In this thesis, detailed investigations were carried out on aromatic 5‐membered heterocycles containing a low‐coordinated phosphorus atom, such as triazaphosphospoles and the related triazaphospholenium salts. Initially, the focus was placed on 1,2,3,4‐triazaphospholes. Novel triazaphospholes with electron‐withdrawing arylsulfonyl substituents on the N(3) atom were synthesized. For the first time it could be shown that these electron‐withdrawing tosyl and mesitylsulfonyl groups have a major influence on the reactivity of the heterocycle. Upon coordination to a gold(I) center, an unprecedented N2 release and the subsequent formation of a N2P2 heterocycle were observed. This shows a previously unknown reactivity of these new triazaphospholes and presents a new route to the P2N2 heterocycles with the possibility of gaining access to previously inaccessible substitution patterns. Furthermore, it was shown that triazaphospholes react as dienes in [4+2]‐cycloaddition reactions with the electron‐poor hexafluoro‐2‐butyne giving the corresponding CF3‐substituted 2H‐1,2,3‐diazaphospholes in a concerted cycloaddition‐cyclorevision reaction under pivaloyl nitrile elimination. Both the coordination chemistry of the triazaphosphole and that of the diazaphosphole were investigated. The crystallographic characterization of the formed coordination compounds clearly confirms that the heterocycles coordinate to a W(CO)5 fragment via the phosphorus atom. The observed tungsten(0)‐pentacarbonyl complex of the triazaphosphole is the first example of a tungsten complex of a triazaphosphole and one of the few examples of a coordination compound of a triazaphosphole with a coordination via the phosphorus atom. A closer look was also taken at triazaphospholenium salts as this compound class has only recently been described. Triazaphospholenium salts could be synthesized by alkylation of triazaphospholes with Meerwein reagents. For the first time, triazaphospholenium salts with a TMS group in the 5‐position have been synthesized, which provided access to novel protodesilylated products. In addition, these [BF4]− salts of the TMS‐substituted triazaphospholenium cations form novel, previously unknown BF3 adducts by elimination of TMS‐F. These BF3 adducts were isolated and fully characterized, and a targeted synthesis of the related BEt3 adducts could also be shown. The BR3 adducts represent a new and interesting class of compounds, as they can be regarded as phosphorus analogues of tetrazol‐5‐ylidenes with an abnormal substitution pattern. The protodesilylated products are also of interest as the protodesilylating reaction is rarely observed in classical triazaphospholes and this is the first example of a protodesilylated triazaphospholenium salt. Finally, the reactivity of pyridylmethyl‐functionalised triazaphospholes was investigated in quaternization reactions with Meerwein reagents. Due to the different nucleophilicity of the nitrogen atoms, both a chemoselective and a stepwise alkylation of the triazaphosphole derivative can be observed. The choice and stoichiometry of the alkylation reagent plays a crucial role, and allowed access to a large number of mono‐ and di‐cationic species. The coordination chemistry of these charged triazaphospholes and the triazaphospholenium salts with Cu(I) halides shows a versatile coordination chemistry, which manifests itself in different coordination modes depending on the charge of the ligand and the type of Cu(I) halide. Only coordination via the phosphorus atom is observed. These compounds are some of the few examples in which coordination of the triazaphosphol and triazaphospholenium heterocycles occurs via the phosphorus atom.
Weniger anzeigenEine Deutsche Auslandsschule (DAS) lässt bereits in ihrem Namen ein herausforderndes pädagogisches Setting vermuten. Wie gehen DAS mit der paradoxen Situation um, deutsche Bildung im Ausland zu realisieren? Gibt es eine eigene Pädagogik der Deutschen Auslandsschulen (PdDAS) und, wenn ja, welche Gestalt hat sie? Zur Beantwortung dieser Frage wird auf Grundlage der Theorie voneinander differenter Pädagogiken nach Paschen (1979/1997) ein Modell zur Erhebung von Differenzposition und differenzierenden pädagogischen Bestimmungen entwickelt. Mit einem softwaregestützten inhaltsanalytischen Verfahren wird ein empirischer Zugang zum pädagogischen Feld der DAS in Fachpublikationen des Zeitraums 1885 bis 1969 erreicht. Die systematische Abbildung von zuvor aus dem Diskurs verschwundenen pädagogisch-schöpferischen Vorstellungen zeigt kontinuierliche und kongruente pädagogische Strukturen auf. Eine PdDAS kann, so legen die Ergebnis-se dieser Studie nahe, als ein eigenes pädagogisches Gebilde begriffen werden, das wissenschaftliche und gesellschaftliche Relevanz hat. Die gefundenen pädagogischen Strukturen sind auch für die heutigen DAS von Belang, da gezeigt werden kann, dass entscheidende Merkmale des Schultyps unverändert bestehen.
Weniger anzeigenThe climate change is expected to have significant impacts on the water resources in Afghanistan, which could exacerbate existing challenges related to water availability, water quality, and water management in the future. Therefore, this study investigated the impact of climate change on water availability in Upper Kabul River Basin (UKRB) in Afghanistan by analyzing the past and future streamflow dynamics and hydrology related parameters (e.g., water balance components). A hydrological model was developed in UKRB using the Soil and Water Assessment Tool (SWAT) from 2009-2019, calibrated from 2010-2016 and validated from 2017-2018. The model was built, calibrated and validated on daily and on monthly time intervals to provide a comprehensive analysis of the model’s accuracy. The performance of SWAT hydrological model is done by comparing the simulated results to the observed runoff in the Upper Kabul River Basin. SWAT was capable of estimating surface runoff with satisfactory to very good accuracy in 6 observation station across the UKRB during calibration and validation. Four regional climate models (RCMs) were used to project the climate change impact scenarios for the baseline (1986-2005), and future periods of 2030-2049 (hereafter 2040s), and 2080-2099 (hereafter 2090s). The future hydrology projections were built under RCP4.5 and RCP8.5 scenarios. The precipitation and temperature from the RCMs were bias corrected using three bias correction methods including the linear scaling (Ls), delta change (Dc) and empirical quantile mapping (Eqm). The bias corrected results in the baseline period were validated with APHRODTE precipitation and temperature data which is used as observations in the absence of in situ measurements. The precipitation and temperature outputs from bias correction methods were analyzed based on monthly, seasonal and annual intervals, and then the outputs from the linear scaling method were used in SWAT model for further climate change impact analysis. The results indicated that all three bias correction methods improved the raw data of climate model outputs (RMCs), reduced the biases in precipitation and temperature variables based on APHRODITE datasets. However, the outputs from linear scaling performed better than empirical quantile mapping in capturing the distribution of precipitation, maximum temperature (Tmax) and minimum temperature (Tmin) in the historical period. Therefore, the Linear method was selected for further water availability assessment in the study area. According to the bias correction results, under the RCP4.5 scenario, the annual temperature is expected to increase by 1.9 °C in the 2040s and 2.3 °C in the 2090s. However, under the RCP8.5 scenario, the increase in mean annual temperature is projected to be more severe, with an increase of 3.1 °C in the 2040s and 6.1 °C in the 2090s. In addition, this study also examined how the extremes in temperature and precipitation might change in the future, specifically looking at six indices: annual total wet day precipitation (PRCPTOT), extremely wet days (R99p), monthly minimum value of daily minimum temperature (TNn), monthly maximum value of daily maximum temperature (TXx), warm nights and warm days over the course of the 21st century (2006-2100) in UKRB. Results showed that temperatures increased in all seasons, with earlier peaks occurring in June instead of July in both periods of 2040s and 2090s. The results also show that, there was a significant increase in extremes of maximum and minimum temperature’s trend indicating that the future temperature is getting hotter. The future mean annual precipitation observed to be increase in the 2040s and 2090s compared to the baseline, however, an insignificant decreasing trend of annual precipitation observed during 2006-2100. The future mean annual precipitation will increase by 5 % in 2040s and 1 % 2090s under RCP4.5 over the study area. Moreover, under RCP8.5, the mean annual precipitation is expected to increase by 9 % in 2040s and almost + 2% in 2090s compared to the baseline. The annual spatial precipitation changes range from -3 % to +27 % in the 2040s and from -8 % to + 17% in the 2090s under RCP4.5. Similarly, under RCP8.5, it ranges from -3 % to +44 % in the 2040s and from -10 % to +27 % in the 2090s. The future hydrological results show that there will be an increase in mean annual runoff and mean annual total water yield in the 2040s and 2090s compared to the baseline period in UKRB. The results of our study also revealed a backward shift in the annual discharge peaks from May and June to March and April in Tang-i-Gulbahar and Shukhi stations, while in Tang-i-Saidan station, the runoff peak shifted from April to March in both periods of 2040s and 2090s in UKRB due to climate change. The results also show that there has been a significant increase in the future actual evapotranspiration (ET) and potential evapotranspiration (PET) in the UKRB under both RCP4.5 and RCP8.5 scenarios. However, decreases in mean annual snowfall, snowmelt, sublimation, percolation and ground water recharge is expected in the future under both RCP4.5 and RCP8.5 scenarios. The decrease in snowmelt and glacier melt could also lead to changes in the timing and volumes of river flow which can impact the water availability for agriculture, urban use, and hydropower generation. Overall, this study contributes to the growing body of knowledge on climate change impacts on water resources and emphasizes the need for continued research in this field.
