\"a}t. Die zuvor etablierten Farbstoffe (HNB, Calcein und Alizarinrot S) konnten anschließend erfolgreich f{\"u}r die indirekte, fluorimetrische Detektion von Pyrophosphat in einer LAMP-optimierten Emulsion eingesetzt werden. Die Stabilit{\"a}t und Homogenit{\"a}t der generierten Emulsion wurde durch den Zusatz des Emulgators Poloxamer 188 verbessert. Durch die fluoreszenzmikroskopische Analyse der Emulsion war eine eindeutige Diskriminierung der positiven und negativen Tr{\"o}pfchen vor allem bei Einsatz von Calcein und Alizarinrot S m{\"o}glich. Aufgrund des komplexen Primer-Designs und der hohen Wahrscheinlichkeit unspezifischer Amplifikation in der LAMP wurde eine neue Bst DNA-Polymerase-abh{\"a}ngige isothermale Amplifikationsreaktion entwickelt. Durch die Integration einer spezifischen Linkerstruktur (abasische Stelle oder Hexaethylenglykol) zwischen zwei Primersequenzen konnte ein bifunktioneller Primer die effiziente Regenerierung der Primerbindungsstellen gew{\"a}hrleisten. Der neue Primer induziert nach der spezifischen Hybridisierung auf dem Templat die R{\"u}ckfaltung zu einer Haarnadelstruktur und blockiert gleichzeitig die Polymeraseaktivit{\"a}t am Gegenstrang, wodurch eine autozyklische Amplifikation trotz konstanter Reaktionstemperatur m{\"o}glich ist. Die Effizienz der „Hinge-initiated Primer dependent Amplification" (HIP) konnte abschließend durch die Verk{\"u}rzung der Distanz zwischen einem modifizierten Hinge-Primer und einem PCR-{\"a}hnlichen Primer verbessert werden. Schlussfolgerung: Die LAMP hat sich aufgrund der hohen Robustheit und Effizienz zu einer leistungsf{\"a}higen Alternative f{\"u}r die klassische PCR in der molekularbiologischen Diagnostik entwickelt. Unterschiedliche Detektionsverfahren verbessern die Leistungsf{\"a}higkeit der qualitativen und quantitativen LAMP f{\"u}r die Feldanwendungen und f{\"u}r die Diagnostik, da die neuen DNA- und Pyrophosphat-abh{\"a}ngigen Nachweismethoden in einer geschlossenen Reaktion eingesetzt werden k{\"o}nnen und so eine einfache Pathogendiagnostik erm{\"o}glichen. Die gezeigten Methoden k{\"o}nnen dar{\"u}ber hinaus zu einer Kostensenkung und Zeitersparnis gegen{\"u}ber den herk{\"o}mmlichen Methoden beitragen. Ein attraktives Ziel stellt die Weiterentwicklung der HIP f{\"u}r den Pathogennachweis als Alternative zur LAMP dar. Hierbei k{\"o}nnen die neuen LAMP-Detektionsverfahren ebenfalls Anwendung finden. Die Verwendung von Bst DNA-Polymerase-abh{\"a}ngigen Reaktionen erm{\"o}glicht dar{\"u}ber hinaus die Integration einer robusten isothermalen Amplifikation in mikrofluidische Systeme. Durch die Kombination der Probenvorbereitung, Amplifikation und Detektion sind zuk{\"u}nftige Anwendungen mit kurzer Analysezeit und geringem apparativen Aufwand insbesondere in der Pathogendiagnostik m{\"o}glich.},
  language  = {de}
}
@phdthesis{Foti2017,
  author    = {Foti, Alessandro},
  title     = {Characterization of the human aldehyde oxidase},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-410107},
  school      = {Universit{\"a}t Potsdam},
  pages     = {157},
  year      = {2017},
  abstract  = {In this work the human AOX1 was characterized and detailed aspects regarding the expression, the enzyme kinetics and the production of reactive oxygen species (ROS) were investigated. The hAOX1 is a cytosolic enzyme belonging to the molybdenum hydroxylase family. Its catalytically active form is a homodimer with a molecular weight of 300 kDa. Each monomer (150 kDa) consists of three domains: a N-terminal domain (20 kDa) containing two [2Fe-2S] clusters, a 40 kDa intermediate domain containing a flavin adenine dinucleotide (FAD), and a C-terminal domain (85 kDa) containing the substrate binding pocket and the molybdenum cofactor (Moco). The hAOX1 has an emerging role in the metabolism and pharmacokinetics of many drugs, especially aldehydes and N- heterocyclic compounds. In this study, the hAOX1 was hetereogously expressed in E. coli TP1000 cells, using a new codon optimized gene sequence which improved the expressed protein yield of around 10-fold compared to the previous expression systems for this enzyme. To increase the catalytic activity of hAOX1, an in vitro chemical sulfuration was performed to favor the insertion of the equatorial sulfido ligand at the Moco with consequent increased enzymatic activity of around 10-fold. Steady-state kinetics and inhibition studies were performed using several substrates, electron acceptors and inhibitors. The recombinant hAOX1 showed higher catalytic activity when molecular oxygen was used as electron acceptor. The highest turn over values were obtained with phenanthridine as substrate. Inhibition studies using thioridazine (phenothiazine family), in combination with structural studies performed in the group of Prof. M.J. Rom{\~a}o, Nova Universidade de Lisboa, showed a new inhibition site located in proximity of the dimerization site of hAOX1. The inhibition mode of thioridazine resulted in a noncompetitive inhibition type. Further inhibition studies with loxapine, a thioridazine-related molecule, showed the same type of inhibition. Additional inhibition studies using DCPIP and raloxifene were carried out. Extensive studies on the FAD active site of the hAOX1 were performed. Twenty new hAOX1 variants were produced and characterized. The hAOX1 variants generated in this work were divided in three groups: I) hAOX1 single nucleotide polymorphisms (SNP) variants; II) XOR- FAD loop hAOX1 variants; III) additional single point hAOX1 variants. The hAOX1 SNP variants G46E, G50D, G346R, R433P, A439E, K1231N showed clear alterations in their catalytic activity, indicating a crucial role of these residues into the FAD active site and in relation to the overall reactivity of hAOX1. Furthermore, residues of the bovine XOR FAD flexible loop (Q423ASRREDDIAK433) were introduced in the hAOX1. FAD loop hAOX1 variants were produced and characterized for their stability and catalytic activity. Especially the variants hAOX1 N436D/A437D/L438I, N436D/A437D/L438I/I440K and Q434R/N436D/A437D/L438I/I440K showed decreased catalytic activity and stability. hAOX1 wild type and variants were tested for reactivity toward NADH but no reaction was observed. Additionally, the hAOX1 wild type and variants were tested for the generation of reactive oxygen species (ROS). Interestingly, one of the SNP variants, hAOX1 L438V, showed a high ratio of superoxide prodction. This result showed a critical role for the residue Leu438 in the mechanism of oxygen radicals formation by hAOX1. Subsequently, further hAOX1 variants having the mutated Leu438 residue were produced. The variants hAOX1 L438A, L438F and L438K showed superoxide overproduction of around 85\%, 65\% and 35\% of the total reducing equivalent obtained from the substrate oxidation. The results of this work show for the first time a characterization of the FAD active site of the hAOX1, revealing the importance of specific residues involved in the generation of ROS and effecting the overall enzymatic activity of hAOX1. The hAOX1 SNP variants presented here indicate that those allelic variations in humans might cause alterations ROS balancing and clearance of drugs in humans.},
  language  = {en}
}
@phdthesis{Garcia2017,
  author    = {Garcia, Francisca},
  title     = {Mundos comunes},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-400582},
  school      = {Universit{\"a}t Potsdam},
  pages     = {270},
  year      = {2017},
  abstract  = {Vor dem Hintergrund unterschiedlicher Bewegungen und k{\"u}nstlerischer Dialoge in den siebziger und achtziger Jahren, stellt ihre Doktorarbeit den Begriff des „Lateinamerikanischen" auf dem Gebiet der Kunst und Kultur in Frage. {\"U}ber eine „sammelnde Reise" von Spuren, Zeichen und F{\"a}hrten durch europ{\"a}ische St{\"a}dte, analysiert die Arbeit die Begriffe Ort, Gemeinschaft und kulturelles Ged{\"a}chtnis, um eine neue Form des lateinamerikanischen Kontinents bilden zu k{\"o}nnen.},
