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Three-dimensional tracking of cells is one of the most powerful methods to investigate multicellular phenomena, such as ontogenesis, tumor formation or wound healing. However, 3D tracking in a biological environment usually requires fluorescent labeling of the cells and elaborate equipment, such as automated light sheet or confocal microscopy. Here we present a simple method for 3D tracking large numbers of unlabeled cells in a collagen matrix. Using a small lensless imaging setup, consisting of an LED and a photo sensor only, we were able to simultaneously track ~3000 human neutrophil granulocytes in a collagen droplet within an unusually large field of view (>50 mm2) at a time resolution of 4 seconds and a spatial resolution of ~1.5 μm in xy- and ~30 μm in z-direction. The setup, which is small enough to fit into any conventional incubator, was used to investigate chemotaxis towards interleukin-8 (IL-8 or CXCL8) and N-formylmethionyl-leucyl-phenylalanine (fMLP). The influence of varying stiffness and pore size of the embedding collagen matrix could also be quantified. Furthermore, we demonstrate our setup to be capable of telling apart healthy neutrophils from those where a condition of inflammation was (I) induced by exposure to lipopolysaccharide (LPS) and (II) caused by a pre-existing asthma condition. Over the course of our experiments we have tracked more than 420.000 cells. The large cell numbers increase statistical relevance to not only quantify cellular behavior in research, but to make it suitable for future diagnostic applications, too.

In this doctoral thesis, I am assessing competition trends in the banking sector in the European Union. In recent years, market power and market concentration have increased in the European banking markets. I argue that competition policy needs to play a strong role to protect economic prosperity in the European Union. The doctoral thesis contains three chapters covering the main instruments of European competition policy: antitrust, merger control and state aid control. In the first chapter, I analyze the effects on retail interest rates of the merger between ABN AMRO and Fortis Bank NL in the Dutch banking market. Using a structural model, I simulate decreases in interest rates of up to 30 basis points for the merging banks. Depending on the measure for the change in consumer welfare, the model suggests that the merger caused annual losses of up to 50 euros for customers of the merging banks and between two and seven euros for the average consumer. Accounting for efficiency gains partially offsets the anti-competitive effects for consumers. In the second chapter, I quantify the potential effects of common ownership on retail interest rates in the Dutch banking market. Using a structural model combining ownership data and survey data on consumers' choice of savings accounts, I simulate interest rates under different assumptions on common ownership. Conditional on a common ownership mechanism, I simulate substantial decreases in interest rates of up to 50 basis points. These results suggest that antitrust authorities should cautiously observe trends in common ownership and assess its potential anti-competitive effects on consumers. In the third chapter, I investigate the impact of bank bailout during the financial crisis on competition in the European Union. Combining information on individual bank rescues with bank-level measures of market power, I find a substantial decrease of six percentage points in the Lerner index for rescued banks. The estimated effects are heterogeneous and only driven by banks rescued in the first two years of the financial crisis before the European sovereign debt crisis started in 2010. This finding casts a positive light on state aid control in the European Union as beneficiaries of state aid did not abuse public funds to distort competition in their favor. Protecting competition in banking remains a pertinent task in light of possible further public interventions triggered by the ongoing COVID-19 pandemic.

Common ownership has increased across countries and industries in recent years. I focus on the potential anti-competitive effects of rising common ownership on consumer prices conducting a case study for the Dutch banking market. My analysis draws on retail pricing data for savings accounts in 2014 and ownership data on the investor level. Using a structural approach, I project the impact of increasing common ownership on interest rates for savings accounts. Depending on the different levels of common ownership assumed, I simulate decreases in interest rates of up to 50 basis points for large banks and predict substantial average losses of interest for consumers ranging between 12 and 33 euros per year.

I investigate whether bank bailouts since the outbreak of the financial crisis affected competition in the European banking markets. Using a unique dataset on large bank rescues I compare the development of market power of rescued and non-rescued banks between 2000 and 2018. I find that bank bailout coincides with a substantial drop of six percentage points in the Lerner index. Effects are heterogeneous and driven by bank rescues directly after the outbreak of the financial crisis in 2008 and not by bank rescues triggered during the European sovereign debt crisis starting in 2010. My findings cast positive light on European competition policy as banks do not appear to have capitalized on rescue money in terms of market power. Protecting competition in European banking markets remains a topical policy issue in light of rising levels of market power and potential public interventions in the course of the ongoing COVID-19 pandemic.

