THE ADULA NAPPE: STRATIGRAPHY, STRUCTURE AND KINEMATICS OF AN EXHUMED HIGH-PRESSURE NAPPE

This study analyses the stratigraphy, structure and kinematics of the northern part of the Adula nappe of the Central Alps. The Adula nappe is one of the highest basement nappes in the Lower Penninic nappe stack of the Lepontine Dome. This structural position makes possible the investigation of the transition between the Helvetic and North Penninic paleogeographic domains. The Adula nappe is principally composed of crystalline basement rocks. The investigation of the pre-Triassic basement shows that it contains several Palaeozoic detrital metasedimentary formations dated from the Cambrian to the Ordovician. These formations contain also some volcanic or intrusive magmatic rocks. Ordovician metagranites dated at ~450 Ma are also a common rock-type of the Adula basement. These formations underwent Alpine and Variscan deformation and metamorphism. Permian granites (Zervreila orthogneiss, dated at ~290 Ma) have intruded this pre-structured basement in a post-orogenic geodynamic context. Due to their age, the Zervreila orthogneiss are good markers for alpine deformation. The stratigraphy of the Mesozoic and Paleogene sedimentary cover of the Adula nappe is essential to unraveling its pre- orogenic history. The autochthonous cover is assigned to a North Penninic Triassic series that testifies for a transition between the Helvetic and Briançonnais Triassic domains. The Adula domain goes through an emersion during the Middle Jurassic, and is part of a topographic high during the first phase of the Alpine rift. The sediments of the late Middle Jurassic show a drowning phase associated with a tectonic activity and a breccia formation. In the neighbouring domains, coeval with the drowning phase in the Adula domain, a strong extensional crustal delamination and a scattered magmatic activity is associated with the main opening of the North Penninic domain. The Upper Jurassic of the Adula nappe is characterized by a carbonate formation comparable with those in the Helvetic or Subbriaçonnais domains. Flysch s.l. deposition starts probably at the end of the Cretaceous. These sediments are deposited on a large unconformity testifying for a Cretaceous sedimentary gap. The Adula nappe exhibits a very complex structure. This structure is formed by several deformation phases. Two ductile deformations are responsible for the nappe emplacement. The first deformation phase is associated with a folding compatible with a top-to-south movement at the top of the nappe. The second phase is dominant and pervasive throughout the whole nappe. It goes with a strong north vergent folding and the main nappe emplacement. These two phases cause the exhumation and emplacement of a coherent, although pre-structured, piece of continental crust. Two further deformation phases postdate the nappe emplacement. - Ce travail concerne l'étude géologique de la partie nord de la nappe de l'Adula dans les Alpes centrales. La nappe de l'Adula est l'une des nappes cristallines la plus élevée dans la pile des nappes du Pennique inférieur des Alpes lepontines. Cette position particulière permet d'étudier la transition entre les nappes des domaines helvétique et pennique inférieur. La nappe de l'Adula est principalement composée de socle cristallin : l'étude de l'histoire géologique du socle est donc l'un des thèmes de cette recherche. Ce socle contient plusieurs formations métasédimentaires paléozoïques du Cambrien à I'Ordovicien. Ces métasédiments sont issus de formations clastiques comprenant souvent des roches magmatiques volcaniques et intrusives. Ces métasédiments ont subi les cycles orogéniques varisque et alpin. La nappe de l'Adula contient plusieurs corps magmatiques granitiques métamorphisés. Les premiers métagranites sont Ordovicien et témoignent d'un environnement de marge active. Ces granites sont aussi polymétamorphiques. Les deuxièmes métagranites sont représentés par les orthogneiss de type Zervreila. Ce métagranite est d'âge permien (-290 Ma). Il est mis en place dans un contexte tectonique post-orogénique. Ce granite est un maqueur de la déformation alpine car il n'est pas affecté par les orogenèses précédentes, flippy Le contenu stratigraphique des roches mésozoïques et cénozoiques de la couverture sédimentaire de la nappe de l'Adula est'important pour en étudier son histoire pré-alpine. La couverture autochtone est composée d'une série d'âge triasique d'affinité nord-pennique, un faciès qui marque la transition entre les domaines helvétiques et briançonnais au Trias. Le domaine paléogéographique représenté dans la nappe de l'Adula connaît une émersion pendant le Jurassique moyen. Cette émersion marque le commencement du rift dans le domaine alpin. La sédimentation de la fin du Jurassique moyen est marquée par une transgression marine accompagnée par des mouvements tectoniques et la formation d'une brèche. Cette transgression est contemporaine des importants mouvements tectoniques et des manifestations magmatiques dans les unités voisines qui marquent la phase principale d'ouverture du bassin nord-pennique. Le Jurassique supérieur est caractérisé par l'instauration d'une sédimentation carbonatée comparable à celle du domaine helvétique ou subbriançonnais. Une sédimentation flyschoïde, probablement du Crétacé à Tertiaire, est déposée sur une importante discordance qui témoigne d'une lacune au Crétacé. La structure complexe de la nappe de l'Adula témoigne de nombreuses phases de déformation. Ces phases de déformation sont en partie issues de la mise en place de la nappe et de déformations plus tardives. La mise en place de la nappe produit deux phases de déformation ductile : la première produit un plissement compatible avec un cisaillement top-vers-le sud dans la partie supérieure de la nappe; la deuxième produit un intense plissement qui accompagne la mise en place de la nappe vers le nord. Ces deux phases de déformation témoignent d'un mécanisme d'exhumation par déformation ductile d'un bloc cohérent.

