@phdthesis{Stengele2017,
  author    = {Stengele, Anja},
  title     = {Systematische Analyse der Abbindereaktion von Magnesiumphosphat mit Polyacryls{\"a}ure im Vergleich zu klassischen w{\"a}ssrigen Zementsystemen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153871},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Gegenstand der vorliegenden Arbeit war eine systematische Analyse der Ver-arbeitbarkeit, Abbindedauer, pH Wert- und Temperatur-Verl{\"a}ufe w{\"a}hrend des Abbindens und der Eigenschaften der ausgeh{\"a}rteten Zementpaste, welche je-weils aus Farringtonit (Mg3(PO4)2) unterschiedlicher Reaktivit{\"a}t bestand und mit Diammoniumhydrogenphosphat und Polyacryls{\"a}ure zur Reaktion gebracht und konventionellen w{\"a}ssrigen Zementsystemen gegen{\"u}bergestellt wurde. Ein besonderer Fokus wurde hierbei auf die Beurteilbarkeit der Eignung dieser Zementsysteme als injizierbare Zementpasten in m{\"o}glicherweise lasttragenden Bereichen gelegt. Eine Reaktivierung von Farringtonit und anschließendes Ab-binden mit Wasser konnte durch Hochenergiemahlung f{\"u}r 2 h bis 24 h erzielt werden. Mechanisch aktiviertes Farringtonit mit Polyacryls{\"a}ure (100.000 g/mol) bzw. kurzzeitig gemahlenes Farringtonit mit h{\"o}her molekulargewichtiger Polyac-ryls{\"a}ure f{\"u}hrte auf Grund der zum Teil summierten Reaktivit{\"a}t in der sauren Umgebung der Polyacryls{\"a}ure zu einer schlechten Verarbeitbarkeit und unzu-reichenden Druckfestigkeiten. Um chelatisiertes Farringtonit mit angemessenen Festigkeiten zu erhalten, zeigte sich die Anwesenheit von Ammoniumionen als vielversprechende Strategie. Als hydratisierte Produkte wurden je nach Formu-lierung Struvit (MgNH4PO4·6H2O), Newberyit (MgHPO4·3H2O) oder Mag-nesiumphosphathydrat (Mg3(PO4)2·22H2O) gewonnen. Besonders die Kombina-tion von kurzzeitig gemahlenem Farringtonit mit 17,5 Gew.\%iger Poly-acryls{\"a}ure L{\"o}sung und 23,1 Gew.\%iger Diammoniumhydrogenphos-phat L{\"o}sung mit einem Pulver-zu-Fl{\"u}ssigkeitsverh{\"a}ltnis von 1,5 g/ml f{\"u}hrte zu Zementpasten, die hinsichtlich ihres Abbindeverhaltens und der mechanischen Eigenschaften denen der Einzelbestandteile {\"u}berlegen waren. Die entwickelten Zementsysteme zeigten 60 min nach Beginn des Abbindevor-gangs einen pH-Wert von 4,7 bis 6,4 und Temperaturmaxima von 28,5 °C bis 52 °C je nach Zusammensetzung. Der Mischzement, f{\"u}r welchen maximale Druckfestigkeiten von 15,0±4,1 MPa gemessen wurden, zeigte ein deutlich we-niger spr{\"o}des Bruchverhalten im Vergleich zu den reinen Verd{\"u}nnungen. Da der spr{\"o}de Charakter klassischer mineralische Knochenzemente einen limitie-renden Faktor f{\"u}r die Anwendung in lasttragenden Bereichen darstellt, kann dies als deutliche Verbesserung der mechanischen Eigenschaften beurteilt wer-den. Immerhin lagen die erzielten Festigkeitswerte in der Gr{\"o}ßenordnung der humanen Spongiosa. Besonders hervorzuheben ist außerdem der synergisti-sche Effekt, welcher bei Zementformulierungen aus kurzzeitig gemahlenem Farringtonit mit 17,5 Gew.\%iger Polyacryls{\"a}ure L{\"o}sung und 23,1 Gew.\%iger Diammoniumhydrogenphosphat L{\"o}sung mit einem Pulver-zu-Fl{\"u}ssigkeitsver-h{\"a}ltnis von 1,5 g/ml beobachtet werden konnte. Diese Formulierung wies bis zu vierfach h{\"o}here Festigkeitswerte als die Einzelbestandteile auf. Somit bildet das entwickelte Mischzement-System eine gute Basis f{\"u}r weitere Entwicklungen hin zu mechanisch lasttragenden Defekten.},
  subject      = {Magnesiumphosphate},
  language  = {de}
}
@phdthesis{Gupta2017,
  author    = {Gupta, Sanjay Kumar},
  title     = {The human CCHC-type Zinc Finger Nucleic Acid Binding Protein (CNBP) binds to the G-rich elements in target mRNA coding sequences and promotes translation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142917},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {The genetic information encoded with in the genes are transcribed and translated to give rise to the functional proteins, which are building block of a cell. At first, it was thought that the regulation of gene expression particularly occurs at the level of transcription by various transcription factors. Recent discoveries have shown the vital role of gene regulation at the level of RNA also known as post-transcriptional gene regulation (PTGR). Apart from non-coding RNAs e.g. micro RNAs, various RNA binding proteins (RBPs) play essential role in PTGR. RBPs have been implicated in different stages of mRNA life cycle ranging from splicing, processing, transport, localization and decay. In last 20 years studies have shown the presence of hundreds of RBPs across eukaryotic systems many of which are widely conserved. Given the rising number of RBPs and their link to human diseases it is quite evident that RBPs have major role in cellular processes and their regulation. The current study is aimed to describe the so far unknown molecular mechanism of CCHC-type Zinc Finger Nucleic Acid Binding Protein (CNBP/ZNF9) function in vivo. CNBP is ubiquitously expressed across various human tissues and is a highly conserved RBP in eukaryotes. It is required for embryonic development in mammals and has been implicated in transcriptional as well as post-transcriptional gene regulation; however, its molecular function and direct target genes remain elusive. Here, we use multiple systems-wide approaches to identify CNBP targets and document the consequences of CNBP binding. We established CNBP as a cytoplasmic RNA-binding-protein and used Photoactivatable Ribonucleoside Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) to identify direct interactions of CNBP with 4178 mRNAs. CNBP preferentially bound a G-rich motif in the target mRNA coding sequences. Functional analyses, including ribosome profiling, RNA sequencing, and luciferase assays revealed the CNBP mode of action on target transcripts. CNBP binding was found to increase the translational efficiency of its target genes. We hypothesize that this is consistent with an RNA chaperone function of CNBP helping to resolve secondary structures, thus promoting translation. Altogether this study provides a novel mechanism of CNBP function in vivo and acts as a step-stone to study the individual CNBP targets that will bring us closer to understand the disease onset.},
  subject      = {CNBP},
  language  = {en}
}
@phdthesis{Swimm2017,
  author    = {Swimm, Katrin},
  title     = {Experimentelle und theoretische Untersuchungen zur gasdruckabh{\"a}ngigen W{\"a}rmeleitf{\"a}higkeit von por{\"o}sen Materialien},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153887},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Als W{\"a}rmed{\"a}mmstoffe werden {\"u}blicherweise makropor{\"o}se Stoffsysteme wie Sch{\"a}ume, Pul-versch{\"u}ttungen, Faservliese und - wolle eingesetzt. Zus{\"a}tzlich finden mikro- und mesopor{\"o}se D{\"a}mmstoffe wie Aerogele Anwendung. Um effiziente W{\"a}rmed{\"a}mmstoffe entwickeln zu k{\"o}nnen, muss der Gesamtw{\"a}rmetransport in por{\"o}sen Materialien verstanden werden. Die ein-zelnen W{\"a}rmetransport-Mechanismen Festk{\"o}rperw{\"a}rmeleitung, Gasw{\"a}rmeleitung und W{\"a}rme-strahlung k{\"o}nnen zuverl{\"a}ssig analytisch beschrieben werden. Bei manchen por{\"o}sen Materialien liefert jedoch auch eine Wechselwirkung zwischen den verschiedenen W{\"a}rmetransport-Mechanismen, d.h. die Kopplung von Festk{\"o}rper- und Gasw{\"a}rmeleitung, einen hohen Beitrag zur Gesamtw{\"a}rmeleitf{\"a}higkeit. Wie hoch dieser Kopplungseffekt bei einer bestimmten Probe ausf{\"a}llt, kann bisher schwer abgesch{\"a}tzt werden. Um den Kopplungseffekt von Festk{\"o}rper- und Gasw{\"a}rmeleitung besser zu verstehen, sind sowohl experimentelle als auch theoretische Untersuchungen an verschiedenen por{\"o}sen Stoffsystemen erforderlich. Zus{\"a}tzlich kann ein zuverl{\"a}ssiges theoretisches Modell dazu beitragen, die mittlere Porengr{\"o}ße von por{\"o}sen Mate-rialien zerst{\"o}rungsfrei anhand von gasdruckabh{\"a}ngigen W{\"a}rmeleitf{\"a}higkeitsmessungen zu bestimmen. Als Modellsystem f{\"u}r die experimentellen Untersuchungen wurde der hochpor{\"o}se Feststoff Aerogel verwendet, da seine strukturellen Eigenschaften wie Porengr{\"o}ße und Dichte