Design and evaluation of a panel os single-nucleotide polymorphisms in microRNA genomic regions for association studies in human disease

MicroRNAs (miRNA) are recognized posttranscriptional gene repressors involved in the control of almost every biological process. Allelic variants in these regions may be an important source of phenotypic diversity and contribute to disease susceptibility. We analyzed the genomic organization of 325 human miRNAs (release 7.1, miRBase) to construct a panel of 768 single-nucleotide polymorphisms (SNPs) covering approximately 1 Mb of genomic DNA, including 131 isolated miRNAs (40%) and 194 miRNAs arranged in 48 miRNA clusters, as well as their 5-kb flanking regions. Of these miRNAs, 37% were inside known protein-coding genes, which were significantly associated with biological functions regarding neurological, psychological or nutritional disorders. SNP coverage analysis revealed a lower SNP density in miRNAs compared with the average of the genome, with only 24 SNPs located in the 325 miRNAs studied. Further genotyping of 340 unrelated Spanish individuals showed that more than half of the SNPs in miRNAs were either rare or monomorphic, in agreement with the reported selective constraint on human miRNAs. A comparison of the minor allele frequencies between Spanish and HapMap population samples confirmed the applicability of this SNP panel to the study of complex disorders among the Spanish population, and revealed two miRNA regions, hsa-mir-26a-2 in the CTDSP2 gene and hsa-mir-128-1 in the R3HDM1 gene, showing geographical allelic frequency variation among the four HapMap populations, probably because of differences in natural selection. The designed miRNA SNP panel could help to identify still hidden links between miRNAs and human disease.

Automated Segmentation of Cerebral Vasculature with Aneurysms in 3DRA and TOF-MRA using Geodesic Active Regions: an Evaluation Study

Purpose: To evaluate the suitability of an improved version of an automatic segmentation method based on geodesic active regions (GAR) for segmenting cerebral vasculature with aneurysms from 3D X-ray reconstruc-tion angiography (3DRA) and time of °ight magnetic resonance angiography (TOF-MRA) images available in the clinical routine.Methods: Three aspects of the GAR method have been improved: execution time, robustness to variability in imaging protocols and robustness to variability in image spatial resolutions. The improved GAR was retrospectively evaluated on images from patients containing intracranial aneurysms in the area of the Circle of Willis and imaged with two modalities: 3DRA and TOF-MRA. Images were obtained from two clinical centers, each using di®erent imaging equipment. Evaluation included qualitative and quantitative analyses ofthe segmentation results on 20 images from 10 patients. The gold standard was built from 660 cross-sections (33 per image) of vessels and aneurysms, manually measured by interventional neuroradiologists. GAR has also been compared to an interactive segmentation method: iso-intensity surface extraction (ISE). In addition, since patients had been imaged with the two modalities, we performed an inter-modality agreement analysis with respect to both the manual measurements and each of the two segmentation methods. Results: Both GAR and ISE di®ered from the gold standard within acceptable limits compared to the imaging resolution. GAR (ISE, respectively) had an average accuracy of 0.20 (0.24) mm for 3DRA and 0.27 (0.30) mm for TOF-MRA, and had a repeatability of 0.05 (0.20) mm. Compared to ISE, GAR had a lower qualitative error in the vessel region and a lower quantitative error in the aneurysm region. The repeatabilityof GAR was superior to manual measurements and ISE. The inter-modality agreement was similar between GAR and the manual measurements. Conclusions: The improved GAR method outperformed ISE qualitatively as well as quantitatively and is suitable for segmenting 3DRA and TOF-MRA images from clinical routine.

Regions of rationality: Maps for bounded agents

An important problem in descriptive and prescriptive research in decision making is to identify regions of rationality, i.e., the areas for which heuristics are and are not effective. To map the contours of such regions, we derive probabilities that heuristics identify the best of m alternatives (m > 2) characterized by k attributes or cues (k > 1). The heuristics include a single variable (lexicographic), variations of elimination-by-aspects, equal weighting, hybrids of the preceding, and models exploiting dominance. We use twenty simulated and four empirical datasets for illustration. We further provide an overview by regressing heuristic performance on factors characterizing environments. Overall, sensible heuristics generally yield similar choices in many environments. However, selection of the appropriate heuristic can be important in some regions (e.g., if there is low inter-correlation among attributes/cues). Since our work assumes a hit or miss decision criterion, we conclude by outlining extensions for exploring the effects of different loss functions.

