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We examine the impact of house prices on labour supply decisions using UK micro data. We combine household survey data with local level house price measures and controls for local labour demand. Our micro data also allows us to control for individual level income expectations. We find significant house price effects on labour supply, consistent with leisure being a normal good. Labour supply responses to house prices are concentrated among young married female owners and older owners. This finding suggests house prices affect the decisions of marginal workers in the economy. Our estimates imply house prices are economically important for the participation decisions for these workers.
We study money creation and destruction in today’s monetary architecture and examine the impact of monetary policy and capital regulation in a general equilibrium setting. There are two types of money created and destructed: bank deposits, when banks grant loans to firms or to other banks and central bank money, when the central bank grants loans to private banks. We show that equilibria yield the first-best level of money creation and lending when prices are flexible, regardless of the monetary policy or capital regulation. When prices are rigid, we identify the circumstances in which money creation is excessive or breaks down and the ones in which an adequate combination of monetary policy and capital regulation can restore efficiency.
The dramatic shift from traditional pension plans to participant-directed 401(k) plans has increased the decision-making responsibility of individual investors for their own retirement planning. With this shift comes increasing evidence that investors are making poor decisions in choosing how much to save for retirement and in selecting among their investment options. Studies question the value of efforts to improve these decisions through regulatory reforms or investor education.
This article posits that deficiencies in workplace retirement savings cannot be adequately addressed until the reasons for poor investment decisions are better understood. We report the results of an exploratory study that asked subjects to complete a simulated retirement investment task and collected information about their financial knowledge and preferences. The study enabled us to measure financial literacy and evaluate its relationship to retirement investment decision-making. In line with existing research, we found a strong relationship between financial literacy and successful retirement investing. Our results suggest, however, that the relevant understanding in this context is not about math so much as it is a basic knowledge of the relative costs and benefits of the major investment categories. Finally, we present results suggesting that financial literacy is separate from investment preferences — specifically, that tolerance for risk is a separate and highly predictive variable in estimating retirement planning success.
Our research suggests that individual employees are likely to lack the skills necessary to support the current regulatory model of participant-directed retirement investing. The structure and regulation of retirement plans ought to take this fact seriously. We explore the potential for investor education and professional advice, respectively, to overcome the limitations of individualized choice.
Directors have traditionally been elected by a plurality of the votes cast. This means that in uncontested elections, a candidate who receives even a single vote is elected. Proponents of “shareholder democracy” have advocated a shift to a majority voting rule in which a candidate must receive a majority of the votes cast to be elected. Over the past decade, they have been successful, and the shift to majority voting has been one of the most popular and successful governance reforms.
Yet critics are skeptical as to whether majority voting improves board accountability. Tellingly, directors of companies with majority voting rarely fail to receive majority approval – even more rarely than directors of companies with plurality voting. Even when such directors fail to receive majority approval, they are unlikely to be forced to leave the board. This poses a puzzle: why do firms switch to majority voting and what effect does the switch have, if any, on director behavior?
We empirically examine the adoption and impact of a majority voting rule using a sample of uncontested director elections from 2007 to 2013. We test and find partial support for four hypotheses that could explain why directors of majority voting firms so rarely fail to receive majority support: selection; deterrence/accountability; electioneering by firms; and restraint by shareholders.
Our results further suggest that the reasons for and effects of adopting majority voting may differ between early and later adopters. We find that early adopters of majority voting were more shareholder-responsive than other firms even before they adopted majority voting. These firms seem to have adopted majority voting voluntarily, and the adoption of majority voting has made little difference in their responsiveness to shareholders responsiveness going forward. By contrast, for late adopters, we find no evidence that they were more shareholder-responsive than other firms before they adopted majority voting, but strong evidence that they became more responsive after adopting majority voting.