Weniger anzeigenIn der vorliegenden randomisierten und prospektiven Studie wurden die Auswirkungen des Nahrungsergänzungsmittels ARTHROSHINE®HA² (AS), welches als Grundbestandteil nicht-denaturiertes Kollagen Typ 2 (T2NDC) enthält, auf die Genesungszeit nach einer Tibial Plateau Leveling Osteotomy (TPLO) bei Hunden untersucht. Fünfzig Hunde mit einem Gewicht zwischen 25 und 45 Kilogramm und einer einseitigen partiellen oder vollständigen Ruptur des kranialen Kreuzbandes wurden dabei näher evaluiert. Orthopädische oder neurologische Begleiterkrankungen wurden zuvor ausgeschlossen. Die in die Studie inkludierten Hunde wurden nach dem Zufallsprinzip der Gruppe A oder B zugeteilt. Patienten der Gruppe A erhielten nach der operativen Versorgung mittels TPLO eine tägliche orale Supplementation von AS über den gesamten Studienzeitraum von 24 Wochen, wobei je nach Körpergewicht zwischen 4 und 6,1 mg/kg reines T2NDC verabreicht wurde. Währenddessen erhielten Patienten der Gruppe B keine Supplementation. Die Hunde wurden einander paarweise zugeordnet und ähnelten sich dabei hinsichtlich ihrer Rasse sowie ihres Phänotyps, Geschlechts, Alters und Gewichts. Die klinischen Auswirkungen wurden sowohl subjektiv als auch objektiv bewertet. Der Liverpool Osteoarthritis in Dogs (LOAD)-Besitzerfragebogen ermöglichte die Evaluierung der subjektiven Besitzereinschätzung. Durch eine kinetische Laufband- und Ganganalyse konnten gruppenvergleichende, objektive Werte für die vertikale Spitzenkraft (PVF), die Differenz der PVF zwischen gesunder und betroffener, TPLO-operierter Hintergliedmaße (dPVF) und den Symmetrieindex (SI) ermittelt werden. Postoperative Kontrolluntersuchungen fanden nach 6 Wochen, 12 Wochen und 24 Wochen statt und beinhalteten jeweils alle der benannten Untersuchungsparameter. Darüber hinaus wurden in einer weiteren Studie die orthopädischen Untersuchungsbefunde sowie röntgenologischen Befunde ausgewertet. Im Rahmen der kinetischen Ganganalyse konnte gezeigt werden, dass Patienten der Gruppe A zu jedem Kontrollzeitpunkt signifikant höhere PVF-Werte aufwiesen als Patienten der Gruppe B. Auch in Bezug auf die Werte für die dPVF und den SI wurde in Gruppe A eine früher ausgeglichene Kräfteverteilung zwischen der linken und rechten Hintergliedmaße deutlich. Zum Zeitpunkt der 12-Wochen-Kontrolle war das Gangbild in Gruppe A wieder physiologisch, während Gruppe B diese Normalisierung erst nach 24 Wochen erreichte. Die Studiengruppen waren dabei zu einem hohen Maß miteinander vergleichbar. Der LOAD-Besitzerfragebogen zeigte eine lediglich schwache Korrelation mit den Daten der Laufbandanalyse und unterschied sich zu keiner Kontrolluntersuchung signifikant zwischen den Gruppen. Zusammenfassend konnte, unter Berücksichtigung verschiedener Limitation wie dem Fehlen einer Placebokontrolle oder eines reinen T2NDC-Präparats, festgestellt werden, dass AS die laufbandanalytischen Werte in der mittelfristigen postoperativen Phase nach einer TPLO bei Hunden verbessern kann. Hunde, die nach einer TPLO zur Behandlung der unilateralen vorderen Kreuzbandruptur AS erhalten, erholen sich möglicherweise schneller von der Operation und sind früher als lahmheitsfrei zu bewerten. Ob die positiven Eigenschaften von AS auf den vergleichsweise hohen Gehalt an T2NDC oder auf die spezifische Produktzusammensetzung, durch die womöglich synergistische Effekte zu erwarten sind, zurückzuführen ist bleibt unklar und bedarf weiterer Untersuchungen.
Weniger anzeigenThis dissertation consists of four independent chapters in the field of contract theory. I study the influence of private information of different parties (be it static or dynamic information) on the optimal contracts depending on the context.
Chapters 1 and 2 deal with a crowdfunding model, which usually illustrates a static direct exchange between a seller and potential buyers contributing to the production of a good. In the first chapter (Crowdfunding platforms, E. Gorbunova) I study crowdfunding platforms, which are becoming more present in numerous domains (education, the energy sector, creative work). In order to explain contribution schemes found on such platforms, I enrich the crowdfunding model by introducing a platform / a broker between the seller and the potential buyers. I then derive the optimal direct incentive-compatible mechanism which maximizes the platform's expected profit and offer an implementation of the optimal mechanism.
In the second chapter (Sequential screening in the presence of fixed costs, E. Gorbunova, based on joint work with P. Pillath) we consider a direct interaction between the seller and the buyers but introduce dynamic formation of the buyers' valuations for the good and study its influence on the crowdfunding procedures. Doing so allows us, in particular, to address the case where the seller faces the decision on whether or not to incur production costs and what pricing scheme to offer long before the buyers have full information about their demand for the good. We first characterize the optimal selling mechanism for this case and later address the case where the seller can postpone production until the buyers have learned their true valuations.
Chapters 3 and 4 are on delegated expertise, where a firm (a principal) delegates information acquisition about a quality of a risky project to an expert (an agent) before investing. In the third chapter (Dynamic information collection: two-sided tests, E. Gorbunova, based on joint work with D. Gromb and F. de Vericourt) we consider an information collection problem with symmetric two-sided tests, which are informative about the project quality, with no false positives and no false negatives; whereas in the forth chapter (Search order in delegated data analytics, E. Gorbunova, based on joint work with D. Gromb and F. de Vericourt) we consider the tests with no false positives but allow for false negatives, and we tailor the model to the domain of data analytics specifically. Distinctiveness of these papers compared to the literature on delegated testing / delegated search lies in the research question itself (the optimal order of the available information sources) and in the fact that we consider heterogeneous information sources (two tests / data sets differing in the precision of their findings and the cost of analysis). We tackle two building blocks of delegated expertise: optimal compensation - characterizing optimal incentive contracts for each order of the tests under a combined moral hazard and adverse selection problem; and task design - finding the optimal order.