During recent years, central banks have increased the levels of their international reserves at an unprecedented pace. In this paper, we introduce new country-specific reserve data and examine determinants of the composition of inter- national reserves. Using a dataset of 36 countries (and the euro area) for the years from 1996 to 2016, we identify currency pegs and trade patterns as determinants of currency compositions. Our results emphasize the importance of transaction moti- ves for the composition of currency reserves. The euro crisis appears to have been a setback for the euro, which temporarily seemed to challenge the US dollar as the most important international reserve currency and potentially impacted the deter- mination of international reserve compositions.

We analyze a large merger in the Dutch banking market during the financial crisis using disaggregated data. Based on a merger simulation model, we evaluate merger-induced changes in the interest rates for savings accounts. We find that the merging banks decreased interest rates by 3 to 5 percent and competitors by up to 1 percent. These anti-competitive effects translate into a loss of consumer welfare by roughly 69 million euros in 2010. We identify heterogeneous effects indicating that less educated consumers with lower savings are most affected. Our findings highlight the important role of competition policy during financial crisis mitigation.

We analyze a large merger in the Dutch banking market during the financial crisis using disaggregated data. Based on a merger simulation model, we evaluate merger-induced changes in the interest rates for savings accounts. We find that the merging banks decreased interest rates by 3 to 5 percent and competitors by up to 1 percent. These anti-competitive effects translate into a loss of consumer welfare by roughly 69 million euros in 2010. We identify heterogeneous effects indicating that less educated consumers with lower savings are most affected. Our findings highlight the important role of competition policy during financial crisis mitigation.

Offentliche Kampagnen thematisieren oft die Gesundheitspravention von malignen und infektiosen Erkrankungen. Vielfach unbekannt bleibt, dass der plotzliche Herztod eine der haufigsten Todesursachen in Deutschland ist. Wurden Laien, die einen Herzkreislauf-Stillstand beobachten, ofter mit einer Herzdruckmassage beginnen, liesen sich die Uberlebensraten deutlich steigern.