Differences between early and late adopters can have important implications for understanding the spread of corporate governance reforms and evaluating their effects on firms. Reform advocates, rather than targeting the firms that, by their measures, are most in need of reform, instead seem to have targeted the firms that are already most responsive. They may then have used the widespread adoption of majority voting to create pressure on the nonadopting firms. Empirical studies of the effects of governance changes thus need to be sensitive to the possibility that early adopters and late adopters of reforms differ from each other and that the reforms may have different effects on these two groups of firms.
The article discusses the methodology adopted for a cross-linguistic synchronic and diachronic corpus study on indefinites. The study covered five indefinite expressions, each in a different language. The main goal of the study was to verify the distribution of these indefinites synchronically and to attest their historical development. The methodology we used is a form of functional labeling which combines both context (syntax) and meaning (semantics) using as a starting point Haspelmath’s (1997) functional map. In the article we identify Haspelmath’s functions with logico-semantic interpretations and propose a binary branching decision tree assigning each instance of an indefinite exactly one function in the map.
Event studies have become increasingly important in securities fraud litigation after the Supreme Court’s decision in Halliburton II. Litigants have used event study methodology, which empirically analyzes the relationship between the disclosure of corporate information and the issuer’s stock price, to provide evidence in the evaluation of key elements of federal securities fraud, including materiality, reliance, causation, and damages. As the use of event studies grows and they increasingly serve a gatekeeping function in determining whether litigation will proceed beyond a preliminary stage, it will be critical for courts to use them correctly.
This Article explores an array of considerations related to the use of event studies in securities fraud litigation. It starts by describing the basic function of the event study: to determine whether a highly unusual price movement has occurred and the traditional statistical approach to making that determination. The Article goes on to identify special features of securities fraud litigation that distinguish litigation from the scholarly context in which event studies were developed. The Article highlights the fact that the standard approach can lead to the wrong conclusion and describes the adjustments necessary to address the litigation context. We use the example of six dates in the Halliburton litigation to illustrate these points.
Finally, the Article highlights the limitations of event studies – what they can and cannot prove – and explains how those limitations relate to the legal issues for which they are introduced. These limitations bear upon important normative questions about the role event studies should play in securities fraud litigation.
Cells perform a wide range of functions such as signalling, transportation, immunoprotection and metabolism. Unravelling the molecular mechanism behind those processes will provide a platform for more targeted and rational drug design. This is achieved by discerning the structural and functional aspects of the biological macromolecules involved. This thesis discusses about the biophysical characterization of protein structures and the biological importance of protein dynamics. Membrane receptors and enzymes which are ubiquitously present in our biological systems and regulate wide variety of functions are excellent choice for such study. From a pharmaceutical point of view, receptor and enzymes are exceptionally important drug targets as they represent the major share (receptor, 30% and enzymes, 47%) of all marketed drugs. Therefore, apart from biological insights, the detailed study of receptors and enzymes will provide the basis for new pharmaceutical applications. Most information about receptor activation and enzyme activity come from the structural and functional analysis of target members of the above mentioned systems.
In “Chapter 1 – General Introduction” the readers are introduced to the world of proteins with special focus on G-protein coupled receptors (GPCRs) and methyltransferases. The first part of this chapter discusses about GPCRs with emphasis on their classification, structural features and functions. GPCRs are the most abundant membrane receptors present in mammalian cells, accounting for almost 15% of all membrane proteins. The GPCR superfamily consists of ~800 members and can be subdivided into six classes (A-F). Class A containing rhodopsin, peptide hormones, olfactory GPCRs, is the most abundant with a large share of 85% of GPCR protein family. GPCRs share a common architecture of 7 transmembrane a-helices, with different ligand binding sites. Although a variety of ligands ranging from subatomic particles (a photon) to large proteins can activate a GPCR, their mechanism of signal transduction is almost similar. There are two major signal transduction pathways identified for GPCRs: the cAMP pathway and the phosphatidylinositol pathway. The therapeutic relevance of GPCRs has also been pointed out here since a large share (30%) of modern marketed drugs target GPCRs.
