ASYN and tau interaction : new drug target for neurodegenerative diseases

Tese de doutoramento, Bioquímica (Biotecnologia), Universidade de Lisboa, Faculdade de Ciências, 2014

Affective Computing to Enhance E-Learning in Segregated Societies

According to UN Women, to build stronger economies, it is essential to empower women to participate fully in economic life across all sectors. Increasing women and girls’ education enhances their chances to participate in the labor market. In certain cultures, like in Saudi Arabia, women contribution to the public economy growth is very limited. According to the World Bank, less than 20 percent of the female population participate in the labor force. This low participation rate has many reasons. One of them, is the educational level and educational quality for females. Although Saudi Arabia has about thirty three universities, opportunities are still limited for women because of the restrictions of access put upon them. A mixture of local norms, traditions, social beliefs, and principles preventing women from receiving full benefits from the educational system. Gender segregation is one of the challenges that limits the women access for education. It causes a problem due to the shortage of female faculty throughout the country. To overcome this problem, male faculty are allowed to teach female students under certain regulations and following a certain method of education delivery and interaction. However, most of these methods lack face-to-face communication between the teacher and students, which lowers the interactivity level and, accordingly, the students’ engagement, and increases the need for other alternatives. The e-learning model is one of high benefit for female students in such societies. Recognizing the students’ engagement is not straightforward in the e-learning model. To measure the level of engagement, the learner’s mood or emotions should be taken into consideration to help understanding and judging the level of engagement. This paper is to investigate the relationship between emotions and engagement in the e-learning environment, and how recognizing the learner’s emotions and change the content delivery accordingly can affect the efficiency of the e-learning process. The proposed experiment alluded to herein should help to find ways to increase the engagement of the learners, hence, enhance the efficiency of the learning process and the quality of learning, which will increase the chances and opportunities for women in such societies to participate more effectively in the labor market.

(Un)suitability of the use of pH buffers in biological, biochemical and environmental studies and their interaction with metal ions – a review

The use of buffers to maintain the pH within a desired range is a very common practice in chemical, biochemical and biological studies. Among them, zwitterionic N-substituted aminosulfonic acids, usually known as Good’s buffers, although widely used, can complex metals and interact with biological systems. The present work reviews, discusses and updates the metal complexation characteristics of thirty one commercially available buffers. In addition, their impact on biological systems is also presented. The influences of these buffers on the results obtained in biological, biochemical and environmental studies, with special focus on their interaction with metal ions, are highlighted and critically reviewed. Using chemical speciation simulations, based on the current knowledge of the metal–buffer stability constants, a proposal of the most adequate buffer to employ for a given metal ion is presented.

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).

Honey proteins and their interaction with polyphenols

This project aimed to determine the protein prof i les and concent rat ion in honeys, ef fect of storage condi t ions on the protein content and the interact ion between proteins and polyphenols. Thi r teen honeys f rom di f ferent botanical or igins were analyzed for thei r protein prof i les using SDS-PAGE, protein concent rat ion and phenol ic content , using the Pierce Protein Assay and Fol in-Ciocal teau methods, respectively. Protein-polyphenol interact ions were analyzed by a combinat ion of the ext ract ion of honeys wi th solvents of di f ferent polar i t ies fol lowed by LCjMS analysis of the obtained f ract ions. Results demonst rated a di f ferent protein content in the tested honeys, wi th buckwheat honey possessing the highest protein concent rat ion. We have shown that the reduct ion of proteins dur ing honey storage was caused, partially, by the protein complexat ion wi th phenolics. The LCjMS analysis of the peak elut ing at retent ion t ime of 10 to 14 min demonst rated that these phenolics included f lavonoids such as Pinobanksin, Pinobanksin acetate, Apigenin, Kaemferol and Myricetin and also cinnamic acid.

Job Demands and Organizational Citizenship Behavior: The Roles of Organizational Commitment and Social Interaction

Drawing from the Job Demands-Resources (JD-R) model and research on social exchange relationships, this study investigates the impact of three job demands (work overload, interpersonal conflict, and dissatisfaction with the organization’s current situation) on employees’ organizational citizenship behavior (OCB), the hitherto unexplored mediating role of organizational commitment in the link between job demands and organizational citizenship behavior (OCB), as well as how this mediating effect might be moderated by social interaction. Using a multi-source, two-wave research design, surveys were administered to 707 employees and their supervisors in a Mexican-based organization. The hypotheses were tested with hierarchical regression analysis. The results indicate a direct negative relationship between interpersonal conflict and OCB, and a mediating effect of organizational commitment for interpersonal conflict and dissatisfaction with the organization’s current situation. Further, social interaction moderates the mediating effect of organizational commitment for each of the three job demands such that the mediating effect is weaker at higher levels of social interaction. The study suggests that organizations aiming to instill OCB among their employees should match the immediate work context surrounding their task execution with an internal environment that promotes informal relationship building.

