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This dissertation is concerned with the phenomenon of intervention effects, observed in three different domains: wh-questions, alternative questions (AltQ) and Negative Polarity Item (NPI) licensing. I propose that these three domains share some common properties, namely, they all involve focus-sensitive licensing, and are thus sensitive to an intervening focus phrase. The overview of the dissertation is as follows. In chapter 2, I discuss the phenomenon of intervention effects in wh-questions, brought to light in the discussion of German in Beck (1996), and Korean in Beck and Kim (1997). The basic idea of their analysis is that quantifiers block LF wh-movement. I show that intervention effects are observed in many other languages, too, suggesting that the intervention effect has a universal character. I then point out some problems with the analysis proposed by Beck (1996) and Beck and Kim (1997). In chapter 3, I propose a new generalization of the wh-intervention effects, namely that the core set of interveners, which is crosslinguistically stable, consists of focus phrases (and not quantifiers in general). Furthermore, I argue that the wh-intervention effect is actually an instance of the more general intervention effect, the "Focus Intervention Effect", which says that in a focus-sensitive licensing construction, no independent focus phrase may intervene between the licensor Op and the licensee XP. The underlying idea is that the Q operator is a focus-sensitive operator and that wh-phrases in-situ are dependent (i.e., semantically deficient) focus elements, which must be associated with the Q operator in order to be interpreted. An intervening independent focus operator precisely blocks that association. I further propose that the domain of focus-sensitive licensing includes not only wh-licensing, but also AltQ-licensing and NPI-licensing. In chapter 4, I show that alternative questions are also subject to the focus intervention effect, just like wh-questions. I provide evidence that the intervention effect in wh-questions and in alternative questions should receive a parallel analysis, in terms of focus-sensitivity. In chapter 5, I discuss a third construction which is sensitive to the focus intervention effect: the licensing of Negative Polarity Items (NPIs). I show that focus consistently blocks NPI licensing, with data from German and Korean. I propose that NPIs are also semantically deficient focus elements, which need to be associated with a NEG operator. Finally, chapter 6 summarizes the intervention effects and suggests some topics for future research into the precise nature of the intervention effect.
Electron tomography was used to investigate membrane proteins in a variety of contexts. A high-angle tilt holder, suitable for electron tomography was designed, constructed and characterised. 2D crystals of membrane proteins, NhaA and YidC, were examined as a resolution test, and a method established for determining planarity of crystals. A model for specific gold binding to NhaA crystals was also presented. ATP synthase, a membrane protein complex in mitochondria, were imaged in a frozen hydrated state. They were found to form ribbons of dimers at highly curved regions of the membrane. Dimers from bovine heart and rat liver were excised from the tomographic volumes and averaged. Based on the location of the dimers in the mitochondrion, a model was established whereby ATP synthase, a molecular motor driven by the proton motive force, benefits from the high curvature that it induces in the membrane. Whole yeast mitochondria, imaged by electron cryo-tomography, also contained long ribbons of dimeric ATP synthase. Multiple copies of an unknown membrane protein complex were visualised by electron cryo-tomography, excised and averaged. A general method for the identification of unknown proteins was presented to deal with this inevitable issue, as native tissues and organelles are imaged, and the structures of complexes determined in situ.
3.11.2008 - 4.11.2008 fand in Frankfurt am Main folgende Tagung statt: 21st Century Libraries: Changing Forms, Changing Challenges, Changing Objectives = 8th Frankfurt Scientific Symposium: 3.11.2008 - 4.11.2008. Sie wurde von der Universitätsbiblithek Johann Christian Senckenberg in Zusammanarbeit mit dem Deutschem Architektur Museum (Frankfurt am Main) und der Akademie der Architekten- und Stadtplanerkammer Hessen (Wiesbaden) organisiert Das 8. Frankfurt Symposium stellt den zeitgenössischen Bibliotheksbau, die Entwicklungen und die Probleme des gegenwärtigen Bibliotheksbaus zur Diskussion. Einige theoretische und technische Beiträge runden das Programm ab. Zwei zentrale Schwerpunkte des Symposiums werden die Einbindung von Bibliotheksbauten in das Stadtumfeld und die Auswirkungen gesellschaftspolitischer und technischer Entwicklungen auf die Architektur von Bibliotheken sein.
In this paper, we examine the impact of mergers among German savings banks on the extent to which these savings banks engage in small business lending. The ongoing consolidation in the banking industry has sparked concerns about the continuous availability of credit to small businesses which has been further fueled by empirical studies that partly confirm a reduction in small business lending in the aftermath of mergers. However, using a proprietary data set of German savings banks we find strong evidence that in Germany merging savings banks do not significantly change the extent to which they lend to small businesses compared to prior to the merger or compared to the contemporaneous lending by non-merging banks. We investigate the merger related effects on small business lending in Germany from a bank-level perspective. Furthermore, we estimate small business lending and its continuous adjustment process simultaneously using recent General Method of Moments (GMM) techniques for panel data as proposed by Arellano and Bond (1991).
