Leishmania major parasites and their interaction with human macrophages

First both life stages of Leishmania major (L. major) FEBNI parasites, promastigotes as well as amastigotes, were characterized. We found that the virulence marker GP63 and cysteine peptidase b (Cpb) were higher expressed by axenic amastigotes as compared to promastigotes. In addition to the L. major FEBNI strain, we applied and successfully modified our novel in vitro method to generate axenic amastigotes of the L. major Friedlin and 5ASKH strains. Interestingly, these L. major strains needed another temperature to be transferred into amastigotes in the axenic culture system. Investigating apoptosis mechanisms in both parasite life stages of L. major FEBNI we found both ROS dependent and independent cell death mechanisms. Focusing on promastigote and amastigote interaction with pro-inflammatory (MF I) and anti-inflammatory (MF II) macrophages we found amastigotes to be more infective as compared to promastigotes. Moreover, we could demonstrate that pro-inflammatory MF I were less susceptible to infection than anti-inflammatory MF II. Finally we investigated parasite stage-specific responses of MF I + II and their defense mechanisms against L. major. Using knockdown techniques for primary human macrophages we identified a new mechanism enabling intracellular killing of promastigotes inside MF I. This mechanism depends on the antimicrobial molecule cathelicidin (LL-37).

Contributions to the contextualization of human-machine spoken interaction systems