Chroma binary similarity and local alignment applied to cover song identification

We present a new technique for audio signal comparison based on tonal subsequence alignment and its application to detect cover versions (i.e., different performances of the same underlying musical piece). Cover song identification is a task whose popularity has increased in the Music Information Retrieval (MIR) community along in the past, as it provides a direct and objective way to evaluate music similarity algorithms.This article first presents a series of experiments carried outwith two state-of-the-art methods for cover song identification.We have studied several components of these (such as chroma resolution and similarity, transposition, beat tracking or Dynamic Time Warping constraints), in order to discover which characteristics would be desirable for a competitive cover song identifier. After analyzing many cross-validated results, the importance of these characteristics is discussed, and the best-performing ones are finally applied to the newly proposed method. Multipleevaluations of this one confirm a large increase in identificationaccuracy when comparing it with alternative state-of-the-artapproaches.

Development of Abutment Design Standards for Local Bridge Designs, Volume 1 of 3, Development of Design Methodology, August 2004

Several superstructure design methodologies have been developed for low volume road bridges by the Iowa State University Bridge Engineering Center. However, to date no standard abutment designs have been developed. Thus, there was a need to establish an easy to use design methodology in addition to generating generic abutment standards and other design aids for the more common substructure systems used in Iowa. The final report for this project consists of three volumes. The first volume (this volume) summarizes the research completed in this project. A survey of the Iowa County Engineers was conducted from which it was determined that while most counties use similar types of abutments, only 17 percent use some type of standard abutment designs or plans. A literature review revealed several possible alternative abutment systems for future use on low volume road bridges in addition to two separate substructure lateral load analysis methods. These consisted of a linear and a non-linear method. The linear analysis method was used for this project due to its relative simplicity and the relative accuracy of the maximum pile moment when compared to values obtained from the more complex non-linear analysis method. The resulting design methodology was developed for single span stub abutments supported on steel or timber piles with a bridge span length ranging from 20 to 90 ft and roadway widths of 24 and 30 ft. However, other roadway widths can be designed using the foundation design template provided. The backwall height is limited to a range of 6 to 12 ft, and the soil type is classified as cohesive or cohesionless. The design methodology was developed using the guidelines specified by the American Association of State Highway Transportation Officials Standard Specifications, the Iowa Department of Transportation Bridge Design Manual, and the National Design Specifications for Wood Construction. The second volume introduces and outlines the use of the various design aids developed for this project. Charts for determining dead and live gravity loads based on the roadway width, span length, and superstructure type are provided. A foundation design template was developed in which the engineer can check a substructure design by inputting basic bridge site information. Tables published by the Iowa Department of Transportation that provide values for estimating pile friction and end bearing for different combinations of soils and pile types are also included. Generic standard abutment plans were developed for which the engineer can provide necessary bridge site information in the spaces provided. These tools enable engineers to design and detail county bridge substructures more efficiently. The third volume provides two sets of calculations that demonstrate the application of the substructure design methodology developed in this project. These calculations also verify the accuracy of the foundation design template. The printouts from the foundation design template are provided at the end of each example. Also several tables provide various foundation details for a pre-cast double tee superstructure with different combinations of soil type, backwall height, and pile type.