Duisburg, Essen, Univ., Diss., 2010

Titelblatt, Inhaltsverzeichnis und Abkürzungen 1\. Einleitung 1 2\. Zielstellung 23 3\. Material und Methoden 25 4\. Ergebnisse 57 5\. Diskussion 109 6\. Zusammenfassung 125 7\. Summary 127 8\. Literatur 129 Anhang, Das stimulatorische Guaninnukleotid-bindende Protein (Gs) überträgt Signale von Gs-gekoppelten Rezeptoren (GPCR) zu Adenylylcyclasen und erhöht dadurch die Produktion des second messengers cAMP. In Geweben von Säugerorganismen werden vier Spleißvarianten der α-Untereinheit von Gs (Gαs) exprimiert. Die einzelnen Spleißvarianten sind in zahlreichen Untersuchungen charakterisiert worden, jedoch sind die Ergebnisse wegen unterschiedlicher Messparameter und -systeme weder einheitlich noch vergleichbar. Für heterolog exprimierte, aufgereinigte Spleißvarianten wurden Unterschiede in den biochemischen Eigenschaften beschrieben, aber es ist nicht bekannt, ob diese Unterschiede über die gesamte Signalkaskade verstärkt oder abgeschwächt werden. Daher wurde in der vorliegenden Arbeit die Effektivität der Signaltransduktion über die vier Formen des Gαs anhand variantenspezifischer Repression (knock down) oder durch Rekonstitution unmodifizierter Spleißvarianten in Gαs-defizienten Zellinien verglichen. Mehrere Methoden zur transienten Repression wurden mit Hilfe eines Luziferase-Reportersystems verglichen. Katalytisch aktive DNA (DNAzym) war wegen der geringen Aktivität bei physiologischen Magnesiumkonzentrationen ungeeignet. Dagegen wurde eine bis zu 90 %ige Inhibition der Luziferase-Expression durch die Verwendung von Propin- modifizierten Oligodeoxynukleotiden oder durch intrazelluläre Expression von small interfering RNA erreicht. Aufgrund ihrer größeren Flexibilität bei der Wahl der Zielsequenz wurden Propin-modifizierte Oligodeoxynukleotide zur Repression von Gαs ausgewählt. Sie verminderten die Expression von transient transfiziertem, aber nicht von endogenem Gαs. In Sf9-Insektenzellen wurden Gαs-Spleißvarianten mit unterschiedlichen GPCR koexprimiert. Die Wechselwirkung zwischen GPCR und Gαs wurde mit Hilfe von ligandenabhängigen Bindungskinetiken des GTP-Analogs [35S]GTPγS an Plasmamembranen analysiert. Die Spleißvarianten wurden mit vergleichbaren Nukleotid-Bindungskonstanten durch die β2-adrenergen, Glucagon-, Histamin- und Secretin-Rezeptoren aktiviert (kapp ≈ 0,1 min-1). In der Gαs-defizienten Maus-Fibroblastenzellinie 2B2 wurde die Signaltransduktionskaskade GPCR Gαs Adenylylcyclase durch transiente Expression der Gαs Spleißvarianten rekonstituiert und auf der Ebene der Adenylylcyclase untersucht. Die Interaktion der Spleißvarianten mit der Adenylylcyclase wurde durch direkte Aktivierung des G-Proteins in Plasmamembranen verglichen. Die vier Spleißvarianten aktivierten die Adenylylcyclase mit halbmaximal wirksamen Konzentrationen von 0,24-0,31 nM und waren vergleichbar effizient. Weil diese Werte äquivalent waren, konnte die Adenylylcyclase-Aktivität als Maß für die Interaktion zwischen GPCR und Gαs verwendet werden. Die Spleißvarianten waren vergleichbar potent in der Adenylylcyclase-Aktivierung durch β2-adrenergen, Glucagon-, Histamin-, Secretin-, Vasopressin- und Luteinisierungshormon-Rezeptor. Zusammenfassend zeigte diese Arbeit, dass sich die Gαs-Spleißvarianten in der GPCR- vermittelten Adenylylcyclase-Aktivierung vergleichbar verhalten. Daher muss der Grund für die Expression der vier Spleißvarianten noch gefunden werden; die bisher wenig untersuchten Interaktionen mit weiteren Signalmolekülen, wie Tubulin oder den Src-Kinasen, werden diskutiert., The stimulatory guanine nucleotide-binding protein (Gs) transmits signals from stimulatory G protein-coupled receptors (GPCR) to adenylyl cyclases, thereby increasing the production of the second messenger cAMP. Four splice variants of the α-subunit of Gs (Gαs) are expressed in mammalian tissues. Numerous studies have analysed their function, but due to differing experimental parameters and systems, the results were neither consistent nor comparable. Differences in the biochemical properties of heterologously expressed, purified splice variants have been described, but it is not known whether they are enhanced or weakened by transmission through the full signalling cascade. Therefore, the effectiveness of signal transduction via the four splice variants was compared using specific repression (knock down) or reconstitution of unmodified proteins in Gαs-deficient cell lines. Several methods of transient repression were compared using a luciferase reporter system. Catalytically active DNA (DNAzyme) was unsuitable because of its low activity at physiological magnesium concentrations. In contrast, up to 90 % inhibition of luciferase expression was achieved by either propyne-modified oligodeoxynucleotides or intracellular expression of small interfering RNA. The propyne-modified oligodeoxynucleotides were chosen for inhibition of Gαs on account of their greater flexibility in the choice of target sequences. They inhibited expression of transiently transfected but not of endogenous Gαs. In Sf9 insect cells, Gαs splice variants were co-expressed with various GPCR. The interaction between GPCR and Gαs in plasma membranes was compared by measuring ligand-dependent binding kinetics of the GTP analogue [35S]GTPγS. The four splice variants were activated with comparable apparent rate constants by the β2-adrenergic, glucagon, histamine and secretin receptors (kapp ≈ 0,1 min-1). In the Gαs-deficient mouse fibroblast cell line 2B2, the signal transduction cascade GPCR Gαs adenylyl cyclase was reconstituted by transiently expressing Gαs splice variants. Adenylyl cyclase activity was measured in the plasma membranes. Direct activation of Gαs splice variants showed them to be comparably effective and potent in activating adenylyl cyclase with half-maximal effective concentrations of 0.24-0.31 nM. Due to the similarity of these values, adenylyl cyclase activity could be taken as a measure of the interaction between GPCR and Gαs. The splice variants were comparably potent in receptor-mediated adenylyl cyclase activation by the β2-adrenergic, glucagon, histamine, secretin, vasopressin, and luteinising hormone receptors. However, the reason for the expression of four different splice variants remains to be elucidated; interactions with other signalling molecules such as tubulin and Src family tyrosine kinases are discussed.