The design and development of spoken interaction systems has been a thoroughly studied research scope for the last decades. The aim is to obtain systems with the ability to interact with human agents with a high degree of naturalness and efficiency, allowing them to carry out the actions they desire using speech, as it is the most natural means of communication between humans. To achieve that degree of naturalness, it is not enough to endow systems with the ability to accurately understand the user’s utterances and to properly react to them, even considering the information provided by the user in his or her previous interactions. The system has also to be aware of the evolution of the conditions under which the interaction takes place, in order to act the most coherent way as possible at each moment. Consequently, one of the most important features of the system is that it has to be context-aware. This context awareness of the system can be reflected in the modification of the behaviour of the system taking into account the current situation of the interaction. For instance, the system should decide which action it has to carry out, or the way to perform it, depending on the user that requests it, on the way that the user addresses the system, on the characteristics of the environment in which the interaction takes place, and so on. In other words, the system has to adapt its behaviour to these evolving elements of the interaction. Moreover that adaptation has to be carried out, if possible, in such a way that the user: i) does not perceive that the system has to make any additional effort, or to devote interaction time to perform tasks other than carrying out the requested actions, and ii) does not have to provide the system with any additional information to carry out the adaptation, which could imply a lesser efficiency of the interaction, since users should devote several interactions only to allow the system to become adapted. In the state-of-the-art spoken dialogue systems, researchers have proposed several disparate strategies to adapt the elements of the system to different conditions of the interaction (such as the acoustic characteristics of a specific user’s speech, the actions previously requested, and so on). Nevertheless, to our knowledge there is not any consensus on the procedures to carry out these adaptation. The approaches are to an extent unrelated from one another, in the sense that each one considers different pieces of information, and the treatment of that information is different taking into account the adaptation carried out. In this regard, the main contributions of this Thesis are the following ones: Definition of a contextualization framework. We propose a unified approach that can cover any strategy to adapt the behaviour of a dialogue system to the conditions of the interaction (i.e. the context). In our theoretical definition of the contextualization framework we consider the system’s context as all the sources of variability present at any time of the interaction, either those ones related to the environment in which the interaction takes place, or to the human agent that addresses the system at each moment. Our proposal relies on three aspects that any contextualization approach should fulfill: plasticity (i.e. the system has to be able to modify its behaviour in the most proactive way taking into account the conditions under which the interaction takes place), adaptivity (i.e. the system has also to be able to consider the most appropriate sources of information at each moment, both environmental and user- and dialogue-dependent, to effectively adapt to the conditions aforementioned), and transparency (i.e. the system has to carry out the contextualizaton-related tasks in such a way that the user neither perceives them nor has to do any effort in providing the system with any information that it needs to perform that contextualization). Additionally, we could include a generality aspect to our proposed framework: the main features of the framework should be easy to adopt in any dialogue system, regardless of the solution proposed to manage the dialogue. Once we define the theoretical basis of our contextualization framework, we propose two cases of study on its application in a spoken dialogue system. We focus on two aspects of the interaction: the contextualization of the speech recognition models, and the incorporation of user-specific information into the dialogue flow. One of the modules of a dialogue system that is more prone to be contextualized is the speech recognition system. This module makes use of several models to emit a recognition hypothesis from the user’s speech signal. Generally speaking, a recognition system considers two types of models: an acoustic one (that models each of the phonemes that the recognition system has to consider) and a linguistic one (that models the sequences of words that make sense for the system). In this work we contextualize the language model of the recognition system in such a way that it takes into account the information provided by the user in both his or her current utterance and in the previous ones. These utterances convey information useful to help the system in the recognition of the next utterance. The contextualization approach that we propose consists of a dynamic adaptation of the language model that is used by the recognition system. We carry out this adaptation by means of a linear interpolation between several models. Instead of training the best interpolation weights, we make them dependent on the conditions of the dialogue. In our approach, the system itself will obtain these weights as a function of the reliability of the different elements of information available, such as the semantic concepts extracted from the user’s utterance, the actions that he or she wants to carry out, the information provided in the previous interactions, and so on. One of the aspects more frequently addressed in Human-Computer Interaction research is the inclusion of user specific characteristics into the information structures managed by the system. The idea is to take into account the features that make each user different from the others in order to offer to each particular user different services (or the same service, but in a different way). We could consider this approach as a user-dependent contextualization of the system. In our work we propose the definition of a user model that contains all the information of each user that could be potentially useful to the system at a given moment of the interaction. In particular we will analyze the actions that each user carries out throughout his or her interaction. The objective is to determine which of these actions become the preferences of that user. We represent the specific information of each user as a feature vector. Each of the characteristics that the system will take into account has a confidence score associated. With these elements, we propose a probabilistic definition of a user preference, as the action whose likelihood of being addressed by the user is greater than the one for the rest of actions. To include the user dependent information into the dialogue flow, we modify the information structures on which the dialogue manager relies to retrieve information that could be needed to solve the actions addressed by the user. Usage preferences become another source of contextual information that will be considered by the system towards a more efficient interaction (since the new information source will help to decrease the need of the system to ask users for additional information, thus reducing the number of turns needed to carry out a specific action). To test the benefits of the contextualization framework that we propose, we carry out an evaluation of the two strategies aforementioned. We gather several performance metrics, both objective and subjective, that allow us to compare the improvements of a contextualized system against the baseline one. We will also gather the user’s opinions as regards their perceptions on the behaviour of the system, and its degree of adaptation to the specific features of each interaction. Resumen El diseño y el desarrollo de sistemas de interacción hablada ha sido objeto de profundo estudio durante las pasadas décadas. El propósito es la consecución de sistemas con la capacidad de interactuar con agentes humanos con un alto grado de eficiencia y naturalidad. De esta manera, los usuarios pueden desempeñar las tareas que deseen empleando la voz, que es el medio de comunicación más natural para los humanos. A fin de alcanzar el grado de naturalidad deseado, no