Síntesi de siRNAs (short interfering RNAs) modificats amb nucleobases 5-metil i 5-propinil pirimidíniques i avaluació de la seva activitat in vitro en cultius cel•lulars i de la seva estabilitat en sèrum humà. Disseny de siRNAs dirigits a la inhibició de l'expressió de mutacions de l'oncogen K-ras.

Projecte de recerca elaborat a partir d’una estada a la Stanford University, EEUU, entre 2007 i 2009. El present projecte es basa 1) en la síntesi de cadenes d'ARN dirigides a la inhibició de l'expressió gènica per un mecanisme d'ARN d'interferència (siRNAs o short interefering RNAs) i 2) en l'avaluació de l'activitat in vitro d'aquests oligonucleòtids en cultius cel•lulars. Concretament, la meva recerca ha estat enfocada principalment a l'estudi de cadenes de siRNA modificades amb nucleobases 5-metil i 5-propinil pirimidíniques. Es tractava d'avaluar l'efecte que exerceixen els factors estèrics en el major groove (solc major) dels siRNAs sobre la seva activitat biològica. En aquest sentit, he dut aterme síntesi de fosforamidits de nucleòsis pirimidínics modificats a la posició C-5 de la nucleobase. A continuació he incorporat aquestes unitats nucleosídiques en cadenes d'ARN emprant un sintetitzador d’ADN/ARN i he estudiat l'estabilitat dels corresponents dúplexs d'ARN mitjançant experiments de desnaturalització tèrmica. Finalment he dut a terme experiments d'inhibició de l'expressió gènica en cèl.lules HeLa per tal d'avaluar l'activitat biològia d'aquests siRNAs modificats. Els resultats d'aquests estudis han posat de manifest que la presència de grups voluminosos com el propinil a l'extrem 5' del dúplex de siRNA (definit per la cadena guia o antisense) influeix de forma molt negativa en la seva activitat biològica. En canvi, grups menys voluminosos com el metil hi influeixen positivament, de manera que algunes de les cadenes sintetitzades han resultat ser més actives que els corresponents siRNAs naturals (wild type siRNAs). A més, aquest tipus de modificació contribueix positivament en l'estabilitat de cadenes de siRNA en sèrum humà. Aquest treball ha estat publicat (Terrazas, M.; Kool, E.T. "Major Groove Modifications Improve siRNA Stability and Biological Activity" Nucleic Acids Res. 2009, in press).

Art contemporani xinès en el segle XXI : introducció a la pugna entre la creació i el mercat a través de cinc artistes destacats i les seves cotitzacions en les subhastes

En el relativament breu lapse de temps que suposen les tres darreres dècades, l'art contemporani xinès ha passat de ser pràcticament invisible i desconegut per al públic general, a ser present en un gran nombre d'escenaris a nivell internacional relacionats amb el món de l'art, sobre tot des de finals de la dècada dels noranta. El present TdR ha intentat apropar-se a qüestions com la imatge i les idees que sobre la RP Xina s'han transmès en l'última dècada a través de les obres o de les accions dels artistes xinesos contemporanis més exposats o cotitzats internacionalment i que viuen a la Xina, i a com s'ha arribat a inserir la producció artística d'aquests autors en el procés de globalització i hibridació de la cultura que estem vivint. Hem delimitat el camp de recerca, bàsicament a l'estudi de l'obra de cinc autors (Song Dong, Ai Weiwei, Zeng Fanzhi, Yue Minjun i Wang Qingsong) i a la seva presència en l'escena internacional de l'art contemporani a través de les subhastes de les dues cases més importants del món, Christie's i Sotheby's.

Conversation is the Key : A Short History of Smarthistory.org

Smarthistory.org is a proven, sustainable model for open educational resources in the Humanities. We discuss lessons learned during its agile development. Smarthistory.org is a free, creative-commons licensed, multi-media web-book designed as a dynamic enhancement or substitute for the traditional art history textbook. It uses conversation instead of the impersonal voice of the typical textbook in-order to reveal disagreement, emotion, and the experience of looking. The listener remains engaged with both the content and the interaction of the speakers. These conversations model close looking and a willingness to encounter and engage the unfamiliar. Smarthistory takes the inherent dialogic and multimedia nature of the web and uses it as a pedagogical method. This extendable Humanities framework uses an open-source content management system making Smarthistory inexpensive to create, and easy to manage and update. Its chronological timeline/chapter-based format integrates new contributions into a single historical framework, a structure applicable across the Humanities.

