Analysis of gene expression patterns in animals

During my PhD, my aim was to provide new tools to increase our capacity to analyse gene expression patterns, and to study on a large-scale basis the evolution of gene expression in animals. Gene expression patterns (when and where a gene is expressed) are a key feature in understanding gene function, notably in development. It appears clear now that the evolution of developmental processes and of phenotypes is shaped both by evolution at the coding sequence level, and at the gene expression level.Studying gene expression evolution in animals, with complex expression patterns over tissues and developmental time, is still challenging. No tools are available to routinely compare expression patterns between different species, with precision, and on a large-scale basis. Studies on gene expression evolution are therefore performed only on small genes datasets, or using imprecise descriptions of expression patterns.The aim of my PhD was thus to develop and use novel bioinformatics resources, to study the evolution of gene expression. To this end, I developed the database Bgee (Base for Gene Expression Evolution). The approach of Bgee is to transform heterogeneous expression data (ESTs, microarrays, and in-situ hybridizations) into present/absent calls, and to annotate them to standard representations of anatomy and development of different species (anatomical ontologies). An extensive mapping between anatomies of species is then developed based on hypothesis of homology. These precise annotations to anatomies, and this extensive mapping between species, are the major assets of Bgee, and have required the involvement of many co-workers over the years. My main personal contribution is the development and the management of both the Bgee database and the web-application.Bgee is now on its ninth release, and includes an important gene expression dataset for 5 species (human, mouse, drosophila, zebrafish, Xenopus), with the most data from mouse, human and zebrafish. Using these three species, I have conducted an analysis of gene expression evolution after duplication in vertebrates.Gene duplication is thought to be a major source of novelty in evolution, and to participate to speciation. It has been suggested that the evolution of gene expression patterns might participate in the retention of duplicate genes. I performed a large-scale comparison of expression patterns of hundreds of duplicated genes to their singleton ortholog in an outgroup, including both small and large-scale duplicates, in three vertebrate species (human, mouse and zebrafish), and using highly accurate descriptions of expression patterns. My results showed unexpectedly high rates of de novo acquisition of expression domains after duplication (neofunctionalization), at least as high or higher than rates of partitioning of expression domains (subfunctionalization). I found differences in the evolution of expression of small- and large-scale duplicates, with small-scale duplicates more prone to neofunctionalization. Duplicates with neofunctionalization seemed to evolve under more relaxed selective pressure on the coding sequence. Finally, even with abundant and precise expression data, the majority fate I recovered was neither neo- nor subfunctionalization of expression domains, suggesting a major role for other mechanisms in duplicate gene retention.

Etat des lieux et potentiel de l'agriculture urbaine en Suisse : analyse de deux projets d'agriculture urbaine sous l'angle des régimes institutionnels des ressources naturelles