  language  = {es}
}
@phdthesis{Georgiev2017,
  author    = {Georgiev, Vasil},
  title     = {Light-induced transformations in biomembranes},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-395309},
  school      = {Universit{\"a}t Potsdam},
  pages     = {81},
  year      = {2017},
  abstract  = {Cellular membranes constantly experience remodeling, as exemplified by morphological changes during endo- and exocytosis. Regulation of membrane morphology is essential for these processes. In this work, we attempt to establish a regulation path based on the use of photoswitches exhibiting conformational changes in model membranes, namely, giant unilamellar vesicles (GUVs). The mechanism of the changes in the GUVs' morphology caused by isomerization of the photosensitive molecules has been previously explored but still remains elusive. We examine the morphological reshaping of GUVs in the presence of the photoswitch o-tetrafluoroazobenzene (F-azo) and show that the mechanism behind the resulting morphological changes involves both an increase in the membrane area and generation of a positive spontaneous curvature. First, we characterize the partitioning of F-azo in a single-component membrane using both experimental and computational approaches. The partition coefficient calculated from molecular dynamic simulations agrees with experimental data obtained with size-exclusion chromatography. Then, we implement the approach of vesicle electrodeformation in order to assess the increase in the membrane area, which is observed as a result of the conformational change of F-azo. Finally, the local and the effective membrane spontaneous curvatures were estimated from the observed shapes of vesicles exhibiting outward budding. We then extend the application of the F-azo to multicomponent lipid membranes, which exhibit a coexistence of domains in different liquid phases due to a miscibility gap between the lipids. We perform initial experiments to investigate whether F-azo can be employed to modulate the lateral lipid packing and organization. We observe either complete mixing of the domains or the appearing of disordered domains within the domains of more ordered phase. The type of behavior observed in response to the photoisomerization of F-azo was dependent on the used lipid composition. We believe that the findings introduced here will have an impact in understanding and controlling both lipid phase modulation and regulation of the membrane morphology in membrane systems.},
  language  = {en}
}
@phdthesis{Golly2017,
  author    = {Golly, Antonius},
  title     = {Formation and evolution of channel steps and their role for sediment dynamics in a steep mountain stream},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-411728},
  school      = {Universit{\"a}t Potsdam},
  pages     = {180},
  year      = {2017},
  abstract  = {Steep mountain channels are an important component of the fluvial system. On geological timescales, they shape mountain belts and counteract tectonic uplift by erosion. Their channels are strongly coupled to hillslopes and they are often the main source of sediment transported downstream to low-gradient rivers and to alluvial fans, where commonly settlements in mountainous areas are located. Hence, mountain streams are the cause for one of the main natural hazards in these regions. Due to climate change and a pronounced populating of mountainous regions the attention given to this threat is even growing. Although quantitative studies on sediment transport have significantly advanced our knowledge on measuring and calibration techniques we still lack studies of the processes within mountain catchments. Studies examining the mechanisms of energy and mass exchange on small temporal and spatial scales in steep streams remain sparse in comparison to low-gradient alluvial channels. In the beginning of this doctoral project, a vast amount of experience and knowledge of a steep stream in the Swiss Prealps had to be consolidated in order to shape the principal aim of this research effort. It became obvious, that observations from within the catchment are underrepresented in comparison to experiments performed at the catchment's outlet measuring fluxes and the effects of the transported material. To counteract this imbalance, an examination of mass fluxes within the catchment on the process scale was intended. Hence, this thesis is heavily based on direct field observations, which are generally rare in these environments in quantity and quality. The first objective was to investigate the coupling of the channel with surrounding hillslopes, the major sources of sediment. This research, which involved the monitoring of the channel and adjacent hillslopes, revealed that alluvial channel steps play a key role in coupling of channel and hillslopes. The observations showed that hillslope stability is strongly associated with the step presence and an understanding of step morphology and stability is therefore crucial in understanding sediment mobilization. This finding refined the way we think about the sediment dynamics in steep channels and motivated continued research of the step dynamics. However, soon it became obvious that the technological basis for developing field tests and analyzing the high resolution geometry measured in the field was not available. Moreover, for many geometrical quantities in mountain channels definitions and a clear scientific standard was not available. For example, these streams are characterized by a high spatial variability of the channel banks, preventing straightforward calculations of the channel width without a defined reference. Thus, the second and inevitable part of this thesis became the development and evaluation of scientific tools in order to investigate the geometrical content of the study reach thoroughly. The developed framework allowed the derivation of various metrics of step and channel geometry which facilitated research on the a large data set of observations of channel steps. In the third part, innovative, physically-based metrics have been developed and compared to current knowledge on step formation, suggested in the literature. With this analyses it could be demonstrated that the formation of channel steps follow a wide range of hydraulic controls. Due to the wide range of tested parameters channel steps observed in a natural stream were attributed to different mechanisms of step formation, including those based on jamming and those based on key-stones. This study extended our knowledge on step formation in a steep stream and harmonized different, often time seen as competing, processes of step formation. This study was based on observations collected at one point in time. In the fourth part of this project, the findings of the snap-shot observations were extended in the temporal dimension and the derived concepts have been utilized to investigate reach-scale step patterns in response to large, exceptional flood events. The preliminary results of this work based on the long-term analyses of 7 years of long profile surveys showed that the previously observed channel-hillslope mechanism is the responsible for the short-term response of step formation. The findings of the long-term analyses of step patterns drew a bow to the initial observations of a channel-hillslope system which allowed to join the dots in the dynamics of steep stream. Thus, in this thesis a broad approach has been chosen to gain insights into the complex system of steep mountain rivers. The effort includes in situ field observations (article I), the development of quantitative scientific tools (article II), the reach-scale analyses of step-pool morphology (article III) and its temporal evolution (article IV). With this work our view on the processes within the catchment has been advanced towards a better mechanistic understanding of these fluvial system relevant to improve applied scientific work.},