basta con dotar a los sistemas de la abilidad de comprender las intervenciones de los usuarios y reaccionar a ellas de manera apropiada (teniendo en consideración, incluso, la información proporcionada en previas interacciones). Adicionalmente, el sistema ha de ser consciente de las condiciones bajo las cuales transcurre la interacción, así como de la evolución de las mismas, de tal manera que pueda actuar de la manera más coherente en cada instante de la interacción. En consecuencia, una de las características primordiales del sistema es que debe ser sensible al contexto. Esta capacidad del sistema de conocer y emplear el contexto de la interacción puede verse reflejada en la modificación de su comportamiento debida a las características actuales de la interacción. Por ejemplo, el sistema debería decidir cuál es la acción más apropiada, o la mejor manera de llevarla a término, dependiendo del usuario que la solicita, del modo en el que lo hace, etcétera. En otras palabras, el sistema ha de adaptar su comportamiento a tales elementos mutables (o dinámicos) de la interacción. Dos características adicionales son requeridas a dicha adaptación: i) el usuario no ha de percibir que el sistema dedica recursos (temporales o computacionales) a realizar tareas distintas a las que aquél le solicita, y ii) el usuario no ha de dedicar esfuerzo alguno a proporcionar al sistema información adicional para llevar a cabo la interacción. Esto último implicaría una menor eficiencia de la interacción, puesto que los usuarios deberían dedicar parte de la misma a proporcionar información al sistema para su adaptación, sin ningún beneficio inmediato. En los sistemas de diálogo hablado propuestos en la literatura, se han propuesto diferentes estrategias para llevar a cabo la adaptación de los elementos del sistema a las diferentes condiciones de la interacción (tales como las características acústicas del habla de un usuario particular, o a las acciones a las que se ha referido con anterioridad). Sin embargo, no existe una estrategia fija para proceder a dicha adaptación, sino que las mismas no suelen guardar una relación entre sí. En este sentido, cada una de ellas tiene en cuenta distintas fuentes de información, la cual es tratada de manera diferente en función de las características de la adaptación buscada. Teniendo en cuenta lo anterior, las contribuciones principales de esta Tesis son las siguientes: Definición de un marco de contextualización. Proponemos un criterio unificador que pueda cubrir cualquier estrategia de adaptación del comportamiento de un sistema de diálogo a las condiciones de la interacción (esto es, el contexto de la misma). En nuestra definición teórica del marco de contextualización consideramos el contexto del sistema como todas aquellas fuentes de variabilidad presentes en cualquier instante de la interacción, ya estén relacionadas con el entorno en el que tiene lugar la interacción, ya dependan del agente humano que se dirige al sistema en cada momento. Nuestra propuesta se basa en tres aspectos que cualquier estrategia de contextualización debería cumplir: plasticidad (es decir, el sistema ha de ser capaz de modificar su comportamiento de la manera más proactiva posible, teniendo en cuenta las condiciones en las que tiene lugar la interacción), adaptabilidad (esto es, el sistema ha de ser capaz de considerar la información oportuna en cada instante, ya dependa del entorno o del usuario, de tal manera que adecúe su comportamiento de manera eficaz a las condiciones mencionadas), y transparencia (que implica que el sistema ha de desarrollar las tareas relacionadas con la contextualización de tal manera que el usuario no perciba la manera en que dichas tareas se llevan a cabo, ni tampoco deba proporcionar al sistema con información adicional alguna). De manera adicional, incluiremos en el marco propuesto el aspecto de la generalidad: las características del marco de contextualización han de ser portables a cualquier sistema de diálogo, con independencia de la solución propuesta en los mismos para gestionar el diálogo. Una vez hemos definido las características de alto nivel de nuestro marco de contextualización, proponemos dos estrategias de aplicación del mismo a un sistema de diálogo hablado. Nos centraremos en dos aspectos de la interacción a adaptar: los modelos empleados en el reconocimiento de habla, y la incorporación de información específica de cada usuario en el flujo de diálogo. Uno de los módulos de un sistema de diálogo más susceptible de ser contextualizado es el sistema de reconocimiento de habla. Este módulo hace uso de varios modelos para generar una hipótesis de reconocimiento a partir de la señal de habla. En general, un sistema de reconocimiento emplea dos tipos de modelos: uno acústico (que modela cada uno de los fonemas considerados por el reconocedor) y uno lingüístico (que modela las secuencias de palabras que tienen sentido desde el punto de vista de la interacción). En este trabajo contextualizamos el modelo lingüístico del reconocedor de habla, de tal manera que tenga en cuenta la información proporcionada por el usuario, tanto en su intervención actual como en las previas. Estas intervenciones contienen información (semántica y/o discursiva) que puede contribuir a un mejor reconocimiento de las subsiguientes intervenciones del usuario. La estrategia de contextualización propuesta consiste en una adaptación dinámica del modelo de lenguaje empleado en el reconocedor de habla. Dicha adaptación se lleva a cabo mediante una interpolación lineal entre diferentes modelos. En lugar de entrenar los mejores pesos de interpolación, proponemos hacer los mismos dependientes de las condiciones actuales de cada diálogo. El propio sistema obtendrá estos pesos como función de la disponibilidad y relevancia de las diferentes fuentes de información disponibles, tales como los conceptos semánticos extraídos a partir de la intervención del usuario, o las acciones que el mismo desea ejecutar. Uno de los aspectos más comúnmente analizados en la investigación de la Interacción Persona-Máquina es la inclusión de las características específicas de cada usuario en las estructuras de información empleadas por el sistema. El objetivo es tener en cuenta los aspectos que diferencian a cada usuario, de tal manera que el sistema pueda ofrecer a cada uno de ellos el servicio más apropiado (o un mismo servicio, pero de la manera más adecuada a cada usuario). Podemos considerar esta estrategia como una contextualización dependiente del usuario. En este trabajo proponemos la definición de un modelo de usuario que contenga toda la información relativa a cada usuario, que pueda ser potencialmente utilizada por el sistema en un momento determinado de la interacción. En particular, analizaremos aquellas acciones que cada usuario decide ejecutar a lo largo de sus diálogos con el sistema. Nuestro objetivo es determinar cuáles de dichas acciones se convierten en las preferencias de cada usuario. La información de cada usuario quedará representada mediante un vector de características, cada una de las cuales tendrá asociado un valor de confianza. Con ambos elementos proponemos una definición probabilística de una preferencia de uso, como aquella acción cuya verosimilitud es mayor que la del resto de acciones solicitadas por el usuario. A fin de incluir la información dependiente de usuario en el flujo de diálogo, llevamos a cabo una modificación de las estructuras de información en las que se apoya el gestor de diálogo para recuperar información necesaria para resolver ciertos diálogos. En dicha modificación las preferencias de cada usuario pasarán a ser una fuente adicional de información contextual, que será tenida en cuenta por el sistema en aras de una interacción más eficiente (puesto que la nueva fuente de información contribuirá a reducir la necesidad del sistema de solicitar al usuario información adicional, dando lugar en consecuencia a una reducción del número de intervenciones necesarias para llevar a cabo una acción determinada). Para determinar los beneficios de las aplicaciones del marco de contextualización propuesto, llevamos a cabo una evaluación de un sistema de diálogo que incluye las estrategias mencionadas. Hemos recogido diversas métricas, tanto objetivas como subjetivas, que nos permiten determinar las mejoras aportadas por un sistema contextualizado en comparación con el sistema sin contextualizar. De igual manera, hemos recogido las opiniones de los participantes en la evaluación acerca de su percepción del comportamiento del sistema, y de su capacidad de adaptación a las condiciones concretas de cada interacción.

