Etablierung und molekulare Charakterisierung von Mammakarzinom-Organoiden

Viele Frauen werden im Laufe ihres Lebens mit der Diagnose Mamma-Ca konfrontiert, und trotz bereits weit entwickelter Therapien stirbt noch eine große Anzahl dieser Frauen an ihrer Tumorerkrankung. Es bedarf deshalb weiterführender Forschung der Pathomechanismen von Brusttumoren sowie neuer Ansätze für Therapien. Organoide als „Mini-Modelle“ von Mamma-Ca können einen neuen Baustein für die Weiterentwicklung von Therapien darstellen. Ziel der vorliegenden Arbeit war es, neue Mamma-Ca-Organoide im Labor als Organoidlinien zu etablieren, ihren Aufbau aufzuschlüsseln und die Expression von Matrixkomponenten, ihrer Rezeptoren und von Matrix-Proteasen zu analysieren. Für die Bearbeitung der Aufgabenstellungen sollten Organoide aus Brustkrebsgewebe generiert werden, wobei sich die Kulturbedingungen v. a. an Protokollen der Arbeitsgruppe um Prof. Hans Clevers (Hubrecht Institute, Utrecht, Niederlande) orientieren sollten. Die zellulären Gewebeproben stammten von Patientinnen und Patienten der Universitäts-Frauenklinik Tübingen. Das erste Ziel (und Voraussetzung für die weitere Arbeit) war die erfolgreiche Etablierung von Organoidlinien (> 5 Passagen). Kryokonservierung und Fixierung der Brustkrebs-Organoide waren Teilaspekte der Arbeit, die bei den Organoidkulturen überprüft oder neu definiert werden mussten. Im nächsten Schritt wurde die Expression der für Parenchyme essenziellen Bauteile wie Laminine und Integrine, Marker für eine polare Differenzierung in basale und luminale Zellen sowie Vertreter der Matrix-Metalloproteasen und TIMPs qualitativ mittels Immunfluoreszenzfärbungen und RT-PCR-Analyse (reverse Transkriptase Polymerase Chain Reaction) untersucht. Der biologische Aufbau der Mamma-Ca-Organoide wurde in 2D-Techniken wie in 3D-Techniken untersucht und dabei herkömmliche Auflicht-Mikroskopie sowie neuere Multiphoton-/LSM-Mikroskopie angewandt. Die Immunfluoreszenzfärbung diente v. a. einer morphologischen Beurteilung der Organoide, an der abzulesen war, inwiefern sich der zelluläre Aufbau von Brustkrebs-Organoiden vom Originalgewebe ableiten ließ. Durch die Verwendung proteotypischer Marker für die Immunfluoreszenzfärbung konnte ein Vergleich zwischen den Organoidlinien angestellt und die Reproduzierbarkeit des Aufbaus direkt gegenübergestellt werden. Dem gegenüber sollte die RT-PCR-Analyse die Expression in einem detaillierteren Bild darstellen. Die grundlegende Untersuchung von Mamma-Ca-Organoiden hinsichtlich ihrer Repräsentativität für die Primärtumore ist das Fundament für weitere Schritte, die zur Entwicklung neuer Therapien führen können

Hedging decisions and firm value: a cross-validation study of Australian and Canadian industries

This study examines hedging decisions and firm value for Australian and Canadian firms. Results show that hedging, per se, is not value-enhancing across both countries and that industry settings need to be considered carefully when evaluating whether firms should hedge or not, and to what extent they should use derivatives