In the second part of this chapter, the structural and functional characterizations of methyltransferases (MTs) are discussed in detail. Several important biological processes in cells e.g. drug metabolism, gene transcription, epigenetic regulations are modulated by methylation of targets ranging from small biomolecules to large proteins. MTs are the proteins which catalyze this methylation reaction and transfer the methyl group to an acceptor molecule through SN2 like nucleophilic substitution reaction. The MTs can be classified on the basis of the substrate atoms they methylate: O (54% of all MTs), N (23%), C (18%), S (3%) and other acceptors (such as halides; 2%). They can also be categorized into five different classes (Class I-V) depending upon distinctive structural features facilitating substrate binding or catalytic activity. Rossmann fold and SET (acronym acquired from the Drosophila Su(var)3-9 and 'Enhancer of zeste' proteins) domain are the two characteristic structural motifs commonly found in MTs. Similar to GPCRs, MTs dysfunction has been shown to be involved in various diseases including neuropsychiatric diseases and cancer. Therefore they are also interesting targets for drug development. The final part of this chapter discusses the importance of structural biology in gathering information related to structure and conformational dynamics of proteins. The two prominent biophysical techniques used in structural biology, X-ray crystallography and NMR, are discussed with focus on their advantages and limitation. The importance of NMR spectroscopic techniques to investigate different dynamic processes of protein at atomic resolution under physiological conditions is also discussed. Real time NMR spectroscopy required for the analysis of slow protein dynamic processes (protein folding, enzyme catalysis, domain rearrangement) has been explained in detail.
The second part of the thesis (Chapters 3-4), which is the cumulative part, comprises the original publications grouped into 2 chapters according to their topic:
• NMR-spectroscopic characterization of the transiently populated photointermediates of bovine rhodopsin and it’s interaction with arrestin (Chapter 3)
• Structural and biophysical characterization of PaMTH1, a putative SAM dependent O-methyltransferase from filamentous fungi Podospora anserina (Chapter 4)
Each chapter is initiated by a detailed introduction to the topic, providing the framework for the following papers. The personal contribution of this thesis’ author to each publication is stated in the introduction to the respective article.
In dieser Arbeit wurden die Strukturen von drei Membranproteinen mittels Einzelpartikel-Kryo‑Elektronenmikroskopie (Kryo‑EM) gelöst. Bei den Membranproteinen handelt es sich um den humanen TRP-Kanal Polycystin‑2, den sekundär-aktiven Transporter BetP aus Corynebacterium glutamicum und den Rotor-Ring der N‑Typ ATPase aus Burkholderia pseudomallei.
Kanäle sind Membranproteine, die Ionen durch eine Pore über die Membran diffundieren lassen. Durch einen präzisen, kanalabhängigen Regulationsmechanismus wird die Pore nur bei Bedarf geöffnet. TRP (transient receptor potential) Kanäle sind anhand von DNA-Sequenzvergleichen identifiziert worden und kommen ausschließlich in Eukaryonten vor. In dieser Arbeit lag der Fokus auf der Strukturbestimmung des humanen TRP Kanals Polycystin‑2 (PC‑2). PC‑2 wurde in einer Studie entdeckt, in der Patienten mit der autosomal dominanten Erbkrankheit „polyzystische Nierenerkrankung“ untersucht wurden. Patienten mit dieser Krankheit tragen eine Mutation in einem der beiden Gene PKD1 oder PKD2, welche für die Proteine Polycystin‑1 und ‑2 kodieren. In dieser Arbeit wurden verschiedene Deletionsmutanten von PC‑2 hergestellt und in das Genom menschlicher HEK293 GnTI‑ Zellen inseriert. Die Zellen, die PC‑2 bzw. die Deletionskonstrukte am stärksten synthetisierten, wurden isoliert und für die rekombinante Proteinherstellung verwendet. Die Expression von PC‑2 führte zu der Entstehung von kristalloidem endoplasmatischem Retikulum. Mutationsstudien in dieser Arbeit zeigen, dass diese morphologische Veränderung durch die Akkumulation von Membranproteinen, die mit sich selbst interagieren, begünstigt wird. Weiter ist es in dieser Arbeit gelungen, PC‑2 zu reinigen und die Struktur des Proteins mit Hilfe von Einzelpartikel Kryo-EM mit einer Auflösung von 4.6 Å zu bestimmen. Die Membrandomäne von PC‑2 ist sehr ähnlich zu den bekannten TRP Kanal Strukturen. Ein Vergleich der PC‑2 Struktur mit dem offenen und geschlossenen TRPV1 Kanal legt nahe, dass PC‑2 in seiner offenen Konformation gelöst wurde.