  language  = {en}
}
@phdthesis{Graglia2017,
  author    = {Graglia, Micaela},
  title     = {Lignin valorization},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-104863},
  school      = {Universit{\"a}t Potsdam},
  pages     = {133},
  year      = {2017},
  abstract  = {The topic of this project is the use of lignin as alternative source of aromatic building blocks and oligomers to fossil feedstocks. Lignin is known as the most abundant aromatic polymer in nature and is isolated from the lignocellulosic component of plants by different possible extraction treatments. Both the biomass source and the extraction method affect the structure of the isolated lignin, therefore influencing its further application. Lignin was extracted from beech wood by two different hydrothermal alkaline treatments, which use NaOH and Ba(OH)2 as base and by an acid-catalyzed organosolv process. Moreover, lignin was isolated from bamboo, beech wood and coconut by soda treatment of the biomasses. A comparison of the structural features of such isolated lignins was performed through the use of a wide range of analytical methods. Alkaline lignins resulted in a better candidate as carbon precursor and macromonomers for the synthesis of polymer than organosolv lignin. In fact, alkaline lignins showed higher residual mass after carbonization and higher content of the reactive hydroxy functionalities. In contrast, the lignin source turned out to slightly affect the lignin hydroxyl content. One of the most common lignin modifications is its deconstruction to obtain aromatic molecules, which can be used as starting materials for the synthesis of fine chemicals. Lignin deconstruction leads to a complex mixture of aromatic molecules. A gas chromatographic analytical method was developed to characterize the mixture of products obtained by lignin deconstruction via heterogeneous catalytic hydrogenolysis. The analytical protocol allowed the quantification of three main groups of molecules by means of calibration curves, internal standard and a preliminary silylation step of the sample. The analytical method was used to study the influence of the hydrogenolysis catalyst, temperature and system (flow and batch reactor) on the yield and selectivity of the aromatic compounds. Lignin extracted from beech wood by a hydrothermal process using Ba(OH)2 as base, was functionalized by aromatic nitration in order to add nitrogen functionalities. The final goal was the synthesis of a nitrogen doped carbon. Nitrated lignin was reduced to the amino form in order to compare the influence of different nitrogen functionalities on the porosity of the final carbon. The carbons were obtained by ionothermal treatment of the precursors in the presence of the eutectic salt mixture KCl/ZnCl2 Such synthesized carbons showed micro-, macro- and mesoporosity and were tested for their electrocatalytic activity towards the oxygen reduction reaction. Mesoporous carbon derived from nitro lignin displayed the highest electrocatalytic activity. Lignins isolated from coconut, beech wood and bamboo were used as macromonomers for the synthesis of biobased polyesters. A condensation reaction was performed between lignin and a hyper branched poly(ester-amine), previously obtained by condensation of triethanolamine and adipic acid. The influence of the lignin source and content on the thermochemical and mechanical properties of the final material was investigated. The prepolymer showed adhesive properties towards aluminum and its shear strength was therefore measured. The gluing properties of such synthesized glues turned out to be independent from the lignin source but affected by the amount of lignin in the final material. This work shows that, although still at a laboratory scale, the valorization of lignin can overcome the critical issues of lignin´s structure variability and complexity.},
  language  = {en}
}
@phdthesis{GrimmSeyfarth2017,
  author    = {Grimm-Seyfarth, Annegret},
  title     = {Effects of climate change on a reptile community in arid Australia},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-412655},
  school      = {Universit{\"a}t Potsdam},
  pages     = {IX, 184},
  year      = {2017},
  abstract  = {Dies ist eine kumulative Dissertation, die drei Originalstudien umfasst (eine publiziert, eine in Revision, eine eingereicht; Stand Dezember 2017). Sie untersucht, wie Reptilienarten im ariden Australien auf verschiedene klimatische Parameter verschiedener r{\"a}umlicher Skalen reagieren und analysiert dabei zwei m{\"o}gliche zugrunde liegende Hauptmechanismen: Thermoregulatorisches Verhalten und zwischenartliche Wechselwirkungen. In dieser Dissertation wurden umfassende, individuenbasierte Felddaten verschiedener trophischer Ebenen kombiniert mit ausgew{\"a}hlten Feldexperimenten, statistischen Analysen, und Vorhersagemodellen. Die hier erkannten Mechanismen und Prozesse k{\"o}nnen nun genutzt werden, um m{\"o}gliche Ver{\"a}nderungen der ariden Reptiliengesellschaft in der Zukunft vorherzusagen. Dieses Wissen wird dazu beitragen, dass unser Grundverst{\"a}ndnis {\"u}ber die Konsequenzen des globalen Wandels verbessert und Biodiversit{\"a}tsverlust in diesem anf{\"a}lligen {\"O}kosystem verhindert wird.},
  language  = {en}
}
@phdthesis{Gudipudi2017,
  author    = {Gudipudi, Venkata Ramana},
  title     = {Cities and global sustainability},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-407113},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xxii, 101},
  year      = {2017},
  abstract  = {In the wake of 21st century, humanity witnessed a phenomenal raise of urban agglomerations as powerhouses for innovation and socioeconomic growth. Driving much of national (and in few instances even global) economy, such a gargantuan raise of cities is also accompanied by subsequent increase in energy, resource consumption and waste generation. Much of anthropogenic transformation of Earth's environment in terms of environmental pollution at local level to planetary scale in the form of climate change is currently taking place in cities. Projected to be crucibles for entire humanity by the end of this century, the ultimate fate of humanity predominantly lies in the hands of technological innovation, urbanites' attitudes towards energy/resource consumption and development pathways undertaken by current and future cities. Considering the unparalleled energy, resource consumption and emissions currently attributed to global cities, this thesis addresses these issues from an efficiency point of view. More specifically, this thesis addresses the influence of population size, density, economic geography and technology in improving urban greenhouse gas (GHG) emission efficiency and identifies the factors leading to improved eco-efficiency in cities. In order to investigate the in uence of these factors in improving emission and resource efficiency in cities, a multitude of freely available datasets were coupled with some novel methodologies and analytical approaches in this thesis. Merging the well-established Kaya Identity to the recently developed urban scaling laws, an Urban Kaya Relation is developed to identify whether large cities are more emission efficient and the intrinsic factors leading to such (in)efficiency. Applying Urban Kaya Relation to a global dataset of 61 cities in 12 countries, this thesis identifed that large cities in developed regions of the world will bring emission efficiency gains because of the better technologies implemented in these cities to produce and utilize energy consumption