How do thyroid hormone receptors bind to structurally diverse response elements?

Three classes of thyroid hormone response elements have been described. They are composed of two half-sites arranged either as a palindromic, a direct repeat or as an inverted palindromic array. Receptor homodimers as well as heterodimers can bind to all three types of response element. While the ligand binding domain of the receptors provides the major dimerization surface, asymmetric contacts between the DNA binding domains are necessary for binding to a direct repeat. Moreover, some recent findings suggest that in TR, compared to RXR, the ligand binding domain has a 180 degrees rotation with respect to the DNA binding domain. This feature could explain the preferential binding of the RXR-TR heterodimer to the direct repeat response element, in which RXR exclusively binds the 5' half-site, and of the TR homodimer to the inverted palindrome response element.

Plasma membrane H+-ATPase regulation is required for auxin gradient formation preceding phototropic growth.

Phototropism is a growth response allowing plants to align their photosynthetic organs toward incoming light and thereby to optimize photosynthetic activity. Formation of a lateral gradient of the phytohormone auxin is a key step to trigger asymmetric growth of the shoot leading to phototropic reorientation. To identify important regulators of auxin gradient formation, we developed an auxin flux model that enabled us to test in silico the impact of different morphological and biophysical parameters on gradient formation, including the contribution of the extracellular space (cell wall) or apoplast. Our model indicates that cell size, cell distributions, and apoplast thickness are all important factors affecting gradient formation. Among all tested variables, regulation of apoplastic pH was the most important to enable the formation of a lateral auxin gradient. To test this prediction, we interfered with the activity of plasma membrane H(+)-ATPases that are required to control apoplastic pH. Our results show that H(+)-ATPases are indeed important for the establishment of a lateral auxin gradient and phototropism. Moreover, we show that during phototropism, H(+)-ATPase activity is regulated by the phototropin photoreceptors, providing a mechanism by which light influences apoplastic pH.

Essays in general equilibrium asset pricing

ABSTRACT : Research in empirical asset pricing has pointed out several anomalies both in the cross section and time series of asset prices, as well as in investors' portfolio choice. This dissertation aims to discover the forces driving some of these "puzzling" asset pricing dynamics and portfolio decisions observed in the financial market. Through the dissertation I construct and study dynamic general equilibrium models of heterogeneous investors in the presence of frictions and evaluate quantitatively their implications for financial-market asset prices and portfolio choice. I also explore the potential roots of puzzles in international finance. Chapter 1 shows that, by introducing jointly endogenous no-default type of borrowing constraints and heterogeneous beliefs in a dynamic general-equilibrium economy, many empirical features of stock return volatility can be reproduced. While most of the research on stock return volatility is empirical, this paper provides a theoretical framework that is able to reproduce simultaneously the cross section and time series stylized facts concerning stock returns and their volatility. In contrast to the existing theoretical literature related to stock return volatility, I don't impose persistence or regimes in any of the exogenous state variables or in preferences. Volatility clustering, asymmetry in the stock return-volatility relationship, and pricing of multi-factor volatility components in the cross section all arise endogenously as a consequence of the feedback between the binding of no-default constraints and heterogeneous beliefs. Chapters 2 and 3 explore the implications of differences of opinion across investors in different countries for international asset pricing anomalies. Chapter 2 demonstrates that several international finance "puzzles" can be reproduced by a single risk factor which captures heterogeneous beliefs across international investors. These puzzles include: (i) home equity preference; (ii) the dependence of firm returns on local and foreign factors; (iii) the co-movement of returns and international capital flows; and (iv) abnormal returns around foreign firm cross-listing events in the local market. These are reproduced in a setup with symmetric information and in a perfectly integrated world with multiple countries and independent processes producing the same good. Chapter 3 shows that by extending this framework to multiple goods and correlated production processes; the "forward premium puzzle" arises naturally as a compensation for the heterogeneous expectations about the depreciation of the exchange rate held by international investors. Chapters 2 and 3 propose differences of opinion across international investors as the potential resolution of several international finance `puzzles'. In a globalized world where both capital and information flow freely across countries, this explanation seems more appealing than existing asymmetric information or segmented markets theories aiming to explain international finance puzzles.

Gene loss and evolutionary rates following whole-genome duplication in teleost fishes.