w{\"a}hrend der Synthese gut eingestellt werden k{\"o}nnen. Es wurden Resorcin-Formaldehyd-Aerogele mit mittleren Porengr{\"o}ßen von etwa 600 nm, 1 µm und 8 µm sowie daraus mittels Pyrolyse abge-leitete Kohlenstoff-Aerogele synthetisiert und jeweils hinsichtlich ihrer Struktur und W{\"a}rme-leitf{\"a}higkeiten experimentell charakterisiert. Die Gesamtw{\"a}rmeleitf{\"a}higkeiten dieser Aerogele wurden f{\"u}r verschiedene Gasatmosph{\"a}ren (Kohlenstoffdioxid, Argon, Stickstoff und Helium) in Abh{\"a}ngigkeit vom Gasdruck durch das Hitzdraht-Verfahren bestimmt. Hierf{\"u}r wurde der Messbereich der Hitzdraht-Apparatur des ZAE Bayern mittels einer Druckzelle auf 10 MPa erweitert. Die Messergebnisse zeigen, dass bei allen Aerogel-Proben Festk{\"o}rper- und Gasw{\"a}r-meleitung einen deutlichen Kopplungsbeitrag liefern: Die gemessenen gasdruckabh{\"a}ngigen W{\"a}rmeleitf{\"a}higkeiten sind um Faktor 1,3 bis 3,3 h{\"o}her als die entsprechenden reinen Gas-w{\"a}rmeleitf{\"a}higkeiten. Die jeweilige H{\"o}he h{\"a}ngt sowohl vom verwendeten Gas (Gasw{\"a}rmeleitf{\"a}higkeit) als auch vom Aerogeltyp (Festk{\"o}rperw{\"a}rmeleitf{\"a}higkeit und Festk{\"o}rperstruktur) ab. Ein stark vernetzter Festk{\"o}rper verursacht beispielsweise einen niedrigeren Kopplungsbei-trag als ein weniger stark vernetzter Festk{\"o}rper. Andererseits wurde die gasdruckabh{\"a}ngige W{\"a}rmeleitf{\"a}higkeit von Melaminharzschaum - einem flexiblen, offenporigen und hochpor{\"o}sen Material - in einer evakuierbaren Zwei-Plattenapparatur unter Stickstoff-Atmosph{\"a}re bestimmt. Das Material zeichnet sich dadurch aus, dass die Addition der Einzelw{\"a}rmeleitf{\"a}higkeiten gut erf{\"u}llt ist, d.h. kein Kopplungsef-fekt auftritt. Allerdings konnte gezeigt werden, dass die gestauchte und damit unregelm{\"a}ßige Struktur von Melaminharzschaum die Kopplung von Festk{\"o}rper- und Gasw{\"a}rmeleitung deut-lich beg{\"u}nstigt. Je st{\"a}rker die Melaminharzschaumprobe komprimiert wird, umso st{\"a}rker f{\"a}llt der Kopplungseffekt aus. Bei einer Kompression um 84 \% ist beispielsweise die gemessene gasdruckabh{\"a}ngige W{\"a}rmeleitf{\"a}higkeit bei 0,1 MPa um ca. 17 \% gegen{\"u}ber der effektiven W{\"a}rmeleitf{\"a}higkeit von freiem Stickstoff erh{\"o}ht. Die experimentellen Untersuchungen wurden durch theoretische Betrachtungen erg{\"a}nzt. Zum einen wurde die Kopplung von Festk{\"o}rper- und Gasw{\"a}rmeleitung anhand einer Serienschal-tung der thermischen Widerst{\"a}nde von Festk{\"o}rper- und Gasphase dargestellt, um die Abh{\"a}n-gigkeit von verschiedenen Parametern zu untersuchen. Dadurch konnte gezeigt werden, dass der Kopplungsterm stets von den Verh{\"a}ltnissen aus Festk{\"o}rper- und Gasw{\"a}rmeleitf{\"a}higkeit sowie aus den geometrischen Parametern beider Phasen abh{\"a}ngt. Des Weiteren wurden mit dem Computerprogramm HEAT2 Finite-Differenzen-Simulationen an Modellstrukturen durchgef{\"u}hrt, die f{\"u}r por{\"o}se Stoffsysteme, insbesondere Aerogel, charakteristisch sind (Stege, H{\"a}lse, Windungen und tote Enden). Die simulierten gasdruckabh{\"a}ngigen W{\"a}rmeleitf{\"a}higkeiten zeigen deutlich, dass die Festk{\"o}rperstruktur mit der geringsten Vernetzung, d.h. das tote Ende, am meisten zur Kopplung von Festk{\"o}rper- und Gasw{\"a}rmeleitung beitr{\"a}gt. Dies korre-liert mit den experimentellen Ergebnissen. Dar{\"u}ber hinaus kann man erkennen, dass die Ge-samtw{\"a}rmeleitf{\"a}higkeit eines schlecht vernetzten por{\"o}sen Systems, wo also ein hoher Kopp-lungseffekt (Serienschaltung) auftritt, niemals gr{\"o}ßer wird als die eines gut vernetzten Sys-tems mit gleicher Porosit{\"a}t, wo haupts{\"a}chlich paralleler W{\"a}rmetransport durch beide Phasen stattfindet. Schließlich wurden drei Modelle entwickelt bzw. modifiziert, um die gasdruckabh{\"a}ngige W{\"a}rmeleitf{\"a}higkeit von por{\"o}sen Stoffsystemen theoretisch beschreiben zu k{\"o}nnen. Zun{\"a}chst wurde ein f{\"u}r Kugelsch{\"u}ttungen entwickeltes Modell f{\"u}r Aerogel angepasst, d.h. Kopplung von Festk{\"o}rper- und Gasw{\"a}rmeleitung wurde nur in den L{\"u}cken zwischen zwei benachbarten Partikeln ber{\"u}cksichtigt. Ein Vergleich mit den Messkurven zeigt, dass der ermittelte Kopplungsterm zu gering ausf{\"a}llt. Daher wurde ein bereits existierendes Aerogelmodell mit kubischer Einheitszelle, welches zus{\"a}tzlich Kopplung zwischen den einzelnen Partikelstr{\"a}ngen beinhaltet, verbessert. Auch dieses Modell liefert keine zufriedenstellende {\"U}bereinstimmung mit den Messwerten, denn der Kopplungsbeitrag wird immer noch untersch{\"a}tzt. Das liegt daran, dass die gew{\"a}hlte regelm{\"a}ßige kubische Struktur f{\"u}r Aerogel zu ungenau ist. So geht bei der Berechnung des Kopplungsterms der bereits erw{\"a}hnte hohe Beitrag durch tote Enden (und auch Windungen) verloren. Erfahrungsgem{\"a}ß k{\"o}nnen jedoch alle f{\"u}r Aerogel erhaltenen gasdruckabh{\"a}ngigen Messkurven mit dem sogenannten Skalierungsmodell relativ gut beschrieben werden. Das entspricht dem Knudsen-Modell f{\"u}r reine Gasw{\"a}rmeleitung, welches mit einem konstanten Faktor skaliert wird. Die Anwendung dieses einfachen Modells auf die Messdaten hat gezeigt, dass die Akkommodationskoeffizienten von Helium in Aerogel deut-lich h{\"o}her sind als die Literaturwerte (ca. 0,3 auf Metalloberfl{\"a}chen): In den vermessenen RF- und Kohlenstoff-Aerogelen lassen sich Akkommodationskoeffizienten nahe 1 f{\"u}r Helium ab-leiten. Dar{\"u}ber hinaus ist das Skalierungsmodell gut geeignet, die mittleren Porengr{\"o}ßen por{\"o}ser Materialien zuverl{\"a}ssig aus gasdruckabh{\"a}ngig gemessenen W{\"a}rmeleitf{\"a}higkeitskurven zu bestimmen. Dies stellt somit eine unkomplizierte und zerst{\"o}rungsfreie Charakterisierungsmethode dar.},
  subject      = {W{\"a}rmeleitf{\"a}higkeit},
  language  = {de}
}
@phdthesis{JuergensgebDufner2017,
  author    = {J{\"u}rgens [geb. Dufner], Patricia Alexandra},
  title     = {Analyse der Versorgungsqualit{\"a}t von Tumorpatienten am Lebensende anhand klinischer Qualit{\"a}tsindikatoren},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153745},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {The benefits of an early integration of palliative care in patients with cancer were already shown in various studies. Regarding the increase of palliative care it is important to ensure an adequate end of life care (EoL Care). One possibility is the use of clinical quality indicators (cQIs). Therefore the present study sought to explore the applicability of cQIs in the German health care system and in certification programs of the German Cancer Society. Retrospective clinical routine data from patients with recurrent or newly diagnosed lung cancer, gastrointestinal cancer, melanoma or brain tumor treated at the University Hospital W{\"u}rzburg were used. 331 patients were included in the analysis. 18,1\% underwent a tumorspecific therapy in the last 14 days of life and 21.8\% had a new tumorspecific therapy in the last 30 days of life. This was most common in patients with lung cancer and newly diagnosed cancer. 56.2\% had contact with palliative care services. 17.2\% were admitted to an intensive care unit and 3.7\% had more than one emergency admission during the last 30 days of life. This was most common in patients with gastrointestinal or lung cancer and in patients with newly diagnosed cancer or tumorspecific therapy. Only 22.4\% had a documented formal living will. Due to the variant results shown between the different cancer diagnoses we concluded that it is possible to compare the quality of EoL Care in different samples using cQIs. As shown in various studies the benchmarks defined by C. Earle could not be achieved in all cQIs. Therefore we conclude that the use of cQIs comparing the quality of EoL Care in an international approach is limited. On the other hand it could be stated, that cQIs are valuable tools to assess the quality of EoL Care in individual hospitals to detect gaps in the quality of care and to provide the basis for a quality improvement. Therefore it could be advisable to implement cQIs in certification programs of the German Cancer Society.},
  subject      = {Working Committee on Quality Indicators},