Ce travail de recherche dresse un panorama de l'état du développement des pratiques d'agriculture urbaine en Suisse et analyse le potentiel que celles-ci pourraient y développer, compte tenu des particularités du contexte national. La démarche adoptée suit une logique allant du général au particulier, de la théorie à la pratique, du descriptif vers l'analytique. Dans un premier temps, l'agriculture urbaine est abordée sous un angle conceptuel, comprenant un retour historique sur la relation ville-campagne et sur l'apparition récente du terme d'agriculture urbaine, un tour d'horizon de la littérature sur le sujet, une revue de ses diverses approches scientifiques et la circonscription des enjeux de sa définition. Dans un deuxième temps, l'agriculture urbaine est envisagée sous sa forme pratique, en Suisse comme à l'étranger. En ressort un inventaire étendu de ses différents types de mises en application, auquel correspond un panel d'atouts identifiés selon les trois versants du développement durable : social, écologique et économique. En troisième lieu les spécificités du contexte helvétique sont étudiées afin de comprendre quel est le cadre dans lequel le potentiel de l'agriculture urbaine pourrait se développer. Finalement, ce sont deux cas concrets d'agriculture urbaine qui sont analysés et évalués dans les détails, selon l'approche dite des régimes institutionnels des ressources naturelles (RIRN): le « plantage » lausannois du quartier de la Bourdonnette et le Stadiongarten dans le quartier Kreis 5 à Zurich. Au fil de cette recherche, il apparaît que l'agriculture urbaine révèle toute une série d'avantages en termes de développement durable, alors même que les villes suisses sont unanimement reconnues comme présentant un déficit dans ce domaine. De même, malgré les bienfaits importants que présentent ses diverses pratiques, l'agriculture urbaine reste encore très peu répandue en Suisse, le concept lui-même n'apparaissant que très rarement dans le discours des pouvoirs publics. Le principal frein à l'agriculture en ville est identifié comme étant le manque d'espace disponible dans les agglomérations, contrainte pourtant largement surmontable en y regardant de plus près. De par sa configuration topographique, le territoire suisse est particulièrement sujet à une étroite proximité entre espaces urbains et étendues agricoles, accroissant de ce fait la problématique de l'étalement urbain et du mitage du paysage. Parmi les enjeux de la lutte contre ces phénomènes concomitants, l'agriculture urbaine aurait un rôle important à jouer. En conclusion, une série de recommandations sont proposées afin que les projets d'agriculture urbaine puissent se développer et perdurer en Suisse. Abstract : This research paper provides an overview of the state of development of urban agriculture practices in Switzerland. It analyzes their potential of expansion while taking into account the particularities of the national context. The method follows a general to particular, theory to practice and descriptive to analytical reasoning. Firstly, urban agriculture is approached through a conceptual view, including a historical overview of the relationship between town and country and of the recent appearance of the term "urban agriculture". An outline of the literature on the subject, an examination of its various scientific approaches and riding issues of its definition are elaborated as well. In a second step, urban agriculture is considered in its practical form, both in Switzerland and abroad. From this we created an extensive inventory of various types of implementations which corresponds to a panel of assets identified according to the three aspects of sustainable development: social, ecology and economics. Thirdly the specificities of Swiss context are studied in order to understand the frame in which the potential of urban agriculture could be developed. Finally, two case studies of urban agriculture are analyzed and evaluated in detail, according to the so-called institutional regimes of natural resources (RIRN) approach: the "plantage" of the Bourdonnette neighborhood in Lausanne and the "Stadiongarten" in the Kreis 5 neighborhood in Zurich. Throughout this research, urban agriculture reveals a number of advantages in terms of sustainable development, even though the Swiss cities are unanimously recognized as having a deficit in this area. As well, despite the significant benefits that are its various practices, urban agriculture is still very uncommon in Switzerland, the concept itself appearing only rarely in public debates. The main obstacle to city agriculture is identified as the lack of available space in urban areas, however this constraint can easily be surpassed. By its topographical configuration, Switzerland is particularly prone to a close proximity between urban and agricultural spaces, thereby increasing the problems of urban sprawl. Among the stakes in the struggle against these interrelated phenomena, urban agriculture could play an important role. In conclusion, a series of recommendations are proposed so that urban agriculture projects can grow and persist in Switzerland.

Essays in equilibrium asset pricing

Introduction This dissertation consists of three essays in equilibrium asset pricing. The first chapter studies the asset pricing implications of a general equilibrium model in which real investment is reversible at a cost. Firms face higher costs in contracting than in expanding their capital stock and decide to invest when their productive capital is scarce relative to the overall capital of the economy. Positive shocks to the capital of the firm increase the size of the firm and reduce the value of growth options. As a result, the firm is burdened with more unproductive capital and its value lowers with respect to the accumulated capital. The optimal consumption policy alters the optimal allocation of resources and affects firm's value, generating mean-reverting dynamics for the M/B ratios. The model (1) captures convergence of price-to-book ratios -negative for growth stocks and positive for value stocks - (firm migration), (2) generates deviations from the classic CAPM in line with the cross-sectional variation in expected stock returns and (3) generates a non-monotone relationship between Tobin's q and conditional volatility consistent with the empirical evidence. The second chapter proposes a standard portfolio-choice problem with transaction costs and mean reversion in expected returns. In the presence of transactions costs, no matter how small, arbitrage activity does not necessarily render equal all riskless rates of return. When two such rates follow stochastic processes, it is not optimal immediately to arbitrage out any discrepancy that arises between them. The reason is that immediate arbitrage would induce a definite expenditure of transactions costs whereas, without arbitrage intervention, there exists some, perhaps sufficient, probability that these two interest rates will come back together without any costs having been incurred. Hence, one can surmise that at equilibrium the financial market will permit the coexistence of two riskless rates that are not equal to each other. For analogous reasons, randomly fluctuating expected rates of return on risky assets will be allowed to differ even after correction for risk, leading to important violations of the Capital Asset Pricing Model. The combination of randomness in expected rates of return and proportional transactions costs is a serious blow to existing frictionless pricing models. Finally, in the last chapter I propose a two-countries two-goods general equilibrium economy with uncertainty about the fundamentals' growth rates to study the joint behavior of equity volatilities and correlation at the business cycle frequency. I assume that dividend growth rates jump from one state to other, while countries' switches are possibly correlated. The model is solved in closed-form and the analytical expressions for stock prices are reported. When calibrated to the empirical data of United States and United Kingdom, the results show that, given the existing degree of synchronization across these business cycles, the model captures quite well the historical patterns of stock return volatilities. Moreover, I can explain the time behavior of the correlation, but exclusively under the assumption of a global business cycle.

