Showing papers by "Pompeu Fabra University published in 2001"

The sequence of the human genome.

Abstract: A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

A Scaled Difference Chi-square Test Statistic for Moment Structure Analysis

Abstract: A family of scaling corrections aimed to improve the chi-square approximation of goodness-of-fit test statistics in small samples, large models, and nonnormal data was proposed in Satorra and Bentler (1994). For structural equations models, Satorra-Bentler's (SB) scaling corrections are available in standard computer software. Often, however, the interest is not on the overall fit of a model, but on a test of the restrictions that a null model sayM 0 implies on a less restricted oneM 1. IfT 0 andT 1 denote the goodness-of-fit test statistics associated toM 0 andM 1, respectively, then typically the differenceT d =T 0−T 1 is used as a chi-square test statistic with degrees of freedom equal to the difference on the number of independent parameters estimated under the modelsM 0 andM 1. As in the case of the goodness-of-fit test, it is of interest to scale the statisticT d in order to improve its chi-square approximation in realistic, that is, nonasymptotic and nonormal, applications. In a recent paper, Satorra (2000) shows that the difference between two SB scaled test statistics for overall model fit does not yield the correct SB scaled difference test statistic. Satorra developed an expression that permits scaling the difference test statistic, but his formula has some practical limitations, since it requires heavy computations that are not available in standard computer software. The purpose of the present paper is to provide an easy way to compute the scaled difference chi-square statistic from the scaled goodness-of-fit test statistics of modelsM 0 andM 1. A Monte Carlo study is provided to illustrate the performance of the competing statistics.

Navier-stokes, fluid dynamics, and image and video inpainting

Abstract: Image inpainting involves filling in part of an image or video using information from the surrounding area. Applications include the restoration of damaged photographs and movies and the removal of selected objects. We introduce a class of automated methods for digital inpainting. The approach uses ideas from classical fluid dynamics to propagate isophote lines continuously from the exterior into the region to be inpainted. The main idea is to think of the image intensity as a 'stream function for a two-dimensional incompressible flow. The Laplacian of the image intensity plays the role of the vorticity of the fluid; it is transported into the region to be inpainted by a vector field defined by the stream function. The resulting algorithm is designed to continue isophotes while matching gradient vectors at the boundary of the inpainting region. The method is directly based on the Navier-Stokes equations for fluid dynamics, which has the immediate advantage of well-developed theoretical and numerical results. This is a new approach for introducing ideas from computational fluid dynamics into problems in computer vision and image analysis.

Filling-in by joint interpolation of vector fields and gray levels

Abstract: A variational approach for filling-in regions of missing data in digital images is introduced. The approach is based on joint interpolation of the image gray levels and gradient/isophotes directions, smoothly extending in an automatic fashion the isophote lines into the holes of missing data. This interpolation is computed by solving the variational problem via its gradient descent flow, which leads to a set of coupled second order partial differential equations, one for the gray-levels and one for the gradient orientations. The process underlying this approach can be considered as an interpretation of the Gestaltist's principle of good continuation. No limitations are imposed on the topology of the holes, and all regions of missing data can be simultaneously processed, even if they are surrounded by completely different structures. Applications of this technique include the restoration of old photographs and removal of superimposed text like dates, subtitles, or publicity. Examples of these applications are given. We conclude the paper with a number of theoretical results on the proposed variational approach and its corresponding gradient descent flow.

European Inflation Dynamics

Abstract: We provide evidence on the fit of the New Phillips Curve (NPQ for the Euro area over the period 1970-1998, and use it as a tool to compare the characteristics of European inflation dynamics with those observed in the U.S. We also analyze the factors underlying inflation inertia by examining the cyclical behavior of marginal costs, as well as that of its two main components, namely, labor productivity and real wages. Some of the findings can be summarized as follows: (a) the NPC fits Euro area data very well, possibly better than U.S. data, (b) the degree of price stickiness implied by the estimates is substantial, but in line with survey evidence and U.S. estimates, (c) inflation dynamics in the Euro area appear to have a stronger forward- looking component (i.e., less inertia) than in the U.S., (d) labor market frictions, as manifested in the behavior of the wage markup, appear to have played a key role in shaping the behavior of marginal costs and, consequently, inflation in Europe.

Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of β-catenin signaling

Abstract: The β-catenin signaling pathway is deregulated in nearly all colon cancers. Nonhypercalcemic vitamin D3 (1α,25-dehydroxyvitamin D3) analogues are candidate drugs to treat this neoplasia. We show that these compounds promote the differentiation of human colon carcinoma SW480 cells expressing vitamin D receptors (VDRs) (SW480-ADH) but not that of a malignant subline (SW480-R) or metastasic derivative (SW620) cells lacking VDR. 1α,25(OH)2D3 induced the expression of E-cadherin and other adhesion proteins (occludin, Zonula occludens [ZO]-1, ZO-2, vinculin) and promoted the translocation of β-catenin, plakoglobin, and ZO-1 from the nucleus to the plasma membrane. Ligand-activated VDR competed with T cell transcription factor (TCF)-4 for β-catenin binding. Accordingly, 1α,25(OH)2D3 repressed β-catenin–TCF-4 transcriptional activity. Moreover, VDR activity was enhanced by ectopic β-catenin and reduced by TCF-4. Also, 1α,25(OH)2D3 inhibited expression of β-catenin–TCF-4-responsive genes, c-myc, peroxisome proliferator-activated receptor δ, Tcf-1, and CD44, whereas it induced expression of ZO-1. Our results show that 1α,25(OH)2D3 induces E-cadherin and modulates β-catenin–TCF-4 target genes in a manner opposite to that of β-catenin, promoting the differentiation of colon carcinoma cells.

European Inflation Dynamics

Abstract: We provide evidence on the fit of the New Phillips Curve (NPC) for the Euro area over the period 1970–1998, and use it as a tool to compare the characteristics of European inflation dynamics with those observed in the U.S. We also analyse the factors underlying inflation inertia by examining the cyclical behaviour of marginal costs, as well as that of its two main components, namely, labour productivity and real wages. Some of the findings can be summarized as follows: (a) the NPC fits Euro area data very well, possibly better than US data, (b) the degree of price stickiness implied by the estimates is substantial, but in line with survey evidence and US estimates, (c)\ inflation dynamics in the Euro area appear to have a stronger forward-looking component (i.e., less inertia) than in the US, (d) labour market frictions, as manifested in the behaviour of the wage markup, appear to have played a key role in shaping the behaviour of marginal costs and, consequenty, inflation in Europe.

Functional Interaction between Opioid and Cannabinoid Receptors in Drug Self-Administration

Abstract: The present study was designed to explore the relationship between the cannabinoid and opioid receptors in animal models of opioid-induced reinforcement. The acute administration of SR141716A, a selective central cannabinoid CB1 receptor antagonist, blocked heroin self-administration in rats, as well as morphine-induced place preference and morphine self-administration in mice. Morphine-dependent animals injected with SR141716A exhibited a partial opiate-like withdrawal syndrome that had limited consequences on operant responses for food and induced place aversion. These effects were associated with morphine-induced changes in the expression of CB1 receptor mRNA in specific nuclei of the reward circuit, including dorsal caudate putamen, nucleus accumbens, and septum. Additionally, the opioid antagonist naloxone precipitated a mild cannabinoid-like withdrawal syndrome in cannabinoid-dependent rats and blocked cannabinoid self-administration in mice. Neither SR141716A nor naloxone produced any intrinsic effect on these behavioral models. The present results show the existence of a cross-interaction between opioid and cannabinoid systems in behavioral responses related to addiction and open new strategies for the treatment of opiate dependence.

Making Descriptive Use of Prospect Theory to Improve the Prescriptive Use of Expected Utility

Abstract: This paper proposes a quantitative modification of standard utility elicitation procedures, such as the probability and certainty equivalence methods, to correct for commonly observed violations of expected utility. Traditionally, decision analysis assumes expected utility not only for the prescriptive purpose of calculating optimal decisions but also for the descriptive purpose of eliciting utilities. However, descriptive violations of expected utility bias utility elicitations. That such biases are effective became clear when systematic discrepancies were found between different utility elicitation methods that, under expected utility, should have yielded identical utilities. As it is not clear how to correct for these biases without further knowledge of their size or nature, most utility elicitations still calculate utilities by means of the expected utility formula. This paper speculates on the biases and their sizes by using the quantitative assessments of probability transformation and loss aversion suggested by prospect theory. It presents quantitative corrections for the probability and certainty equivalence methods. If interactive sessions to correct for biases are not possible, then the authors propose to use the corrected utilities rather than the uncorrected ones in prescriptions of optimal decisions. In an experiment, the discrepancies between the probability and certainty equivalence methods are removed by the authors' proposal.

How wide is the gap? An investigation of gender wage differences using quantile regression

Abstract: In this paper we re-examine the link between subjective perceptions and objective measures of wage discrimination by estimating the mean and several quantiles in the conditional wage distribution of men and women in order to decompose the gender wage gap into the part attributed to different characteristics and the part attributable to differential returns to these characteristics at points other than the conditional expectation. In the process we take into account the endogeneity of educational choice and the participation decision of women. The results suggest that the absolute wage gap and the component of the latter that can be attributed to different returns to characteristics increase over the wage scale.