Der sekundär aktive Transporter BetP von C. glutamicum gehört zu der Familie der BCC- (betaine-carnitine-choline) Transporter und wird durch osmotischen Schock aktiviert. Nach seiner Aktivierung importiert BetP zwei Natriumionen und ein Glycinbetain Molekül. Durch die Akkumulierung von Glycinbetain in der Zelle steigt das osmotische Potential des Zytoplasmas, was den Wasserausstrom aus der Zelle stoppt. Viele Strukturen, die BetP in unterschiedlichen Stadien des Transportprozesses zeigen, konnten bereits mittels Röntgenkristallographie gelöst werden. Allerdings ist die N‑terminale Domäne für die Kristallisation entfernt worden und die C‑terminale Domäne, die komplett aufgelöst ist, ist an einem wichtigen Kristallkontakt beteiligt. Um strukturelle Informationen über die N‑ und C‑terminale Domäne ohne Kristallisationsartefakte zu erhalten, wurde in dieser Arbeit die Struktur von BetP mittels Einzelpartikel Kryo‑EM bestimmt. Die Struktur mit einer Auflösung von 6.8 Å zeigt BetP in einem zum Zytoplasma geöffneten Zustand. Der größte Unterschied zu allen Kristallstrukturen ist die Position der C‑terminalen α‑Helix, die um ~30° rotiert ist und dadurch deutlich enger am Protein zu liegen kommt. Da BetP in Abwesenheit von aktivierenden Stoffen analysiert wurde, wird vermutet, dass es sich bei der gelösten Struktur um den inaktiven Zustand von BetP handelt.
Rotierende ATPasen sind membrangebunden Enzymkomplexe, die bei der zellulären Energieumwandlung eine entscheidende Rolle einnehmen. Sie bestehen aus einem löslichen und einem membrangebundenen Teil. Während in dem löslichen Teil der zelluläre Energieträger Adenosintriphosphat (ATP) entweder synthetisiert oder hydrolysiert wird, baut der membrangebundene Teil entweder einen Ionengradienten auf oder nutzt die Energie eines existierenden Gradienten für die ATP Synthese. Ein wesentlicher Bestandteil des membrangebundenen Teils einer rotierenden ATPase ist der Rotor-Ring. Dieser transportiert Ionen über die Membran und rotiert dabei um seine eigene Achse. In dieser Arbeit wurde eine Studie fortgesetzt, die den Rotor-Ring der N‑Typ ATPase von B. pseudomallei mittels Kryo‑EM untersuchte und zeigte, dass der Rotor-Ring aus 17 identischen Untereinheiten aufgebaut ist. Damit hat die N‑Typ ATPase das größte Ionen-zu-ATP-Verhältnis aller bisher charakterisierten ATPasen. In dieser Arbeit wurde die c17 Stöchiometrie des N‑Typ ATPase Rotor-Rings bestätigt und die Struktur mittels Kryo‑EM bestimmt. Im besonderen Fokus lag dabei der Einfluss von Detergenzien auf die Strukturbestimmung. Es konnte gezeigt werden, dass die beiden Parameter Dichte und Mizellengröße der verwendeten Detergenzien ausschlaggebend für den Erfolg der Strukturbestimmung dieses sehr kleinen Membranproteins sind.