Quantitative integration of high-resolution hydrogeophysical data through Monte-Carlo-type conditional simulations

Geophysical techniques can help to bridge the inherent gap with regard to spatial resolution and the range of coverage that plagues classical hydrological methods. This has lead to the emergence of the new and rapidly growing field of hydrogeophysics. Given the differing sensitivities of various geophysical techniques to hydrologically relevant parameters and their inherent trade-off between resolution and range the fundamental usefulness of multi-method hydrogeophysical surveys for reducing uncertainties in data analysis and interpretation is widely accepted. A major challenge arising from such endeavors is the quantitative integration of the resulting vast and diverse database in order to obtain a unified model of the probed subsurface region that is internally consistent with all available data. To address this problem, we have developed a strategy towards hydrogeophysical data integration based on Monte-Carlo-type conditional stochastic simulation that we consider to be particularly suitable for local-scale studies characterized by high-resolution and high-quality datasets. Monte-Carlo-based optimization techniques are flexible and versatile, allow for accounting for a wide variety of data and constraints of differing resolution and hardness and thus have the potential of providing, in a geostatistical sense, highly detailed and realistic models of the pertinent target parameter distributions. Compared to more conventional approaches of this kind, our approach provides significant advancements in the way that the larger-scale deterministic information resolved by the hydrogeophysical data can be accounted for, which represents an inherently problematic, and as of yet unresolved, aspect of Monte-Carlo-type conditional simulation techniques. We present the results of applying our algorithm to the integration of porosity log and tomographic crosshole georadar data to generate stochastic realizations of the local-scale porosity structure. Our procedure is first tested on pertinent synthetic data and then applied to corresponding field data collected at the Boise Hydrogeophysical Research Site near Boise, Idaho, USA.

Notch1 and T-cell development: insights from conditional knockout mice.

Notch proteins influence cell-fate decisions in many developmental systems. Gain-of-function studies have suggested a crucial role for Notch1 signaling at several stages during lymphocyte development, including the B/T, alphabeta/gammadelta and CD4/CD8 lineage choices. Here, we critically re-evaluate these conclusions in the light of recent studies that describe inducible and tissue-specific targeting of the Notch1 gene.

Influence of seasons and sampling strategy on assessment of bioaerosols in sewage treatment plants in Switzerland

An assessment of sewage workers' exposure to airborne cultivable bacteria, fungi and inhaled endotoxins was performed at 11 sewage treatment plants. We sampled the enclosed and unenclosed treatment areas in each plant and evaluated the influence of seasons (summer and winter) on bioaerosol levels. We also measured personal exposure to endotoxins of workers during special operation where a higher risk of bioaerosol inhalation was assumed. Results show that only fungi are present in significantly higher concentrations in summer than in winter (2331 +/- 858 versus 329 +/- 95 CFU m(-3)). We also found that there are significantly more bacteria in the enclosed area, near the particle grids for incoming water, than in the unenclosed area near the aeration basins (9455 +/- 2661 versus 2435 +/- 985 CFU m(-3) in summer and 11 081 +/- 2299 versus 2002 +/- 839 CFU m(-3) in winter). All bioaerosols were frequently above the recommended values of occupational exposure. Workers carrying out special tasks such as cleaning tanks were exposed to very high levels of endotoxins (up to 500 EU m(-3)) compared to routine work. The species composition and concentration of airborne Gram-negative bacteria were also studied. A broad spectrum of different species within the Pseudomonadaceae and the Enterobacteriaceae families were predominant in nearly all plants investigated. [Authors]