  language  = {de}
}
@phdthesis{YazdaniRashvanlouei2017,
  author    = {Yazdani Rashvanlouei, Kourosh},
  title     = {Developing a Framework for International Projects of ERP Implementation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154000},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Enterprise Systeme werden immer mehr von Bedeutung, was sie in die Mitte der Aufmerksamkeit und der Ber{\"u}cksichtigung durch Organisationen in verschiedensten Formen r{\"u}ckt - seien es Unternehmen oder Industrien von riesigen {\"o}ffentlichen oder privaten Organisationen bis hin zu mittleren und kleinen Dienstleistungsunternehmen. Diese Systeme verbessern sich st{\"a}ndig, sowohl funktionell, als auch technologisch und sie sind unumg{\"a}nglich f{\"u}r Unternehmen, um ihre Produktivit{\"a}t zu vergr{\"o}ßern und um in dem nationalen und globalen Wettbewerb mitzuhalten. Da lokale Softwarel{\"o}sungen die Bedingungen, speziell von großen Betrieben, funktionell und technologisch nicht erf{\"u}llen konnten und da riesige globale Softwarehersteller, wie SAP, Oracle und Microsoft ihre L{\"o}sungen rapide verbessern und sie ihren Markt immer mehr {\"u}ber den Globus expandieren, nimmt die Nachfrage f{\"u}r diese globalen Marken und deren nahezu einwandfreien Softwarel{\"o}sungen t{\"a}glich zu. Die Zustimmung f{\"u}r internationale ERP Unternehmensberatungsanwendungen nimmt deswegen exponentiell zu, w{\"a}hrend die Forschung der beeinflussenden Faktoren und des Fachwissens wenig verbreitet ist. Deswegen ist es so dringlich, dieses Gebiet zu erforschen. Das schlussendliche f{\"u}nf-in-f{\"u}nf Framework dieser Studie sammelt zum ersten Mal in der Geschichte alle historisch erw{\"a}hnten, kritischen Erfolgsfaktoren und Projektaktivit{\"a}ten. Diese wurden in f{\"u}nf Phasen unterteilt und nach den f{\"u}nf Schwerpunkten der internationalen ERP Projektdurchf{\"u}hrung kategorisiert. Dieses Framework bietet einen {\"U}berblick und bildet einen umfassenden Fahrplan f{\"u}r solche Projekte.},
  subject      = {ERP},
  language  = {en}
}
@phdthesis{Wolf2017,
  author    = {Wolf, Beat},
  title     = {Reducing the complexity of OMICS data analysis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153687},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {The field of genetics faces a lot of challenges and opportunities in both research and diagnostics due to the rise of next generation sequencing (NGS), a technology that allows to sequence DNA increasingly fast and cheap. NGS is not only used to analyze DNA, but also RNA, which is a very similar molecule also present in the cell, in both cases producing large amounts of data. The big amount of data raises both infrastructure and usability problems, as powerful computing infrastructures are required and there are many manual steps in the data analysis which are complicated to execute. Both of those problems limit the use of NGS in the clinic and research, by producing a bottleneck both computationally and in terms of manpower, as for many analyses geneticists lack the required computing skills. Over the course of this thesis we investigated how computer science can help to improve this situation to reduce the complexity of this type of analysis. We looked at how to make the analysis more accessible to increase the number of people that can perform OMICS data analysis (OMICS groups various genomics data-sources). To approach this problem, we developed a graphical NGS data analysis pipeline aimed at a diagnostics environment while still being useful in research in close collaboration with the Human Genetics Department at the University of W{\"u}rzburg. The pipeline has been used in various research papers on covering subjects, including works with direct author participation in genomics, transcriptomics as well as epigenomics. To further validate the graphical pipeline, a user survey was carried out which confirmed that it lowers the complexity of OMICS data analysis. We also studied how the data analysis can be improved in terms of computing infrastructure by improving the performance of certain analysis steps. We did this both in terms of speed improvements on a single computer (with notably variant calling being faster by up to 18 times), as well as with distributed computing to better use an existing infrastructure. The improvements were integrated into the previously described graphical pipeline, which itself also was focused on low resource usage. As a major contribution and to help with future development of parallel and distributed applications, for the usage in genetics or otherwise, we also looked at how to make it easier to develop such applications. Based on the parallel object programming model (POP), we created a Java language extension called POP-Java, which allows for easy and transparent distribution of objects. Through this development, we brought the POP model to the cloud, Hadoop clusters and present a new collaborative distributed computing model called FriendComputing. The advances made in the different domains of this thesis have been published in various works specified in this document.},
  subject      = {Bioinformatik},
  language  = {en}
}
@phdthesis{Stockinger2017,
  author    = {Stockinger, Bastian},
  title     = {Causes and effects of worker mobility between firms: empirical studies for Germany},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153894},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {This dissertation investigates selected causes and effects of worker mobility between firms in three empirical studies for Germany. Chapter 2 investigates the productivity effects of worker inflows to manufacturing establishments, distinguishing inflows by their previous employers' wage level, as a proxy for productivity. The chapter is motivated by several empirical studies which find that worker inflows from more productive or higher-paying firms increase hiring firms' productivity. The analyses in chapter 2 are based on a unique linked employer-employee data set. The findings indicate that inflows from higher-paying establishments do not increase hiring establishments' productivity, but inflows from lower-paying establishments do. Further analyses suggest that this effect is due to a positive selectivity of such inflows from their sending establishments. These findings can be interpreted as evidence of a reallocation process by which the best employees of lower-paying establishments become hired by higher-paying establishments. This process reflects the assortative pattern of worker mobility in Germany documented by Card et al. (2013) for the past decades. The chapter thus contributes to the literature by linking establishment-level productivity analysis to the assortative pattern of inter-firm worker mobility, thereby providing a micro-foundation for the latter. Chapter 3 focuses on a positive selection of workers moving between firms from another, more specific perspective. The analysis focuses on the importance of regional labor market competition for establishments' apprentice training and poaching of apprenticeship completers. Previous studies have found that firms provide less training if they are located in regions with strong labor market competition. This finding is usually interpreted as evidence of a higher risk of poaching in these regions. Yet, there is no direct evidence that regional competition is positively correlated with poaching. Building on a recently established approach to ex-post identify poaching of apprenticeship completers, this chapter is the first to directly investigate the correlation between regional labor market competition and poaching. Using German administrative data, it is found that competition indeed increases training establishments' probability of becoming poaching victims. However, poaching victims do not change their apprenticeship training activity in reaction to poaching. Instead, the findings indicate that the lower training activity in competitive regions can be attributed to lower retention rates, as well as a less adverse selection and lower labor and hiring costs of apprenticeship completers hired from rivals. Chapter 4 investigates the effects of local broadband internet availability on establishment-level employment growth. The analysis uses data for Germany in the years 2005-2009, when broadband was introduced in rural regions of Western Germany and in large parts of Eastern Germany. Technical frictions in broadband rollout are exploited to obtain exogenous variation in local broadband availability. The results suggest that broadband expansion had a positive effect on employment growth in the Western German service sector and a negative effect in Western German manufacturing, suggesting that broadband expansion has accelerated the reallocation of workers from manufacturing to services. Furthermore, this pattern of results is driven by pronounced positive effects in knowledge- and computer-intensive industries, suggesting that it is the actual use of broadband in the production process that leads to complementary hiring, respectively a slowdown of employment growth, in the respective sectors. For Eastern Germany, no significant employment growth effects are found.},