Weniger anzeigenDie ASP ist eine schwerwiegende hämorrhagische Erkrankung der Familie der Suidae. Sie betrifft Haus- und Wildschweine. Das ASP-Seuchengeschehen in den meisten EU-Mitgliedsstaaten ist von infizierten Wildschweinbeständen geprägt, in denen sich die ASP eigenständig hält. Für die Bekämpfung der ASP sind eine passive Überwachung und weitere Maßnahmen durchzuführen, welche das Tiergesundheitsrecht vorschreibt. Bei der Umsetzung dieser Maßnahmen bei Wildschweinen sind die örtlichen Jäger wichtige Akteure. Ihre Bereitschaft, die Jagd zu intensivieren, Wildschweinkadaver zu suchen, Proben zu nehmen und Biosicherheitsmaßnahmen zu implementieren, ist für den Erfolg der ASP-Bekämpfung essenziell. Darüber hinaus sind ihre Kenntnisse über örtliche Gegebenheiten, insbesondere der Wildschweinbestände, eine wichtige Grundlage für die Planung und Durchführung von Maßnahmen. Um diese Bereitschaft der Jäger zu erfassen, sind partizipatorische Methoden geeignet. Die im Rahmen dieser Dissertation durchgeführten PE-Studien hatten das Ziel, die Akzeptanz von verschiedenen Bekämpfungsmaßnahmen und passiver Überwachung der Jäger in Estland und Lettland zu ermitteln. Hierzu wurden in den beiden Ländern Fokusgruppendiskussionen mit insgesamt 96 Jägern veranstaltet. In diesen Diskussionen wurden die Zusammenarbeit mit verschiedenen Akteuren der ASP-Bekämpfung, spezifische Bekämpfungsmethoden, sowie motivierende und demotivierende Faktoren der passiven Überwachung bewertet. In den beiden Ländern wurde die Jägerschaft selbst als die vertrauenswürdigste Organisation in der Bekämpfung eingestuft. Der geringe Kontakt zu den nationalen Forschungszentren wurde problematisiert. Alle Jäger bewerteten die Impfung und die Jagd als die vertrauenswürdigsten Maßnahmen zur Bekämpfung der ASP und die Jagd als sehr zufriedenstellend in der Umsetzung. Der moralische Konflikt bei der Erzeugung von Waisen durch die Jagd auf weibliche Wildschweine, die Frischlinge führen, wurde in den Diskussionen in beiden Ländern erwähnt. Außerdem glichen sich die Aussagen bezüglich der Zäune in beiden Ländern. Zäune wurden als negativ bewertet, da sie auch andere Wildtiere behindern. Um die Akzeptanz von Bekämpfungsmaßnahmen zu steigern, könnte die Kommunikation und Zusammenarbeit mit den Jägern verstärkt werden, insbesondere wenn es um den Entscheidungsprozess geht. Dies sollte mit den nationalen Forschungszentren gemeinsam durchgeführt werden, da sich die Jägerschaft in die wissenschaftliche Diskussion mit einbringen möchte. In diesem Zusammenhang können Workshops oder Fortbildungen genutzt werden, um Jägern die Gründe und die möglichen positiven Auswirkungen von Maßnahmen zu erläutern. Auch mögliche Modifikationen bereits eingesetzter Maßnahmen könnten diskutiert und angepasst werden, wie z.B. die Bejagung weiblicher Wildschweine nur im Herbst und Winter. Nach Wahrnehmung der Jäger in beiden Ländern hatte das Auffinden von toten Wildschweinen primär negative Folgen für sie. Vor allem wurden zusätzliche Arbeit, Zeitverlust, finanzielle Kosten genannt. Das Vermeiden dieser Nachteile könnte die Akzeptanz der passiven Überwachung deutlich erhöhen. Die Teilnehmer waren sich einig, dass die Erhöhung finanzieller Unterstützung und die Einbindung der Armee in die Kadaversuche und -beseitigung unter Anleitung der Jäger im Vordergrund stehen sollte. Die Pflichten der Jäger sollten nach Meinung der Teilnehmer verringert werden. Die Studien zeigten, dass Methoden der PE helfen können, Bekämpfungsmaßnahmen gegen eine Tierseuche durch die ausführenden Schlüsselpersonen zu analysieren und zu optimieren.
Weniger anzeigenDie prognostische Einschätzung kardiologischer Befunde bei Warmblütern ist eine anspruchsvolle Aufgabe. Für Pferdehalter, Tierärzte und Wissenschaftler stellen sich oftmals die Fragen nach Entwicklung der Herzbefunde. Für diesen Zweck werden nach Erstuntersuchung eines Patienten oft Nachuntersuchungen empfohlen. Pferdebesitzer fragen sich jedoch auch schon bei Erstuntersuchung, wie sich die Herzuntersuchungsergebnisse ihrer Pferde langfristig auf Überleben, Reitbarkeit, Leistung und Wert ihrer Pferde auswirken. Um diese Fragen besser beantworten zu können und die Zuverlässigkeit von Langzeitprognosen zu verbessern, wird zum einen die Entwicklung kardiologischer und klinischer Befunde von Erst- zu Nachuntersuchung bei 104 Warmblütern untersucht und zum anderen die sportliche Entwicklung von 450 Warmblütern anhand der FN-Datenbank analysiert, die zuvor sowohl einer allgemeinen als auch einer spezifischen Herzuntersuchung unterzogen wurden. Die Daten zur Auswertung der Befundentwicklung von Erst- zu Nachuntersuchung werden über einen Zeitraum von 22 Jahren gesammelt. Die klinischen Daten der Pferde, deren sportliche Karrieren ausgewertet werden, entstammen aus einem Zeitraum von 18 Jahren.
Der Herzultraschall gilt als geeignetes Mittel für präzise Diagnostik und Prognoseeinschätzung. Die Studien zeigen, dass ein vergrößerter linker Vorhof in der Erstuntersuchung häufig zu Vorhofflimmern (Odds Ratio (OR)=7,5; p=0,007) und Leistungsinsuffizienz (OR=4,380; p=0,027) in der Folgeuntersuchung führte. Die Größenzunahme des linken Vorhofes ist auch abhängig von der Dauer des Untersuchungsintervalls, insbesondere wenn dieses größer als 15 Monate war (OR = 5,647; p = 0,019). Die Studie bestätigt, dass sich kardiologische Befunde im Laufe der Zeit meist nur geringfügig verschlechtern und selten eine klinisch relevante Ausprägung entwickeln.
Die Studien zeigen auch, dass besonders Pferde mit Veränderungen in den Herzdimensionen dazu neigen, ihre sportliche Karriere um den Zeitpunkt der Diagnose zu beenden. Pferde mit Vorhofflimmern zeigten ebenso vermehrtes Beenden der sportlichen Karrieren. Die prognostischen Einschätzungen der Tierärzte erwiesen sich als genau, besonders bei weniger günstigen Prognosen.
Zukünftige Studien sollten pferdespezifische Daten wie Gewicht, Alter und Größe einbeziehen und die Genauigkeit der Dokumentation in Kliniken verbessern, um präzisere retrospektive Studien zu ermöglichen. Die Nutzung internationaler Sportdaten beziehungsweise Datenbanken wird ebenfalls empfohlen, um das Verständnis der Faktoren, die die Langlebigkeit und den Erfolg von Sportkarrieren in der Pferdepopulation beeinflussen, zu vertiefen und relevante prognostische Werte für Tierärzte und Pferdebesitzer zu liefern.