A participatory design agenda for ubiquitous computing and multimodal interaction: A case study of dental practice

This paper reflects upon our attempts to bring a participatory design approach to design research into interfaces that better support dental practice. The project brought together design researchers, general and specialist dental practitioners, the CEO of a dental software company and, to a limited extent, dental patients. We explored the potential for deployment of speech and gesture technologies in the challenging and authentic context of dental practices. The paper describes the various motivations behind the project, the negotiation of access and the development of the participant relationships as seen from the researchers' perspectives. Conducting participatory design sessions with busy professionals demands preparation, improvisation, and clarity of purpose. The paper describes how we identified what went well and when to shift tactics. The contribution of the paper is in its description of what we learned in bringing participatory design principles to a project that spanned technical research interests, commercial objectives and placing demands upon the time of skilled professionals. Copyright © 2010 ACM, Inc

Computer simulation of radio-frequency methane/hydrogen plasmas and their interaction with GaAs Surfaces

The following thesis describes the computer modelling of radio frequency capacitively coupled methane/hydrogen plasmas and the consequences for the reactive ion etching of (100) GaAs surfaces. In addition a range of etching experiments was undertaken over a matrix of pressure, power and methane concentration. The resulting surfaces were investigated using X-ray photoelectron spectroscopy and the results were discussed in terms of physical and chemical models of particle/surface interactions in addition to the predictions for energies, angles and relative fluxes to the substrate of the various plasma species. The model consisted of a Monte Carlo code which followed electrons and ions through the plasma and sheath potentials whilst taking account of collisions with background neutral gas molecules. The ionisation profile output from the electron module was used as input for the ionic module. Momentum scattering interactions of ions with gas molecules were investigated via different models and compared against results given by quantum mechanical code. The interactions were treated as central potential scattering events and the resulting neutral cascades were followed. The resulting predictions for ion energies at the cathode compared well to experimental ion energy distributions and this verified the particular form of the electrical potentials used and their applicability in the particular geometry plasma cell used in the etching experiments. The final code was used to investigate the effect of external plasma parameters on the mass distribution, energy and angles of all species impingent on the electrodes. Comparisons of electron energies in the plasma also agreed favourably with measurements made using a Langmuir electric probe. The surface analysis showed the surfaces all to be depleted in arsenic due to its preferential removal and the resultant Ga:As ratio in the surface was found to be directly linked to the etch rate. The etch rate was determined by the methane flux which was predicted by the code.