Development of Abutment Design Standards for Local Bridge Designs, Volume 3 of 3, Verification of Design Methodology, August 2004

Several superstructure design methodologies have been developed for low volume road bridges by the Iowa State University Bridge Engineering Center. However, to date no standard abutment designs have been developed. Thus, there was a need to establish an easy to use design methodology in addition to generating generic abutment standards and other design aids for the more common substructure systems used in Iowa. The final report for this project consists of three volumes. The first volume summarizes the research completed in this project. A survey of the Iowa County Engineers was conducted from which it was determined that while most counties use similar types of abutments, only 17 percent use some type of standard abutment designs or plans. A literature review revealed several possible alternative abutment systems for future use on low volume road bridges in addition to two separate substructure lateral load analysis methods. These consisted of a linear and a non-linear method. The linear analysis method was used for this project due to its relative simplicity and the relative accuracy of the maximum pile moment when compared to values obtained from the more complex non-linear analysis method. The resulting design methodology was developed for single span stub abutments supported on steel or timber piles with a bridge span length ranging from 20 to 90 ft and roadway widths of 24 and 30 ft. However, other roadway widths can be designed using the foundation design template provided. The backwall height is limited to a range of 6 to 12 ft, and the soil type is classified as cohesive or cohesionless. The design methodology was developed using the guidelines specified by the American Association of State Highway Transportation Officials Standard Specifications, the Iowa Department of Transportation Bridge Design Manual, and the National Design Specifications for Wood Construction. The second volume introduces and outlines the use of the various design aids developed for this project. Charts for determining dead and live gravity loads based on the roadway width, span length, and superstructure type are provided. A foundation design template was developed in which the engineer can check a substructure design by inputting basic bridge site information. Tables published by the Iowa Department of Transportation that provide values for estimating pile friction and end bearing for different combinations of soils and pile types are also included. Generic standard abutment plans were developed for which the engineer can provide necessary bridge site information in the spaces provided. These tools enable engineers to design and detail county bridge substructures more efficiently. The third volume (this volume) provides two sets of calculations that demonstrate the application of the substructure design methodology developed in this project. These calculations also verify the accuracy of the foundation design template. The printouts from the foundation design template are provided at the end of each example. Also several tables provide various foundation details for a pre-cast double tee superstructure with different combinations of soil type, backwall height, and pile type.

Development of Abutment Design Standards for Local Bridge Designs, Volume 2 of 3, Design Manual, August 2004