Weniger anzeigenEine Anpassung der Rohproteinmenge im Zuge der bedarfsdeckenden Rationsgestaltung ist für den Landwirt ein probates Mittel zur Einhaltung emissionsregulierender Verordnungen und kann gleichzeitig zur Verbesserung der Tiergesundheit, zu Einsparungen von Futtermittelkosten und zur Verbesserung der Betriebswirtschaftlichkeit beitragen. Die gleichzeitige Zulage von essenziellen pansengeschützten Aminosäuren soll das entstandene Nährstoffdefizit ausgleichen. Erfolgt diese nutritive Anpassung bereits im peripartalen Zeitraum kann dies weitgreifende Auswirkungen auf die Gesundheit und das Leistungspotenzial der Folgelaktation haben. Das Ziel dieser Studie war es, die Auswirkungen einer postpartalen Rohproteinreduzierung bei gleichzeitiger peripartaler Ergänzung der pansengeschützten Aminosäuren Methionin und Lysin auf die Milchleistung, die Fruchtbarkeit und die Tiergesundheit während des ersten Laktationsdrittels der Folgelaktation zu untersuchen. Dazu wurden von Juni 2018 bis Januar 2019 insgesamt 72 pluripare Holstein-Friesian Kühe eines konventionellen Milchviehbetriebes im Nordosten Deutschlands für eine vergleichende Fütterungsstudie ausgewählt. Der Untersuchungszeitraum erstreckte sich vom 24. Tag a.p. bis zum 105. Tag p.p. Die Probanden wurden während dieses Zeitraums in zwei Gruppen (Aminosäure-Gruppe ASG, Vergleichsgruppe VG) unterteilt. Ante partum erhielten beide Untersuchungsgruppen eine Vorbereiterration mit gängigen Rohproteingehalten. Zusätzlich wurde ein Mikromineralfutter gefüttert, welches ausschließlich in der ASG mit den pansengeschützten AS Methionin und Lysin supplementiert wurde (22,5 g MetaSmart/Kuh/d und 20 g LysiGEM/Kuh/d). Post partum wurde das Rohproteinangebot in der ASG leicht reduziert (150 g statt 161 g XP/kg TM bzw. 153 g statt 157 g nXP/kg TM). Gleichzeitig wurde die Menge an pansengeschützten AS im Mikromineralfutter verdoppelt (45 g MetaSmart/Kuh/d und 40 g LysiGEM/Kuh/d). Um diese differenzierte Fütterung zu ermöglichen, wurden transpondergestützte Fress-Wiegetröge verwendet, die einen tierindividuellen Zugang zu dem gruppenspezifischen Futter ermöglichten. Während des Untersuchungszeitraums wurde die Milchmengenleistung täglich aufgezeichnet. Die Analyse der Milchinhaltsstoffe (Fett, Eiweiß, Laktose, Zellzahl, Harnstoffkonzentration, Stickstoffmenge) erfolgte wöchentlich. Zur Beurteilung der Fruchtbarkeit sind die Fruchtbarkeitskennzahlen und die Anzahl der für eine Trächtigkeit notwendigen Samenportionen ausgewertet worden. Die Feststellung der Trächtigkeit erfolgte über Blutanalysen (P4 am 19. Tag und PAG zwischen dem 31. und 33. Tag nach Erstbesamung). Die Abkalbung, das Geburtsgewicht der Kälber und die Qualität des Kolostrums wurden ebenfalls dokumentiert. Die Untersuchung der postpartalen Tiergesundheit umfasste die Dokumentation an typischen Erkrankungen (Mastitis, Stoffwechselstörungen, Lahmheiten, Labmagenverlagerungen). Zu sechs Zeitpunkten (7 Tage a.p., 1-3, 14, 21, 35 und 63 Tage p.p.) wurde eine Blutprobenuntersuchung relevanter Parameter und die ultrasonographische Konditionsbeurteilungen durchgeführt. Ante partum wurde zusätzlich eine Harnprobe gewonnen. Die tierindividuellen täglichen Trockenmasseaufnahmen wurden für den gesamten Untersuchungszeitraum erfasst. Die ASG zeigte im Vergleich zur VG eine signifikant geringe Milchmengenleistung während des Untersuchungszeitraums (p = 0,046). Außerdem konnten tendenziell geringere Milcheiweißmengen (p = 0,061) und tendenziell höhere Milchfettgehalte (p = 0,069) beobachtet werden. Die Milchharnstoffkonzentrationen und die Milchstickstoffausscheidungen waren in der ASG hingegen signifikant geringer als in der VG (p < 0,001). Zusätzlich war die Wahrscheinlichkeit einer Mastitis in der ASG 5-mal geringer (p = 0,019). Die Ergebnisse der Blutanalyse zeigten eine signifikante Verringerung der GLDH- und AST-Aktivität in der ASG (p < 0,001 und p = 0,003) und damit eine Entlastung des Leberstoffwechsels. Zudem war die BUN-Konzentration in dieser Gruppe signifikant geringer als in der VG (p = 0,001). Die anderen untersuchten Parameter wiesen keine statistisch signifikanten Unterschiede zwischen den beiden Untersuchungsgruppen auf. Abschließend lässt sich festhalten, dass die differenzierte Fütterung im Rahmen dieser Studie einen negativen Effekt auf die Milchleistung hatte. Die Fruchtbarkeit zeigte sich durch die Fütterung nicht beeinflusst, während einige Aspekte der Tiergesundheit sich zum Positiven verändert haben.
Weniger anzeigenAdvanced methods for estimating reaction rates of rare events in molecular dynamics (MD) simulations are crucial for molecular processes like chemical reactions, nucleation, and pro- tein folding. These processes commonly involve high energy barriers, making them infrequent and challenging to capture with conventional MD due to long waiting times. Some rare event methods apply enhanced sampling techniques where potential energy functions are biased to accelerate molecular transitions. In this thesis, different rare event methods employing enhanced sampling are introduced, applied and compared. A first case study focuses on thermal cis-trans isomerization of retinal, a crucial process in opsins involved in biological light responses. The enormous disparity between accessible simulation times (nanoseconds to microseconds depending on level of theory) and actual reaction times (hours to days) requires careful application of rate theories. Results from rare event methods based in both numerical sampling of transitions and effective dynamics were compared to results from transition state optimization followed by application of Eyring’s transition state theory (TST). Numerical sampling, enabled by infrequent metadynamics simulation, yielded rates in good agreement with Eyring’s TST, especially when the classical limit was enforced. Methods based in ef- fective dynamics proved highly sensitive to the choice of reaction coordinate. Only after optimizing the reaction coordinate using adaptive path collective variables did rates approx- imate those from Eyring’s TST well. Additionally, the thesis explores dynamical reweighting techniques, particularly Girsanov reweighting, to recover kinetics and reaction dynamics from biased simulations. Girsanov reweighting factors were derived for a number of integrators for underdamped Langevin dynamics. The reweighting factors were subsequently tested for a [Ca-Cl]+ dimer system. The dissociation rates obtained from biased trajectories successfully estimated reference rates for the unbiased system, demonstrating the effectiveness of these methods for accurately recovering reaction dynamics as well as their potential for future reaction dynamics studies.