Renal transplantation following aorto-iliac reconstruction is a safe a strategy

Introduction: Renal transplantation is considered the treatment of choice for end-stage renal disease. However, the association of occlusive aorto-iliac disease and chronic renal failure is frequent and aorto-iliac reconstruction may be necessary prior to renal transplantation. This retrospective study reviews the results of this operative strategy.Material and Methods: Between January 2001 and June 2010, 309 patients underwent renal transplantation at our institution and 8 patients had prior aorto-iliac reconstruction using prosthetic material. There were 6 men and 2 women with a median age of 62 years (range 51-70). Five aorto-bifemoral and 2 aorto-bi-iliac bypasses were performed for stage II (n=5), stage IV (n=1) and aortic aneurysm (n=1). In one patient, iliac kissing stents and an ilio-femoral bypass were implanted. 4 cadaveric and 4 living donor renal transplantations were performed with an interval of 2 months to 10 years after revascularization.The results were analysed with respect of graft and patients survival. Differences between groups were tested by the log rank method.Results: No complications and no death occurred in the post-operative period. All bypasses remained patent during follow-up. The median time of post transplantation follow-up was 46 months for all patients and 27 months for patients with prior revascularization. In the revascularized group and control group, the graft and patient survival at 1 year were respectively 100%/96%, 100%/99% and at 5 years 86%/86%, 86%/94%, without significant differences between both groups.Discussion: Our results suggest that renal transplantation following prior aorto-iliac revascularisation with prosthetic material is safe and effective. Patients with end-stage renal disease and concomitant aorto-iliac disease should therefore be considered for renal transplantation. However, caution in the interpretation of the results is indicated due to the small sample size of our study.

Which screening strategy using BMD measurements would be most cost effective for hip fracture prevention in elderly women? A decision analysis based on a Markov model.

INTRODUCTION: Hip fractures are responsible for excessive mortality, decreasing the 5-year survival rate by about 20%. From an economic perspective, they represent a major source of expense, with direct costs in hospitalization, rehabilitation, and institutionalization. The incidence rate sharply increases after the age of 70, but it can be reduced in women aged 70-80 years by therapeutic interventions. Recent analyses suggest that the most efficient strategy is to implement such interventions in women at the age of 70 years. As several guidelines recommend bone mineral density (BMD) screening of postmenopausal women with clinical risk factors, our objective was to assess the cost-effectiveness of two screening strategies applied to elderly women aged 70 years and older. METHODS: A cost-effectiveness analysis was performed using decision-tree analysis and a Markov model. Two alternative strategies, one measuring BMD of all women, and one measuring BMD only of those having at least one risk factor, were compared with the reference strategy "no screening". Cost-effectiveness ratios were measured as cost per year gained without hip fracture. Most probabilities were based on data observed in EPIDOS, SEMOF and OFELY cohorts. RESULTS: In this model, which is mostly based on observed data, the strategy "screen all" was more cost effective than "screen women at risk." For one woman screened at the age of 70 and followed for 10 years, the incremental (additional) cost-effectiveness ratio of these two strategies compared with the reference was 4,235 euros and 8,290 euros, respectively. CONCLUSION: The results of this model, under the assumptions described in the paper, suggest that in women aged 70-80 years, screening all women with dual-energy X-ray absorptiometry (DXA) would be more effective than no screening or screening only women with at least one risk factor. Cost-effectiveness studies based on decision-analysis trees maybe useful tools for helping decision makers, and further models based on different assumptions should be performed to improve the level of evidence on cost-effectiveness ratios of the usual screening strategies for osteoporosis.

Ventricular arrhythmia in coronary artery disease: limits of a risk stratification strategy based on the ejection fraction alone and impact of infarct localization.

AIMS: Estimates of the left ventricular ejection fraction (LVEF) in patients with life-threatening ventricular arrhythmias related to coronary artery disease (CAD) have rarely been reported despite it has become the basis for determining patient's eligibility for prophylactic defibrillator. We aimed to determine the extent and distribution of reduced LVEF in patients with sustained ventricular tachycardia or ventricular fibrillation. METHODS AND RESULTS: 252 patients admitted for ventricular arrhythmia related to CAD were included: 149 had acute myocardial infarction (MI) (Group I, 59%), 54 had significant chronic obstructive CAD suggestive of an ischaemic arrhythmic trigger (Group II, 21%) and 49 patients had an old MI without residual ischaemia (Group III, 19%). 34% of the patients with scar-related arrhythmias had an LVEF > or =40%. Based on pre-event LVEF evaluation, it can be estimated that less than one quarter of the whole study population had a known chronic MI with severely reduced LVEF. In Group III, the proportion of inferior MI was significantly higher than anterior MI (81 vs. 19%; absolute difference, -62; 95% confidence interval, -45 to -79; P < or = 0.0001), though median LVEF was higher in inferior MI (0.37 +/- 10 vs. 0.29 +/- 10; P = 0.0499). CONCLUSION: Patients included in defibrillator trials represent only a minority of the patients at risk of sudden cardiac death. By applying the current risk stratification strategy based on LVEF, more than one third of the patients with old MI would not have qualified for a prophylactic defibrillator. Our study also suggests that inferior scars may be more prone to ventricular arrhythmia compared to anterior scars.