High-Resolution Analysis of Human Y-Chromosome Variation Shows a Sharp Discontinuity and Limited Gene Flow between Northwestern Africa and the Iberian Peninsula

Abstract: In the present study we have analyzed 44 Y-chromosome biallelic polymorphisms in population samples from northwestern (NW) Africa and the Iberian Peninsula, which allowed us to place each chromosome unequivocally in a phylogenetic tree based on >150 polymorphisms. The most striking results are that contemporary NW African and Iberian populations were found to have originated from distinctly different patrilineages and that the Strait of Gibraltar seems to have acted as a strong (although not complete) barrier to gene flow. In NW African populations, an Upper Paleolithic colonization that probably had its origin in eastern Africa contributed 75% of the current gene pool. In comparison, ∼78% of contemporary Iberian Y chromosomes originated in an Upper Paleolithic expansion from western Asia, along the northern rim of the Mediterranean basin. Smaller contributions to these gene pools (constituting 13% of Y chromosomes in NW Africa and 10% of Y chromosomes in Iberia) came from the Middle East during the Neolithic and, during subsequent gene flow, from Sub-Saharan to NW Africa. Finally, bidirectional gene flow across the Strait of Gibraltar has been detected: the genetic contribution of European Y chromosomes to the NW African gene pool is estimated at 4%, and NW African populations may have contributed 7% of Iberian Y chromosomes. The Islamic rule of Spain, which began in a.d. 711 and lasted almost 8 centuries, left only a minor contribution to the current Iberian Y-chromosome pool. The high-resolution analysis of the Y chromosome allows us to separate successive migratory components and to precisely quantify each historical layer.

Inhibition of integrin linked kinase (ILK) suppresses beta-catenin-Lef/Tcf-dependent transcription and expression of the E-cadherin repressor, snail, in APC-/- human colon carcinoma cells.

Abstract: Loss of functional adenomatous polyposis coli (APC) protein results in the stabilization of cytosolic β-catenin and activation of genes that are responsive to Lef/Tcf family transcription factors. We have recently shown that an independent cell adhesion and integrin linked kinase (ILK)-dependent pathway can also activate β-catenin/LEF mediated gene transcription and downregulate E-cadherin expression. In addition, ILK activity and expression are elevated in adenomatous polyposis and colon carcinomas. To examine the role of this pathway in the background of APC mutations we inhibited ILK activity in APC−/− human colon carcinoma cell lines. In all cases, inhibition of ILK resulted in substantial inhibition of TCF mediated gene transcription and inhibition of transcription and expression of the TCF regulated gene, cyclin D1. Inhibition of ILK resulted in decreased nuclear beta-catenin expression, and in the inhibition of phosphorylation of GSK-3 and stimulation of its activity, leading to accelerated degradation of β-catenin. In addition, inhibition of ILK suppressed cell growth in culture as well as growth of human colon carcinoma cells in SCID mice. Strikingly, inhibition of ILK also resulted in the transcriptional stimulation of E-cadherin expression and correlated with the inhibition of gene transcription of snail, a repressor of E-cadherin gene expression. Overexpression of ILK caused a stimulation of expression of snail, but snail expression was found not to be regulated by β-catenin/Tcf. These data demonstrate that ILK can regulate β-catenin/TCF and snail transcription factors by distinct pathways. We propose that inhibition of ILK may be a useful strategy in the control of progression of colon as well as other carcinomas.

The Survival of the Welfare State

Abstract: This Paper provides an analytical characterization of Markov perfect equilibria in a model with repeated majority voting, where agents vote over income redistribution. The key feature of the theory is that the future constituency of redistributive policies depends positively on the current level of redistribution, since this affects both private investments and the future distribution of voters. Agents vote rationally, and fully anticipate the effects of their political choice on both private incentives and future voting outcomes. The equilibrium features multiple steady-states, one with and one without a welfare state. The theory can explain why welfare state institutions, originally introduced in response to specific shocks (e.g., the Great Depression), have been so persistent. complementarity, wage inequality, education

Regulation of the Sko1 transcriptional repressor by the Hog1 MAP kinase in response to osmotic stress