while the opposite is the case for cities in developing regions. Large cities in developing countries are less efficient mainly because of their affluence and lack of efficient technologies. Apart from the in uence of population size on emission efficiency, this thesis identified the crucial role played by population density in improving building and on-road transport sector related emission efficiency in cities. This is achieved by applying the City Clustering Algorithm (CCA) on two different gridded land use datasets and a standard emission inventory to attribute these sectoral emissions to all inhabited settlements in the USA. Results show that doubling the population density would entail a reduction in the total CO2 emissions in buildings and on-road sectors typically by at least 42 \%. Irrespective of their population size and density, cities are often blamed for their intensive resource consumption that threatens not only local but also global sustainability. This thesis merged the concept of urban metabolism with benchmarking and identified cities which are eco-efficient. These cities enable better socioeconomic conditions while being less burden to the environment. Three environmental burden indicators (annual average NO2 concentration, per capita waste generation and water consumption) and two socioeconomic indicators (GDP per capita and employment ratio) for 88 most populous European cities are considered in this study. Using two different non-parametric ranking methods namely regression residual ranking and Data Envelopment Analysis (DEA), eco-efficient cities and their determining factors are identified. This in-depth analysis revealed that mature cities with well-established economic structures such as Munich, Stockholm and Oslo are eco-efficient. Further, correlations between objective eco-efficiency ranking with each of the indicator rankings and the ranking of urbanites' subjective perception about quality of life are analyzed. This analysis revealed that urbanites' perception about quality of life is not merely confined to the socioeconomic well-being but rather to their combination with lower environmental burden. In summary, the findings of this dissertation has three general conclusions for improving emission and ecological efficiency in cities. Firstly, large cities in emerging nations face a huge challenge with respect to improving their emission efficiency. The task in front of these cities is threefold: (1) deploying efficient technologies for the generation of electricity and improvement of public transportation to unlock their leap frogging potential, (2) addressing the issue of energy poverty and (3) ensuring that these cities do not develop similar energy consumption patterns with infrastructure lock-in behavior similar to those of cities in developed regions. Secondly, the on-going urban sprawl as a global phenomenon will decrease the emission efficiency within the building and transportation sector. Therefore, local policy makers should identify adequate fiscal and land use policies to curb urban sprawl. Lastly, since mature cities with well-established economic structures are more eco-efficient and urbanites' perception re ects its combination with decreasing environmental burden; there is a need to adopt and implement strategies which enable socioeconomic growth in cities whilst decreasing their environment burden.},
  language  = {en}
}
@phdthesis{Guidi2017,
  author    = {Guidi, Giovanni},
  title     = {Connecting simulations and observations in galaxy formation studies},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-396876},
  school      = {Universit{\"a}t Potsdam},
  pages     = {141},
  year      = {2017},
  abstract  = {Observational and computational extragalactic astrophysics are two fields of research that study a similar subject from different perspectives. Observational extragalactic astrophysics aims, by recovering the spectral energy distribution of galaxies at different wavelengths, to reliably measure their properties at different cosmic times and in a large variety of environments. Analyzing the light collected by the instruments, observers try to disentangle the different processes occurring in galaxies at the scales of galactic physics, as well as the effect of larger scale processes such as mergers and accretion, in order to obtain a consistent picture of galaxy formation and evolution. On the other hand, hydrodynamical simulations of galaxy formation in cosmological context are able to follow the evolution of a galaxy along cosmic time, taking into account both external processes such as mergers, interactions and accretion, and internal mechanisms such as feedback from Supernovae and Active Galactic Nuclei. Due to the great advances in both fields of research, we have nowadays available spectral and photometric information for a large number of galaxies in the Universe at different cosmic times, which has in turn provided important knowledge about the evolution of the Universe; at the same time, we are able to realistically simulate galaxy formation and evolution in large volumes of the Universe, taking into account the most relevant physical processes occurring in galaxies. As these two approaches are intrinsically different in their methodology and in the information they provide, the connection between simulations and observations is still not fully established, although simulations are often used in galaxies' studies to interpret observations and assess the effect of the different processes acting on galaxies on the observable properties, and simulators usually test the physical recipes implemented in their hydrodynamical codes through the comparison with observations. In this dissertation we aim to better connect the observational and computational approaches in the study of galaxy formation and evolution, using the methods and results of one field to test and validate the methods and results of the other. In a first work we study the biases and systematics in the derivation of the galaxy properties in observations. We post-process hydrodynamical cosmological simulations of galaxy formation to calculate the galaxies' Spectral Energy Distributions (SEDs) using different approaches, including radiative transfer techniques. Comparing the direct results of the simulations with the quantities obtained applying observational techniques to these synthetic SEDs, we are able to make an analysis of the biases intrinsic in the observational algorithms, and quantify their accuracy in recovering the galaxies' properties, as well as estimating the uncertainties affecting a comparison between simulations and observations when different approaches to obtain the observables are followed. Our results show that for some quantities such as the stellar ages, metallicities and gas oxygen abundances large differences can appear, depending on the technique applied in the derivation. In a second work we compare a set of fifteen galaxies similar in mass to the Milky Way and with a quiet merger history in the recent past (hence expected to have properties close to spiral galaxies), simulated in a cosmological context, with data from the Sloan Digital Sky Survey (SDSS). We use techniques to obtain the observables as similar as possible to the ones applied in SDSS, with the aim of making an unbiased comparison between our set of hydrodynamical simulations and SDSS observations. We quantify the differences in the physical properties when these are obtained directly from the simulations without post-processing, or mimicking the SDSS observational techniques. We fit linear relations between the values derived directly from the simulations and following SDSS observational procedures, which in most of the cases have relatively high correlation, that can be easily used to more