This paper discusses the so-called commercial approach to microfinance under economic and ethical aspects. It first shows how microfinance has developed from a purely welfare-oriented activity to a commercially relevant line of banking business. The background of this stunning success is the – almost universal – adoption of the so-called commercial approach to microfinance in the course of the last decade. As the author argues, this commercial approach is the only sound approach to adopt if one wanted microfinance to have any social and developmental impact, and therefore the wide-spread “moralistic” criticism of the commercial approach, which has again and again been expressed in the 1990s, is ill-placed from an economic and an ethical perspective. However, some recent events in microfinance raise doubts as to whether the commercial approach has not, in a number of cases, gone too far. The evident example for such a development is the Mexican microfinance institution Compartamos, which recently undertook a financially extremely successful IPO. As it seems, some microfinance institutions have by now become so radically commercial that all of those social and development considerations, which have traditionally motivated work in the field of microfinance, seem to have lost their importance. Thus there is a conflict between commercial and developmental aspirations. However, this conflict is not inevitable. The paper concludes by showing that, and how, a microfinance institution can try to combine using the strengths of the capital market and at the same time maintaining its developmental focus and importance.
The research presented in this thesis characterizes U2AF homology motifs (UHM) and their interactions with UHM ligand motifs (ULM) in the context of splicing regulation. UHM domains are a subgroup of RNA recognition motifs (RRM) originally discovered in the proteins U2AF65 and U2AF35. Whereas canonical RRMs are usually involved in binding of RNA, UHM domains bind tryptophan containing linear protein motifs (ULM) instead. In the first article, we analyze the complex network of interactions between splicing factors and RNA that initiate the assembly of the spliceosome at the 3´ splice site of an intron. The protein U2AF65 binds a pyrimidine-rich element in introns and recruits U2snRNP by binding its protein component SF3b155. My contribution was to define the binding site of the protein U2AF65 to the intrinsically unstructured N-terminus of the scaffolding protein SF3b155. I could show that the UHM domain of U2AF65 recognizes a ULM in SF3b155, and that this binding site is not overlapping with the binding sites of other splicing factors, like p14, to SF3b155. As the U2AF65-UHM:SF3b155-ULM interaction is mutually exclusive with an interaction between U2AF65-UHM and a ULM in the splicing factor SF1, which was reported to initially recognize the branch point sequence, my results provide the molecular details on how SF3b155 replaces SF1 during spliceosomal reorganizations. In the second article, we show that overexpression of the UHM domain of the splicing factor SPF45 induces exon 6 skipping in the pre-mRNA of Fas (CD95/APO-1). I provide evidence for in vitro binding of SPF45-UHM to ULM sequences in the splicing factors U2AF65, SF1, and SF3b155. I crystallized free and SF3b155-bound SPF45 UHM and solved both structures by X-ray crystallography. The analysis of the complex interface and sequence differences in the ULMs allowed me to design mutations of SPF45-UHM, which selectively inhibit binding to distinct ULMs. After assessing the ULM binding properties in vitro, we could show that the activity of SPF45-UHM in influencing the splicing pattern of Fas relies on interactions with SF3b155 and/or SF1, but that an interaction with U2AF65 is dispensable. A mechanism for the activity of SPF45-UHM could thus be engaging in ULM interactions and thus interfering with the network of interactions that initiate the assembly of the spliceosome at the 3´splice site, as described above. In the third article, we describe an unusual flexible homodimerization mode of the UHM in the splicing factor Puf60, which enables simultaneous interactions with ULM sequences on other splicing factors. I could show that the NMR relaxation properties of Puf60-UHM are inconsistent with a model of a rigid dimer, but rather indicate a dimerization via a flexible linker. I identified a flexible loop in the peptide backbone of Puf60-UHM, and showed that mutiation of acidic residues in this loop impairs the dimerization. To analyze the dimerization interface in further detail, I solved the structure of Puf60-UHM by X-ray crystallography. The acidic residues in the flexible loop of one UHM dimer subunit mediate the dimerization by contacting basic residues on the β-sheet surface of the other dimer subunit. Differences in the four dimer interfaces observed for the eight molecules in the asymmetric unit of the crystal support the model of an undescribed, flexible mode of dimerization, and thus complement the NMR relaxation data. Furthermore, I could show that the Puf60-UHM dimer and U2AF65-UHM contact different ULM sequences on the SF3b155 N-terminus in vitro, thus providing a possible explanation for the mutual cooperative activation of Puf60 and U2AF65 in splicing assays described in the literature. The fourth article is a review about recent research on the recognition of DNA double strand breaks (DSB) by covalent histone modifications. The p53 binding protein 1 (53BP1) is a DSB sensor and a checkpoint protein for mitosis. Recent crystallographic evidence indicates that 53BP1 recognizes DSB sites by binding histone H4 dimetylated at lysine 20 (H4-K20). We provide a comprehensive overview of the atomic resolution structures that revealed how proteins can specifically recognize histone tail modifications, especially methylated lysines, to read the information stored in what is called the histone code.
We examine insurance markets with two types of customers: those who regret suboptimal decisions and those who don.t. In this setting, we characterize the equilibria under hidden information about the type of customers and hidden action. We show that both pooling and separating equilibria can exist. Furthermore, there exist separating equilibria that predict a positive correlation between the amount of insurance coverage and risk type, as in the standard economic models of adverse selection, but there also exist separating equilibria that predict a negative correlation between the amount of insurance coverage and risk type, i.e. advantageous selection. Since optimal choice of regretful customers depends on foregone alternatives, any equilibrium includes a contract which is o¤ered but not purchased.