  subject      = {Arbeitsmarkt},
  language  = {en}
}
@phdthesis{Hilz2017,
  author    = {Hilz, Teresa Magdalena},
  title     = {Die antiapoptotischen Effekte der Pim-1 Kinase im Rahmen der isch{\"a}mischen und Desfluran-induzierten Postkonditionierung},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153998},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Die antiapoptotischen Effekte der Pim-1 Kinase im Rahmen der isch{\"a}mischen und Desfluran-induzierten Postkonditionierung},
  subject      = {Pim-1 Kinase},
  language  = {de}
}
@phdthesis{Schmitt2017,
  author    = {Schmitt, Dominik},
  title     = {Structural Characterization of the TFIIH Subunits p34 and p44 from C. thermophilum},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-104851},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Several important cellular processes, including transcription, nucleotide excision repair and cell cycle control are mediated by the multifaceted interplay of subunits within the general transcription factor II H (TFIIH). A better understanding of the molecular structure of TFIIH is the key to unravel the mechanism of action of this versatile protein complex within these pathways. This becomes especially important in the context of severe diseases like xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy, that arise from single point mutations in some of the TFIIH subunits. In an attempt to structurally characterize the TFIIH complex, we harnessed the qualities of the eukaryotic thermophile Chaetomium thermophilum, a remarkable fungus, which has only recently been recognized as a novel model organism. Homologues of TFIIH from C. thermophilum were expressed in E. coli, purified to homogeneity and subsequently utilized for crystallization trials and biochemical studies. The results of the present work include the first crystal structure of the p34 subunit of TFIIH, comprising the N-terminal domain of the protein. The structure revealed a von Willebrand Factor A (vWA) like fold, which is generally known to be involved in a multitude of protein-protein interactions. Structural comparison allowed to delineate similarities as well as differences to already known vWA domains, providing insight into the role of p34 within TFIIH. These results indicate that p34 assumes the role of a structural scaffold for other TFIIH subunits via its vWA domain, while likely serving additional functions, which are mediated through its C-terminal zinc binding domain and are so far unknown. Within TFIIH p34 interacts strongly with the p44 subunit, a positive regulator of the XPD helicase, which is required for regulation of RNA Polymerase II mediated transcription and essential for eukaryotic nucleotide excision repair. Based on the p34 vWA structure putative protein-protein interfaces were analyzed and binding sites for the p34 p44 interaction suggested. Continuous crystallization efforts then led to the first structure of a p34 p44 minimal complex, comprising the N-terminal vWA domain of p34 and the C-terminal C4C4 RING domain of p44. The structure of the p34 p44 minimal complex verified the previous hypothesis regarding the involved binding sites. In addition, careful analysis of the complex interface allowed to identify critical residues, which were subsequently mutated and analyzed with respect to their significance in mediating the p34 p44 interaction, by analytical size exclusion chromatography, electrophoretic mobility shift assays and isothermal titration calorimetry. The structure of the p34 p44 complex also revealed a binding mode of the p44 C4C4 RING domain, which differed from that of other known RING domains in several aspects, supporting the hypothesis that p44 contains a novel variation of this domain.},
  subject      = {DNA-Reparatur},
  language  = {en}
}
@phdthesis{Hagen2017,
  author    = {Hagen, Franziska},
  title     = {Sphingolipids in gonococcal infection},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153852},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea, has the potential to spread in the human host and cause a severe complication called disseminated gonococcal infection (DGI). The expression of the major outer membrane porin PorBIA is a characteristic of most gonococci associated with DGI. PorBIA binds to the scavenger receptor expressed on endothelial cells (SREC-I), which mediates the so-called low phosphate-dependent invasion (LPDI). This uptake mechanism enables N. gonorrhoeae to rapidly invade epithelial and endothelial cells in a phosphate-sensitive manner. We recently demonstrated that the neutral sphingomyelinase, which catalyses the hydrolysis of sphingomyelin to ceramide and phosphorylcholine, is required for the LPDI of gonococci in non-phagocytic cells. Neutral sphingomyelinase 2 (NSM2) plays a key role in the early PorBIA signaling by recruiting the PI3 kinase to caveolin. The following activation of the PI3 kinase-dependent downstream signaling leads to the engulfment of the bacteria. As a part of this work, I could confirm the involvement of the NSM2. The role of the enzyme was further elucidated by the generation of antibodies directed against NSM2 and the construction of an epithelium-based NSM2 knockout cell line using CRISPR/Cas9. The knockout of the NSM2 strongly inhibits the LPDI. The invasion could be, however, restored by the complementation of the knockout using an NSM2-GFP construct. However, the results could not be reproduced. In this work, I could show the involvement of further members of the sphingolipid pathway in the PorBIA-mediated invasion. Lipidome analysis revealed an increase of the bioactive molecules ceramide and sphingosine due to gonococcal infection. Both molecules do not only affect the host cell, but seem to influence the bacteria as well: while ceramide seems to be incorporated by the gonococci, sphingosine is toxic for the bacteria. Furthermore, the sphingosine kinase 2 (SPHK2) plays an important role in invasion, since the inhibition and knockdown of the enzyme revealed a negative effect on gonococcal invasion. To elucidate the role of the sphingosine kinases in invasion in more detail, an activity assay was established in this study. Additionally, the impact of the sphingosine-1-phosphate lyase (S1PL) on invasion was investigated. Inhibitor studies and infection experiments conducted with a CRISPR/Cas9 HeLa S1PL knockout cell line revealed a role of the enzyme not only in the PorBIA-mediated invasion, but also in the Opa50/HSPG-mediated gonococcal invasion. The signaling experiments allowed the categorization of the SPHK and S1PL activation in the context of infection. Like the NSM2, both enzymes play a role in the early PorBIA signaling events leading to the uptake of the bacteria. All those findings indicate an important role of sphingolipids in the invasion and survival of N. gonorrhoeae. In the last part of this work, the role of the NSM2 in the inhibition of apoptosis in neutrophils due to gonococcal infection was investigated. It could be demonstrated that the delayed onset of apoptosis is independent of neisserial porin and Opa proteins. Furthermore, the influence of neisserial peptidoglycan on PMN apoptosis was analysed using mutant strains, but no connection could be determined. Since the NSM2 is the most prominent sphingomyelinase in PMNs, fulfils manifold cell physiological functions and has already been connected to apoptosis, the impact of the enzyme on apoptosis inhibition due to gonococcal infection was investigated using inhibitors, with no positive results.},