reliably compare simulations with SDSS data. When mimicking SDSS techniques, these simulated galaxies are photometrically similar to galaxies in the SDSS blue sequence/green valley, but have in general older ages, lower SFRs and metallicities compared to the majority of the spirals in the observational dataset. In a third work, we post-process hydrodynamical simulations of galaxies with radiative transfer techniques, to generate synthetic data that mimic the properties of the CALIFA Integral Field Spectroscopy (IFS) survey. We reproduce the main characteristics of the CALIFA observations in terms of field of view and spaxel physical size, data format, point spread functions and detector noise. This 3-dimensional dataset is suited to be analyzed by the same algorithms applied to the CALIFA dataset, and can be used as a tool to test the ability of the observational algorithms in recovering the properties of the CALIFA galaxies. To this purpose, we also generate the resolved maps of the simulations' properties, calculated directly from the hydrodynamical snapshots, or from the simulated spectra prior to the addition of the noise. Our work shows that a reliable connection between the models and the data is of crucial importance both to judge the output of galaxy formation codes and to accurately test the observational algorithms used in the analysis of galaxy surveys' data. A correct interpretation of observations will be particularly important in the future, in light of the several ongoing and planned large galaxy surveys that will provide the community with large datasets of properties of galaxies (often spatially-resolved) at different cosmic times, allowing to study galaxy formation physics at a higher level of detail than ever before. We have shown that neglecting the observational biases in the comparison between simulations and an observational dataset may move the simulations to different regions in the planes of the observables, strongly affecting the assessment of the correctness of the sub-resolution physical models implemented in galaxy formation codes, as well as the interpretation of given observational results using simulations.},
  language  = {en}
}
@phdthesis{Heck2017,
  author    = {Heck, Christian},
  title     = {Gold and silver nanolenses self-assembled by DNA origami},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-409002},
  school      = {Universit{\"a}t Potsdam},
  pages     = {ix, 125},
  year      = {2017},
  abstract  = {Nanolenses are linear chains of differently-sized metal nanoparticles, which can theoretically provide extremely high field enhancements. The complex structure renders their synthesis challenging and has hampered closer analyses so far. Here, the technique of DNA origami was used to self-assemble DNA-coated 10 nm, 20 nm, and 60 nm gold or silver nanoparticles into gold or silver nanolenses. Three different geometrical arrangements of gold nanolenses were assembled, and for each of the three, sets of single gold nanolenses were investigated in detail by atomic force microscopy, scanning electron microscopy, dark-field scattering and Raman spectroscopy. The surface-enhanced Raman scattering (SERS) capabilities of the single nanolenses were assessed by labelling the 10 nm gold nanoparticle selectively with dye molecules. The experimental data was complemented by finite-difference time-domain simulations. For those gold nanolenses which showed the strongest field enhancement, SERS signals from the two different internal gaps were compared by selectively placing probe dyes on the 20 nm or 60 nm gold particles. The highest enhancement was found for the gap between the 20 nm and 10 nm nanoparticle, which is indicative of a cascaded field enhancement. The protein streptavidin was labelled with alkyne groups and served as a biological model analyte, bound between the 20 nm and 10 nm particle of silver nanolenses. Thereby, a SERS signal from a single streptavidin could be detected. Background peaks observed in SERS measurements on single silver nanolenses could be attributed to amorphous carbon. It was shown that the amorphous carbon is generated in situ.},
  language  = {en}
}
@phdthesis{Heinke2017,
  author    = {Heinke, David},
  title     = {Entwicklung biokompatibler superparamagnetischer Nanopartikel f{\"u}r den Einsatz als in vivo-Diagnostikum insbesondere im Magnetic Particle Imaging},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-406196},
  school      = {Universit{\"a}t Potsdam},
  pages     = {142},
  year      = {2017},
  abstract  = {Magnetische Eisenoxidnanopartikel werden bereits seit geraumer Zeit erfolgreich als MRT-Kontrastmittel in der klinischen Bildgebung eingesetzt. Durch Optimierung der magnetischen Eigenschaften der Nanopartikel kann die Aussagekraft von MR-Aufnahmen verbessert und somit der diagnostische Wert einer MR-Anwendung weiter erh{\"o}ht werden. Neben der Verbesserung bestehender Verfahren wird die bildgebende Diagnostik ebenso durch die Entwicklung neuer Verfahren, wie dem Magnetic Particle Imaging, vorangetrieben. Da hierbei das Messsignal von den magnetischen Nanopartikeln selbst erzeugt wird, birgt das MPI einen enormen Vorteil hinsichtlich der Sensitivit{\"a}t bei gleichzeitig hoher zeitlicher und r{\"a}umlicher Aufl{\"o}sung. Da es aktuell jedoch keinen kommerziell vertriebenen in vivo-tauglichen MPI-Tracer gibt, besteht ein dringender Bedarf an geeigneten innovativen Tracermaterialien. Daraus resultierte die Motivation dieser Arbeit biokompatible und superparamagnetische Eisenoxidnanopartikel f{\"u}r den Einsatz als in vivo-Diagnostikum insbesondere im Magnetic Particle Imaging zu entwickeln. Auch wenn der Fokus auf der Tracerentwicklung f{\"u}r das MPI lag, wurde ebenso die MR-Performance bewertet, da geeignete Partikel somit alternativ oder zus{\"a}tzlich als MR-Kontrastmittel mit verbesserten Kontrasteigenschaften eingesetzt werden k{\"o}nnten. Die Synthese der Eisenoxidnanopartikel erfolgte {\"u}ber die partielle Oxidation von gef{\"a}lltem Eisen(II)-hydroxid und Green Rust sowie eine diffusionskontrollierte Kopr{\"a}zipitation in einem Hydrogel. Mit der partiellen Oxidation von Eisen(II)-hydroxid und Green Rust konnten erfolgreich biokompatible und {\"u}ber lange Zeit stabile Eisenoxidnanopartikel synthetisiert werden. Zudem wurden geeignete Methoden zur Formulierung und Sterilisierung etabliert, wodurch zahlreiche Voraussetzungen f{\"u}r eine Anwendung als in vivo-Diagnostikum geschaffen wurden. Weiterhin ist auf Grundlage der MPS-Performance eine hervorragende Eignung dieser Partikel als MPI-Tracer zu erwarten, wodurch die Weiterentwicklung der MPI-Technologie maßgeblich vorangetrieben werden k{\"o}nnte. Die Bestimmung der NMR-Relaxivit{\"a}ten sowie ein initialer in vivo-Versuch zeigten zudem das große Potential der formulierten Nanopartikelsuspensionen als MRT-Kontrastmittel. Die Modifizierung der Partikeloberfl{\"a}che erm{\"o}glicht ferner die Herstellung zielgerichteter Nanopartikel sowie die Markierung von Zellen, wodurch das m{\"o}gliche Anwendungsspektrum maßgeblich erweitert wurde. Im zweiten Teil wurden Partikel durch eine diffusionskontrollierte Kopr{\"a}zipitation im Hydrogel, wobei es sich um eine bioinspirierte Modifikation der klassischen Kopr{\"a}zipitation handelt, synthetisiert, wodurch Partikel mit einer durchschnittlichen Kristallitgr{\"o}ße von 24 nm generiert werden konnten. Die Bestimmung der MPS- und MR-Performance elektrostatisch stabilisierter Partikel ergab vielversprechende Resultate. In Vorbereitung auf die Entwicklung eines in vivo-Diagnostikums wurden die Partikel anschließend erfolgreich sterisch stabilisiert, wodurch der kolloidale Zustand in MilliQ-Wasser {\"u}ber lange Zeit aufrechterhalten werden konnte. Durch Zentrifugation konnten die Partikel zudem erfolgreich in verschiedene Gr{\"o}ßenfraktionen aufgetrennt werden. Dies erm{\"o}glichte die Bestimmung der idealen Aggregatgr{\"o}ße dieses Partikelsystems in Bezug auf die MPS-Performance.},