Peroxisomal polyhydroxyalkanoate biosynthesis is a promising strategy for bioplastic production in high biomass crops.

Polyhydroxyalkanoates (PHAs) are bacterial carbon storage polymers with diverse plastic-like properties. PHA biosynthesis in transgenic plants is being developed as a way to reduce the cost and increase the sustainability of industrial PHA production. The homopolymer polyhydroxybutyrate (PHB) is the simplest form of these biodegradable polyesters. Plant peroxisomes contain the substrate molecules and necessary reducing power for PHB biosynthesis, but peroxisomal PHB production has not been explored in whole soil-grown transgenic plants to date. We generated transgenic sugarcane (Saccharum sp.) with the three-enzyme Ralstonia eutropha PHA biosynthetic pathway targeted to peroxisomes. We also introduced the pathway into Arabidopsis thaliana, as a model system for studying and manipulating peroxisomal PHB production. PHB, at levels up to 1.6%-1.8% dry weight, accumulated in sugarcane leaves and A. thaliana seedlings, respectively. In sugarcane, PHB accumulated throughout most leaf cell types in both peroxisomes and vacuoles. A small percentage of total polymer was also identified as the copolymer poly (3-hydroxybutyrate-co-3-hydroxyvalerate) in both plant species. No obvious deleterious effect was observed on plant growth because of peroxisomal PHA biosynthesis at these levels. This study highlights how using peroxisomal metabolism for PHA biosynthesis could significantly contribute to reaching commercial production levels of PHAs in crop plants.

In vivo conditional Pax4 overexpression in mature islet β-cells prevents stress-induced hyperglycemia in mice.

OBJECTIVE To establish the role of the transcription factor Pax4 in pancreatic islet expansion and survival in response to physiological stress and its impact on glucose metabolism, we generated transgenic mice conditionally and selectively overexpressing Pax4 or a diabetes-linked mutant variant (Pax4R129 W) in β-cells. RESEARCH DESIGN AND METHODS Glucose homeostasis and β-cell death and proliferation were assessed in Pax4- or Pax4R129 W-overexpressing transgenic animals challenged with or without streptozotocin. Isolated transgenic islets were also exposed to cytokines, and apoptosis was evaluated by DNA fragmentation or cytochrome C release. The expression profiles of proliferation and apoptotic genes and β-cell markers were studied by immunohistochemistry and quantitative RT-PCR. RESULTS Pax4 but not Pax4R129 W protected animals against streptozotocin-induced hyperglycemia and isolated islets from cytokine-mediated β-cell apoptosis. Cytochrome C release was abrogated in Pax4 islets treated with cytokines. Interleukin-1β transcript levels were suppressed in Pax4 islets, whereas they were increased along with NOS2 in Pax4R129 W islets. Bcl-2, Cdk4, and c-myc expression levels were increased in Pax4 islets while MafA, insulin, and GLUT2 transcript levels were suppressed in both animal models. Long-term Pax4 expression promoted proliferation of a Pdx1-positive cell subpopulation while impeding insulin secretion. Suppression of Pax4 rescued this defect with a concomitant increase in pancreatic insulin content. CONCLUSIONS Pax4 protects adult islets from stress-induced apoptosis by suppressing selective nuclear factor-κB target genes while increasing Bcl-2 levels. Furthermore, it promotes dedifferentiation and proliferation of β-cells through MafA repression, with a concomitant increase in Cdk4 and c-myc expression.

Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies.

Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age <60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m(-2) (continuous infusion for 5 days), doxorubicin 30 mg m(-2) day(-1) x 3 (total dose 90 mg m(-2)), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1-6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33-63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade > or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.

Les symbioses agro-industrielles en Afrique de l'Ouest : évaluation du potentiel d'une nouvelle stratégie pour un développement durable

RésuméCette thèse traite de l'utilisation des concepts de Symbiose Industrielle dans les pays en développement et étudie le potentiel de cette stratégie pour stimuler un développement régional durable dans les zones rurales d'Afrique de l'Ouest. En particulier, lorsqu'une Symbiose Industrielle est instaurée entre une usine et sa population alentour, des outils d'évaluation sont nécessaires pour garantir que le projet permette d'atteindre un réel développement durable. Les outils existants, développés dans les pays industrialisés, ne sont cependant pas complètement adaptés pour l'évaluation de projets dans les pays en développement. En effet, les outils sont porteurs d'hypothèses implicites propres au contexte socio-économique dans lequel ils ont été conçus.L'objectif de cette thèse est de développer un cadre méthodologique pour l'évaluation de la durabilité de projets de Symbiose Industrielle dans les pays en développement.Pour ce faire, je m'appuie sur une étude de cas de la mise en place d'une Symbiose Industrielle au nord du Nigéria, à laquelle j'ai participé en tant qu'observatrice dès 2007. AshakaCem, une usine productrice de ciment du groupe Lafarge, doit faire face à de nombreuses tensions avec la population rurale alentour. L'entreprise a donc décidé d'adopter une nouvelle méthode inspirée des concepts de Symbiose Industrielle. Le projet consiste à remplacer jusqu'à 10% du carburant fossile utilisé pour la cuisson de la matière crue (calcaire et additifs) par de la biomasse produite par les paysans locaux. Pour ne pas compromettre la fragile sécurité alimentaire régionale, des techniques de lutte contre l'érosion et de fertilisation naturelle des sols sont enseignées aux paysans, qui peuvent ainsi utiliser la culture de biomasse pour améliorer leurs cultures vivrières. A travers cette Symbiose Industrielle, l'entreprise poursuit des objectifs sociaux (poser les bases nécessaires à un développement régional), mais également environnementaux (réduire ses émissions de CO2 globales) et économiques (réduire ses coûts énergétiques). Elle s'ancre ainsi dans une perspective de développement durable qui est conditionnelle à la réalisation du projet.A travers l'observation de cette Symbiose et par la connaissance des outils existants je constate qu'une évaluation de la durabilité de projets dans les pays en développement nécessite l'utilisation de critères d'évaluation propres à chaque projet. En effet, dans ce contexte, l'emploi de critères génériques apporte une évaluation trop éloignée des besoins et de la réalité locale. C'est pourquoi, en m'inspirant des outils internationalement reconnus comme l'Analyse du Cycle de Vie ou la Global Reporting Initiative, je définis dans cette thèse un cadre méthodologique qui peut, lui, être identique pour tous les projets. Cette stratégie suit six étapes, qui se réalisent de manière itérative pour permettre une auto¬amélioration de la méthodologie d'évaluation et du projet lui-même. Au cours de ces étapes, les besoins et objectifs en termes sociaux, économiques et environnementaux des différents acteurs sont déterminés, puis regroupés, hiérarchisés et formulés sous forme de critères à évaluer. Des indicateurs quantitatifs ou qualitatifs sont ensuite définis pour chacun de ces critères. Une des spécificités de cette stratégie est de définir une échelle d'évaluation en cinq graduations, identique pour chaque indicateur, témoignant d'un objectif totalement atteint (++) ou pas du tout atteint (--).L'application de ce cadre méthodologique à la Symbiose nigériane a permis de déterminer quatre critères économiques, quatre critères socio-économiques et six critères environnementaux à évaluer. Pour les caractériser, 22 indicateurs ont été définis. L'évaluation de ces indicateurs a permis de montrer que le projet élaboré atteint les objectifs de durabilité fixés pour la majorité des critères. Quatre indicateurs ont un résultat neutre (0), et un cinquième montre qu'un critère n'est pas atteint (--). Ces résultats s'expliquent par le fait