  subject      = {gonococcal},
  language  = {en}
}
@phdthesis{Muthers2017,
  author    = {Muthers, Johannes},
  title     = {Essays in Industrial Organization},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141671},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {The dissertation deals with the market and welfare effects of different business practices and the firm's incentives to use them: resale price maintenance, revenue sharing of a platform operator, membership fees to buyers using a platform and patent licensing. In the second chapter we investigate the incentives of two manufacturers with common retailers to use resale price maintenance (RPM). Retailers provide product specific services that increase demand and manufacturers use minimum RPM to compete for favorable services for their products. Minimum RPM increases consumer pricesby voiding retailer price competition and can create a prisoner's dilemma for manufacturers without increasing, and possibly even decreasing the overall service level. If manufacturer market power is asymmetric, minimum RPM tends to distort the allocation of sales services towards the high-priced products of the manufacturer with more market power. These results challenge the service argument as an efficiency defense for minimum RPM. The third chapter deals with trade platforms whose operators not only allow third party sellers to offer their products to consumers, but also offer products themselves. In this context, the platform operator faces a hold-up problem if he uses classical two-part tariffs only (which previous literature on two-sided markets has focused on) as potential competition between the platform operator and sellers reduces platform attractiveness. Since some sellers refuse to join the platform, some products that are not known to the platform operator will not be offered at all. We discuss the effects of different platform tariffs on this hold-up problem. We find that revenue-based fees lower the platform operator's incentives to compete with sellers, increasing platform attractiveness. Therefore, charging such proportional fees can be profitable, what may explain why several trade platforms indeed charge proportional fees. The fourth chapter investigates the optimal tariff system in a model in which buyers are heterogeneous. A platform model is presented in which transactions are modeled explicitly and buyers can differ in their expected valuations when they decide to join the platform. The main effect that the model identifies is that the participation decision sorts buyers according to their expected valuations. This affects the pricing of sellers. Furthermore diffing form the usual approach, in which buyers are ex-ante homogeneous, the platform does not internalize the full transaction surplus. Hence it does not implement the socially efficient price on the platform, also it has control of the price with the transaction fee. The fifth chapter investigates the effects of licensing on the market outcome after the patent has expired. In a setting with endogenous entry, a licensee has a head start over the competition which translated into a first mover advantage if strategies are strategic substitutes. As competitive strategies quantities and informative advertising are considered explicitly. We find that although licensing increases the joint profit of the patentee and licensee, this does not necessarily come from a reduction in consumer surplus or other firms profits. For the case of quantity competition we show that licensing is welfare improving. For the case of informative advertising, however, we show that licensing increases prices and is thus detrimental to consumer surplus.},
  subject      = {Wettbewerbsverhalten},
  language  = {en}
}
@phdthesis{Bauer2017,
  author    = {Bauer, Steffen},
  title     = {Kombinierte Versorgung osteoporotischer Kompressionsfrakturen mit dorsaler Instrumentierung und Ballonkyphoplastie des betroffenen Wirbelk{\"o}rpers - Vergleich von konventioneller offener und minimalinvasiver Operationstechnik},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153947},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {In dieser Studie wurden Daten zur minimalinvasiven dorsalen Versorgung instabiler Frakturen der thorakolumbalen Wirbels{\"a}ule in Kombination mit Kyphoplastie erhoben. Das Patientenkollektiv umfasst 64 Patienten, welche im Zeitraum von 6/2009 bis 5/2011 an 67 Frakturen versorgt wurden. Das Durchschnittsalter bei Operation betrug 71,3 ± 8,9 Jahre. Es wurden hierzu die mono- und bisegmentalen Grund-Deckplatten-Winkel pr{\"a}operativ, postoperativ sowie an drei Nachuntersuchungszeitpunkten (6w, 3-6m, >9m) bestimmt. Weiterhin wurden mittels der Visuellen-Analog-Skala die Beschwerden vor dem Unfall und unmittelbar vor der Operation retrospektiv erhoben. Das funktionelle Ergebnis wurde am dritten Nachuntersuchungszeitpunkt mittels der VAS-Pain und des VAS-Wirbels{\"a}ulenscores der Arbeitsgemeinschaft „Wirbels{\"a}ule" der DGU ermittelt. Außerdem wurde nach einer regelm{\"a}ßigen Schmerzmitteleinnahme zu den Zeitpunkten „vor dem Unfall", „direkt nach dem Unfall" und „zurzeit" gefragt. Es konnten in anderen Studien schon einige Vorteile der minimalinvasiven dorsalen Stabilisierung hinsichtlich eines geringeren Blutverlustes, eines geringeren Gewebetraumas mit weniger postoperativer Schmerzen, einer besseren postoperativen Muskelfunktion, eines besseren kosmetischen Ergebnisses, schnellerer Mobilisierung sowie geringeren operativen Komplikationen gezeigt werden. Bisher gibt es aber keine Langzeitdaten, welche die funktionellen Ergebnisse und die Wiederaufrichtung oder den Korrekturverlust einer minimalinvasiven dorsalen Instrumentierung mit zeitgleicher Kyphoplastie von traumatischen Frakturen der thorakalen und lumbalen Wirbels{\"a}ule beschreiben. Hierbei konnten zu einem offen operierten Vergleichskollektiv keine signifikanten Unterschiede bzgl. der Wiederaufrichtung (5.2 ± 5.2 Grad perkutan vs. 6.4 ± 3.3 Grad offen, GDW bisegmental ermittelt) und des Korrekturverlustes des Grund-Deckplatten-Winkels gefunden werden (5.2 ± 5.6 Grad perkutan vs. 6.1 ± 2.4 Grad offen bei 3. NU, GDW bisegmental ermittelt). Signifikante Unterschiede ergaben sich aber bei den funktionellen Ergebnissen (VAS-Wirbels{\"a}ulenscore der Arbeitsgemeinschaft „Wirbels{\"a}ule" der DGU) zugunsten des minimalinvasiv versorgten Kollektivs zum Zeitpunkt der dritten Nachuntersuchung.},
  subject      = {Wirbels{\"a}ulenverletzung},
  language  = {de}
}
@phdthesis{MorgenrothgebDiehlmann2017,
  author    = {Morgenroth [geb. Diehlmann], D{\´e}sir{\´e}e},
  title     = {Auswirkungen der Hypoxia Inducible Factor (HIF) - 1 - Hemmung durch Chetomin auf Hypoxie-abh{\"a}ngige Transkription und Strahlensensibilit{\"a}t in humanen Fibrosarkomzellen vom Typ HT 1080},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153922},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Hintergrund: Die {\"U}berexpression von Hypoxia Inducible Factor 1 (HIF-1) wird mit Tumorprogression und schlechter Prognose in Zusammenhang gebracht. Wir untersuchten, ob die pharmakologische Hemmung des Transkriptionsfaktors HIF-1 mittels Chetomin, einem Inhibitor der Interaktion von HIF-1 mit dem Koaktivator Protein p300, die Hypoxie-induzierte Strahlenresistenz menschlicher Fibrosarkomzellen vom Typ HT 1080 beeinflusst. Methoden: Die optimale Dosis von Chetomin wurde durch Versuchsreihen mit Hypoxie-sensiblem Promotor in mit destabilisiertem EGFP-Vektor transfizierten HT 1080 HRE-Zellen bestimmt. HT 1080 Zellen wurden mittels RT-PCR sowie Western Blot auf die Transkription der HIF-1-regulierten Gene Carboanhydrase IX (CA9) und Vascular Endothelial Growth Factor (VEGF) untersucht. Außerdem wurden sie zur Erstellung klonogener Assays unter normoxischen sowie hypoxischen (0,1\% O2, 12 Stunden) Bedingungen in vitro mit 0, 2, 5 oder 10 Gy bestrahlt mit oder ohne Chetominbehandlung (150 nM, 12 Stunden, Vorbehandlung 4 Stunden). Ergebnisse: In der RT-PCR zeigte sich eine signifikante Reduktion (Signifikanzniveau p<0,05) der mRNS-Expression von CA9 und VEGF unter Chetomin und Hypoxie auf 44,4 +/- 7,2\% beziehungsweise 39,6 +/- 16,0\%, im Western Blot supprimierte Chetomin auch die Downstream-Genprodukte von CA9 und VEGF. In den {\"U}berlebenskurven erh{\"o}hte Chetomin die Wirksamkeit der Bestrahlung wesentlich, der modifizierte Sauerstoffeffekt (modified Oxygen Enhancement Ratio, OER') war mit Ausnahme der 50\% SF in Bezug auf die Kontrollen bei 50\%, 37\% und 10\% Relativem {\"U}berleben (SF) von 1,57 auf 1,58, von 1,56 auf 1,42 und von 1,38 auf 1,22 reduziert. Schlussfolgerung: Die HIF-1-Hemmung durch Chetomin reduziert effektiv die Hypoxie-abh{\"a}ngige Transkription und verst{\"a}rkt die Strahlensensibilit{\"a}t von hypoxischen HT 1080 Fibrosarkomzellen in vitro.},