Several superstructure design methodologies have been developed for low volume road bridges by the Iowa State University Bridge Engineering Center. However, to date no standard abutment designs have been developed. Thus, there was a need to establish an easy to use design methodology in addition to generating generic abutment standards and other design aids for the more common substructure systems used in Iowa. The final report for this project consists of three volumes. The first volume summarizes the research completed in this project. A survey of the Iowa County Engineers was conducted from which it was determined that while most counties use similar types of abutments, only 17 percent use some type of standard abutment designs or plans. A literature review revealed several possible alternative abutment systems for future use on low volume road bridges in addition to two separate substructure lateral load analysis methods. These consisted of a linear and a non-linear method. The linear analysis method was used for this project due to its relative simplicity and the relative accuracy of the maximum pile moment when compared to values obtained from the more complex non-linear analysis method. The resulting design methodology was developed for single span stub abutments supported on steel or timber piles with a bridge span length ranging from 20 to 90 ft and roadway widths of 24 and 30 ft. However, other roadway widths can be designed using the foundation design template provided. The backwall height is limited to a range of 6 to 12 ft, and the soil type is classified as cohesive or cohesionless. The design methodology was developed using the guidelines specified by the American Association of State Highway Transportation Officials Standard Specifications, the Iowa Department of Transportation Bridge Design Manual, and the National Design Specifications for Wood Construction. The second volume (this volume) introduces and outlines the use of the various design aids developed for this project. Charts for determining dead and live gravity loads based on the roadway width, span length, and superstructure type are provided. A foundation design template was developed in which the engineer can check a substructure design by inputting basic bridge site information. Tables published by the Iowa Department of Transportation that provide values for estimating pile friction and end bearing for different combinations of soils and pile types are also included. Generic standard abutment plans were developed for which the engineer can provide necessary bridge site information in the spaces provided. These tools enable engineers to design and detail county bridge substructures more efficiently. The third volume provides two sets of calculations that demonstrate the application of the substructure design methodology developed in this project. These calculations also verify the accuracy of the foundation design template. The printouts from the foundation design template are provided at the end of each example. Also several tables provide various foundation details for a pre-cast double tee superstructure with different combinations of soil type, backwall height, and pile type.

Testing for local adaptation in brown trout using reciprocal transplants.

ABSTRACT: BACKGROUND: Local adaptation can drive the divergence of populations but identification of the traits under selection remains a major challenge in evolutionary biology. Reciprocal transplant experiments are ideal tests of local adaptation, yet rarely used for higher vertebrates because of the mobility and potential invasiveness of non-native organisms. Here, we reciprocally transplanted 2500 brown trout (Salmo trutta) embryos from five populations to investigate local adaptation in early life history traits. Embryos were bred in a full-factorial design and raised in natural riverbeds until emergence. Customized egg capsules were used to simulate the natural redd environment and allowed tracking the fate of every individual until retrieval. We predicted that 1) within sites, native populations would outperform non-natives, and 2) across sites, populations would show higher performance at 'home' compared to 'away' sites. RESULTS: There was no evidence for local adaptation but we found large differences in survival and hatching rates between sites, indicative of considerable variation in habitat quality. Survival was generally high across all populations (55% +/- 3%), but ranged from 4% to 89% between sites. Average hatching rate was 25% +/- 3% across populations ranging from 0% to 62% between sites. CONCLUSION: This study provides rare empirical data on variation in early life history traits in a population network of a salmonid, and large-scale breeding and transplantation experiments like ours provide powerful tests for local adaptation. Despite the recently reported genetic and morphological differences between the populations in our study area, local adaptation at the embryo level is small, non-existent, or confined to ecological conditions that our experiment could not capture.

Symbolic meaning of local identity – A case study on Barcelona place brand representation

The core objective of this research process was to design an operational tool for place brand analysis. By modelling the emotional significance and the deeper-lying symbols associated to a specific place identity I expected to create a semiotic tool that could be applied, mutatis mutandis, on other similar place brands. As a field case study to develop the instrument, my choice of the research arena was Barcelona city, the capital of Catalonia Autonomous Community, Spain. Barcelona brand identity was approached in the line of the Chicago Urban Anthropology School. The research methods were designed according to the prescriptions of the urban anthropology, namely qualitative methods: in-depth interviews and discourse analysis. The final research outcome was a model summarizing a range of specific emotional values that support a place brand to position in the collective mindset and to assume a positively valued status and identity in the world order.

Repeated exposure to Lutzomyia intermedia sand fly saliva induces local expression of interferon-inducible genes both at the site of injection in mice and in human blood.