The Quest for the Oracle Birds: Researching the Chinese Community in Colonial Mexico (1565-1700)

The Asian Diaspora in the Americas in the 16th and 17th has been neglected by scholars for a long time. This fact is baffling, not only for the great interest of this topic in of itself, but also because it could provide new knowledge of colonial Mexico, especially in terms of the interaction among the many groups that populated the colony. This early movement of people and ideas across the largest extension of water in the planet is characteristic of what has been called the ¿archaic globalization,¿ and thus research on these matters could contribute to the history of globalization.In this presentation, I seek to further elaborate on the themes outlined by Edward Slack in The Chinos in New Spain: A Corrective Lens for a Distorted Image, an article published in 2009 in the Journal of World History. Firstly, I would like to bring forth some evidence that indicates that Asian religious practices were present in Mexico in the 1600s. Furthermore, I will argue that the traces of these practices are still visible today, in the form of a popular fortune-telling tradition. Secondly, I intend to provide some information about the arrival, settlement and distribution of the Asian Diaspora. I will focus on their distribution within Mexico City. Thirdly, I will elaborate on their occupations, social status and daily life, as well as in the patterns in marriages and relations with other groups. And lastly, I will show how the guild of barbers served as an Asian immigrant reception network.

Time-series regression models to study the short-term effects of environmental factors on health

Time series regression models are especially suitable in epidemiology for evaluating short-term effects of time-varying exposures on health. The problem is that potential for confounding in time series regression is very high. Thus, it is important that trend and seasonality are properly accounted for. Our paper reviews the statistical models commonly used in time-series regression methods, specially allowing for serial correlation, make them potentially useful for selected epidemiological purposes. In particular, we discuss the use of time-series regression for counts using a wide range Generalised Linear Models as well as Generalised Additive Models. In addition, recently critical points in using statistical software for GAM were stressed, and reanalyses of time series data on air pollution and health were performed in order to update already published. Applications are offered through an example on the relationship between asthma emergency admissions and photochemical air pollutants

El sector hotelero en China : el fenómeno "low cost" en la nueva clase urbana

Aquest treball es justifica per la complementarietat que, d'una banda ofereix el potencial i volum d'un mercat en plena efervescència com és l'àmbit urbà de la Xina, on el seu incipient maduresa, com a conseqüència de l'efecte d'arrossegament que la inversió estrangera - intensa i innovadora - ha provocat, facilitant l'aparició d'una demanda d'un nivell superior, no primària, com les activitats emmarcades en el lleure i el turisme. D'altra banda, per una proposta de negoci dins d'un sector amb grans expectatives de desenvolupament com és el turístic i, finalment, també per l'opció d'un consum basat en el factor preu, amb unes característiques socioeconòmiques determinades de demanda, i en què la societat urbana de la Xina ja comença a veure's reflectida. Més enllà del paper tradicional de la Xina com a procés avantatjós dins de la cadena productiva o com a mercat d'outputs de volum, es dibuixa una nova classe mitjana urbana, inserint-se de ple i en molt poc temps en les dinàmiques de consum global, recolzada en les noves tecnologies - on el procés productiu low cost basa gran part del seu desenvolupament -.

The History of the European Union (Chinese version)

Descriu i analitza el procés d'integració europea des dels seus inicis, els anys cinquanta, fins als nostres dies. L'objectiu consisteix a oferir una visió de conjunt d'un procés que va començar modestament amb la integració dels mercats del carbó i de l'acer dels sis membres fundadors i que ha derivat en una Unió Europea de 27 estats membres i més de 500 milions d'habitants, amb polítiques comunes, una cooperació estreta en els àmbits més sensibles de la sobirania estatal i una moneda única en setze estats

Islands of euchromatin-like sequence and expressed polymorphic sequences within the short arm of human chromosome 21

The goals of the human genome project did not include sequencing of the heterochromatic regions. We describe here an initial sequence of 1.1 Mb of the short arm of human chromosome 21 (HSA21p), estimated to be 10% of 21p. This region contains extensive euchromatic-like sequence and includes on average one transcript every 100 kb. These transcripts show multiple inter- and intrachromosomal copies, and extensive copy number and sequence variability. The sequencing of the "heterochromatic" regions of the human genome is likely to reveal many additional functional elements and provide important evolutionary information.