  subject      = {Hypoxie},
  language  = {de}
}
@misc{OPUS4-15355,
  title     = {Jahresbericht 2016 des Rechenzentrums der Universit{\"a}t W{\"u}rzburg},
  edition   = {1. Auflage},
  organization    = {Rechenzentrum (Universit{\"a}t W{\"u}rzburg)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153558},
  pages     = {72},
  year      = {2017},
  abstract  = {Das Dokument umfasst eine j{\"a}hrliche Zusammenfassung der Aktivit{\"a}ten des Rechenzentrums als zentraler IT-Dienstleister der Universit{\"a}t W{\"u}rzburg},
  subject      = {Jahresbericht},
  language  = {de}
}
@techreport{GriefAltmannBogaschewsky2017,
  type      = {Working Paper},
  author    = {Grief, Lukas and Altmann, Michael and Bogaschewsky, Ronald},
  title     = {The impact of sustainable supply chain management practices on performance metrics - A meta-analysis},
  doi       = {10.25972/OPUS-15383},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153833},
  pages     = {105},
  year      = {2017},
  abstract  = {Die vorliegende Arbeit untersucht mittels einer Meta-Analyse den Zusammenhang zwischen nachhaltigkeitsorientierter Supply Chain-Aktivit{\"a}ten und der Unternehmensperformance. Es sollen auf Grundlage einer breiten Datenbasis aus den Jahren 2000 bis 2013 fundierte und aussagekr{\"a}ftige Zusammenh{\"a}nge zwischen {\"o}kologisch nachhaltigen Supply Chain Aktivit{\"a}ten und deren Wirkung auf unterschiedliche Bereiche der Unternehmensperformance hergestellt werden},
  subject      = {Supply Chain Management},
  language  = {de}
}
@phdthesis{Spinner2017,
  author    = {Spinner, Simon},
  title     = {Self-Aware Resource Management in Virtualized Data Centers},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153754},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Enterprise applications in virtualized data centers are often subject to time-varying workloads, i.e., the load intensity and request mix change over time, due to seasonal patterns and trends, or unpredictable bursts in user requests. Varying workloads result in frequently changing resource demands to the underlying hardware infrastructure. Virtualization technologies enable sharing and on-demand allocation of hardware resources between multiple applications. In this context, the resource allocations to virtualized applications should be continuously adapted in an elastic fashion, so that "at each point in time the available resources match the current demand as closely as possible" (Herbst el al., 2013). Autonomic approaches to resource management promise significant increases in resource efficiency while avoiding violations of performance and availability requirements during peak workloads. Traditional approaches for autonomic resource management use threshold-based rules (e.g., Amazon EC2) that execute pre-defined reconfiguration actions when a metric reaches a certain threshold (e.g., high resource utilization or load imbalance). However, many business-critical applications are subject to Service-Level-Objectives defined on an application performance metric (e.g., response time or throughput). To determine thresholds so that the end-to-end application SLO is fulfilled poses a major challenge due to the complex relationship between the resource allocation to an application and the application performance. Furthermore, threshold-based approaches are inherently prone to an oscillating behavior resulting in unnecessary reconfigurations. In order to overcome the deficiencies of threshold-based approaches and enable a fully automated approach to dynamically control the resource allocations of virtualized applications, model-based approaches are required that can predict the impact of a reconfiguration on the application performance in advance. However, existing model-based approaches are severely limited in their learning capabilities. They either require complete performance models of the application as input, or use a pre-identified model structure and only learn certain model parameters from empirical data at run-time. The former requires high manual efforts and deep system knowledge to create the performance models. The latter does not provide the flexibility to capture the specifics of complex and heterogeneous system architectures. This thesis presents a self-aware approach to the resource management in virtualized data centers. In this context, self-aware means that it automatically learns performance models of the application and the virtualized infrastructure and reasons based on these models to autonomically adapt the resource allocations in accordance with given application SLOs. Learning a performance model requires the extraction of the model structure representing the system architecture as well as the estimation of model parameters, such as resource demands. The estimation of resource demands is a key challenge as they cannot be observed directly in most systems. The major scientific contributions of this thesis are: - A reference architecture for online model learning in virtualized systems. Our reference architecture is based on a set of model extraction agents. Each agent focuses on specific tasks to automatically create and update model skeletons capturing its local knowledge of the system and collaborates with other agents to extract the structural parts of a global performance model of the system. We define different agent roles in the reference architecture and propose a model-based collaboration mechanism for the agents. The agents may be bundled within virtual appliances and may be tailored to include knowledge about the software stack deployed in a specific virtual appliance. - An online method for the statistical estimation of resource demands. For a given request processed by an application, the resource time consumed for a specified resource within the system (e.g., CPU or I/O device), referred to as resource demand, is the total average time the resource is busy processing the request. A request could be any unit of work (e.g., web page request, database transaction, batch job) processed by the system. We provide a systematization of existing statistical approaches to resource demand estimation and conduct an extensive experimental comparison to evaluate the accuracy of these approaches. We propose a novel method to automatically select estimation approaches and demonstrate that it increases the robustness and accuracy of the estimated resource demands significantly. - Model-based controllers for autonomic vertical scaling of virtualized applications. We design two controllers based on online model-based reasoning techniques in order to vertically scale applications at run-time in accordance with application SLOs. The controllers exploit the knowledge from the automatically extracted performance models when determining necessary reconfigurations. The first controller adds and removes virtual CPUs to an application depending on the current demand. It uses a layered performance model to also consider the physical resource contention when determining the required resources. The second controller adapts the resource allocations proactively to ensure the availability of the application during workload peaks and avoid reconfiguration during phases of high workload. We demonstrate the applicability of our approach in current virtualized environments and show its effectiveness leading to significant increases in resource efficiency and improvements of the application performance and availability under time-varying workloads. The evaluation of our approach is based on two case studies representative of widely used enterprise applications in virtualized data centers. In our case studies, we were able to reduce the amount of required CPU resources by up to 23\% and the number of reconfigurations by up to 95\% compared to a rule-based approach while ensuring full compliance with application SLO. Furthermore, using workload forecasting techniques we were able to schedule expensive reconfigurations (e.g., changes to the memory size) during phases of load load and thus were able to reduce their impact on application availability by over 80\% while significantly improving application performance compared to a reactive controller. The methods and techniques for resource demand estimation and vertical application scaling were developed and evaluated in close collaboration with VMware and Google.},