Bridging the Gap Between Human Language and Computer-Oriented Representations

Information can be expressed in many ways according to the different capacities of humans to perceive it. Current systems deals with multimedia, multiformat and multiplatform systems but another « multi » is still pending to guarantee global access to information, that is, multilinguality. Different languages imply different replications of the systems according to the language in question. No solutions appear to represent the bridge between the human representation (natural language) and a system-oriented representation. The United Nations University defined in 1997 a language to be the support of effective multilinguism in Internet. In this paper, we describe this language and its possible applications beyond multilingual services as the possible future standard for different language independent applications.

A practical system for hands-off computer interaction based on electromyogram (EMG)/eye gaze tracking (EGT)

Effective interaction with personal computers is a basic requirement for many of the functions that are performed in our daily lives. With the rapid emergence of the Internet and the World Wide Web, computers have become one of the premier means of communication in our society. Unfortunately, these advances have not become equally accessible to physically handicapped individuals. In reality, a significant number of individuals with severe motor disabilities, due to a variety of causes such as Spinal Cord Injury (SCI), Amyothrophic Lateral Sclerosis (ALS), etc., may not be able to utilize the computer mouse as a vital input device for computer interaction. The purpose of this research was to further develop and improve an existing alternative input device for computer cursor control to be used by individuals with severe motor disabilities. This thesis describes the development and the underlying principle for a practical hands-off human-computer interface based on Electromyogram (EMG) signals and Eye Gaze Tracking (EGT) technology compatible with the Microsoft Windows operating system (OS). Results of the software developed in this thesis show a significant improvement in the performance and usability of the EMG/EGT cursor control HCI.

Computer interaction : its effect on attitude and performance in older adults

This study examined the interaction of age, attitude, and performance within the context of an interactive computer testing experience. Subjects were 13 males and 47 females between the ages of 55 and 82, with a minimum of a high school education. Initial attitudes toward computers, as measured by the Cybernetics Attitude Scale (CAS), demonstrated overall equivalence between these older subjects and previously tested younger subjects. Post-intervention scores on the CAS indicated that attitudes toward computers were unaffected by either a "fun" or a "challenging" computer interaction experience. The differential effects of a computerized vs. a paperand- pencil presentation format of a 20-item, multiple choice vocabulary test were examined. Results indicated no significant differences in the performance of subjects in the two conditions, and no interaction effect between attitude and performance. These findings suggest that the attitudes of older adults towards computers do not affect their computerized testing performance, at least for short term testing of verbal abilities. A further implication is that, under the conditions presented here, older subjects appear to be unaffected by mode of testing. The impact of recent advanced in technology on older adults is discussed.

Use of virtual screening, flexible docking, and molecular interaction fields to design novel HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia

Dietary changes associated with drug therapy can reduce high serum cholesterol levels and dramatically decrease the risk of coronary artery disease, stroke, and overall mortality. Statins are hypolipemic drugs that are effective in the reduction of cholesterol serum levels, attenuating cholesterol synthesis in liver by competitive inhibition regarding the substrate or molecular target HMG-CoA reductase. We have herewith used computer-aided molecular design tools, i.e., flexible docking, virtual screening in large data bases, molecular interaction fields to propose novel potential HMG-CoA reductase inhibitors that are promising for the treatment of hypercholesterolemia.