Assessing chronic disease management in European health systems : concepts and approaches

This book comprises two volumes and builds on the findings of the DISMEVAL project (Developing and validating DISease Management EVALuation methods for European health care systems), funded under the European Union's (EU) Seventh Framework Programme (FP7) (Agreement no. 223277). DISMEVAL was a three-year European collaborative project conducted between 2009 and 2011. It contributed to developing new research methods and generating the evidence base to inform decision-making in the field of chronic disease management evaluation (www.dismeval.eu). In this book, we report on the findings of the project's first phase, capturing the diverse range of contexts in which new approaches to chronic care are being implemented and evaluating the outcomes of these initiatives using an explicit comparative approach and a unified assessment framework. In this first volume, we describe the range of approaches to chronic care adopted in 12 European countries. By reflecting on the facilitators and barriers to implementation, we aim to provide policy-makers and practitioners with a portfolio of options to advance chronic care approaches in a given policy context.

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Summary and conclusion: One of the main challenges facing the Swiss health care system remains continued fragmentation as a consequence of the federal structure and the division of responsibilities. This constitutes a major barrier for the implementation of a nationwide public health strategy and a more rational organization of health care. Much of the health reform agenda during the past decade was driven by cost-containment efforts. Despite the absence of a national regulatory framework targeting prevention and care of chronic diseases, national strategies and programmes have been developed within a growing recognition of the need to address chronic disease in the health care system. In addition, several small-scale pilot and preliminary structured care programmes have been implemented in selected localities. The latter are however still too few and limited in scope to cover the needs of the majority of patients with chronic diseases residing in Switzerland. Given the continued high satisfaction with the system among health care users, of around 80%, pressure to actually initiate larger scale changes might not yet be sufficiently strong.

Asset freezing, corporate political resources and the Tullock paradox

In 1967, Gordon Tullock asked why firms do not spend more on campaign contributions, despite the large rents that could be generated from political activities. We suggest in this paper that part of the puzzle could come from the fact that one important type of political activity has been neglected by the literature which focuses on campaign contributions or political connections. We call this neglected activity "asset freezing": situations in which firms delay lay-offs or invest in specific technologies to support local politicians' re-election objectives. In doing so, firms bear a potentially significant cost as they do not use a portion of their economic assets in the most efficient or productive way. The purpose of this paper is to provide a first theoretical exploration of this phenomenon. Building on the literature on corporate political resources, we argue that a firm's economic assets can be evaluated based on their degree of "political freezability," which depends on the flexibility of their use and on their value for policy-makers. We then develop a simple model in which financial contributions and freezing assets are alternative options for a firm willing to lawfully influence public policy-making, and derive some of our initial hypotheses more formally.

Financial integration, capital misallocation and global imbalances

This paper shows that in a stylized model with two countries, characterized by different levels of financial development, the following facts can be replicated: 1) persistent current account surpluses and 2) high TFP growth in China. Under autarky, entrepreneurs in the emerging country overinvest in short-term projects and underinvest in long-term projects because short-term assets help them secure long-term investments in the presence of credit constraints. This creates an aggregate misallocation of capital. When financial markets integrate, entrepreneurs with long-term projects can have access to cheaper short-term assets abroad, which leaves them more resources to invest in their projects. This both reduces capital misallocations and generates capital outflows.

Safety Traps

Fear of risk provides a rationale for protracted economic downturns. We develop a real business cycle model where investors with decreasing relative risk aversion choose between a risky and a safe technology that exhibit decreasing returns. Because of a feedback effect from the interest rate to risk aversion, two equilibria can emerge: a standard equilibrium and a "safe" one in which investors invest in safer assets. We refer to the dynamics of this second equilibrium as a safety trap because it is self-reinforcing as investors accumulate more wealth and show it to be consistent with Japan's lost decade.