  language  = {de}
}
@phdthesis{Heise2017,
  author    = {Heise, Janine},
  title     = {Phylogenetic and physiological characterization of deep-biosphere microorganisms in El'gygytgyn Crater Lake sediments},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-403436},
  school      = {Universit{\"a}t Potsdam},
  pages     = {117},
  year      = {2017},
  abstract  = {The existence of diverse and active microbial ecosystems in the deep subsurface - a biosphere that was originally considered devoid of life - was discovered in multiple microbiological studies. However, most of the studies are restricted to marine ecosystems, while our knowledge about the microbial communities in the deep subsurface of lake systems and their potentials to adapt to changing environmental conditions is still fragmentary. This doctoral thesis aims to build up a unique data basis for providing the first detailed high-throughput characterization of the deep biosphere of lacustrine sediments and to emphasize how important it is to differentiate between the living and the dead microbial community in deep biosphere studies. In this thesis, up to 3.6 Ma old sediments (up to 317 m deep) of the El'gygytgyn Crater Lake were examined, which represents the oldest terrestrial climate record of the Arctic. Combining next generation sequencing with detailed geochemical characteristics and other environmental parameters, the microbial community composition was analyzed in regard to changing climatic conditions within the last 3.6 Ma to 1.0 Ma (Pliocene and Pleistocene). DNA from all investigated sediments was successfully extracted and a surprisingly diverse (6,910 OTUs) and abundant microbial community in the El'gygytgyn deep sediments were revealed. The bacterial abundance (10³-10⁶ 16S rRNA copies g⁻¹ sediment) was up to two orders of magnitudes higher than the archaeal abundance (10¹-10⁵) and fluctuates with the Pleistocene glacial/interglacial cyclicality. Interestingly, a strong increase in the microbial diversity with depth was observed (approximately 2.5 times higher diversity in Pliocene sediments compared to Pleistocene sediments). The increase in diversity with depth in the Lake El'gygytgyn is most probably caused by higher sedimentary temperatures towards the deep sediment layers as well as an enhanced temperature-induced intra-lake bioproductivity and higher input of allochthonous organic-rich material during Pliocene climatic conditions. Moreover, the microbial richness parameters follow the general trends of the paleoclimatic parameters, such as the paleo-temperature and paleo-precipitation. The most abundant bacterial representatives in the El'gygytgyn deep biosphere are affiliated with the phyla Proteobacteria, Actinobacteria, Bacteroidetes, and Acidobacteria, which are also commonly distributed in the surrounding permafrost habitats. The predominated taxon was the halotolerant genus Halomonas (in average 60\% of the total reads per sample). Additionally, this doctoral thesis focuses on the live/dead differentiation of microbes in cultures and environmental samples. While established methods (e.g., fluorescence in situ hybridization, RNA analyses) are not applicable to the challenging El'gygytgyn sediments, two newer methods were adapted to distinguish between DNA from live cells and free (extracellular, dead) DNA: the propidium monoazide (PMA) treatment and the cell separation adapted for low amounts of DNA. The applicability of the DNA-intercalating dye PMA was successfully evaluated to mask free DNA of different cultures of methanogenic archaea, which play a major role in the global carbon cycle. Moreover, an optimal procedure to simultaneously treat bacteria and archaea was developed using 130 µM PMA and 5 min of photo-activation with blue LED light, which is also applicable on sandy environmental samples with a particle load of ≤ 200 mg mL⁻¹. It was demonstrated that the soil texture has a strong influence on the PMA treatment in particle-rich samples and that in particular silt and clay-rich samples (e.g., El'gygytgyn sediments) lead to an insufficient shielding of free DNA by PMA. Therefore, a cell separation protocol was used to distinguish between DNA from live cells (intracellular DNA) and extracellular DNA in the El'gygytgyn sediments. While comparing these two DNA pools with a total DNA pool extracted with a commercial kit, significant differences in the microbial composition of all three pools (mean distance of relative abundance: 24.1\%, mean distance of OTUs: 84.0\%) was discovered. In particular, the total DNA pool covers significantly fewer taxa than the cell-separated DNA pools and only inadequately represents the living community. Moreover, individual redundancy analyses revealed that the microbial community of the intra- and extracellular DNA pool are driven by different environmental factors. The living community is mainly influenced by life-dependent parameters (e.g., sedimentary matrix, water availability), while the extracellular DNA is dependent on the biogenic silica content. The different community-shaping parameters and the fact, that a redundancy analysis of the total DNA pool explains significantly less variance of the microbial community, indicate that the total DNA represents a mixture of signals of the live and dead microbial community. This work provides the first fundamental data basis of the diversity and distribution of microbial deep biosphere communities of a lake system over several million years. Moreover, it demonstrates the substantial importance of extracellular DNA in old sediments. These findings may strongly influence future environmental community analyses, where applications of live/dead differentiation avoid incorrect interpretations due to a failed extraction of the living microbial community or an overestimation of the past community diversity in the course of total DNA extraction approaches.},
  language  = {en}
}
@phdthesis{Hendriyana2017,
  author    = {Hendriyana, Andri},
  title     = {Detection and Kirchhoff-type migration of seismic events by use of a new characteristic function},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-398879},
  school      = {Universit{\"a}t Potsdam},
  pages     = {v, 139},
  year      = {2017},
  abstract  = {The classical method of seismic event localization is based on the picking of body wave arrivals, ray tracing and inversion of travel time data. Travel time picks with small uncertainties are required to produce reliable and accurate results with this kind of source localization. Hence recordings, with a low Signal-to-Noise Ratio (SNR) cannot be used in a travel time based inversion. Low SNR can be related with weak signals from distant and/or low magnitude sources as well as with a high level of ambient noise. Diffraction stacking is considered as an alternative seismic event localization method that enables also the processing of low SNR recordings by mean of stacking the amplitudes of seismograms along a travel time function. The location of seismic event and its origin time are determined based on the highest stacked amplitudes (coherency) of the image function. The method promotes an automatic processing since it does not need travel time picks as input data. However, applying diffraction stacking may require longer computation times if only limited computer resources are used. Furthermore, a simple diffraction stacking of recorded amplitudes could possibly fail to locate the seismic sources if the focal mechanism leads to complex radiation patterns which typically holds for both natural and induced seismicity. In my PhD project, I have developed a new work flow for the