Weniger anzeigenEps15-homology domain containing protein 2 (EHD2) is a dynamin-related ATPase which is thought to localize to the neck of caveolae and participate in their stabilization at the plasma membrane. Similar to other members of the dynamin family, EHD2 oligomerizes upon recruitment to artificial lipid bilayers and induces membrane tubulation. X-ray crystallography and cryo-Electron Tomography (cryo-ET) studies indicated that EHDs exist as open dimers in solution and as closed oligomers on membranes, and that the transition between the two states is triggered by membrane curvature. However, structural and mechanistic details about how EHD2 restricts caveolae mobility, the regulatory roles of specific domains in oligomeric assembly and the coordination of the ATP hydrolysis cycle with conformational changes in EHD2 have remained obscure. To address these open questions, full-length (FL) and N-terminally truncated (ΔN) EHD2 were reconstituted on tubular membranes. Cryo-Electron Tomography (cryo-ET) and Subtomogram Averaging (StA) yielded structures of membrane-bound oligomeric EHD2-FL and EHD2ΔN at an average resolution of 6.7 and 11 Å, respectively, and a model of the EHD2 oligomers was obtained by a flexible fitting and refinement approach. EHD2 in its closed conformation forms ring-shaped oligomers, which embrace the most highly curved regions of the membrane tubules, while adjacent membrane regions without an EHD2 coat bulge out, suggesting membrane curvature stabilization via a scaffolding and wedging mechanism. In the cryo-ET map, an N-terminal sequence stretch projects towards the membrane. Its deletion did not abolish oligomerization and membrane tubulation but led to a tight compaction of adjacent EHD2 oligomeric filaments, in line with a role of the N-terminus in coordinating membrane binding with proper spatial organization of the EHD2 filaments in their environment. A large-scale movement consisting of distancing and rotation of the EH domains from their position in the closed EHD2 dimer, allows assembly via the G-interface, thereby explaining the auto-inhibition role of the EH domain. Biochemical and cryo-ET studies revealed that ATP binding is required for oligomeric assembly, whereas ATP hydrolysis appears to drive the disassembly. Finally, it was shown that the necks of caveolae are significantly narrower and more elongated in the absence of EHD2, supporting a role of EHD2 in the stabilization of caveolae at the plasma membrane. Results of this thesis refine our knowledge of the structural transition from EHD2 dimers in solution to ring-shaped filaments on membranes as a prerequisite to understand the cellular function of EHD2 in restricting caveolae to the plasma membrane.
Weniger anzeigenThe combined parts of this thesis aimed to elucidate the transition mechanisms of thermoresponsive glycerol-based polymers and utilize these insights to establish a robust platform for the fabrication of thermally detached cell sheets. Conclusions from temperature-dependent studies of PGE and PGE-like alkoxy hydroxypropyl [meth]acrylate (AHP[M]A) polymers led to a PEHPA-based brush coating for cell sheet fabrication. A comparison of PGE and PEHPA brush coating properties and cell harvesting performance before and after sterilization highlighted the upside of the newly developed PEHPA polymer design. The phase transition behavior of thin brush layers with transition temperatures below the physiological range was studied using 10 and 22 kDa PGE chains, which were immobilized on inert gold surfaces by precedingly introduced thiol anchor blocks. Optimized grafting procedures were adapted to obtain molecular control of brush properties with dry thicknesses of 1.6 – 10 nm and grafting densities of 0.07 – 0.5 chains nm-2. Remarkably, similar transition temperatures in solution and on surface were detected between 26 and 31 °C and attributed to the non-interacting gold surface, which does not affect the reversible transition process. However, the phase transition concluded between 35 and 40 °C, which could hamper effective cell attachment due to remaining coating hydration and should be considered when designing cell-adhesive functional surfaces. Furthermore, the phase transition mechanism of surface-tethered PGE chains was found to be primarily dependent on the grafting density. Low GD regimes (0.07 – 0.12 chains nm-2) exhibited a brush-to-mushroom transition with parallel chain dehydration and collapse processes. In contrast, middle GD regimes (0.3 – 0.5 chains nm-2) displayed a brush-to-brush transition, with initially more distinct dehydration and a more pronounced brush collapse after water molecules were expelled. In the following study, AHP[M]A monomers were derived through molecular design, to establish an alternative to PGE polymers. The design featured PGE-like short alkoxy side chains for similar functionality and hydroxy groups to balance the hydrophobic aliphatic backbone. Polymerization under optimized RAFT conditions yielded narrow dispersed 22-25 kDa polymers. Subsequent phase transition studies of 20 – 5 mg mL-1 concentrated aqueous solutions of PHMPMA, PEHPA and PEHPMA revealed transition temperatures of 37 – 43 °C, 22 – 25 °C, and 8 – 10 °C, respectively. The increase in side-chain hydrophobicity from a methoxy to an ethoxy group resulted in less concentration- and molecular weight-dependent cloud point temperatures, particularly in the comparison of isomeric PHMPMA and PEHPA polymers, where a methyl group was “shifted” from the PHMPMA backbone to the end of the PEHPA side chain through molecular monomer design. Furthermore, NMR spectra of PHMPMA in deuterated water did not reveal any chain dehydration, indicating an LLPS transition type. In contrast, a distinct dehydration of all PEHP[M]A chain parts was observed in temperature-dependent NMR spectra after passing the cloud point temperature, indicating a pronounced CTG behavior which is an important precondition for cell harvesting coatings. The conclusions from PGE brush studies revealed the concordance of transition temperatures of solutions and thin brush layers, as well as the possible impact of broad transition ranges. Keeping that in mind, PEHPA and PEHPMA polymers with CTG transition type and sufficiently low Tcp values in solution were chosen for the preparation of coatings for cell sheet fabrication on applicable hydrophobic PS surfaces. An immobilization strategy through self-assembly, directed by a short (2 – 4 repeating units) hydrophobic benzophenone (meth)acrylate block (BP), copolymerized to the homopolymer chains, was transferred from previous PGE reports. Layers of surface tethered 22 – 24 kDa PEHP[M]A-BP polymers with thicknesses up to ~3 nm were obtained after UV irradiation, which induced a covalent crosslinking reaction between BP and PS, followed by layer extraction. Protein adsorption on these brush surfaces was an order of magnitude lower compared to TCPS surfaces (20 – 90 ng cm-2 and 800 ng cm-2, respectively) under cell culture conditions (37 °C), which is typically linked with cell-repellent surfaces. Nevertheless, both polymer coatings enabled the adhesion, proliferation and detachment of human dermal fibroblasts. PEHPA-BP brushes reliably detached cell sheets after cooling to room temperature, whereas PEHPMA-BP surfaces required cooling to 4 °C and performed less reliably, sometimes resulting in sheet fragmentation. Consequently, DIN normed sterilization with formaldehyde gas or gamma radiation were performed with PEHPA-BP coatings and previously established PGE brush coatings on PS and TCPS substrates. Gamma sterilization with a dose of 45 kGy degraded PGE brush coatings and significantly altered the properties of PEHPA-BP brush coatings, rendering them unable to detach cell sheets post-sterilization. In contrast, FO gas treatment had no adverse effects on the brush coatings. However, after the timeframe of sterilization and transport processes (14 – 18 d), the thickness of PGE brush coatings, irrespective of FO sterilization, decreased significantly, possibly due to a drying effect of the brush layer. At the same time, no changes were detected for PEHPA-BP brushes. Consequently, detachment times on PGE brushes increased markedly from 60 to a maximum of 180 min. Only a slight increase was observed on PEHPA-BP brushes, from 60 to 90 min maximum time, showing the advantage of the new polymer design. In conclusion, thermoresponsive PHMPMA, PEHPA and PEHPMA polymers were established through molecular design, inspired through PGE structures. The investigation of the phase transition in solution, combined with insights from phase transition studies of PGE brush layers, were used to select PEHPA and PEHPMA polymers for designing functional coatings for cell sheet fabrication. The CTG transition-type polymers supported cell proliferation and detachment and PEHPA-based coatings exhibited enhanced durability. These findings highlight the benefit of the aliphatic backbone, compared to polyether-based PGE coatings.