que le projet n'en est encore qu'à sa phase pilote et n'a donc pas encore atteint la taille et la diffusion optimales. Un suivi sur plusieurs années permettra de garantir que ces manques seront comblés.Le cadre méthodologique que j'ai développé dans cette thèse est un outil d'évaluation participatif qui pourra être utilisé dans un contexte plus large que celui des pays en développement. Son caractère générique en fait un très bon outil pour la définition de critères et indicateurs de suivi de projet en terme de développement durable.SummaryThis thesis examines the use of industrial symbiosis in developing countries and studies its potential to stimulate sustainable regional development in rural areas across Western Africa. In particular, when industrial symbiosis is instituted between a factory and the surrounding population, evaluation tools are required to ensure the project achieves truly sustainable development. Existing tools developed in industrialized countries are not entirely suited to assessing projects in developing countries. Indeed, the implicit hypotheses behind such tools reflect the socioeconomic context in which they were designed. The goal of this thesis is to develop a methodological framework for evaluating the sustainability of industrial symbiosis projects in developing countries.To accomplish this, I followed a case study about the implementation of industrial symbiosis in northern Nigeria by participating as an observer since 2007. AshakaCem, a cement works of Lafarge group, must confront many issues associated with violence committed by the local rural population. Thus, the company decided to adopt a new approach inspired by the concepts of industrial symbiosis.The project involves replacing up to 10% of the fossil fuel used to heat limestone with biomass produced by local farmers. To avoid jeopardizing the fragile security of regional food supplies, farmers are taught ways to combat erosion and naturally fertilize the soil. They can then use biomass cultivation to improve their subsistence crops. Through this industrial symbiosis, AshakaCem follows social objectives (to lay the necessary foundations for regional development), but also environmental ones (to reduce its overall CO2 emissions) and economical ones (to reduce its energy costs). The company is firmly rooted in a view of sustainable development that is conditional upon the project's execution.By observing this symbiosis and by being familiar with existing tools, I note that assessing the sustainability of projects in developing countries requires using evaluation criteria that are specific to each project. Indeed, using generic criteria results in an assessment that is too far removed from what is needed and from the local reality. Thus, by drawing inspiration from such internationally known tools as Life Cycle Analysis and the Global Reporting Initiative, I define a generic methodological framework for the participative establishment of an evaluation methodology specific to each project.The strategy follows six phases that are fulfilled iteratively so as to improve the evaluation methodology and the project itself as it moves forward. During these phases, the social, economic, and environmental needs and objectives of the stakeholders are identified, grouped, ranked, and expressed as criteria for evaluation. Quantitative or qualitative indicators are then defined for each of these criteria. One of the characteristics of this strategy is to define a five-point evaluation scale, the same for each indicator, to reflect a goal that was completely reached (++) or not reached at all (--).Applying the methodological framework to the Nigerian symbiosis yielded four economic criteria, four socioeconomic criteria, and six environmental criteria to assess. A total of 22 indicators were defined to characterize the criteria. Evaluating these indicators made it possible to show that the project meets the sustainability goals set for the majority of criteria. Four indicators had a neutral result (0); a fifth showed that one criterion had not been met (--). These results can be explained by the fact that the project is still only in its pilot phase and, therefore, still has not reached its optimum size and scope. Following up over several years will make it possible to ensure these gaps will be filled.The methodological framework presented in this thesis is a highly effective tool that can be used in a broader context than developing countries. Its generic nature makes it a very good tool for defining criteria and follow-up indicators for sustainable development.