Teleost fishes provide the first unambiguous support for ancient whole-genome duplication in an animal lineage. Studies in yeast or plants have shown that the effects of such duplications can be mediated by a complex pattern of gene retention and changes in evolutionary pressure. To explore such patterns in fishes, we have determined by phylogenetic analysis the evolutionary origin of 675 Tetraodon duplicated genes assigned to chromosomes, using additional data from other species of actinopterygian fishes. The subset of genes, which was retained in double after the genome duplication, is enriched in development, signaling, behavior, and regulation functional categories. The evolutionary rate of duplicate fish genes appears to be determined by 3 forces: 1) fish proteins evolve faster than mammalian orthologs; 2) the genes kept in double after genome duplication represent the subset under strongest purifying selection; and 3) following duplication, there is an asymmetric acceleration of evolutionary rate in one of the paralogs. These results show that similar mechanisms are at work in fishes as in yeast or plants and provide a framework for future investigation of the consequences of duplication in fishes and other animals.

Molecular and Functional Characterization of Neuroblastoma-Initiating Cells

Neuroblastoma (NB) is the most common extracranial malignant tumor in young children and arises at any site of the sympathetic nervous system. The disease exhibits a remarkable phenotypic diversity ranging from spontaneous regression to fatal disease. Poor outcome results from a rapidly progressive, metastatic and drug-resistant disease. Recent studies have suggested that solid tumors may arise from a minor population of cancer stem cells (CSCs) with stem cell markers and typical properties such as self-renewal ability, asymmetric division and drug resistance. In this model, CSCs possess the exclusive ability to initiate and maintain the tumor, and to produce distant metastases. Tumor cell subpopulations with stem-like phenotypes have indeed been identified in several cancer including leukemia, breast, brain and colon cancers. CSC hypothesis still needs to be validated in the other cancers including NB.NB originates from neural crest-derived malignant sympatho-adrenal cells. We have identified rare cells that express markers in conformity with neural crest stem cells and their derived lineages within primary NB tissue and cell lines, leading us to postulate the existence of CSCs in NB tumors.In the absence of specific markers to isolate CSCs, we adapted to NB tumor cells the sphere functional assay, based on the ability of stem cells to grow as spheres in non-adherent conditions. By serial passages of spheres from bone marrow NB metastases, a subset of cells was gradually selected and its specific gene expression profile identified by micro-array time-course analysis. The differentially expressed genes in spheres are enriched in genes implicated in development including CD133, ABC-transporters, WNT and NOTCH genes, identified in others solid cancers as CSCs markers, and other new markers, all referred by us as the Neurosphere Expression Profile (NEP). We confirmed the presence of a cell subpopulation expressing a combination of the NEP markers within a few primary NB samples.The tumorigenic potential of NB spheres was assayed by in vivo tumor growth analyses using orthotopic (adrenal glands) implantations of tumor cells into immune-compromised mice. Tumors derived from the sphere cells were significantly more frequent and were detected earlier compared to whole tumor cells. However, NB cells expressing the neurosphere-associated genes and isolated from the bulk tumors did not recapitulate the CSC-like phenotype in the orthotopic model. In addition, the NB sphere cells lost their higher tumorigenic potential when implanted in a subcutaneous heterotopic in vivo model.These results highlighted the complex behavior of CSC functions and led us to consider the stem-like NB cells as a dynamic and heterogeneous cell population influenced by microenvironment signals.Our approach identified for the first time candidate genes that may be associated with NB self-renewal and tumorigenicity and therefore would establish specific functional targets for more effective therapies in aggressive NB.

Efectos regionales de la política monetaria : implicaciones para los países de la zona euro

De acuerdo con la teoría de las áreas monetàrias óptimas,los shocks asimétricos tienen un papel fundamental en la determinación de los beneficios y los costes derivados del establecimiento de una área monetaria. En este sentido, diferentes estudios recientes señalan una importante reducción del grado de asimetría de los shocks en términos reales a lo largo de los últimos años entre los países europeos como consecuencia de la mayor coordinación de las políticas económicas y de la aproximación de las estructuras productivas. De todas maneras, una de las cuestiones clave en el nuevo entorno económico, y que no ha sido demasiado considerada a la literatura reciente, es el posible papel desestabilitzador de la política monetaria común como consecuencia de las diferencias en los mecanismos de transmisión de la política monetaria en los distintos países y regiones de la Zona Euro. En este trabajo se considera la mencionada cuestión desde un punto de vista teórico y se analiza empíricamente la existencia de diferencias regionales en los efectos de la política monetaria llevada a término en España a lo largo de los últimos años con la finalidad d identificar los principales determinantes de esta asimetría en el ámbito europeo

