Multifunctional ligands for application in Alzheimer’s Disease: molecular modelling and biological evaluation

Projecte de recerca elaborat a partir d’una estada a la University of British Columbia, Canadà, entre 2010 i 2012 La malaltia d'Alzheimer (MA) representa avui la forma més comuna de demència en la població envellida. Malgrat fa 100 anys que va ser descoberta, encara avui no existeix cap tractament preventiu i/o curatiu ni cap agent de diagnòstic que permeti valorar quantitativament l'evolució d'aquesta malaltia. L'objectiu en el que s'emmarca aquest treball és contribuir a aportar solucions al problema de la manca d'agents terapèutics i de diagnosi, unívocs i rigorosos, per a la MA. Des del camp de la química bioinorgànica és fàcil fixar-se en l'excessiva concentració d'ions Zn(II) i Cu(II) en els cervells de malalts de MA, plantejar-se la seva utilització com a dianes terapèutica i, en conseqüència, cercar agents quelants que evitin la formació de plaques senils o contribueixin a la seva dissolució. Si bé aquest va ser el punt de partida d’aquest projecte, els múltiples factors implicats en la patogènesi de la MA fan que el clàssic paradigma d’ ¨una molècula, una diana¨ limiti la capacitat de la molècula de combatre aquesta malaltia tan complexa. Per tant, un esforç considerable s’ha dedicat al disseny d’agentsmultifuncionals que combatin els múltiples factors que caracteritzen el desenvolupament de la MA. En el present treball s’han dissenyat agents multifuncionals inspirats en dos esquelets moleculars ben establers i coneguts en el camp de la química medicinal: la tioflavina-T (ThT) i la deferiprona (DFP). La utilització de tècniques in silico que inclouen càlculs farmacocinètics i modelatge molecular ha estat un procés cabdal per a l’avaluació dels millors candidats en base als següents requeriments: (a) compliment de determinades propietats farmacocinètiques que estableixin el seu possible ús com a fàrmac (b) hidrofobicitat adequada per travessar la BBB i (c) interacció amb el pèptid Aen solució.

Arnau de Montrodon y la catedral de San Carlomagno. Sobre la imagen y el culto al emperador carolingio en Gerona

In 1345, the unique worship of Saint Charlemagne was institutionalized in the cathedral of Gerona. The roots (and for many, the reasons) of this celebration are found in the existence of an old local legend, the well-known testimonies to which go back to the eleventh century. Nevertheless, a lengthy analysis of the facts that marked the life of the cathedral during the long permanence Amau de Montrodon had there—first in quality of canon (1297-1335) and later as bishop (1333-1348)- make it possible for us to verify that the promotion of the cult to San Charlemagne falls within a complex program of ideological and symbolic exaltation of the See of Girona that was designed by this notable and restlessly active ecclesiastic

Unstable equilibrium: young adult women in family and career formation in Southern Europe

The paper examines the relationship between family formation (i.e., living with a partner and having children) and women’s occupational career in southern Europe (i.e., Greece, Italy, Portugal and Spain). The relationship is explored by analysing the impact that different family structures and male [nvolvement in caring activities have on women’s early occupational trajectories (i.e., remaining in the same occupational status, experiencing downward or upward mobility, or withdrawing from paid work). This research shows that male involvement in caring activities does not really push women ahead in their career, but the absolute lack of male support seems to negatively affect women’s permanence in paid work. These results apply to all southern European countries except Portugal, where the absolute absence of the partners’ support in caring activities does not seem to alter women’s determination to remain in paid work. The methodology applied consists of the estimation of multinomial logit regression models and the analysis is based on eight waves (1994-2001) of the European Community Household Panel (ECHP).

What made him change? an individual and national analysis of men's participation in housework in 26 countries

We offer new evidence on multi-level determinants of the gender division of housework. Using data from the 2004 European Social Survey (ESS) for 26 European, we study the micro and macro-level factors which increase the likelihood of men doing an equal or greater share of housework than their female partners. A sample of 11,915 young men and women is analysed with a multi-level logistic regression in order to test at individual level the classic relative-income, time-availability and gender-role values, and a new couple conflict hypothesis. At individual level we find significant relationships between relative resources, values, couple's disagreement, and the division of housework which support more economic dependency than "doing gender" perspectives. At the macro-level, we find important composition effects and also support for gender empowerment, family model and social stratification explanations of cross-country differences.

When mothers work and fathers care. Joint household fertility decisions in Denmark and Spain

We analyze second birth decisions within the theoretical framework of joint household decision making, comparing two countires that represent the international extremes in terms of women's career behaviour, Denmark and Spain. Using all 8 ECHP panels we apply discrete time estimations of the likelihood of a second birth and show that in Spain, fertility behaviour continues to conform to the classic "Becker model" while in Denmark we identify a radically new behavioral pattern according to which career-women's fertility is conditional of their partners' contribution to care for the children.