Targeting mitochondria in the infection strategy of the hepatitis C virus.

Hepatitis C virus (HCV) infection induces a state of oxidative stress more pronounced than that observed in many other inflammatory diseases. Here, we propose a temporal sequence of events in the HCV-infected cell whereby the primary alteration consists of a release of Ca(2+) from the endoplasmic reticulum, followed by uptake into mitochondria. This ensues successive mitochondrial dysfunction leading to the generation of reactive oxygen species and a progressive metabolic adaptive response. Evidence is provided for a positive feed-back mechanism between alterations of calcium and redox homeostasis. This likely involves deregulation of the mitochondrial permeability transition and induces progressive dysfunction of cellular bioenergetics. Pathogenetic implications of the model and new opportunities for therapeutic intervention are discussed. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.

Gender-role alternation in the simultaneously hermaphroditic freshwater snail Physa acuta: not with the same partner

In simultaneous hermaphrodites, gender conflicts that arise from two potential mates sharing the same gender preference may be solved through conditional reciprocity (or gamete trading). Conditional reciprocity had initially been considered widespread, but recent studies suggest that its real occurrence may have been overestimated, possibly because most mating observations have been performed on isolated pairs of individuals. Some resulting patterns (e. g., non-random alternation of sexual roles) were indeed compatible with conditional reciprocity but could also have stemmed from the two partners independently executing their own mating strategy and being experimentally enforced to do so with the same partner. Non-random alternation of gender roles was recently documented in the simultaneously hermaphroditic freshwater snail Physa acuta. To distinguish between conditional and unconditional gender alternations, we observed copulations of individually marked snails reared at three contrasted densities. We showed that density affected the overall frequency of copulations during the first 2 days of the experiment with high-density boxes showing more copulations than low density boxes, but it did not affect gender alternation patterns. A change in gender role was observed more often than expected by chance over two successive copulations by the same individual, confirming previous studies. However, gender switches did not preferentially occur with the same partner. We conclude that gender alternation is not due to conditional reciprocity in P. acuta. It may rather stem from each individual having a preference for gender alternation. We finally discuss the mechanisms and the potential extent of this unconditional reciprocity.

Strategy selection during exploratory behavior: sex differences

This study was designed to assess sex-related differences in the selection of an appropriate strategy when facing novelty. A simple visuo-spatial task was used to investigate exploratory behavior as a specific response to novelty. The exploration task was followed by a visual discrimination task, and the responses were analyzed using signal detection theory. During exploration women selected a local searching strategy in which the metric distance between what is already known and what is unknown was reduced, whereas men adopted a global strategy based on an approximately uniform distribution of choices. Women's exploratory behavior gives rise to a notion of a secure base warranting a sense of safety while men's behavior does not appear to be influenced by risk. This sex-related difference was interpreted as a difference in beliefs concerning the likelihood of uncertain events influencing risk evaluation. Keywords: exploration, spontaneous strategies, sex differences, decision-making.