Efectos regionales de la política monetaria : implicaciones para los países de la zona euro

De acuerdo con la teoría de las áreas monetàrias óptimas,los shocks asimétricos tienen un papel fundamental en la determinación de los beneficios y los costes derivados del establecimiento de una área monetaria. En este sentido, diferentes estudios recientes señalan una importante reducción del grado de asimetría de los shocks en términos reales a lo largo de los últimos años entre los países europeos como consecuencia de la mayor coordinación de las políticas económicas y de la aproximación de las estructuras productivas. De todas maneras, una de las cuestiones clave en el nuevo entorno económico, y que no ha sido demasiado considerada a la literatura reciente, es el posible papel desestabilitzador de la política monetaria común como consecuencia de las diferencias en los mecanismos de transmisión de la política monetaria en los distintos países y regiones de la Zona Euro. En este trabajo se considera la mencionada cuestión desde un punto de vista teórico y se analiza empíricamente la existencia de diferencias regionales en los efectos de la política monetaria llevada a término en España a lo largo de los últimos años con la finalidad d identificar los principales determinantes de esta asimetría en el ámbito europeo

Educational attainment and timing of fertility decisions

This paper focuses on timing of fertility decisions, conditional on the level of educational attainment of parents. Timing of fertility and educational attainment of parents rationalize the negative relationship observed in the data between hourly wages and childbearing. It is shown how the recent evolution in total fertility rates observed in developed countries could be in part the result of a transition from an early childbearing regime to a late childbearing regime. I develop a general equilibrium overlapping generations model in order to understand the joint determination of timing of childbearing decisions together with other household economic decisions in a life cycle framework. I show how idiosyncratic uncertainty might have asymmetric efects on completed fertility depending on timing of childbearing, generating the diferences in completed fertility observed between households that difer in their level of educational attainment.

Auction theory, sequential local service privatization, and the effects of geographical scale economies on effective competition

A sequential weakly efficient two-auction game with entry costs, interdependence between objects, two potential bidders and IPV assumption is presented here in order to give some theoretical predictions on the effects of geographical scale economies on local service privatization performance. It is shown that the first object seller takes profit of this interdependence. The interdependence externality rises effective competition for the first object, expressed as the probability of having more than one final bidder. Besides, if there is more than one final bidder in the first auction, seller extracts the entire bidder¿s expected future surplus differential between having won the first auction and having lost. Consequences for second object seller are less clear, reflecting the contradictory nature of the two main effects of object interdependence. On the one hand, first auction winner becomes ¿stronger¿, so that expected payments rise in a competitive environment. On the other hand, first auction loser becomes relatively ¿weaker¿, hence (probably) reducing effective competition for the second object. Additionally, some contributions to static auction theory with entry cost and asymmetric bidders are presented in the appendix

Worksharing and access discounts in the postal sector with asymmetrics information

This paper analyses the optimal worksharing discount granted to mailers and entrants in a liberalized sector when there is asymmetric information about the Post Office's cost. When the regulator is unable to ascertain which part of total cost of sorting has to be attributed to each sorting facility, the optimal 'accesss discount' given to the entrants is set in a pro-competitive way, thus facilitating the entry of firms that are less afficient than the Post Office. Howerver, with the same asymmetry of information, the optimal 'worksharing discount' given to the mailers is set to favor the Post Office, even when it is less efficient than the mailers in providing the sorting.

Estudi de l'estat de Salut autopercebut: Modelització de l'índex d'utilitat EQ-5D mitjançant un model tobit

Objective: Health status measures usually have an asymmetric distribution and present a highpercentage of respondents with the best possible score (ceiling effect), specially when they areassessed in the overall population. Different methods to model this type of variables have beenproposed that take into account the ceiling effect: the tobit models, the Censored Least AbsoluteDeviations (CLAD) models or the two-part models, among others. The objective of this workwas to describe the tobit model, and compare it with the Ordinary Least Squares (OLS) model,that ignores the ceiling effect.Methods: Two different data sets have been used in order to compare both models: a) real datacomming from the European Study of Mental Disorders (ESEMeD), in order to model theEQ5D index, one of the measures of utilities most commonly used for the evaluation of healthstatus; and b) data obtained from simulation. Cross-validation was used to compare thepredicted values of the tobit model and the OLS models. The following estimators werecompared: the percentage of absolute error (R1), the percentage of squared error (R2), the MeanSquared Error (MSE) and the Mean Absolute Prediction Error (MAPE). Different datasets werecreated for different values of the error variance and different percentages of individuals withceiling effect. The estimations of the coefficients, the percentage of explained variance and theplots of residuals versus predicted values obtained under each model were compared.Results: With regard to the results of the ESEMeD study, the predicted values obtained with theOLS model and those obtained with the tobit models were very similar. The regressioncoefficients of the linear model were consistently smaller than those from the tobit model. In thesimulation study, we observed that when the error variance was small (s=1), the tobit modelpresented unbiased estimations of the coefficients and accurate predicted values, specially whenthe percentage of individuals wiht the highest possible score was small. However, when theerrror variance was greater (s=10 or s=20), the percentage of explained variance for the tobitmodel and the predicted values were more similar to those obtained with an OLS model.Conclusions: The proportion of variability accounted for the models and the percentage ofindividuals with the highest possible score have an important effect in the performance of thetobit model in comparison with the linear model.