In LipL32, the major leptospiral lipoprotein, the C terminus is the primary immunogenic domain and mediates interaction with collagen wand plasma fibronectin

LipL32 is the major leptospiral outer membrane lipoprotein expressed during infection and is the immunodominant antigen recognized during the humoral immune response to leptospirosis in humans. In this study, we investigated novel aspects of LipL32. In order to define the immunodominant domains(s) of the molecule, subfragments corresponding to the N-terminal, intermediate, and C-terminal portions of the UpL32 gene were cloned and the proteins were expressed and purified by metal affinity chromatography. Our immunoblot results indicate that the C-terminal and intermediate domains of LipL32 are recognized by sera of patients with laboratory-confirmed leptospirosis. An immunoglobulin M response was detected exclusively against the LipL32 C-terminal fragment in both the acute and convalescent phases of illness. We also evaluated the capacity of LipL32 to interact with extracellular matrix (ECM) components. Dose-dependent, specific binding of LipL32 to collagen type IV and plasma fibronectin was observed, and the binding capacity could be attributed to the C-terminal portion of this molecule. Both heparin and gelatin could inhibit LipL32 binding to fibronectin in a concentration-dependent manner, indicating that the 30-kDa heparin-binding and 45-kDa gelatin-binding domains of fibronectin are involved in this interaction. Taken together, our results provide evidence that the LipL32 C terminus is recognized early in the course of infection and is the domain responsible for mediating interaction with ECM proteins.

User perception and influencing factors of technology in everyday life

An increasing amount of research is being developed in the area where technology and humans meet. The success or failure of technologies and the question whether technology helps humans to fulfill their goals or whether it hinders them is in most cases not a technical one. User Perception and Influencing Factors of Technology in Everyday Life addresses issues of human and technology interaction. The research in this work is interdisciplinary, ranging from more technical subjects such as computer science, engineering, and information systems, to non-technical descriptions of technology and human interaction from the point of view of sociology or philosophy. This book is perfect for academics, researchers, and professionals alike as it presents a set of theories that allow us to understand the interaction of technology and humans and to put it to practical use.

Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies

The very high antiproliferative activity of [Co(Cl)(H2O)(phendione)(2)][BF4] (phendione is 1,10-phenanthroline-5,6-dione) against three human tumor cell lines (half-maximal inhibitory concentration below 1 mu M) and its slight selectivity for the colorectal tumor cell line compared with healthy human fibroblasts led us to explore the mechanisms of action underlying this promising antitumor potential. As previously shown by our group, this complex induces cell cycle arrest in S phase and subsequent cell death by apoptosis and it also reduces the expression of proteins typically upregulated in tumors. In the present work, we demonstrate that [Co(Cl)(phendione)(2)(H2O)][BF4] (1) does not reduce the viability of nontumorigenic breast epithelial cells by more than 85 % at 1 mu M, (2) promotes the upregulation of proapoptotic Bax and cell-cycle-related p21, and (3) induces release of lactate dehydrogenase, which is partially reversed by ursodeoxycholic acid. DNA interaction studies were performed to uncover the genotoxicity of the complex and demonstrate that even though it displays K (b) (+/- A standard error of the mean) of (3.48 +/- A 0.03) x 10(5) M-1 and is able to produce double-strand breaks in a concentration-dependent manner, it does not exert any clastogenic effect ex vivo, ruling out DNA as a major cellular target for the complex. Steady-state and time-resolved fluorescence spectroscopy studies are indicative of a strong and specific interaction of the complex with human serum albumin, involving one binding site, at a distance of approximately 1.5 nm for the Trp214 indole side chain with log K (b) similar to 4.7, thus suggesting that this complex can be efficiently transported by albumin in the blood plasma.