Essays in higher moment asset pricing and liquidity risk

This thesis focuses on theoretical asset pricing models and their empirical applications. I aim to investigate the following noteworthy problems: i) if the relationship between asset prices and investors' propensities to gamble and to fear disaster is time varying, ii) if the conflicting evidence for the firm and market level skewness can be explained by downside risk, Hi) if costly learning drives liquidity risk. Moreover, empirical tests support the above assumptions and provide novel findings in asset pricing, investment decisions, and firms' funding liquidity. The first chapter considers a partial equilibrium model where investors have heterogeneous propensities to gamble and fear disaster. Skewness preference represents the desire to gamble, while kurtosis aversion represents fear of extreme returns. Using US data from 1988 to 2012, my model demonstrates that in bad times, risk aversion is higher, more people fear disaster, and fewer people gamble, in contrast to good times. This leads to a new empirical finding: gambling preference has a greater impact on asset prices during market downturns than during booms. The second chapter consists of two essays. The first essay introduces a foramula based on conditional CAPM for decomposing the market skewness. We find that the major market upward and downward movements can be well preadicted by the asymmetric comovement of betas, which is characterized by an indicator called "Systematic Downside Risk" (SDR). We find that SDR can efafectively forecast future stock market movements and we obtain out-of-sample R-squares (compared with a strategy using historical mean) of more than 2.27% with monthly data. The second essay reconciles a well-known empirical fact: aggregating positively skewed firm returns leads to negatively skewed market return. We reconcile this fact through firms' greater response to negative maraket news than positive market news. We also propose several market return predictors, such as downside idiosyncratic skewness. The third chapter studies the funding liquidity risk based on a general equialibrium model which features two agents: one entrepreneur and one external investor. Only the investor needs to acquire information to estimate the unobservable fundamentals driving the economic outputs. The novelty is that information acquisition is more costly in bad times than in good times, i.e. counter-cyclical information cost, as supported by previous empirical evidence. Later we show that liquidity risks are principally driven by costly learning. Résumé Cette thèse présente des modèles théoriques dévaluation des actifs et leurs applications empiriques. Mon objectif est d'étudier les problèmes suivants: la relation entre l'évaluation des actifs et les tendances des investisseurs à parier et à crainadre le désastre varie selon le temps ; les indications contraires pour l'entreprise et l'asymétrie des niveaux de marché peuvent être expliquées par les risques de perte en cas de baisse; l'apprentissage coûteux augmente le risque de liquidité. En outre, des tests empiriques confirment les suppositions ci-dessus et fournissent de nouvelles découvertes en ce qui concerne l'évaluation des actifs, les décisions relatives aux investissements et la liquidité de financement des entreprises. Le premier chapitre examine un modèle d'équilibre où les investisseurs ont des tendances hétérogènes à parier et à craindre le désastre. La préférence asymétrique représente le désir de parier, alors que le kurtosis d'aversion représente la crainte du désastre. En utilisant les données des Etats-Unis de 1988 à 2012, mon modèle démontre que dans les mauvaises périodes, l'aversion du risque est plus grande, plus de gens craignent le désastre et moins de gens parient, conatrairement aux bonnes périodes. Ceci mène à une nouvelle découverte empirique: la préférence relative au pari a un plus grand impact sur les évaluations des actifs durant les ralentissements de marché que durant les booms économiques. Exploitant uniquement cette relation générera un revenu excédentaire annuel de 7,74% qui n'est pas expliqué par les modèles factoriels populaires. Le second chapitre comprend deux essais. Le premier essai introduit une foramule base sur le CAPM conditionnel pour décomposer l'asymétrie du marché. Nous avons découvert que les mouvements de hausses et de baisses majeures du marché peuvent être prédits par les mouvements communs des bêtas. Un inadicateur appelé Systematic Downside Risk, SDR (risque de ralentissement systématique) est créé pour caractériser cette asymétrie dans les mouvements communs des bêtas. Nous avons découvert que le risque de ralentissement systématique peut prévoir les prochains mouvements des marchés boursiers de manière efficace, et nous obtenons des carrés R hors échantillon (comparés avec une stratégie utilisant des moyens historiques) de plus de 2,272% avec des données mensuelles. Un investisseur qui évalue le marché en utilisant le risque de ralentissement systématique aurait obtenu une forte hausse du ratio de 0,206. Le second essai fait cadrer un fait empirique bien connu dans l'asymétrie des niveaux de march et d'entreprise, le total des revenus des entreprises positiveament asymétriques conduit à un revenu de marché négativement asymétrique. Nous décomposons l'asymétrie des revenus du marché au niveau de l'entreprise et faisons cadrer ce fait par une plus grande réaction des entreprises aux nouvelles négatives du marché qu'aux nouvelles positives du marché. Cette décomposition révélé plusieurs variables de revenus de marché efficaces tels que l'asymétrie caractéristique pondérée par la volatilité ainsi que l'asymétrie caractéristique de ralentissement. Le troisième chapitre fournit une nouvelle base théorique pour les problèmes de liquidité qui varient selon le temps au sein d'un environnement de marché incomplet. Nous proposons un modèle d'équilibre général avec deux agents: un entrepreneur et un investisseur externe. Seul l'investisseur a besoin de connaitre le véritable état de l'entreprise, par conséquent, les informations de paiement coutent de l'argent. La nouveauté est que l'acquisition de l'information coute plus cher durant les mauvaises périodes que durant les bonnes périodes, comme cela a été confirmé par de précédentes expériences. Lorsque la récession comamence, l'apprentissage coûteux fait augmenter les primes de liquidité causant un problème d'évaporation de liquidité, comme cela a été aussi confirmé par de précédentes expériences.