Teaching Adolescents to Think and Act Responsibly Through Narrative Film-making: A Qualitative Study

The current qualitative study examined an adapted version of the psychoeducational program, Teaching Adolescents to Think and Act Responsibly: The EQUIP Approach (DiBiase, Gibbs, Potter, & Blount, 2012). The adapted version, referred to as the EQUIP – Narrative Filmmaking Program, was implemented as a means of character education. The purpose of this study was three-fold: 1) to examine how the EQUIP – Narrative Film-making Program influenced student’s thoughts, feelings, and behaviours; 2) to explore the students’ and the teacher’s perception of their experience with the program; and 3) to assess whether or not the integrated EQUIP – Narrative Film-making Program addressed the goals of Ontario’s character education initiative. Purposive sampling was used to select one typical Grade 9 Exploring Technologies class, consisting of 15 boys from a Catholic board of education in the southern Ontario region. The EQUIP – Narrative Film-making Program required students to create moral narrative films that first portrayed a set of self-centered cognitive distortions, with follow-up portrayals of behavioural modifications. Before, during, and after intervention questionnaires were administered to the students and teacher. The student questionnaires invited responses to a set of cognitive distortion vignettes. In addition, data was collected through student and teacher interviews, and researcher observation protocol reports. Initially the data was coded according to an a priori set of themes that were further analyzed according to emotion and values coding methods. The results indicated that while each student was unique in his thoughts, feelings, and behavioural responses to the cognitive distortion vignettes after completing the EQUIP program, the overall trends showed students had a more positive attitude, with a decreased proclivity for antisocial behaviour and self-serving cognitive distortion portrayed in the vignettes. Overall, the teacher and students’ learning experiences were mainly positive and the program met the learning expectations of Ontario’s character education initiative. Based on these results of the present study, it is recommended that the EQUIP – Narrative Film-making Program be further evaluated through quantitative research and longitudinal study.

A medical Handbook: for the use of practitioners and students

UANL

Exploring Rac GTPase regulation : the molecular mechanisms governing the DOCK180 and ELMO interaction and the role of this complex in Rac-mediated cell migration

Les protéines DOCK180 et ELMO coopèrent ensemble biochimiquement et génétiquement afin d’activer la GTPase Rac1 lors de plusieurs évènements biologiques. Toutefois, le rôle que jouent ces protéines dans la signalisation par Rac est encore mal compris. Nous émettons l’hypothèse que Dock180 agit comme activateur de Rac, alors que ELMO est requis pour l’intégration de la signalisation de Rac plutôt que son activation per se. Nous postulons que ELMO agit comme signal de localisation intracellulaire afin de restreindre de façon spatio-temporelle la signalisation de Rac en aval de Dock180, et/ou que ELMO agit comme protéine d’échafaudage entre Rac et ses effecteurs pour amplifier la migration cellulaire. Dans l’objectif nº 1, nous démontrons que le domaine PH atypique de ELMO1 est le site d’interaction principal entre cette protéine et DOCK180. De plus, nous démontrons que la liaison entre ELMO et DOCK180 n’est pas nécessaire pour l’activation de Rac, mais est plutôt essentielle pour faciliter la réorganisation du cytosquelette induite par l’activation de Rac en aval de Dock180. Ces résultats impliquent que ELMO pourrait jouer des rôles additionnels dans la signalisation par Rac. Dans l’objectif nº 2, nous avons découvert l’existence d’une homologie structurelle entre ELMO et un module d’autorégulation de la formine Dia1, et avons identifié trois nouveaux domaines dans la protéine ELMO : les domaines RBD, EID et EAD. De façon analogue à Dia1, nous avons découvert que ELMO à l’état basal est autoinhibé grâce à des intéractions intramoléculaires. Nous proposons que l’état d’activation des protéines ELMO est régulé de façon similaire aux formines de la famille Dia, c’est-à-dire grâce à des interactions avec d’autres protéines. Dans l’objectif nº 3, nous identifions un domaine RBD polyvalent chez ELMO. Ce domaine possède une double spécificité pour les GTPases de la famille Rho et Arf. Nous avons découvert que Arl4A agit comme signal de recrutement membranaire pour le module ELMO/DOCK180/Rac. Nos résultats nous permettent de supposer que d’autres GTPases pourraient être impliquées dans l’activation et la localisation de cette voie de signalisation. Nous concluons qu’à l’état basal, ELMO et DOCK180 forment un complexe dans lequel ELMO est dans sa conformation autoinhibée. Bien que le mécanisme d’activation de ELMO ne soit pas encore bien compris, nous avons découvert que, lorsqu’il y a stimulation cellulaire, certaines GTPases liées au GTP peuvent intéragir avec le domaine RBD de ELMO pour relâcher les contacts intramoléculaires et/ou localiser le complexe à la membrane. Ainsi, les GTPases peuvent servir d’ancrage au complexe ELMO/DOCK180 pour assurer une regulation spatiotemporelle adequate de l’activation et de la signalisation de Rac.