The poor stay poor: Non-convergence across countries and regions

We study the issue of income convergence across countries and regions witha Bayesian estimator which allows us to use information in an efficient andflexible way. We argue that the very slow convergence rates to a commonlevel of per-capita income found, e.g., by Barro and Xavier Sala-i-Martin,is due to a 'fixed effect bias' that their cross-sectional analysisintroduces in the results. Our approach permits the estimation of differentconvergence rates to different steady states for each cross sectional unit.When this diversity is allowed, we find that convergence of each unit to(its own) steady state income level is much faster than previously estimatedbut that cross sectional differences persist: inequalities will only bereduced by a small amount by the passage of time. The cross countrydistribution of the steady state is largely explained by the cross countrydistribution of initial conditions.

Do interregional transfers improve the economic performance of poor regions? The case of Spain

The 17 regional governments of Spain receive grants from both thecentral government and the European Union. The grants are generallyredistributive and are intended to stimulate economic activity inthe poorer regions. We evaluate the effectiveness of the grants bycomparing the economic performance of the regions before and afterthe implementation of the grant programs using a differences--in--differences approach. We find that these policies have not beeneffective at stimulating private investment or improving the overalleconomies of the poorer regions.

How do very open economies adjust to large immigration flows? Recent evidence from Spanish regions

In recent years, Spain has received unprecedented immigration flows. Between 2001 and 2006 the fraction of the population born abroad more than doubled, increasing from4.8% to 10.8%. For Spanish provinces with above-median inflows (relative to population),immigration increased by 24% the number of high school dropouts while only increasingcollege graduates by 11%. We study different channels by which regional labor markets haveabsorbed the large increase in relative supply of low educated workers. We identify theexogenous supply shock using historical immigrant settlement patterns by country of origin.Using data from the Labor Force Survey and the decennial Census, we find a large expansion ofemployment in high immigration regions. Disaggregating by industry, the absorption operatedthrough large increases in the share of low-educated workers, compared to the same industry inlow-immigration regions. We do not find changes in sectoral specialization. Overall, andperhaps surprisingly, the pattern of absorption is very similar to the one found in the US.

Why are some Spanish regions so much more efficient than others?

This article investigates the main sources of heterogeneity in regional efficiency. We estimate a translog stochastic frontier production function in the analysis of Spanish regions in the period 1964-1996, to attempt to measure and explain changes in technical efficiency. Our results confirm that regional inefficiency is significantly and positively correlated with the ratio of public capital to private capital. The proportion of service industries in the private capital, the proportion of public capital devoted to transport infrastructures, the industrial specialization, and spatial spillovers from transport infrastructures in neighbouring regions significantly contributed to improve regional efficiency.

How market access shapes human capital investment in a peripheral country

Human capital endowment is one of the main factors influencing the level of development of a region. This paper analyses whether remoteness from economic activity has a negative effect on human capital accumulation and, consequently, on economic development. Making use of microdata this research proves that remoteness from economic activity has contributed to explain the divergences in the level of education observed across Spanish provinces over the last 50 years. The effect is significant even when controlling for the improvement of education supply. Nonetheless, the accessibility effect has been petering out since the 1960s due to the decreasing barriers to mobility.

Projecte d'ús de tauleta per al màrketing de regions vinícoles

Aquest TFC exposa un estudi de les dades i el context en què s'ha de presentar la informació. S'analitza el gruix de dades, la importància de cadascun dels paràmetres, les fonts de coneixement disponibles i l'efecte que es pretén aconseguir.

The geographical concentration of industry across Spanish Regions, 1856-1995

New economic geography models show that there may be a strong relationship between economic integration and the geographical concentration of industries. Nevertheless, this relationship is neither unique nor stable, and may follow a ?-shaped pattern in the long term. The aim of the present paper is to analyze the evolution of the geographical concentration of manufacturing across Spanish regions during the period 1856-1995. We construct several geographical concentration indices for different points in time over these 140 years. The analysis is carried out at two levels of aggregation, in regions corresponding to the NUTS-II and NUTS-III classifications. We confirm that the process of economic integration stimulated the geographical concentration of industrial activity. Nevertheless, the localization coefficients only started to fall after the beginning of the integration of the Spanish Economy into the international markets in the mid-70s, and this new path was not interrupted by Spain¿s entry in the European Union some years later