Red Bull

The aim of this project is to analyze the Red Bull company in order to find out its major potentialities and weaknesses using the concepts and tools learnt in the subject "Dirección Comercial I". To this end we have focused our attention in the Red Bull classic drink, so as to see how the enterprise has positioned its product in the market and the implications it has had.

Financial Development, Financial Fragility, and Growth

This paper studies the apparent contradiction between two strands of the literature on the effects of financial intermediation on economic activity. On the one hand, the empirical growth literature finds a positive effect of financial depth as measured by, for instance, private domestic credit and liquid liabilities (e.g., Levine, Loayza, and Beck 2000). On the other hand, the banking and currency crisis literature finds that monetary aggregates, such as domestic credit, are among the best predictors of crises and their related economic downturns (e.g., Kaminski and Reinhart 1999). The paper accounts for these contrasting effects based on the distinction between the short- and long-run impacts of financial intermediation. Working with a panel of cross-country and time-series observations, the paper estimates an encompassing model of short- and long-run effects using the Pooled Mean Group estimator developed by Pesaran, Shin, and Smith (1999). The conclusion from this analysis is that a positive long-run relationship between financial intermediation and output growth co-exists with a, mostly, negative short-run relationship. The paper further develops an explanation for these contrasting effects by relating them to recent theoretical models, by linking the estimated short-run effects to measures of financial fragility (namely, banking crises and financial volatility), and by jointly analyzing the effects of financial depth and fragility in classic panel growth regressions.

Interpretación versus ejecución : redescubriendo el lenguaje de la música

Interpretación versus Ejecución es un proyecto que pretende sentar las bases para el planteamiento de una versión propia e informada de obras de diferentes estilos musicales. Se presta especial atención a las prácticas propias de cada estilo – barroco, clásico, romántico y contemporáneo - y su posible aplicación con la flauta moderna en cuatro obras concretas. La metodología empleada ha consistido en la búsqueda de información en tratados, libros, artículos, así como entrevistas y clases con músicos expertos en cada uno de los temas. El proyecto pretende impulsar el interés del joven músico por una búsqueda personal e informada de las prácticas interpretativas que redunde en una interpretación propia de las obras que desee tocar.

La heroína trágica en la ópera : personajes femeninos de la tragèdie lyrique y el dramma per musica

El antiguo arte de la tragedia griega volvió a revivir entre las décadas de 1570 y 1580 gracias a la Camerata Florentina, que la convirtió en el punto de partida de un nuevo género: la opera. El gran interés del Renacimiento por revivir el drama del mundo clásico trae como consecuencia el nacimiento de la protagonista de nuestro estudio: la heroína trágica operística. El objetivo del proyecto es el análisis de los personajes femeninos de la tragedia clásica y su posterior conversión en heroínas de las óperas de inspiración clásica. La literatura griega creó una serie de personajes femeninos que adquirieron un protagonismo inusitado en la época y que, posteriormente, cautivaron a los compositores de ópera. A través de esta investigación trataremos de hallar las razones históricas, sociales, políticas o psicológicas que están detrás del origen de la heroína trágica. Igualmente se estudiarán las diversas características que fue desarrollando y que la definirían como personaje hasta que el mundo operístico la convirtió en la protagonista absoluta de la escena lírica.

Influència dels desitjos, les necessitats i les xarxes familiars i d’amistat dels estudiants universitaris de la UAB en els seus itineraris formatius en els estudis superiors

L’objectiu del treball és ajudar a la descripció del fenomen del canvi en els itineraris formatius superiors dels estudiants. L’anàlisi es realitza a partir de dades empíriques generades a la UAB durant l’any 2012 i en base als factors contextuals – socio-demogràfics, de perfil i context de l’estudiant – i motivacionals – de vocació acadèmica, vocació laboral, resultats acadèmics, condicions facilitadores, condicions d’empleabilitat, condicions econòmiques, influència de les amistats, estratègies adaptatives o d’oportunitat – que influeixen en les decisions de canvi dels estudiants. En les conclusions es reflexiona sobre les polítiques orientades a mantenir l’equitat en l’accés i en la permanència dels estudiants.