A short motif in Drosophila SECIS Binding Protein 2 provides differential binding affinity to SECIS RNA hairpins

Selenoproteins contain the amino acid selenocysteine which is encoded by a UGA Sec codon. Recoding UGA Sec requires a complex mechanism, comprising the cis-acting SECIS RNA hairpin in the 3′UTR of selenoprotein mRNAs, and trans-acting factors. Among these, the SECIS Binding Protein 2 (SBP2) is central to the mechanism. SBP2 has been so far functionally characterized only in rats and humans. In this work, we report the characterization of the Drosophila melanogaster SBP2 (dSBP2). Despite its shorter length, it retained the same selenoprotein synthesis-promoting capabilities as the mammalian counterpart. However, a major difference resides in the SECIS recognition pattern: while human SBP2 (hSBP2) binds the distinct form 1 and 2 SECIS RNAs with similar affinities, dSBP2 exhibits high affinity toward form 2 only. In addition, we report the identification of a K (lysine)-rich domain in all SBP2s, essential for SECIS and 60S ribosomal subunit binding, differing from the well-characterized L7Ae RNA-binding domain. Swapping only five amino acids between dSBP2 and hSBP2 in the K-rich domain conferred reversed SECIS-binding properties to the proteins, thus unveiling an important sequence for form 1 binding.

The short arm of the law: judicial institutions and local governance in Brazil

This paper estimates the effect of judicial institutions on governance at the local level in Brazil. Our estimation strategy exploits a unique institutional feature of state judiciary branches which assigns prosecutors and judges to the most populous among contiguous counties forming a judiciary district. As a result of this assignment mechanism there are counties with nearly identical populations, some with and some without local judicial presence, which we exploit to impute counterfactual outcomes. Conditional on observable county characteristics, offenses per civil servant are about 35% lower in counties that have a local seat of the state judiciary. The lower incidence of infractions stems mostly from fewer violations of financial management regulations by local administrators, fewer instances of problems in project execution and project managment, fewer cases of non-existent or ineffective civil society oversight and fewer cases of improper handling of remittances to local residents.

On the closed-form approximation of short-time random strike options

In this paper we propose a general technique to develop first and second order closed-form approximation formulas for short-time options withrandom strikes. Our method is based on Malliavin calculus techniques andallows us to obtain simple closed-form approximation formulas dependingon the derivative operator. The numerical analysis shows that these formulas are extremely accurate and improve some previous approaches ontwo-assets and three-assets spread options as Kirk's formula or the decomposition mehod presented in Alòs, Eydeland and Laurence (2011).

Portfolio delegation under short-selling constraints

In this paper we study delegated portfolio management when themanager's ability to short-sell is restricted. Contrary to previousresults, we show that under moral hazard, linear performance-adjustedcontracts do provide portfolio managers with incentives to gatherinformation. The risk-averse manager's optimal effort is an increasingfunction of her share in the portfolio's return. This result affectsthe risk-averse investor's optimal contract decision. The first best,purely risk-sharing contract is proved to be suboptimal. Usingnumerical methods we show that the manager's share in the portfolioreturn is higher than the rst best share. Additionally, this deviationis shown to be: (i) increasing in the manager's risk aversion and (ii)larger for tighter short-selling restrictions. When the constraint isrelaxed the optimal contract converges towards the first best risksharing contract.

Short-term investment and equilibrium multiplicity

I study the effects of the heterogeneity of traders'horizon in the context of a 2-period NREE model whereall traders are risk averse. Owing to inventory effects,myopic trading behavior generates multiplicity ofequilibria. In particular, two distinct patterns arise.Along the first equilibrium, short term tradersanticipate higher second period price reaction toinformation arrival and, owing to risk aversion,scale back their trading intensity. This, in turn,reduces both risk sharing and information impoundinginto prices enforcing a high returns' volatility-lowprice informativeness equilibrium. In the second one,the opposite happens and a low volatility-high priceinformativeness equilibrium arises.