  subject      = {Cloud Computing},
  language  = {en}
}
@phdthesis{Loeffler2017,
  author    = {L{\"o}ffler, Diana},
  title     = {Color, Metaphor and Culture - Empirical Foundations for User Interface Design},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153782},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Using color in user interface design is both art and science. Often, designers focus on aesthetic properties of color, but neglect that it also carries meaning and entails profound psychological consequences. Color psychology, filling this gap, is in its infancy, and lacks a theoretical approach that predicts and explains color-meaning associations shared by a large group of people in a large variety of contexts. To amend this situation, this work develops Conceptual Metaphor Theory of Color (CMToC), which predicts and explains cross-cultural and experience-based semantic color associations. The theory is based on the idea from cognitive linguistics that the study of metaphorical language provides valuable insights into our mental models involving color. A discussion of three types of metaphors that cover associations with physical and abstract concepts in light of existing empirical evidence provides the basis for deriving empirical research questions. The first research question addresses the use of color for conveying physical information like weight in user interfaces. The results of four online surveys involving a total of 295 German and Japanese participants show the relative impact of hue, saturation and brightness for associations with 16 physical properties. Two thirds of these color associations were correctly predicted by CMToC. Participants frequently matched physical properties to colors based on sensorimotor correspondences and participants of both cultures did not considerably vary in their performance. The second research question addresses the use of color for conveying abstract information like importance in user interfaces. In one experimental study, a total of 75 German and Japanese participants validated color-to-abstract mappings in form of color population stereotypes like important is dark. The majority of these color associations (86\%) were correctly predicted by CMToC. Again, participants of both cultures did not considerably vary in their performance. The third research question addresses whether predicted color associations with physical and abstract information are processed automatically as a precondition for intuitive use. The results of three studies involving a total of 85 German and Japanese participants show on the example of temperature that color automatically influences the identification speed of related physical properties, but not vice versa. Color and abstract information were not automatically associated. As a result of these studies it can be concluded that predictions of CMToC are cross-culturally valid for user interface design. Derived implicit associations with physical properties and explicit associations with abstract concepts can inform design decisions in both hard- and software user interface design.},
  subject      = {Softwareergonomie},
  language  = {en}
}
@phdthesis{Hollmann2017,
  author    = {Hollmann, Claudia Beate},
  title     = {Einfluss der sauren Sphingomyelinase auf anti-virale T-Zellantworten im Masernvirus-Infektionsmodell},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153807},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Die saure Sphingomyelinase (Asm), ein Enzym des Sphingolipidmetabolismus, spaltet Sphingomyelin zu Ceramid und Phosopocholin. Aktiviert wird die Asm unter anderem durch Stimulation des CD28 Rezeptors. CD28 Signale werden auch f{\"u}r die Aktivierung von konventionellen T-Zellen (Tconv) und f{\"u}r die Kostimulation ben{\"o}tigt und sind essentiell f{\"u}r die Differenzierung von regulatorischen T-Zellen (Treg) im Thymus und deren Erhalt in der Peripherie. Wir konnten zeigen, dass sich Tconv und Treg Zellen hinsichtlich der Asm unterscheiden. Treg haben eine h{\"o}here "basale" Asm Aktivit{\"a}t, widergespiegelt im h{\"o}heren Ceramidgehalt und haben eine niedrigere Lipidordnung als Tconv Zellen. Die Abwesenheit der Asm in defizienten M{\"a}usen bewirkt einen relativen Anstieg der Treg-Frequenz innerhalb der CD4+ T-Zellen. Außerdem f{\"u}hrt die Asm-Defizienz in Treg Zellen zu einer erh{\"o}hten Umsatzrate des immunsupprimierenden Molek{\"u}ls CTLA-4 und zu einer verst{\"a}rkten Suppressivit{\"a}t von Treg Zellen aus Asm-/- M{\"a}usen gegen{\"u}ber Wildtyp Zellen. Ein Anstieg in der Treg-Frequenz, {\"a}quivalent zur genetischen Defizienz, kann auch durch Inhibition der Asm, d. h. durch Wirkstoffe wie Amitriptylin und Desipramin erreicht werden. Es konnte gezeigt werden, dass die Inhibitorbehandlung die absolute Anzahl der Tconv Zellen selektiv verringert, da Treg Zellen gegen{\"u}ber dem Asm Inhibitor-induzierten Zelltod resistenter sind. Mechanistisch erkl{\"a}rbar sind die Unterschiede gegen{\"u}ber den proapoptotischen Inhibitoreffekten zwischen Tconv und Treg Zellen dadurch, dass Treg Zellen durch die Anwesenheit von IL-2 gesch{\"u}tzt sind. In Abwesenheit von IL-2 sterben die Treg Zellen ebenfalls. Die gezielte Ver{\"a}nderung des Verh{\"a}ltnisses von Treg zu Tconv durch den Einsatz von Asm-inhibitorischen Medikamenten kann hilfreich bei der therapeutischen Behandlung von inflammatorischen- und Autoimmunerkrankungen sein. Inwiefern die Asm f{\"u}r die Funktion von T-Zellen in der anti-viralen Immunantwort entscheidend ist, wurde im Masernvirus-Infektionsmodell n{\"a}her untersucht. In Asm-/- M{\"a}usen und Amitriptylin-behandelten M{\"a}usen konnte gezeigt werden, dass in Abwesenheit der Asm die Kontrolle der Masernvirusinfektion verschlechtert ist. Treg sind auch hier von entscheidender Bedeutung, da die Asm-abh{\"a}ngige, verst{\"a}rkte Masernvirusinfektion bei Fehlen der Asm nur in Gegenwart von Treg auftritt. In der akuten Phase gibt es in Asm-/- M{\"a}usen weniger masernvirusspezifische T-Zellen und dadurch eine verringerte Beseitigung der Viruslast. In der chronischen Phase ist die Anzahl masernvirusspezifischer T-Zellen zwischen WT und Asm-/- M{\"a}usen vergleichbar. In Letzteren ist allerdings die Anzahl und Frequenz von T-Zellen im Gehirn infizierter M{\"a}use noch deutlich erh{\"o}ht, was die verst{\"a}rkte Maserninfektion widerspiegelt. Zusammenfassend zeigt sich, dass die Asm die Funktion von Treg moduliert und einen Einfluss auf das Verh{\"a}ltnis von Tconv und Treg zueinander hat. Im Masernvirus-Infektionsmodell kann die Ver{\"a}nderung des Tconv zu Treg Verh{\"a}ltnisses in Abwesenheit der Asm urs{\"a}chlich f{\"u}r die verringerte Viruskontrolle sein. Die Asm Inhibitor-induzierte Treg-Aktivierung und die Beeinflussung des Treg zu Tconv Verh{\"a}ltnisses k{\"o}nnen wiederum f{\"u}r therapeutische Zwecke genutzt werden, wie beispielsweise bei Multipler Sklerose und Rheumatoider Arthritis.},
  subject      = {saure Sphingomyelinase},
  language  = {de}
}
@phdthesis{Tabisz2017,