During a blood meal, Lutzomyia intermedia sand flies transmit Leishmania braziliensis, a parasite causing tegumentary leishmaniasis. In experimental leishmaniasis, pre-exposure to saliva of most blood-feeding sand flies results in parasite establishment in absence of any skin damages in mice challenged with dermotropic Leishmania species together with saliva. In contrast, pre-immunization with Lu. intermedia salivary gland sonicate (SGS) results in enhanced skin inflammatory exacerbation upon co-inoculation of Lu. intermedia SGS and L. braziliensis. These data highlight potential unique features of both L. braziliensis and Lu. intermedia. In this study, we investigated the genes modulated by Lu. intermedia SGS immunization to understand their potential impact on the subsequent cutaneous immune response following inoculation of both SGS and L. braziliensis. The cellular recruitment and global gene expression profile was analyzed in mice repeatedly inoculated or not with Lu. intermedia. Microarray gene analysis revealed the upregulation of a distinct set of IFN-inducible genes, an immune signature not seen to the same extent in control animals. Of note this INF-inducible gene set was not induced in SGS pre-immunized mice subsequently co-inoculated with SGS and L. braziliensis. These data suggest the parasite prevented the upregulation of this Lu. intermedia saliva-related immune signature. The presence of these IFN-inducible genes was further analyzed in peripheral blood mononuclear cells (PBMCs) sampled from uninfected human individuals living in a L. braziliensis-endemic region of Brazil thus regularly exposed to Lu. intermedia bites. PBMCs were cultured in presence or absence of Lu. intermedia SGS. Using qRT-PCR we established that the IFN-inducible genes induced in the skin of SGS pre-immunized mice, were also upregulated by SGS in PBMCs from human individuals regularly exposed to Lu. intermedia bites, but not in PBMCs of control subjects. These data demonstrate that repeated exposure to Lu. intermedia SGS induces the expression of potentially host-protective IFN-inducible genes.

Alpine tectonic evolution of a Jurassic subduction-accretionary complex: Deformation, kinematics and 40Ar/39Ar age constraints on the Mesozoic low-grade schists of the Circum-Rhodope Belt in the eastern Rhodope-Thrace region, Bulgaria-Greece

Deformation of the Circum-Rhodope Belt Mesozoic (Middle Triassic to earliest Lower Cretaceous) low-grade schists underneath an arc-related ophiolitic magmatic suite and associated sedimentary successions in the eastern Rhodope-Thrace region occurred as a two-episode tectonic process: (i) Late Jurassic deformation of arc to margin units resulting from the eastern Rhodope-Evros arc-Rhodope terrane continental margin collision and accretion to that margin, and (ii) Middle Eocene deformation related to the Tertiary crustal extension and final collision resulting in the closure of the Vardar ocean south of the Rhodope terrane. The first deformational event D-1 is expressed by Late Jurassic NW-N vergent fold generations and the main and subsidiary planar-linear structures. Although overprinting, these structural elements depict uniform bulk north-directed thrust kinematics and are geometrically compatible with the increments of progressive deformation that develops in same greenschist-facies metamorphic grade. It followed the Early-Middle Jurassic magmatic evolution of the eastern Rhodope-Evros arc established on the upper plate of the southward subducting Maliac-Meliata oceanic lithosphere that established the Vardar Ocean in a supra-subduction back-arc setting. This first event resulted in the thrust-related tectonic emplacement of the Mesozoic schists in a supra-crustal level onto the Rhodope continental margin. This Late Jurassic-Early Cretaceous tectonic event related to N-vergent Balkan orogeny is well-constrained by geochronological data and traced at a regional-scale within distinct units of the Carpatho-Balkan Belt. Following subduction reversal towards the north whereby the Vardar Ocean was subducted beneath the Rhodope margin by latest Cretaceous times, the low-grade schists aquired a new position in the upper plate, and hence, the Mesozoic schists are lacking the Cretaceous S-directed tectono-metamorphic episode whose effects are widespread in the underlying high-grade basement. The subduction of the remnant Vardar Ocean located behind the colliding arc since the middle Cretaceous was responsible for its ultimate closure, Early Tertiary collision with the Pelagonian block and extension in the region caused the extensional collapse related to the second deformational event D-2. This extensional episode was experienced passively by the Mesozoic schists located in the hanging wall of the extensional detachments in Eocene times. It resulted in NE-SW oriented open folds representing corrugation antiforms of the extensional detachment surfaces, brittle faulting and burial history beneath thick Eocene sediments as indicated by 42.1-39.7 Ma Ar-40/Ar-39 mica plateau ages obtained in the study. The results provide structural constraints for the involvement components of Jurassic paleo-subduction zone in a Late Jurassic arc-continental margin collisional history that contributed to accretion-related crustal growth of the Rhodope terrane. (C) 2011 Elsevier Ltd. All rights reserved.