Essays on bounded rationality: Individual decision and strategic interaction

Economics is a social science which, therefore, focuses on people and on the decisions they make, be it in an individual context, or in group situations. It studies human choices, in face of needs to be fulfilled, and a limited amount of resources to fulfill them. For a long time, there was a convergence between the normative and positive views of human behavior, in that the ideal and predicted decisions of agents in economic models were entangled in one single concept. That is, it was assumed that the best that could be done in each situation was exactly the choice that would prevail. Or, at least, that the facts that economics needed to explain could be understood in the light of models in which individual agents act as if they are able to make ideal decisions. However, in the last decades, the complexity of the environment in which economic decisions are made and the limits on the ability of agents to deal with it have been recognized, and incorporated into models of decision making in what came to be known as the bounded rationality paradigm. This was triggered by the incapacity of the unboundedly rationality paradigm to explain observed phenomena and behavior. This thesis contributes to the literature in three different ways. Chapter 1 is a survey on bounded rationality, which gathers and organizes the contributions to the field since Simon (1955) first recognized the necessity to account for the limits on human rationality. The focus of the survey is on theoretical work rather than the experimental literature which presents evidence of actual behavior that differs from what classic rationality predicts. The general framework is as follows. Given a set of exogenous variables, the economic agent needs to choose an element from the choice set that is avail- able to him, in order to optimize the expected value of an objective function (assuming his preferences are representable by such a function). If this problem is too complex for the agent to deal with, one or more of its elements is simplified. Each bounded rationality theory is categorized according to the most relevant element it simplifes. Chapter 2 proposes a novel theory of bounded rationality. Much in the same fashion as Conlisk (1980) and Gabaix (2014), we assume that thinking is costly in the sense that agents have to pay a cost for performing mental operations. In our model, if they choose not to think, such cost is avoided, but they are left with a single alternative, labeled the default choice. We exemplify the idea with a very simple model of consumer choice and identify the concept of isofin curves, i.e., sets of default choices which generate the same utility net of thinking cost. Then, we apply the idea to a linear symmetric Cournot duopoly, in which the default choice can be interpreted as the most natural quantity to be produced in the market. We find that, as the thinking cost increases, the number of firms thinking in equilibrium decreases. More interestingly, for intermediate levels of thinking cost, an equilibrium in which one of the firms chooses the default quantity and the other best responds to it exists, generating asymmetric choices in a symmetric model. Our model is able to explain well-known regularities identified in the Cournot experimental literature, such as the adoption of different strategies by players (Huck et al. , 1999), the inter temporal rigidity of choices (Bosch-Dom enech & Vriend, 2003) and the dispersion of quantities in the context of di cult decision making (Bosch-Dom enech & Vriend, 2003). Chapter 3 applies a model of bounded rationality in a game-theoretic set- ting to the well-known turnout paradox in large elections, pivotal probabilities vanish very quickly and no one should vote, in sharp contrast with the ob- served high levels of turnout. Inspired by the concept of rhizomatic thinking, introduced by Bravo-Furtado & Côrte-Real (2009a), we assume that each per- son is self-delusional in the sense that, when making a decision, she believes that a fraction of the people who support the same party decides alike, even if no communication is established between them. This kind of belief simplifies the decision of the agent, as it reduces the number of players he believes to be playing against { it is thus a bounded rationality approach. Studying a two-party first-past-the-post election with a continuum of self-delusional agents, we show that the turnout rate is positive in all the possible equilibria, and that it can be as high as 100%. The game displays multiple equilibria, at least one of which entails a victory of the bigger party. The smaller one may also win, provided its relative size is not too small; more self-delusional voters in the minority party decreases this threshold size. Our model is able to explain some empirical facts, such as the possibility that a close election leads to low turnout (Geys, 2006), a lower margin of victory when turnout is higher (Geys, 2006) and high turnout rates favoring the minority (Bernhagen & Marsh, 1997).

Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders

Eating disorders (EDs) are complex psychiatric diseases that include anorexia nervosa and bulimia nervosa, and have higher than 50% heritability. Previous studies have found association of BDNF and NTRK2 to ED, while animal models suggest that other neurotrophin genes might also be involved in eating behavior. We have performed a family-based association study with 151 TagSNPs covering 10 neurotrophin signaling genes: NGFB, BDNF, NTRK1, NGFR/p75, NTF4/5, NTRK2, NTF3, NTRK3, CNTF and CNTFR in 371 ED trios of Spanish, French and German origin. Besides several nominal associations, we found a strong significant association after correcting for multiple testing (P = 1.04 × 10−4) between ED and rs7180942, located in the NTRK3 gene, which followed an overdominant model of inheritance. Interestingly, HapMap unrelated individuals carrying the rs7180942 risk genotypes for ED showed higher levels of expression of NTRK3 in lymphoblastoid cell lines. Furthermore, higher expression of the orthologous murine Ntrk3 gene was also detected in the hypothalamus of the anx/anx mouse model of anorexia. Finally, variants in NGFB gene appear to modify the risk conferred by the NTRK3 rs7180942 risk genotypes (P = 4.0 × 10−5) showing a synergistic epistatic interaction. The reported data, in addition to the previous reported findings for BDNF and NTRK2, point neurotrophin signaling genes as key regulators of eating behavior and their altered cross-regulation as susceptibility factors for EDs.