Human-Robot Teams – Paving the Way for the Teams of the Future

Thanks to advances in artificial intelligence and robotics, robots, and especially social robots that can naturally interact with humans, are now found in more and more areas of our lives. At the same time, teams have been the norm in organizations for decades. To bring these two circumstances together, this dissertation addresses the use of social robots together with humans in teams, so-called human-robot teams (HRTs). This work aims to advance knowledge about HRTs and important underlying mechanisms in the establishment of such teams, thereby providing insights in two aspects. First, a structured and universal definition of HRTs is derived from the various perspectives of extant research, and based on a comprehensive literature overview, important characteristics and influencing factors of HRTs as well as research gaps in HRT research are identified. Second, insights into the underlying mechanisms of the establishment of human-robot teams are provided for settings with social robots in two different team roles: team assistant and lower-level (team) manager. For this purpose, this dissertation contains three research studies that cover the currently largely unexplored area of social robots' use in organizational teams at both the employee and lower-level manager levels. The first study (conceptual study) provides a foundation for this dissertation and beyond by developing a structured and universal definition of HRTs. It also structures extant research on HRTs and proposes an agenda for future research on HRTs based on research gaps identified in a comprehensive literature review that includes 194 studies on HRTs. The second and third studies (empirical studies 1 and 2) use empirical online studies to address two of the research gaps identified in the conceptual study. They examine the underlying mechanisms in decisions for social robots in two different team roles: team assistant (empirical study 1) and team manager (empirical study 2). By looking at expectations and experiences of taskwork-/performance-related and teamwork-related/relational features of social robots using polynomial regressions and response surface analyses, these studies rely on expectation disconfirmation theory to provide a detailed investigation of the underlying mechanisms of organizational decisions for social robots. Empirical study 1 thereby shows that for teamwork, positive disconfirmation and high levels of experiences lead to higher acceptance of humanoid and android robotic team assistants, and similar results emerge for a humanoid robot’s taskwork skills. In contrast, for taskwork skills of android team assistants, high levels of positive disconfirmation lead to lower robot acceptance. For robotic lower-level managers, empirical study 2 shows that there are discrepancies in the evaluation of performance-related usefulness and relational attitude. While for usefulness a slight overfulfilment of expectations leads to a positive impact on the readiness to work with, before evaluations decrease with greater overfulfillment, for attitude increasing positive experiences are associated with (decreasing) positive evaluations of readiness. In summary, this dissertation contributes to scientific research on HRTs by advancing the understanding of HRTs, providing a structured and universal definition of HRTs, and suggesting avenues for future research. The systematic investigation of underlying mechanisms for the selection of different types of social robots for different team roles provides a holistic view of this new form of organizational teams. In addition to the research contributions, this thesis also provides practical guidance for the successful establishment of HRTs in organizations

Engineering Negative Cycle Canceling for Wind Farm Cabling

In a wind farm turbines convert wind energy into electrical energy. The generation of each turbine is transmitted, possibly via other turbines, to a substation that is connected to the power grid. On every possible interconnection there can be at most one of various different cable types. Each cable type comes with a cost per unit length and with a capacity. Designing a cost-minimal cable layout for a wind farm to feed all turbine production into the power grid is called the Wind Farm Cabling Problem (WCP). We consider a formulation of WCP as a flow problem on a graph where the cost of a flow on an edge is modeled by a step function originating from the cable types. Recently, we presented a proof-of-concept for a negative cycle canceling-based algorithm for WCP [Sascha Gritzbach et al., 2018]. We extend key steps of that heuristic and build a theoretical foundation that explains how this heuristic tackles the problems arising from the special structure of WCP. A thorough experimental evaluation identifies the best setup of the algorithm and compares it to existing methods from the literature such as Mixed-integer Linear Programming (MILP) and Simulated Annealing (SA). The heuristic runs in a range of half a millisecond to under two minutes on instances with up to 500 turbines. It provides solutions of similar quality compared to both competitors with running times of one hour and one day. When comparing the solution quality after a running time of two seconds, our algorithm outperforms the MILP- and SA-approaches, which allows it to be applied in interactive wind farm planning

Observation of two critical points linked to the high field phase B in CeCu2Si2

We present thermal expansion and magnetostriction measurements on a CeCu2Si2 single crystal of A/S-type up to 17.9T magnetic field applied along the crystallographic a-direction (Delta L ll a ll H) and down to 0.015K temperature. We identify clear thermodynamic anomalies at the superconducting transition T_c and at two second order transitions T_A,B into ordered phases A and B. Our measurements establish for the first time the boundary of phase B at high field and low temperature. No evidence for additional high field phases above B is found up to the maximum field. We speculate based on our experimental results that i) phase B is similar to phase A of spin-density wave type and ii) the first order phase transition between A and B is caused by Fermi surface reconstruction. We furthermore identify a new quantum critical point at H_c ~ 17T, where T_B is suppresssed to zero, and a bicritical point at (0.35K, 7.0T), where phase lines T_A(H) and T_B(H) meet

Does experience matter? Assessing user motivations to accept a vehicle-to-grid charging tariff

Vehicle-to-grid (V2G) could be a cornerstone to ensure the efficient integration of a large number of electric vehicles (EVs) and the resulting electricity demand into the energy system. However, successful V2G adoption requires direct interaction with the EV user. To explore user preferences and requirements in the context of a V2G charging tariff, we conducted a survey (N = 1196). We assess users’ minimum range requirements and willingness to pay for a V2G charging tariff and relate them to users’ experience with EVs. By building a mediation model, we evaluate the importance of three charging strategies to guide users’ minimum range requirements and expected monetary savings. The results reveal EV owners’ preference for a climate-neutral charging strategy, leading to a higher readiness to accept lower minimum ranges and lower monetary savings. These results are especially important to aggregators, aiming to design profitable business models, while accounting for user requirements and preferences