Disseny i implementació en un mòdul linux encastat d’una eina de gestió local per a equips de xarxa de l'empresa W-onesys S.L.

Aquest projecte, s’ha desenvolupat en un marc empresarial, concretament al departamentR+D+i de l’empresa Wonesys S.L. de Sant Cugat del Vallès. L’empresa es dedica aldesenvolupament d’equipament per transmissions òptiques.Les eines de gestió dels equips existents, no satisfan els requeriments de l’empresa i amb aquest projecte es busca la implementació d’una eina per fer-ho. Entre les aplicacions actuals es pot trobar, per una banda, un sistema EMS (Element Management System) que ofereix interfíciegràfica d’usuari, però que requereix una infrastructura complexa per ser executada. Per l’altra banda, fins a tres interfícies diferents per connectar directament amb els equips, dues d’elles basades en protocols estàndard i una tercera que implementa un protocol propietari. Es tractad’interfícies d’intercanvi de text, per tant, la gestió mitjançant les mateixes es fa molt poc pràctica tot i no requerir cap infrastructura complexa com en el cas anterior. Una combinació de les virtuts de les anteriors són, a grans trets, els requeriments de la nova aplicació. Es volconstruir, doncs, una aplicació amb interfície gràfica d’usuari complerta que pugui ser accessible de forma senzilla utilitzant, tan sols, un terminal com a maquinari de suport.Un anàlisi del mercat il·lustra que hi ha molta disparitat en aplicacions similars. Hi ha grans diferències entre aplicacions de fabricants d’equipament i altres que només fan aplicacions per tercers.De les diverses possibilitats presentades per dur a terme la implementació, després d’un detingut anàlisi, es considera que la millor opció és el desenvolupament d’una aplicació web. Com l’aplicació ha de residir en un sistema Linux encastat, es fa un repàs del concepte ‘encastat’. Es defineix el terme i es dóna una mirada al mercat. Es descriuen i es comparen les arquitecturesARM i x86 i es relacionen amb el món encastat.Al tractar-se d’un sistema encastat amb arquitectura diferent a la d’un entorn web habitual, l’elecció de les eines representa un paper molt important, així com el procés de compilació i configuració d’eines que tradicionalment s’obtenen compilades.S’han escollit eines de programari lliure i dissenyades especialment per a entorns encastats. El patró de disseny usat pel desenvolupament de l’aplicació web és el Model View Controller, que facilita l’estructuració i un correcte manteniment de l’aplicació.La utilització de la tecnologia web resulta en una aplicació senzilla d’utilitzar, sense necessitat d’instal·lació de cap tipus per part de l’usuari i amb una interfície gràfica molt versàtil. La valoració per part dels usuaris de l’aplicació, tant treballadors de l’empresa en tasques dedesenvolupament i depuració, com clients en equips en explotació, és molt positiva. Tant és així, que sorgeixen opcions per reformular el sistema EMS per unificar interfícies i reaprofitar codi.