Weniger anzeigenInternational research contends that school counselors are uniquely positioned to support the mental health needs of children and youths in schools yet face multiple challenges such as misconceptions about their roles. This doctoral research seeks to contribute to the field of school counseling research by investigating school counselors in the Kingdom of Bhutan where school counseling services were recently implemented but have yet to be examined. To address this knowledge gap, three studies were carried out to explore the most important challenges faced by school counselors in Bhutan. First, a systematic literature review investigated the most prevalent needs of school counseling services in East and Southeast Asia which retrieved 109 studies from 14 countries. The analysis and summary of results revealed nine areas of need affecting school counseling services in this region of the world, the three most important being the need for up-to-date training, the need for a model of counseling practice and the need to overcome stigma towards mental health issues. Second, a survey of 162 of the 179 school counselors registered in the Kingdom of Bhutan investigated their daily tasks, their roles and responsibilities including how these are perceived by 65 of their colleagues, namely, 49 school teachers and 16 school principals, and their challenges and resources. Significant differences on the International Survey of School Counseling Activities (ISSCA) (Carey et al., 2020) revealed confusion in the roles and responsibilities perceived by school counselors and their colleagues. A Strengths, Weaknesses, Opportunities and Threats (SWOT) analysis of responses to open-ended questions further revealed that school counselors were hindered by insufficient initial training, by the need for material resources such as a counseling room, by insufficient time and opportunities for students to see the school counselor and by the issue of stigma towards mental health issues. Third, online and in-person interviews of 28 Bhutanese school counselors investigated, using thematic analysis by Braun and Clarke (2006), their perceived challenges and resources in more depth. Results both confirmed the review and survey study findings and revealed further challenges potentially unique to Bhutan such as the need for one female and one male school counselor in every school. Triangulation of results guided by Bronfenbrenner’s Ecological Systems Theory (Bronfenbrenner, 1995) revealed Bhutanese school counselors’ 12 most important challenges. These are (1) role confusion, (2) the lack of communication and collaboration with stakeholders, (3) the lack of initial training, (4) the lack of supervision, (5) the role of the COVID-19 pandemic, (6) the role of stigma towards mental health issues, (7) the importance and lack of social support, (8) the role of corporal punishment in Bhutanese schools, (9) the lack of material resources, (10) the need for one female and one male school counselor in each school, (11) the lack of time and opportunities for students to see the school counselor, and finally (12) that the school counseling profession is still relatively new and needs time to establish itself. While these results shed light on the phenomenal efforts of school counselors in the Kingdom of Bhutan, they also serve to illustrate a profession that is as complicated as it is systematically isolated and disempowered, ultimately hindered from achieving its potential to support Bhutanese children and youths’ mental health. The findings of this doctoral research contribute to global research on school counseling, suggest new research paths, such as the need to investigate students’ experiences of school counseling services, and propose specific policy changes to improve school counseling in Bhutan.
Weniger anzeigenChronic Tinnitus denotes the longstanding, conscious awareness of a tonal or composite noise for which there is no identifiable external acoustic source. Depending on the psychological makeup of affected individuals, tinnitus can be highly distressing. Current guidelines view the symptom together with its cognitive-emotional processing as a psychosomatic phenomenon – and suggest (1) medico-audiological treatment for underlying medical influences – if known, and (2) psychological treatment for highly distressed individuals. Anchored within a psychosomatic vulnerability-stress-coping framework, the present thesis sets out to examine chronic tinnitus-related distress. It asks two questions: 1. In how far do direct or indirect psychological factors – that may or may not correlate with ‘somatic’ variables – influence individuals’ experience of a tinnitus symptom as distressing? And: 2. In how far are psychosomatic (i.e. psychologically or medico-audiologically anchored) treatment approaches effective in ameliorating tinnitus-related distress? Chapter 1 [Introduction] briefly reviews evidence on vulnerability-stress-coping contributors to chronic tinnitus symptomatology and related distress-reactions. Chapter 2 [Vulnerability] presents the first two studies of the thesis, which examine chronic tinnitus-related distress at the junctions of (1) biological markers of tinnitus symptom vulnerability or perceived stress experiences and (2) psychological vulnerability-stress interactions. Chapter 3 [Stress] presents the third study, which investigates, whether transdiagnostically relevant psychological variables underlie chronic tinnitus- and pain-related distress experiences. Chapter 4 [Coping] examines the efficacy of psychosomatic treatment approaches. The final three studies of this thesis examine (1) whether a transdiagnostic psychological treatment approach ameliorates different functional symptom clusters, (2) whether a ‘somatic’ treatment approach (hearing amplification) bears psychological benefit, and (3) psychological effects on hearing amplification via hearing aid use-time. Chapter 5 [General Discussion] summarizes the presented papers and discusses theoretical and clinical implications.
Weniger anzeigenEntanglement is a fundamental principle in quantum mechanics, and is known for its crucial part in quantum information science and quantum communication, among others. In attosecond science, the possible effects of entanglement in light-matter interaction are receiving more and more attention. In this research field, typically radiation in the extreme ultraviolet (XUV) or x-ray regime is used to study time-dependent dynamics in time-resolved spectroscopy experiments. The high photon energy of this radiation leads to ionization of any sample placed in the way, thus creating multicomponent quantum systems with possible entangled subsystems, e.g. ion and photoelectron. Entanglement between the subsystems can have measurable effects on the outcome of an experiment, and can even prevent the observation of time-dependent observables. This notion is most prominent if the experiment includes only measurements in one of the subsystems, which means for example in the case of molecular photoionization, that only the ion or photoelectron is measured. This setting leads to interesting questions about the role of entanglement in attosecond photoionization processes. In particular, what is the role of entanglement between the ion and departing photoelectron regarding the observability of coherence-based dynamics in the ion? Furthermore, is it possible to control the degree of coherence in the ion and the degree of ion+photoelectron entanglement, respectively, by alternating the pulse properties of the ionizing pulses? To answer these questions, an experimental protocol is described in this thesis, which utilizes two phase-locked XUV pulses together with a near-infrared pulse (NIR) to dissociatively ionize hydrogen molecules. The main experiments presented here investigate the impact of entanglement between the cation and photo- electron, first on vibrational coherence, and subsequently on electronic coherence created in H2+. In the first experiment, a pair of phase-locked XUV pulses creates a vibrational wave packet in the 1sσg state of H2+ , which is subsequently probed by the NIR pulse dissociating the ion. The spectral properties of the ionizing pulses are tailored by alternating the delay between the two XUV pulses, thus controlling the degree of vibrational coherence and the degree of ion+photoelectron entanglement, respectively. In the second experiment, the two XUV pulses create an entangled ion+photoelectron system during the dissociative ionization of H2. The NIR probe pulse can subsequently project the initially entangled system into a coherent superposition of the first gerade (1sσg) and ungerade (2pσu) electronic states of the H2+ cation. The ability of the NIR pulse to convert the initially entangled system into a coherent superposition of electronic states is controlled by changing the time delay between the ionizing XUV pulses. These studies show the crucial role of ion+photoelectron entanglement in attosecond science, especially in attosecond pump-probe experiments, and they present a first attempt to link ultrafast science with quantum information theory.