localization of seismic events which is based on a diffraction stacking approach. A parallelized code was implemented for the calculation of travel time tables and for the determination of an image function to reduce computation time. In order to address the effects from complex source radiation patterns, I also suggest to compute diffraction stacking from a characteristic function (CF) instead of stacking the original wave form data. A new CF, which is called in the following mAIC (modified from Akaike Information Criterion) is proposed. I demonstrate that, the performance of the mAIC does not depend on the chosen length of the analyzed time window and that both P- and S-wave onsets can be detected accurately. To avoid cross-talk between P- and S-waves due to inaccurate velocity models, I separate the P- and S-waves from the mAIC function by making use of polarization attributes. Then, eventually the final image function is represented by the largest eigenvalue as a result of the covariance analysis between P- and S-image functions. Before applying diffraction stacking, I also apply seismogram denoising by using Otsu thresholding in the time-frequency domain. Results from synthetic experiments show that the proposed diffraction stacking provides reliable results even from seismograms with low SNR=1. Tests with different presentations of the synthetic seismograms (displacement, velocity, and acceleration) shown that, acceleration seismograms deliver better results in case of high SNR, whereas displacement seismograms provide more accurate results in case of low SNR recordings. In another test, different measures (maximum amplitude, other statistical parameters) were used to determine the source location in the final image function. I found that the statistical approach is the preferred method particularly for low SNR. The work flow of my diffraction stacking method was finally applied to local earthquake data from Sumatra, Indonesia. Recordings from a temporary network of 42 stations deployed for 9 months around the Tarutung pull-apart Basin were analyzed. The seismic event locations resulting from the diffraction stacking method align along a segment of the Sumatran Fault. A more complex distribution of seismicity is imaged within and around the Tarutung Basin. Two lineaments striking N-S were found in the middle of the Tarutung Basin which support independent results from structural geology. These features are interpreted as opening fractures due to local extension. A cluster of seismic events repeatedly occurred in short time which might be related to fluid drainage since two hot springs are observed at the surface near to this cluster.},
  language  = {en}
}
@phdthesis{Hentrich2017,
  author    = {Hentrich, Doreen},
  title     = {Grenzfl{\"a}chen-kontrollierte Mineralisation von Calciumphosphat},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-398236},
  school      = {Universit{\"a}t Potsdam},
  pages     = {163},
  year      = {2017},
  abstract  = {In der vorliegenden Arbeit konnte gezeigt werden, dass die beiden verwendeten Amphiphile mit Cholesterol als hydrophoben Block, gute Template f{\"u}r die Mineralisation von Calciumphosphat an der Wasser/Luft-Grenzfl{\"a}che sind. Mittels Infrarot-Reflexions-Absorptions-Spektroskopie (IRRAS), R{\"o}ntgenphotoelektronenspektroskopie (XPS), Energie dispersiver R{\"o}ntgenspektroskopie (EDXS), Elektronenbeugung (SAED) und hochaufl{\"o}sende Transmissionselektronenmikroskopie (HRTEM) konnte die erfolgreiche Mineralisation von Calciumphosphat f{\"u}r beide Amphiphile an der Wasser/Luft-Grenzfl{\"a}che nachgewiesen werden. Es konnte auch gezeigt werden, dass das Phasenverhalten der beiden Amphiphile und die bei der Mineralisation von Calciumphosphat gebildeten Kristallphasen nicht identisch sind. Beide Amphiphile {\"u}ben demnach einen unterschiedlichen Einfluss auf den Mineralisationsverlauf aus. Beim CHOL-HEM konnte sowohl nach 3 h als auch nach 5 h Octacalciumphosphat (OCP) als einzige Kristallphase mittels XPS, SAED, HRTEM und EDXS nachgewiesen werden. Das A-CHOL hingegen zeigte bei der Mineralisation von Calciumphosphat nach 1 h zun{\"a}chst eine nicht eindeutig identifizierbare Vorl{\"a}uferphase aus amorphen Calciumphosphat, Brushit (DCPD) oder OCP. Diese wandelte sich dann nach 3 h und 5 h in ein Gemisch, bestehend aus OCP und ein wenig Hydroxylapatit (HAP) um. Die Schlussfolgerung daraus ist, dass das CHOL-HEM in der Lage ist, dass w{\"a}hrend der Mineralisation entstandene OCP zu stabilisieren. Dies geschieht vermutlich durch die Adsorption des Amphiphils bevorzugt an der OCP Oberfl{\"a}che in [100] Orientierung. Dadurch wird die Spaltung entlang der c-Achse unterdr{\"u}ckt und die Hydrolyse zum HAP verhindert. Das A-CHOL ist hingegen sterisch anspruchsvoller und kann wahrscheinlich aufgrund seiner Gr{\"o}ße nicht so gut an der OCP Kristalloberfl{\"a}che adsorbieren verglichen zum CHOL HEM. Das CHOL-HEM kann also die Hydrolyse von OCP zu HAP besser unterdr{\"u}cken als das A-CHOL. Da jedoch auch beim A-CHOL nach einer Mineralisationszeit von 5 h nur wenig HAP zu finden ist, w{\"a}re auch hier ein Stabilisierungseffekt der OCP Kristalle m{\"o}glich. Um eine genaue Aussage dar{\"u}ber treffen zu k{\"o}nnen, sind jedoch zus{\"a}tzliche Kontrollexperimente notwendig. Es w{\"a}re zum einen denkbar, die Mineralisationsexperimente {\"u}ber einen l{\"a}ngeren Zeitraum durchzuf{\"u}hren. Diese k{\"o}nnten zeigen, ob das CHOL-HEM die Hydrolyse vom OCP zum HAP komplett unterdr{\"u}ckt. Außerdem k{\"o}nnte nachgewiesen werden, ob beim A-CHOL das OCP weiter zum HAP umgesetzt wird oder ob ein Gemisch beider Kristallphasen erhalten bleibt. Um die Mineralisation an der Wasser/Luft-Grenzfl{\"a}che mit der Mineralisation in Bulkl{\"o}sung zu vergleichen, wurden zus{\"a}tzlich Mineralisationsexperimente in Bulkl{\"o}sung durchgef{\"u}hrt. Dazu wurden Nitrilotriessigs{\"a}ure (NTA) und Ethylendiamintetraessigs{\"a}ure (EDTA) als Mineralisationsadditive verwendet, da NTA unter anderem der Struktur der hydrophilen Kopfgruppe des A-CHOLs {\"a}hnelt. Es konnte gezeigt werden, dass ein Vergleich der Mineralisation an der Grenzfl{\"a}che mit der Mineralisation in Bulkl{\"o}sung nicht ohne weiteres m{\"o}glich ist. Bei der Mineralisation in Bulkl{\"o}sung wird bei tiefen pH-Werten DCPD und bei h{\"o}heren pH-Werten HAP gebildet. Diese wurde mittels R{\"o}ntgenpulverdiffraktometrie Messungen nachgewiesen und durch Infrarotspektroskopie bekr{\"a}ftigt. Die Bildung von OCP wie an der Wasser/Luft-Grenzfl{\"a}che konnte nicht beobachtet werden. Es konnte auch gezeigt werden, dass beide Additive NTA und EDTA einen unterschiedlichen Einfluss auf den Verlauf der Mineralisation nehmen. So unterscheiden sich zum einen die Morphologien des gebildeten DCPDs und zum anderen wurde beispielsweise in Anwesenheit von 10 und 15 mM NTA neben DCPD auch HAP bei einem Ausgangs-pH-Wert von 7 nachgewiesen. Da unser Augenmerk speziell auf der Mineralisation von Calciumphosphat an der Wasser/Luft-Grenzfl{\"a}che liegt, k{\"o}nnten Folgeexperimente wie beispielsweise GIXD Messungen durchgef{\"u}hrt werden. Dadurch w{\"a}re es m{\"o}glich, einen {\"U}berblick {\"u}ber die gebildeten Kristallphasen nach unterschiedlichen Reaktionszeiten direkt auf dem Trog zu erhalten. Es konnte weiterhin gezeigt werden, dass auch einfache Amphiphile in der Lage sind, die Mineralisation von Calciumphosphat zu steuern. Amphiphile mit Cholesterol als hydrophoben Block bilden offensichtlich besonders stabile Monolagen an der Wasser/Luft-Grenzfl{\"a}che. Eine Untersuchung des Einflusses {\"a}hnlicher Amphiphile mit unterschiedlichen hydrophilen Kopfgruppen auf das Mineralisationsverhalten von Calciumphosphat w{\"a}re durchaus interessant.},
  language  = {de}
}
@phdthesis{Herbrich2017,
  author    = {Herbrich, Marcus},