  author    = {Tabisz, Barbara},
  title     = {Site Directed Immobilization of BMP-2: Two Approaches for the Production of Osteoinductive Scaffolds},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153766},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Bone fractures typically heal without surgical intervention. However, pathological situations exist which impede the healing process resulting in so-called non-union fractures. Such fractures are nowadays treated with scaffold material being introduced into the defect area. These scaffolds can be doped with osteogenic factors, such as bone morphogenetic protein (BMP)2. BMP2 belongs to the most osteogenic growth factors known to date. Its medical use, efficiency and safety have been approved by FDA for certain applications. Currently, BMP2 is distributed with a stabilizing scaffold, which is simply soaked with the growth factor. Due to fast release kinetics supraphysiological high doses of BMP2 are required which are causally associated with severe side effects observed in certain applications being most harmful in the area of the cervical spine. These side-effects include inflammation, swelling and breathing problems, leading to disastrous consequences or secondary surgical interventions. Since it could be shown that a retardation of BMP2 release from the scaffold resulted in superior bone forming properties in vivo, it seems obvious to further reduce this release to a minimum. This can be achieved by covalent coupling which in the past was already elaborated using mainly classical EDC/NHS chemistry. Using this technique coupling of the protein occurs non-site-directedly leading mainly to an unpredictable product outcome with variable osteogenic activities. In order to improve the reproducibility of scaffold functionalization by BMP2 we created variants one of which contains a unique unnatural amino acid substitution within the mature polypeptide sequence (BMP2-K3Plk) and another, BMP2-A2C, in which an N-terminal alanine has been substituted by cysteine. These modifications enable site-specific and covalent immobilization of BMP2 e.g. onto polymeric beads. Both proteins were expressed in E. coli, renatured and purified by cation-exchange chromatography. Both variants were extensively analyzed in terms of purity and biological activity which was tested by in vitro interaction analyses as well as in cell based assays. Both proteins could be successfully coupled to polymeric beads. The different BMP2 functionalized beads were shown to interact with the ectodomain of the type I receptor BMPR-IA in vitro indicating that the biological activity of both BMP2 variants retained upon coupling. Both functionalized beads induced osteogenic differentiation C2C12 cells but only of those cells which have been in close contact to the particular beads. This strongly indicates that the BMP2 variant are indeed covalently coupled and not just adsorbed. We claim that we have developed a system for a site-specific and covalent immobilization of BMP-2 onto solid scaffolds, potentially eliminating the necessity of high-dose scaffold loading. Since immobilized proteins are protected from removal by extracellular fluids, their activities now rely mainly on the half-life of the used scaffold and the rate of proteolytic degradation. Assuming that due to prolonged times much lower loading capacities might be required we propose that the immobilization strategy employed in this work may be further refined and optimized to replace the currently used BMP2-containing medical products.},
  subject      = {Protein chemistry},
  language  = {en}
}
@phdthesis{Moench2017,
  author    = {M{\"o}nch, Romana},
  title     = {The Growth Factor PDGF and its Signaling Pathways in Colorectal Cancer},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139100},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {A successful therapy for colorectal cancer (CRC), one of the most common malignancies worldwide, requires the greatest possible research effort. Of critical importance is an understanding of the relevant intracellular networks of signaling cascades, their activation, and the resulting cellular changes that are a prerequisite for a more successful CRC therapy. Vascular endothelial growth factor (VEGF) and the appropriate VEGF receptors represent molecular targets that have already been successfully implemented in the clinic (i.e. using monoclonal antibodies, tyrosine kinase inhibitors). However, for platelet derived growth factor (PDGF) and the relevant PDGF receptors, there are currently no clinically approved molecular therapeutics available. However, there are preliminary data to show that PDGF and its associated signaling pathways play an important role in CRC progression. In particular, the PI3K/Akt/mTOR pathway is emerging as an important intracellular partner of PDGF with which to control proliferation, migration, and angiogenesis in tumor cells. Therefore it was the objective of this work to investigate the multifactorial influence of PDGF on proliferation and metabolism, depending on CRC mutation status. The intention was to identify new therapeutic targets for future cancer therapy through analyses of PDGF-induced intracellular changes. For this purpose two human colorectal cancer cell lines were analyzed at gene and/or protein level for components of the PI3K/Akt/mTOR and MAPK signaling pathway, c-Myc, p53, and HIF1α (hypoxia-inducible-factor 1α). Changes in proliferation and metabolism, either during stimulation with PDGF and/or PI3K/Akt/mTOR inhibition, were also investigated. Experiments conducted at protein level during PDGF stimulation and/or PI3K/Akt/mTOR inhibition revealed changes in signaling pathways and crosstalk. The influence of the tumor suppressors (retinoblastoma, Rb), oncogenes (c-Myc, p53mut), and HIF1α during stimulation with PDGF, and their interactions in the tumor cell with respect to proliferation and glycolysis warrant further examination in terms of clinical treatment options. Investigations at the gene level of ex vivo samples (UICC I-IV) complete the study with regards to the clinical relevance of PDGF. PDGF stimulation increases tumor cell proliferation in HT29 cells via the PI3K/Akt/mTOR pathway rather than the MAPK pathway. However, if the PI3K/Akt/mTOR pathway is pharmacologically blocked, PDGF stimulation is mediated by inhibitory crosstalk through the MAPK pathway. Further analyses revealed that specific Akt inhibition impedes tumor cell growth, while PI3K inhibition had little effect on proliferation. Inhibitory crosstalk was found to be responsible for these different effects. Careful intervention strategies are therefore required if future therapies intend to make use of these specific signaling pathways. One aim of future research should be to gain a better understanding of the crosstalk between these signaling pathways. In this fashion, "over-inhibition" of the signal pathways, which would result in additional clinical side effects for patients, could be prevented. In late stage UICC, more mutation events occur, with tumorigenicity promoted by an increased mutation rate. Given that PDGF is increasingly expressed in the late UICC stages, our data would indicate that PDGF's effects are amplified with increasing malignancy. The activating effect of PDGF on the PI3K/Akt/mTOR pathway and subsequent changes in the activity of p53mut, Rb, c-Myc, and HIF1α, lead to an unfavorable prognosis for colon cancer patients. PDGF acts on colon cancer cells in an Akt-activating, glycolysis-dependent manner. PDGF increases glycolysis and the ability of CRC cells to adjust their energy metabolism. These activities should be taken as possible starting points with which to design therapeutic interventions for CRC therapy. PDGF, as another representative of the growth factor family, seems to play a similar role to VEGF in CRC. The data from this study underline the importance of the PDGF - PI3K/Akt/mTOR pathway-axis and its potential as a possible target in colorectal cancer. Thus PDGF represents an attractive therapeutic target, besides the VEGF/EGFR-based therapies already used in CRC.},
  subject      = {Dickdarmkrebs},
  language  = {en}
}