@phdthesis{Becker2018,
  author    = {Becker, Martin},
  title     = {Understanding Human Navigation using Bayesian Hypothesis Comparison},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-163522},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Understanding human navigation behavior has implications for a wide range of application scenarios. For example, insights into geo-spatial navigation in urban areas can impact city planning or public transport. Similarly, knowledge about navigation on the web can help to improve web site structures or service experience. In this work, we focus on a hypothesis-driven approach to address the task of understanding human navigation: We aim to formulate and compare ideas — for example stemming from existing theory, literature, intuition, or previous experiments — based on a given set of navigational observations. For example, we may compare whether tourists exploring a city walk "short distances" before taking their next photo vs. they tend to "travel long distances between points of interest", or whether users browsing Wikipedia "navigate semantically" vs. "click randomly". For this, the Bayesian method HypTrails has recently been proposed. However, while HypTrails is a straightforward and flexible approach, several major challenges remain: i) HypTrails does not account for heterogeneity (e.g., incorporating differently behaving user groups such as tourists and locals is not possible), ii) HypTrails does not support the user in conceiving novel hypotheses when confronted with a large set of possibly relevant background information or influence factors, e.g., points of interest, popularity of locations, time of the day, or user properties, and finally iii) formulating hypotheses can be technically challenging depending on the application scenario (e.g., due to continuous observations or temporal constraints). In this thesis, we address these limitations by introducing various novel methods and tools and explore a wide range of case studies. In particular, our main contributions are the methods MixedTrails and SubTrails which specifically address the first two limitations: MixedTrails is an approach for hypothesis comparison that extends the previously proposed HypTrails method to allow formulating and comparing heterogeneous hypotheses (e.g., incorporating differently behaving user groups). SubTrails is a method that supports hypothesis conception by automatically discovering interpretable subgroups with exceptional navigation behavior. In addition, our methodological contributions also include several tools consisting of a distributed implementation of HypTrails, a web application for visualizing geo-spatial human navigation in the context of background information, as well as a system for collecting, analyzing, and visualizing mobile participatory sensing data. Furthermore, we conduct case studies in many application domains, which encompass — among others — geo-spatial navigation based on photos from the photo-sharing platform Flickr, browsing behavior on the social tagging system BibSonomy, and task choosing behavior on a commercial crowdsourcing platform. In the process, we develop approaches to cope with application specific subtleties (like continuous observations and temporal constraints). The corresponding studies illustrate the variety of domains and facets in which navigation behavior can be studied and, thus, showcase the expressiveness, applicability, and flexibility of our methods. Using these methods, we present new aspects of navigational phenomena which ultimately help to better understand the multi-faceted characteristics of human navigation behavior.},
  subject      = {Bayes-Verfahren},
  language  = {en}
}
@phdthesis{Christensen2003,
  author    = {Christensen, Morten Overby},
  title     = {Dynamics of human DNA Topoisomerases I and II},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-4927},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2003},
  abstract  = {The first goal of this study was to develop cell lines with a stable expression of bio-fluorescent topo II and topo I. This was successfully achieved using a bicistronic vector system. Control experiments showed that proteins of expected size were expressed, and that GFP-tagged topos I, IIa, and IIb were active in the cells and fully integrated in the endogenous pools of the enzymes. These cell-lines provided a novel tool for investigating the cell biology of human DNA topoisomerases. Our most important finding was, that both types of mammalian topoisomerases are entirely mobile proteins that are in continuous and rapid flux between all compartments of the nucleus and between the cytososl and the chromosomes of mitotic cells. This was particularly surprising with regard to topo II, which is considered to be a structural component of the nuclear matrix and the chromosome scaffold. We must conclude that if this was the case, then these architectural structures appear to be much more dynamic than believed until now. In this context it should also be mentioned, that the alignment of topo II with the central axes of the chromosome arms, which has until now been considered a hall-mark of the enzyme's association with the chromosomal scaffold, is not seen in vivo and can be demonstrated to be to some extent an artefact of immunohistochemistry. Furthermore, we show that the two isoforms of topo II (a and b) have a different localisation during mitotic cell division, supporting the general concept that topo II functions at mitosis are exclusively assigned to the a-form, whereas at interphase the two isoenzymes work in concert. Despite unrestricted mobility within the entire nuclear space, topoisomerases I and II impose as mostly nucleolar proteins. We show that this is due to the fact that in the nucleoli they are moving slower than in the nucleoplasm. The decreased nucleolar mobility cannot be due to DNA-interactions, because compounds that fix topoisomerases to the DNA deplete them from the nucleoli. Interestingly, the subnucleolar distribution of topoisomerases I and II was complementary. The type II enzyme filled the entire nucleolar space, but excluded the fibrial centers, whereas topo I accumulated at the fibrial centers, an allocation directed by the enzyme's N-terminus. During mitosis, it also mediates association with the nucleolar organising regions of the acrocentric chromosomes. Thus, topo I stays associated with the rDNA during the entire cell-cycle and consistently colocalizes there with RNA-polymerase I. Finally, we show that certain cancer drugs believed to act by stabilising covalent catalytic DNA-intermediates of topoisomerases, do indeed immobilize the enzymes in living cells. Interestingly, these drugs do not target topoisomerases in the nucleoli but only in the nucleoplasm.},
  subject      = {Mensch},
  language  = {en}
}