  title     = {Einfluss der erosionsbedingten Pedogenese auf den Wasserund Stoffhaushalt ackerbaulich genutzter B{\"o}den der Grundmor{\"a}nenbodenlandschaft NO-Deutschlands - hydropedologische Untersuchungen mittels w{\"a}gbarer Pr{\"a}zisionslysimeter},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-408561},
  school      = {Universit{\"a}t Potsdam},
  pages     = {186},
  year      = {2017},
  abstract  = {In the arable soil landscape of hummocky ground moraines, an erosion-affected spatial differentiation of soils can be observed. Man-made erosion leads to soil profile modifications along slopes with changed solum thickness and modified properties of soil horizons due to water erosion in combination with tillage operations. Soil erosion creates, thereby, spatial patterns of soil properties (e.g., texture and organic matter content) and differences in crop development. However, little is known about the manner in which water fluxes are affected by soil-crop interactions depending on contrasting properties of differently-developed soil horizons and how water fluxes influence the carbon transport in an eroded landscape. To identify such feedbacks between erosion-induced soil profile modifications and the 1D-water and solute balance, high-precision weighing lysimeters equipped with a wide range of sensor technique were filled with undisturbed soil monoliths that differed in the degree of past soil erosion. Furthermore, lysimeter effluent concentrations were analyzed for dissolved carbon fractions in bi-weekly intervals. The water balance components measured by high precision lysimeters varied from the most eroded to the less eroded monolith up to 83 \% (deep drainage) primarily caused due to varying amounts of precipitation and evapotranspiration for a 3-years period. Here, interactions between crop development and contrasting rainfall interception by above ground biomass could explain differences in water balance components. Concentrations of dissolved carbon in soil water samples were relatively constant in time, suggesting carbon leaching was mainly affected by water fluxes in this observation period. For the lysimeter-based water balance analysis, a filtering scheme was developed considering temporal autocorrelation. The minute-based autocorrelation analysis of mass changes from lysimeter time series revealed characteristic autocorrelation lengths ranging from 23 to 76 minutes. Thereby, temporal autocorrelation provided an optimal approximation of precipitation quantities. However, the high temporal resolution in lysimeter time series is restricted by the lengths of autocorrelation. Erosion-induced but also gradual changes in soil properties were reflected by dynamics of soil water retention properties in the lysimeter soils. Short-term and long-term hysteretic water retention data suggested seasonal wettability problems of soils increasingly limited rewetting of previously dried pore regions. Differences in water retention were assigned to soil tillage operations and the erosion history at different slope positions. The threedimensional spatial pattern of soil types that result from erosional soil profile modifications were also reflected in differences of crop root development at different landscape positions. Contrasting root densities revealed positive relations of root and aboveground plant characteristics. Differences in the spatially-distributed root growth between different eroded soil types provided indications that root development was affected by the erosion-induced soil evolution processes. Overall, the current thesis corroborated the hypothesis that erosion-induced soil profile modifications affect the soil water balance, carbon leaching and soil hydraulic properties, but also the crop root system is influenced by erosion-induced spatial patterns of soil properties in the arable hummocky post glacial soil landscape. The results will help to improve model predictions of water and solute movement in arable soils and to understand interactions between soil erosion and carbon pathways regarding sink-or-source terms in landscapes.},
  language  = {en}
}
@phdthesis{Hethey2017,
  author    = {Hethey, Christoph Philipp},
  title     = {Cell physiology based pharmacodynamic modeling of antimicrobial drug combinations},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-401056},
  school      = {Universit{\"a}t Potsdam},
  pages     = {102},
  year      = {2017},
  abstract  = {Mathematical models of bacterial growth have been successfully applied to study the relationship between antibiotic drug exposure and the antibacterial effect. Since these models typically lack a representation of cellular processes and cell physiology, the mechanistic integration of drug action is not possible on the cellular level. The cellular mechanisms of drug action, however, are particularly relevant for the prediction, analysis and understanding of interactions between antibiotics. Interactions are also studied experimentally, however, a lacking consent on the experimental protocol hinders direct comparison of results. As a consequence, contradictory classifications as additive, synergistic or antagonistic are reported in literature. In the present thesis we developed a novel mathematical model for bacterial growth that integrates cell-level processes into the population growth level. The scope of the model is to predict bacterial growth under antimicrobial perturbation by multiple antibiotics in vitro. To this end, we combined cell-level data from literature with population growth data for Bacillus subtilis, Escherichia coli and Staphylococcus aureus. The cell-level data described growth-determining characteristics of a reference cell, including the ribosomal concentration and efficiency. The population growth data comprised extensive time-kill curves for clinically relevant antibiotics (tetracycline, chloramphenicol, vancomycin, meropenem, linezolid, including dual combinations). The new cell-level approach allowed for the first time to simultaneously describe single and combined effects of the aforementioned antibiotics for different experimental protocols, in particular different growth phases (lag and exponential phase). Consideration of ribosomal dynamics and persisting sub-populations explained the decreased potency of linezolid on cultures in the lag phase compared to exponential phase cultures. The model captured growth rate dependent killing and auto-inhibition of meropenem and - also for vancomycin exposure - regrowth of the bacterial cultures due to adaptive resistance development. Stochastic interaction surface analysis demonstrated the pronounced antagonism between meropenem and linezolid to be robust against variation in the growth phase and pharmacodynamic endpoint definition, but sensitive to a change in the experimental duration. Furthermore, the developed approach included a detailed representation of the bacterial cell-cycle. We used this representation to describe septation dynamics during the transition of a bacterial culture from the exponential to stationary growth phase. Resulting from a new mechanistic understanding of transition processes, we explained the lag time between the increase in cell number and bacterial biomass during the transition from the lag to exponential growth phase. Furthermore, our model reproduces the increased intracellular RNA mass fraction during long term exposure of bacteria to chloramphenicol. In summary, we contribute a new approach to disentangle the impact of drug effects, assay readout and experimental protocol on antibiotic interactions. In the absence of a consensus on the corresponding experimental protocols, this disentanglement is key to translate information between heterogeneous experiments and also ultimately to the clinical setting.},
  language  = {en}
}