The regulatory roles of APE1 and Prdx1 interaction

L’apurinic/apyrimidic endonuclease 1 (APE1) est une protéine multifonctionnelle qui joue un rôle important dans la voie de réparation de l’ADN par excision de base. Elle sert également de coactivateur de transcription et est aussi impliquée dans le métabolisme de l’ARN et la régulation redox. APE1 peut cliver les sites AP ainsi que retirer des groupements, sur des extrémités 3’ créées suite à des bris simple brin, qui bloquent les autres enzymes de réparation, permettant de poursuivre la réparation de l’ADN, puisqu’elle possède plusieurs activités de réparation de l’ADN comme une activité phosphodiestérase 3’ et une activité exonucléase 3’→5’. Les cellules de mammifères ayant subi un knockdown d’APE1 présentent une grande sensibilité face à de nombreux agents génotoxiques. APE1 ne possède qu’une seule cystéine située au 65e acide aminé. Celle-ci est nécessaire pour maintenir l’état de réduction de nombreux activateurs de transcription tels que p53, NF-κB, AP-1, c-Jun at c-Fos. Ainsi, elle se retrouve impliquée dans la régulation de l’expression génique. APE1 passe également à travers au moins 4 types de modifications post-traductionnelles : l’acétylation, la désacétylation, la phosphorylation et l’ubiquitylation. La façon dont APE1 est recrutée pour accomplir ses différentes fonctions biologiques demeure un mystère, bien que cela puisse être relié à sa capacité d’interaction avec de multiples partenaires différents. Sous des conditions de croissance normales, il a été démontré qu’APE1 interagit avec de nombreux partenaires impliqués dans de multiples fonctions. Nous émettons l’hypothèse que l’état d’oxydation d’APE1 est ce qui contrôle les partenaires avec lesquels la protéine interagira, lui permettant d’accomplir des fonctions précises. Dans cette étude nous démontrons que le peroxyde d’hydrogène altère le réseau d’interactions d’APE1. Un nouveau partenaire d’interaction d’APE1, Prdx1, un membre de la famille des peroxirédoxines responsable de récupérer le peroxyde d’hydrogène, est caractérisé. Nous démontrons qu’un knockdown de Prdx1 n’affecte pas l’activité de réparation de l’ADN d’APE1, mais altère sa détection et sa distribution cellulaire à l’intérieur des cellules HepG2 conduisant à une induction accrue de l’interleukine 8 (IL-8). L’IL8 est une chimiokine impliquée dans le stress cellulaire en conditions physiologiques et en cas de stress oxydatif. Il a été démontré que l’induction de l’IL-8 est dépendante d’APE1 indiquant que Prdx1 pourrait réguler l’activité transcriptionnelle d’APE1. Il a été découvert que Prdx1 est impliquée dans la régulation redox suite à une réponse initiée par le peroxyde d’hydrogène. Ce dernier possède un rôle important comme molécule de signalisation dans de nombreux processus biologiques. Nous montrons que Prdx1 est nécessaire pour réduire APE1 dans le cytoplasme en réponse à la présence de H2O2. En présence de Prdx1, la fraction d’APE1 présent dans le cytoplasme est réduite suite à une exposition au peroxyde d’hydrogène, et Prdx1 est hyperoxydé suite à l’interaction entre les deux molécules. Cela suggère que le signal, que produit le peroxyde d’hydrogène, sur APE1 passe par Prdx1. Un knockdown d’APE1 diminue la conversion de la forme dimérique de Prdx1 vers la forme monomérique. Cette observation implique qu’APE1 pourrait être impliquée dans la régulation de l’activité catalytique de Prdx1 en accélérant son hyperoxydation.