The empirics of spatial competition: evidence from European regions

The New Economic Geography literature allows detailed analysis of the factors that determine the location decisions of firms in integrated markets. However, the competitive process is modelled in a rather rudimentary way, and the empirical evidence has usually been obtained from reduced-form econometric specifications. This study describes a structural model that takes into account strategic interactions between firms. We investigate the relationship between the degree of perceived competition ¿ not only from local firms but from firms in other regions ¿ and geographic concentration. The preliminary results indicate that, in aggregate terms, local firms present stronger competition than firms in other regions. Moreover, it is confirmed that greater geographical concentration of production reduces market power, due to the intensification of local competition; however, its impact on production costs is unclear.

Thermal modeling and management in ultrathin chip stack technology

This paper presents a thermal modeling for power management of a new three-dimensional (3-D) thinned dies stacking process. Besides the high concentration of power dissipating sources, which is the direct consequence of the very interesting integration efficiency increase, this new ultra-compact packaging technology can suffer of the poor thermal conductivity (about 700 times smaller than silicon one) of the benzocyclobutene (BCB) used as both adhesive and planarization layers in each level of the stack. Thermal simulation was conducted using three-dimensional (3-D) FEM tool to analyze the specific behaviors in such stacked structure and to optimize the design rules. This study first describes the heat transfer limitation through the vertical path by examining particularly the case of the high dissipating sources under small area. First results of characterization in transient regime by means of dedicated test device mounted in single level structure are presented. For the design optimization, the thermal draining capabilities of a copper grid or full copper plate embedded in the intermediate layer of stacked structure are evaluated as a function of the technological parameters and the physical properties. It is shown an interest for the transverse heat extraction under the buffer devices dissipating most the power and generally localized in the peripheral zone, and for the temperature uniformization, by heat spreading mechanism, in the localized regions where the attachment of the thin die is altered. Finally, all conclusions of this analysis are used for the quantitative projections of the thermal performance of a first demonstrator based on a three-levels stacking structure for space application.

The empirics of spatial competition: evidence from European regions

The New Economic Geography literature allows detailed analysis of the factors that determine the location decisions of firms in integrated markets. However, the competitive process is modelled in a rather rudimentary way, and the empirical evidence has usually been obtained from reduced-form econometric specifications. This study describes a structural model that takes into account strategic interactions between firms. We investigate the relationship between the degree of perceived competition ¿ not only from local firms but from firms in other regions ¿ and geographic concentration. The preliminary results indicate that, in aggregate terms, local firms present stronger competition than firms in other regions. Moreover, it is confirmed that greater geographical concentration of production reduces market power, due to the intensification of local competition; however, its impact on production costs is unclear.

Geographical determinants of the creation of manufacturing firms: The regions of Spain

La complexitat dels mecanismes que determinen l'entrada i la sortida de signatures augmenta quan diferències geogràfiques de l'estructura de producció, la capital humana i l'atur són considerades. Variacions interregionals en la tarifa de les noves de signatures dintre de cada activitat industrial persisteixen durant els períodes llargs de temps, una circumstància que indica que hi ha determinants no-conjunturals en la capacitat de regions per a crear nous projectes industrials. Aquest estudi està preocupat amb l'establiment d'influència variables geogràfiques sobre la fundació de nous establiments de la fabricació. Les indústries (NEIX la R 25) en les regions espanyoles (el BOIG 2) han estat preses com les unitats d'anàlisis per al període 1980-1992

The geographical concentration of industry across Spanish Regions, 1856-1995

New economic geography models show that there may be a strong relationship between economic integration and the geographical concentration of industries. Nevertheless, this relationship is neither unique nor stable, and may follow a ?-shaped pattern in the long term. The aim of the present paper is to analyze the evolution of the geographical concentration of manufacturing across Spanish regions during the period 1856-1995. We construct several geographical concentration indices for different points in time over these 140 years. The analysis is carried out at two levels of aggregation, in regions corresponding to the NUTS-II and NUTS-III classifications. We confirm that the process of economic integration stimulated the geographical concentration of industrial activity. Nevertheless, the localization coefficients only started to fall after the beginning of the integration of the Spanish Economy into the international markets in the mid-70s, and this new path was not interrupted by Spain¿s entry in the European Union some years later