Weniger anzeigenThis study is concerned with the interdisciplinary analysis of representations of philosophy in 14thcentury England, particularly in works by Thomas Bradwardine and Geoffrey Chaucer, and the exploration of the intellectual and literary-aesthetic contexts in which these works have been placed. These contexts involve a conception of intellectual history that sees the 14th-century as dominated by a fierce polemic between the philosophical schools of nominalism and realism. Past scholarship has typically associated 14th-century nominalism with a progressive, humanist, and empiricist mind-set, and in this capacity has frequently portrayed nominalism as a precursor of the Renaissance and modernity. Realism, on the other hand, has been associated with a reactionary conservatism, and a clinging to increasingly outdated scholastic methods. Debates between nominalism and realism, also characterized as a ‘battle of the ways’ between a via moderna and via antiqua, were supposed to have resulted in a decisive nominalist victory. In this fashion, the ‘nominalist controversy’ has come to represent the symbolic enactment of a period shift from Middle Ages to Modernity. This conflict has been understood to have excited heated partisan debates not only amongst academics and theologians, but also in other cultural spheres, particularly that of literary production. While this model of intellectual history provides a clear and self-enclosed narrative of epochal transition, it has lately been subjected to withering critique: Not only has the ‘modernity’ of the canonical nominalists been called into question, even the notion that nominalism and realism can be said to represent distinct traditions of thought has now been largely abandoned by specialists. While these developments are increasingly absorbed in the field of the history of philosophy, they have had undeservedly little impact in other areas: In literary criticism, the methodology of the research paradigm of literary nominalism still dominates analyses on the role of philosophy in 14th century literary works. Literary nominalism perpetuates an obsolete model of intellectual history, which assumes nominalism to have embodied a proto-modern Zeitgeist. It heavily emphasizes analogic readings, and the ‘claiming’ of authors for either the nominalist or realist camp. It sees textual features like heteroglossia, play, openendedness, and irony as resulting from a nominalist mind-set, rather than inherent features of the literary text. Apart from its insistence on a nominalism / realism dichotomy, the way literary nominalism conceptualizes the interaction between philosophy and literature is also highly problematic, as it places literary works in a dependent hierarchical relationship to philosophy, allowing literature little generative force of its own. The central aims of this study are as follows: It contributes to the ongoing re-assessment of the 14th-century intellectual landscape through an analysis of Thomas Bradwardine’s De Causa Dei, and its place in the ‘nominalist controversy’. Bradwardine was frequently associated with a realist school and the via antiqua, and was placed in an antagonistic relationship to supposedly nominalist peers like William of Ockham. This study analyses the paradigm of literary nominalism, with the goal also of exposing the central flaws in its understanding of 14th century philosophy, its methodology, and in the relationship between philosophy and literature it proposes. It suggests potential methodological amendments, which are applied in a reading of Geoffrey Chaucer’s Canterbury Tales, whose interpretation was also heavily warped by the problematic application of literary nominalist theories
Weniger anzeigenPluripotency, where cells have the capacity to differentiate into all types of cells in the embryo, is a transient state in early embryonic development. Normally, it lasts for 2-3 days, but many animal species can undergo diapause to halt the development and retain pluripotency under unfavourable conditions. One way to induce the paused state is through inhibition of mechanistic target of rapamycin (mTOR). mTOR is a protein kinase that plays a central role in regulating cellular processes such as growth, metabolism, and autophagy with environmental inputs. Mouse embryos lacking mTOR failed to develop beyond the blastocyst stage. Overall, these indicate that mTOR plays a vital role in pluripotency regulation. However, the mechanisms remain unknown. In this study, I established and applied various biochemical, genetic and NGS technologies to investigate the role of nuclear mTOR in embryonic stem cells (mESCs). mTOR kinase activity was found to be essential for mESC differentiation and mTOR nuclear and chromatin localisation were observed. ChIP-seq experiments revealed that mTOR associates with the promoters of developmental genes at the chromatin in mESCs. In vitro kinase assay showed that mTOR is a histone H2A kinase, phosphorylating H2A at threonine 120 (H2AT120ph). Using integrative analyses of CUT&Tag and TT-SLAM-seq, I found that the level of H2AT120ph at mTOR-associated promoters and their nascent transcription transiently increases during pluripotency exit. These promoters had a high presence of polycomb repressive complex 1 (PRC1) and correlated with the polycomb histone marks, suggesting mTOR works closely with PRC to regulate gene expression. The results reveal a novel mechanism through which mTOR can regulate gene expression and may have implications in other developmental and disease contexts
Weniger anzeigenDiese Habilitationsschrift widmet sich dem Einfluss von sozialen Faktoren auf psychische Erkrankungen und ihre Behandlung: Dabei untersucht die erste Arbeit den Zusammenhang von verschiedenen Wohnformen und Wohnungslosigkeit unter (teil)stationär-psychiatrischen Patient*innen mit dem Fokus auf sozidemografische und klinische Faktoren, sowie das Nutzungsverhalten des Krankenhauses sowie des ambulanten psychosozialen Hilfesystems abhängig von der Wohnform. In der Arbeit zeigt sich, dass ein beträchtlicher Teil der Patient*innen in keiner eigenen Wohnung, sondern entweder auf der Straße, in Wohnungslosen- oder Flüchtlingsheimen (13 %) oder in sozialtherapeutischen Einrichtungen (18,3 %) lebt. Charakterisiert waren wohnungslose Patient*innen vor allem durch ein jüngeres Alter, einem früheren psychiatrischen Erstkontakt, männliches Geschlecht, niedrigeres Bildungsniveau und das Vorliegen einer Substanzgebrauchsstörung und psychotischen Störung. Die Ergebnisse unterstreichen den Bedarf nach alternativen und niedrigschwelligen Wohnangeboten für Menschen mit schweren psychischen Störungen. Weiterhin zeigen die Ergebnisse, dass wohnungslose Menschen in stationär-psychiatrischer Behandlung signifikant kürzere Behandlungszeiten aufweisen, im Kontrast zu anderen europäischen und nordamerikanischen Ländern. In der zweiten Arbeit untersuchten wir im Rahmen der Wohin-Studie finanzielle Belastungen und Schulden bei psychiatrischen Patient*innen, wobei eine signifikante Anzahl von Patient*innen (55,1 %) Schulden, Kredite oder offene Rechnungen aufwies. Substanzabhängigkeit und ein jüngeres Alter waren signifikant assoziierte Faktoren für das Vorliegen von Schulden. Finanzielle Belastungen und Verschuldung bei Menschen mit psychischen Erkrankungen sollten daher im klinischen Kontext stärker berücksichtigt werden. Die dritte Arbeit der Habilitationsschrift untersuchte im Rahmen eines systematischen Reviews mit Metaanalyse problematisches Glücksspielverhalten unter wohnungslosen Menschen. Die Prävalenzraten für problematisches Spielverhalten und Spielsucht waren dabei deutlich erhöht gegenüber Zahlen in der Allgemeinbevölkerung. Modelle zur Früherkennung und Behandlung von problematischem Glücksspiel sollten daher zunehmend entwickelt und implementiert werden insbesondere für vulnerable Gruppen. Die vierte Arbeit widmet sich der Nutzung von Mobiltelefonen und Computern bei Patient*innen in (teil)stationärer psychiatrischer Behandlung. Die Ergebnisse zeigen, dass die Rate des Besitzes von Smartphones (59,3 %) und der regelmäßigen Nutzung von Computern (68,4 %) unter den psychiatrischen Patient*innen niedriger war als in der Allgemeinbevölkerung. Wohnungslosigkeit, die Diagnose einer psychotischen Erkrankung, höheres Alter und ein niedriger Bildungsgrad waren signifikant assoziierte Faktoren damit kein Mobiltelefon zu besitzen bzw. keinen Computer zu nutzen. Zur Verhinderung digitaler Barrieren sollten diese Ergebnisse bei der Planung der digitalen Umgestaltung der Versorgungsangebote als auch Entwicklung von E-Health-Lösungen berücksichtigt werden. Die fünfte Veröffentlichung dieser Habilitationsschrift befasst sich mit der Wohnzufriedenheit in verschiedenen Wohnformen psychiatrischer Patient*innen, wobei die Wohnzufriedenheit signifikant höher ausfiel bei Personen, die eine eigene Wohnung zur Verfügung hatten oder Wohngemeinschaften nutzen im Vergleich zu Personen, die in stärker institutionalisierten Settings oder in Einrichtungen für wohnungslose Menschen lebten. Dies unterstreicht den Bedarf an unabhängigen Wohnformen mit flexiblen Hilfen für Menschen mit schweren psychischen Erkrankungen in Wohnungslosigkeit oder erhöhtem Risiko.