El Tabac al món : la indústria a nivell local i global, legislació, problemes i reptes de futur

Per què a un fumador del Canadà li costa 10 vegades més diners comprar un paquet de tabac que el que li costa a un fumador de Cuba? Què se n’ha fet dels anuncis de Marlboro als cotxes de l’escuderia automovilística Ferrari? Comés que s’han creat espais reservats per a fumadors en els últims anys? Aquestes i altres preguntes sobre el món del tabac conformen l’objecte del nostre treball d’investigació. El nostre propòsit és intentar donar resposta a qüestions com aquestes, i fer que el lector entengui realment a què es deuen aquests canvis en l’estructura del mercat del tabac. Mostrarem, mitjançant una mirada analítica dels diferents factors, que gran part d’aquests efectes en un producte (com pot ser el cigarret, en el cas que ens ocupa) són extrapolables a altres béns i que es poden explicar des del punt de vista econòmic, examinant les decisions d’agents amagats com ara el govern, i considerant les repercussions dels diferents tipus de polítiques.Com tots sabem, el món actual està conformat per un seguit de relacions entre individus, o millor dit, agents econòmics que interactuen entre ells. Els resultats d’aquestes interaccions determinen el comportament de variables que, ben definides, poden ser estudiades, així com els seus efectes. Nosaltres hem intentat mostrar d’una manera senzilla i a l’abast de tothom fins a quin punt arriben aquestes interrelacions. El que preteníem en tot moment basar-nos en dades objectives obtingudes previ estudi. Es per això que, de la mateixa manera que al acabar el treball el lector serà capaç d’entendre per què varia elpreu del mateix bé al creuar una frontera, queda a càrrec de cadascú determinar si, per exemple, els fumadors són objectes de persecució o de si les mesures paternalistes del govern envers la prohibició de la publicitat estan justificades.

Histone deacetylase inhibitors repress macrophage migration inhibitory factor (MIF) expression by targeting MIF gene transcription through a local chromatin deacetylation.

The cytokine macrophage migration inhibitory factor plays a central role in inflammation, cell proliferation and tumorigenesis. Moreover, macrophage migration inhibitory factor levels correlate with tumor aggressiveness and metastatic potential. Histone deacetylase inhibitors are potent antitumor agents recently introduced in the clinic. Therefore, we hypothesized that macrophage migration inhibitory factor would represent a target of histone deacetylase inhibitors. Confirming our hypothesis, we report that histone deacetylase inhibitors of various chemical classes strongly inhibited macrophage migration inhibitory factor expression in a broad range of cell lines, in primary cells and in vivo. Nuclear run on, transient transfection with macrophage migration inhibitory factor promoter reporter constructs and transduction with macrophage migration inhibitory factor expressing adenovirus demonstrated that trichostatin A (a prototypical histone deacetylase inhibitor) inhibited endogenous, but not episomal, MIF gene transcription. Interestingly, trichostatin A induced a local and specific deacetylation of macrophage migration inhibitory factor promoter-associated H3 and H4 histones which did not affect chromatin accessibility but was associated with an impaired recruitment of RNA polymerase II and Sp1 and CREB transcription factors required for basal MIF gene transcription. Altogether, this study describes a new molecular mechanism by which histone deacetylase inhibitors inhibit MIF gene expression, and suggests that macrophage migration inhibitory factor inhibition by histone deacetylase inhibitors may contribute to the antitumorigenic effects of histone deacetylase inhibitors.

Rules vs. political discretion: evidence from constitutionally guaranteed transfers to local governments in Brazil

Can rules be used to shield public resources from political interference? The Brazilian constitution and national tax code stipulate that revenue sharing transfers to municipal governments be determined by the size of counties in terms of estimated population. In this paper I document that the population estimates which went into the transfer allocation formula for the year 1991 were manipulated, resulting in significant transfer differentials over the entire 1990's. I test whether conditional on county characteristics that might account for the manipulation, center-local party alignment, party popularity and the extent of interparty fragmentation at the county level are correlated with estimated populations in 1991. Results suggest that revenue sharing transfers were targeted at right-wing national deputies in electorally fragmented counties as well as aligned local executives.