Financial development, financial fragility and growth

This paper studies the apparent contradiction between two strands of the literature on the effects of financial intermediation on economic activity. On the one hand, the empirical growth literature finds a positive effect of financial depth as measured by, for instance, private domestic credit and liquid liabilities (e.g., Levine, Loayza, and Beck 2000). On the other hand, the banking and currency crisis literature finds that monetary aggregates, such as domestic credit, are among the best predictors of crises and their related economic downturns (e.g., Kaminski and Reinhart 1999). The paper accounts for these contrasting effects based on the distinction between the short- and long-run impacts of financial intermediation. Working with a panel of cross-country and time-series observations, the paper estimates an encompassing model of short- and long-run effects using the Pooled Mean Group estimator developed by Pesaran, Shin, and Smith (1999). The conclusion from this analysis is that a positive long-run relationship between financial intermediation and output growth co-exists with a, mostly, negative short-run relationship. The paper further develops an explanation for these contrasting effects by relating them to recent theoretical models, by linking the estimated short-run effects to measures of financial fragility(namely, banking crises and financial volatility), and by jointly analyzing the effects of financial depth and fragility in classic panel growth regressions.

Tobin meets Oates: Solidarity and the optimal fiscal federal structure

We explore the implications for the optimal degree of fiscal decentralization when people spreferences for goods and services, which classic treatments of fiscal federalism (Oates, 1972)place in the purview of local governments, exhibit specific egalitarianism (Tobin, 1970), orsolidarity. We find that a system in which the central government provides a common minimumlevel of the publicly provided good, and local governments are allowed to use their ownresources to provide an even higher local level, performs better from an efficiency perspectiverelative to all other systems analyzed for a relevant range of preferences over solidarity.

Periodic Solutions in Low-Dimensional Climatic Models

Classic climatic models use constitutive laws without any response time. A more realistic approach to the natural processes governing climate dynamics must introduce response time for heat and radiation fluxes. Extended irreversible thermodynamics (EIT) is a good thermodynamical framework for introducing nonclassical constitutive laws. In the present study EIT has been used to analyze a Budyko–Sellers one-dimensional energybalance model developed by G. R. North. The results present self-sustained periodic oscillations when the response time is greater than a critical value. The high-frequency (few kiloyears) damped and nondamped oscillations obtained can be related to abrupt climatic changes without any variation in the external forcing of the system

Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1.

The ability to regulate specific genes of energy metabolism in response to fasting and feeding is an important adaptation allowing survival of intermittent food supplies. However, little is known about transcription factors involved in such responses in higher organisms. We show here that gene expression in adipose tissue for adipocyte determination differentiation dependent factor (ADD) 1/sterol regulatory element binding protein (SREBP) 1, a basic-helix-loop-helix protein that has a dual DNA-binding specificity, is reduced dramatically upon fasting and elevated upon refeeding; this parallels closely the regulation of two adipose cell genes that are crucial in energy homeostasis, fatty acid synthetase (FAS) and leptin. This elevation of ADD1/SREBP1, leptin, and FAS that is induced by feeding in vivo is mimicked by exposure of cultured adipocytes to insulin, the classic hormone of the fed state. We also show that the promoters for both leptin and FAS are transactivated by ADD1/SREBP1. A mutation in the basic domain of ADD1/SREBP1 that allows E-box binding but destroys sterol regulatory element-1 binding prevents leptin gene transactivation but has no effect on the increase in FAS promoter function. Molecular dissection of the FAS promoter shows that most if not all of this action of ADD1/SREBP1 is through an E-box motif at -64 to -59, contained with a sequence identified previously as the major insulin response element of this gene. These results indicate that ADD1/SREBP1 is a key transcription factor linking changes in nutritional status and insulin levels to the expression of certain genes that regulate systemic energy metabolism.

Towards a theory of the credit-risk balance sheet

This article designs what it calls a Credit-Risk Balance Sheet (the risk being that of default by customers), a tool which, in principle, can contribute to revealing, controlling and managing the bad debt risk arising from a company¿s commercial credit, whose amount can represent a significant proportion of both its current and total assets.To construct it, we start from the duality observed in any credit transaction of this nature, whose basic identity can be summed up as Credit = Risk. ¿Credit¿ is granted by a company to its customer, and can be ranked by quality (we suggest the credit scoring system) and ¿risk¿ can either be assumed (interiorised) by the company itself or transferred to third parties (exteriorised).What provides the approach that leads to us being able to talk with confidence of a real Credit-Risk Balance Sheet with its methodological robustness is that the dual vision of the credit transaction is not, as we demonstrate, merely a classificatory duality (a double risk-credit classification of reality) but rather a true causal relationship, that is, a risk-credit causal duality.Once said Credit-Risk Balance Sheet (which bears a certain structural similarity with the classic net asset balance sheet) has been built, and its methodological coherence demonstrated, its properties ¿static and dynamic¿ are studied.Analysis of the temporal evolution of the Credit-Risk Balance Sheet and of its applications will be the object of subsequent works.