Weniger anzeigenEnvironmental degradation within river basins arises from both natural factors, such as climatic variability and biophysical attributes like topography and soil characteristics, as well as anthropogenic influences. Human-induced degradation, driven by factors such as population growth, urban expansion, and shifts in land use patterns, exacerbates the natural degradation processes. The study sought to model soil erosion risk in the Black Volta River basin. Specifically, the study (1) evaluated and determined the land use and land cover dynamic and drivers of urban expansion in the Wa municipality of Ghana between 1990 and 2020, (2) estimated soil erosion risk in a typical savannah landscape of Wa municipality of Ghana between 1990 and 2020 and (3) estimated and evaluated soil erosion risk across various landscape units of the Black Volta River basin over the periods of 1992, 2006 and 2020. Landsat satellite data (30 x 30 m resolution) was processed using Geographical Information System and remote sensing techniques to establish the spatial and temporal dynamics of land cover in the Wa municipality for the years 1990, 2001, 2010 and 2020. The thematic maps were used to assess the drivers of urban expansion (objective 1) and the potential and soil erosion risk (objective 2) in the Wa municipality. In the basin scale and landscape units’ erosion risk modelling for the years 1992, 2006 and 2020 (objective 3), a 300 x 300 m resolution land cover data from the Copernicus Global Land Cover Services was used. Based on the spatial and temporal analysis of land cover change, it was evident that settlement expansion led to the depletion of woody biomass over the three decades (1990 to 2020). Settlement expansion was influenced by accessibility and connectivity factors, such as distance to existing settlements, rivers, and primary, tertiary, and unclassified roads, which were established as predictors of settlement expansion in the Wa municipality. By employing the Revised Universal Soil Loss Equation model, potential erosion risk was higher in 1990 (mean annual rate = 8.5 t ha⁻¹yr⁻¹) due to higher rainfall erosivity compared to 2020 (6.5 t ha⁻¹yr⁻¹) when rainfall erosivity was lower. However, the estimated soil erosion risk was lower in 1990 (2.6 t ha⁻¹yr⁻¹) due to greater vegetation cover, compared to 2020 (3.1 t ha⁻¹yr⁻¹) when vegetation cover declined. Soil loss was notably high in settlement, urbanising and areas with long and steep slopes, emphasising the influence of human and topographic factors on high erosion risk. This was statistically validated with data from a field survey that measures the spatial extents of soil erosion damages in 2 km² each of settlement, open savannah and closed savannah areas in the Wa municipality. It was established that settlement areas were the most damaged followed by open savannah and closed savannah units. Statistical correlation analysis reveals a positive relationship between the spatial extent of damages and the predicted soil erosion risk rates from the RUSLE model. At the basin scale and across landscape units, erosion risk and soil loss are primarily driven by topographic attributes and rainfall erosivity factors. The Savannah Escarpment and Sahelian Highlands with steep slope characteristics were identified as extreme erosion risk landscape units, while the Low Sahelian Plains and Sahelian Uplands, characterised by flat and gentle slopes, were predicted to have low erosion risk. Also, localised concave areas in the Savannah Escarpment and Sahelian Highland coupled with low TWI characteristics further heightened erosion risk. Additionally, a positive increase in the rainfall erosivity factor resulted in a positive change in soil loss while a decrease in rainfall erosivity factor led to a negative change in soil loss across all the landscape units, thus, underscoring the influence of rainfall erosivity factor on high erosion risk. Overall, the findings enhance the understanding of the erosion risk dynamic in the Black Volta River basin and would serve as a guide in planning management practices in line with global goals that seek to ensure environmental sustainability.
Weniger anzeigenNon-O1/non-O139 Vibrio cholerae (NOVC) is a natural inhabitant of aquatic ecosystems. It can cause both intestinal and extraintestinal infections in humans through the consumption of contaminated food or direct contact with contaminated surfaces, such as seawater or sediment. Previous studies have identified virulence-associated genes in NOVC that may contribute to its ability to cause infections. This doctoral thesis aimed to characterize the virulence mechanisms of NOVC isolated from food and environmental sources. A literature review was conducted to explore the infection routes of NOVC and its virulence-associated gene profiles. The genes were then compared with whole genome sequences of NOVC isolates from seafood (63 strains) and the German sea coastline (31 strains) to determine the presence of virulence-associated genes. Phylogenetic analysis was also performed. Additionally, phenotypic tests, including biofilm formation, hemolytic activity, motility, and serum resistance, were carried out to further validate the genetic findings. The antimicrobial resistance (AMR) of NOVC was also examined at both the genetic and phenotypic levels. Virulence-associated genes were classified into five stages, representing the infection process from ingestion to detachment from the human host. Most of these genes were detected in NOVC isolates from both food and environmental sources, including key toxin-encoding genes (hlyA, rtxA, chxA, stn), pathogenicity islands (VPI-2 and VSP-2), and secretion systems (T3SS and T6SS). A close core genome relationship was observed between the NOVC strains in this study and clinical NOVC strains. Notably, all NOVC strains exhibited increased motility at 37°C compared to 25°C, and most were capable of forming strong biofilms at both temperatures. All strains showed hemolytic activity against both human and sheep erythrocytes, but only a small subset of (6%) NOVC could survive in 60% human serum. In antimicrobial susceptibility tests, five NOVC strains developed non-wildtype resistance to antimicrobials across three different classes (penicillin, carbapenem, cephalosporin). In conclusion, this study characterized the virulence profiles of NOVC isolates from seafood and German coastal waters, highlighting the need for further monitoring and research.
Weniger anzeigenNeurodegenerative diseases (NDDs) encompass a heterogeneous group of chronic neurological disorders characterized by progressive neuron degeneration within specific regions of the central nervous system (CNS). Among these, Alzheimer's disease (AD) stands out as the most prevalent cause of dementia, accounting for approximately 60-80% of all dementia cases. Neuropathologically, AD is marked by the presence of two prominent protein pathological hallmarks: 1) the extracellular accumulation of aggregated amyloid-beta (Aβ) peptides, leading to the formation of amyloid-plaques, and 2) the intracellular aggregation of fibrillar structures composed of neuronal microtubule-associated protein Tau, forming neurofibrillary tangles (NFTs). Despite extensive and prolonged research efforts spanning several decades, the underlying molecular mechanisms of this intricate neurodegenerative condition remain only partially understood. In this context, the present study employs a well-established HEK sensor cell line, constitutively expressing the aggregation-prone mutant Tau repeat domain fused to either cyan fluorescent protein (CFP) or yellow fluorescent protein (YFP) (TauRDP301S-CFP/YFP). By introducing pre-aggregated Tau forms into these cells, a spectrum of distinct Tau assemblies is generated, encompassing large amorphous cytosolic aggregates (CYT) and amyloid-like structures (AMY), compact cytosolic Tau clusters (CLUS), Tau clusters near the nuclear envelope (NE), and nuclear spherical accumulations (NUC). After determining the sequence of accumulation type occurrence by live cell time-lapse imaging, I characterized the packing density of Tau in the different accumulation types using a multimodal microscopy approach. High-resolution FLIM/FRET microscopy, in which the fluorescent lifetime quenching of CFP serves as a proxy for the packing density of Tau, revealed distinct differences between Tau accumulations, as well as confirming a time-dependent hardening of Tau condensates in vitro. Optical diffraction tomography (ODT), which measures absolute protein concentration, revealed differences in the molecular and physical density of Tau accumulations. Additionally, it unveiled a drastic restructuring of 24-hour-old Tau 14 condensates compared to freshly formed 1-hour-old condensates, suggesting the potential transition from soluble Tau to fibrillar Tau aggregates. Lastly, 3D confocal reconstruction microscopy and StED microscopy provided insight into the precise positioning of different Tau accumulations regarding cytoskeletal fibers and cellular landmark organelles, such as the nuclear envelope and the endoplasmic reticulum (ER), revealing multiple interaction partners of Tau and implying possible downstream effects of Tau on cellular processes and mechanisms. By employing various light microscopy techniques, insights into Tau aggregation at different stages was gained, contributing to a deeper understanding of Tau aggregation formation and its implications for cellular processes. Furthermore, ODT emerged as a valuable tool for studying Tau aggregation in both cellular environments and in vitro conditions, revealing new structural insights. This research may offer prospects for understanding Tau transition and potential drug development.
Weniger anzeigen