Higher-order colored-noise effects in multivariable systems

We extend the partial resummation technique of Fokker-Planck terms for multivariable stochastic differential equations with colored noise. As an example, a model system of a Brownian particle with colored noise is studied. We prove that the asymmetric behavior found in analog simulations is due to higher-order terms which are left out in that technique. On the contrary, the systematic ¿-expansion approach can explain the analog results.

Pairing in a two-component ultracold Fermi gas: Phases with broken-space symmetries

We explore the phase diagram of a two-component ultracold atomic Fermi gas interacting with zero-range forces in the limit of weak coupling. We focus on the dependence of the pairing gap and the free energy on the variations in the number densities of the two species while the total density of the system is held fixed. As the density asymmetry is increased, the system exhibits a transition from a homogenous Bardeen-Cooper-Schrieffer (BCS) phase to phases with spontaneously broken global space symmetries. One such realization is the deformed Fermi surface superfluidity (DFS) which exploits the possibility of deforming the Fermi surfaces of the species into ellipsoidal form at zero total momentum of Cooper pairs. The critical asymmetries at which the transition from DFS to the unpaired state occurs are larger than those for the BCS phase. In this precritical region the DFS phase lowers the pairing energy of the asymmetric BCS state. We compare quantitatively the DFS phase to another realization of superconducting phases with broken translational symmetry: the single-plane-wave Larkin-Ovchinnikov-Fulde-Ferrell phase, which is characterized by a nonvanishing center-of-mass momentum of the Cooper pairs. The possibility of the detection of the DFS phase in the time-of-flight experiments is discussed and quantified for the case of 6Li atoms trapped in two different hyperfine states.

Relativistic mean-field interaction with density-dependent meson-nucleon vertices based on microscopical calculations

Although ab initio calculations of relativistic Brueckner theory lead to large scalar isovector fields in nuclear matter, at present, successful versions of covariant density functional theory neglect the interactions in this channel. A new high-precision density functional DD-MEδ is presented which includes four mesons, σ, ω, δ, and ρ, with density-dependent meson-nucleon couplings. It is based to a large extent on microscopic ab initiocalculations in nuclear matter. Only four of its parameters are determined by adjusting to binding energies and charge radii of finite nuclei. The other parameters, in particular the density dependence of the meson-nucleon vertices, are adjusted to nonrelativistic and relativistic Brueckner calculations of symmetric and asymmetric nuclear matter. The isovector effective mass mp*−mn* derived from relativistic Brueckner theory is used to determine the coupling strength of the δ meson and its density dependence.

Synthesis, structure, and magnetic studies on self-assembled BiFeO3-CoFe2O4 nanocomposite thin films

Self-assembled (0.65)BiFeO3-(0.35)CoFe2O4 (BFO-CFO) nanostructures were deposited on SrTiO3 (001) and (111) substrates by pulsed laser deposition at various temperatures from 500 to 800°C. The crystal phases and the lattice strain for the two different substrate orientations have been determined and compared. The films grow epitaxial on both substrates but separation of the spinel and perovskite crystallites, without parasitic phases, is only obtained for growth temperatures of around 600-650°C. The BFO crystallites are out-of-plane expanded on STO(001), whereas they are almost relaxed on (111). In contrast, CFO crystallites grow out-of-plane compressed on both substrates. The asymmetric behavior of the cell parameters of CFO and BFO is discussed on the basis of the role of the epitaxial stress caused by the substrate and the spinel-perovskite interfacial stress. It is concluded that interfacial stress dominates the elastic properties of CFO crystallites and thus it may play a fundamental on the interface magnetoelectric coupling in these nanocomposites.