The Cold Tongue in the South China Sea during Boreal Winter and Its Interaction with the Atmosphere

A distinct cold tongue has recently been noticed in the South China Sea during the winter monsoon, with the cold tongue temperature minimum occurring in the January or February. This cold tongue shows signi¯cant links with the Maritime Continent's rainfall during the winter period. The cold tongue and its interaction with the Maritime Continent's weather were studied using Reynolds SST data, wind ¯elds from the NCEP{NCAR reanalysis dataset and the quikSCAT dataset. In addition, rainfall from the GOES Precipitation Index (GPI) for the periods 2000 to 2008 was also used. The propagation of the cold tongue towards the south is explained using wind dynamics and the western boundary current. During the period of strong cold tongue, the surface wind is strong and the western boundary current advects the cold tongue to the south. During the period of strong winds the zonal gradient of SST is high [0.5±C (25 km)¡1]. The cold tongue plays an important role in regulating the climate over the Maritime Continent. It creates a zonal/meridional SST gradient and this gradient ultimately leads in the formation of convection. Hence, two maximum precipitation zones are found in the Maritime Continent, with a zone of relatively lower precipitation between, which coincides with the cold tongue's regions. It was found that the precipitation zones have strong links with the intensity of the cold tongue. During stronger cold tongue periods the precipitation on either side of the cold tongue is considerably greater than during weaker cold tongue periods. The features of convection on the eastern and western sides of the cold tongue behave di®erently. On the eastern side convection is preceded by one day with SST gradient, while on the western side it is four days.

Racial and spatial interaction for neighborhood dynamics in Chicago

We look at at the empirical validity of Schelling’s models for racial residential segregation applied to the case of Chicago. Most of the empirical literature has focused exclusively the single neighborhood model, also known as the tipping point model and neglected a multineighborhood approach or a unified approach. The multi-neighborhood approach introduced spatial interaction across the neighborhoods, in particular we look at spatial interaction across neighborhoods sharing a border. An initial exploration of the data indicates that spatial contiguity might be relevant to properly analyse the so call tipping phenomena of predominately non-Hispanic white neighborhoods to predominantly minority neighborhoods within a decade. We introduce an econometric model that combines an approach to estimate tipping point using threshold effects and a spatial autoregressive model. The estimation results from the model disputes the existence of a tipping point, that is a discontinuous change in the rate of growth of the non-Hispanic white population due to a small increase in the minority share of the neighborhood. In addition we find that racial distance between the neighborhood of interest and it surrounding neighborhoods has an important effect on the dynamics of racial segregation in Chicago.

Overcoming difficulties with number : supporting dyscalculia and students who struggle with maths.

El autor subraya la importancia de comenzar con materiales concretos y manipulables, antes de pasar a materiales más simbólicos. Su enseñanza se basa en la comprensión actual del alumno, en lugar de en su rendimiento. Ofrece una gran cantidad de actividades y juegos numéricos con una gran variedad de materiales, incluyendo regletas de Cuisenaire y los dominós de las etapas más tempranas. A medida que los alumnos progresan se introducen razonamientos más complejos. Proporciona métodos muy claros para las áreas donde muchos niños tienen grandes dificultades con el concepto de número. Incluye Un CD-ROM que contiene todos los recursos que se describen en el texto, una versión imprimible de la guía y una lista de actividades para los padres.

Living geography : exciting futures for teachers and students.

Este recurso pensado para los profesores trata de inducir el pensamiento geográfico en los jóvenes y darles a conocer la utilidad del aprendizaje de la geografía. Para lo cual, el docente desafía a los alumnos con preguntas sobre sus vidas, su futuro y cómo están conectadas con otras personas y lugares, en una escala que va desde lo local hasta lo mundial. También, examina como la geografía se presenta en los programas de estudio de educación secundaria sobre la base de una forma de comprender el mundo.