Abstract: Exposure of yeast to increases in extracellular osmolarity activates the Hog1 mitogen-activated protein kinase (MAPK), which is essential for the induction of gene expression required for cell survival upon osmotic stress. Several genes are regulated in response to osmotic stress by Sko1, a transcriptional repressor of the ATF/CREB family. We show by in vivo coprecipitation and phosphorylation studies that Sko1 and Hog1 interact and that Sko1 is phosphorylated upon osmotic stress in a Hog1-dependent manner. Hog1 phosphorylates Sko1 in vitro at multiple sites within the N-terminal region. Phosphorylation of Sko1 disrupts the Sko1–Ssn6–Tup1 repressor complex, and consistently, a mutant allele of Sko1, unphosphorylatable by Hog1, exhibits less derepression than the wild type. Interestingly, Sko1 repressor activity is further enhanced in strains with high protein kinase A (PKA) activity. PKA phosphorylates Sko1 near the bZIP domain and mutation of these sites eliminates modulation of Sko1 responses to high PKA activity. Thus, Sko1 transcriptional repression is controlled directly by the Hog1 MAPK in response to stress, and this effect is further modulated by an independent signaling mechanism through the PKA pathway.

Gender inequalities in health among workers: the relation with family demands

Abstract: OBJECTIVES To analyse whether there are gender inequalities in health among male and female workers who are married or cohabiting and to assess whether there are gender differences in the relation between family demands and health. Additionally, for both objectives it will be examined whether these gender patterns are similar for manual and non-manual workers. DESIGN AND SETTING The data have been taken from the 1994 Catalonian Health Survey (CHS), a cross sectional survey based on a representative sample of the non-institutionalised population of Catalonia, a region in the north east of Spain that has about 6 million inhabitants. The dependent variables were four ill health indicators (self perceived health status, limiting longstanding illness, having at least one chronic condition and mental health) and two health related behaviours closely related to having time for oneself (no leisure time physical activity and sleeping six hours or less a day). Family demands were measured with three variables: household size, living with children under 15 years and living with adults older than 65 years. The analysis was separated for gender and social class (manual and non-manual workers) and additionally adjusted for age. Gender differences for all dependent and independent variables were first tested at the bivariate level using the χ 2 test for categorical variables and the t test for age. Secondly, multivariate logistic regression models were fitted. PARTICIPANTS Persons who were employed, married or cohabiting, aged 25 to 64 years (2148 men and 1185 women). RESULTS A female excess for all the ill health indicators was found, while there were no gender differences in the health related behaviours analysed. Family demands had a greater impact on health and health related behaviours of female manual workers. In this group household size was positively related to four dependent variables. The adjusted odds ratios (ORs) to living in family units of more than four persons versus living only with the spouse were 2.74 (95%CI=1.22, 6.17) for poor self perceived health status, 3.16 (95%CI=0.98, 10.15) for limiting long standing illness, 3.28 (95%CI=1.45, 7.44) for having at least one chronic condition, and 2.60 (95%CI=1.12, 6.00) for sleeping six hours or less a day. Among female manual workers living with children under 15 years was positively associated with no leisure time physical activity (adjusted OR=2.37; 95% CI=1.43, 3.92) and with sleeping six hours or less a day (adjusted OR=1.91; 95% CI=1.13, 3.32). Living with adults older than 65 years had an unexpected negative relation with poor self perceived health status (adjusted OR=0.33; 95%CI=0.16, 0.66), and with chronic conditions (adjusted OR=0.45; 95%CI=0.24, 0.87) in female manual workers. Among male manual workers living with children under 15 years was positively associated with longstanding limiting illness (adjusted OR=2.44; 95%CI=1.36, 4.38). CONCLUSION When gender differences in health are analysed, both the paid and the non-paid work should be considered as well as the interaction between these two dimensions, gender and social class. In Catalonia, as probably in Spain and in other countries, private changes such as sharing domestic responsibilities, as well as active public policies for facilitating family care are needed in order to reduce gender health inequalities attributable to the unequal distribution of family demands.

From stem cells to beta cells: new strategies in cell therapy of diabetes mellitus.

Abstract: Islet transplantation as a potential treatment for diabetes has been investigated extensively over the past 10 years. Such an approach, however, will always be limited mainly because it is difficult to obtain sufficiently large numbers of purified islets from cadaveric donors. One alternative to organ or tissue transplantation is to use a renewable source of cells. Stem cells are clonogenic cells capable of both self-renewal and multilineage differentiation. These cells have the potential to proliferate and differentiate into any type of cell and to be genetically modified in vitro, thus providing cells which can be isolated and used for transplantation. Recent studies have given well-defined differentiation protocols, which can be used to guide stem cells into specific cell lineages as neurons, cardiomyocytes and insulin-secreting cells. Moreover, these derived cells have been useful in different animal models. In this regard, insulin-secreting cells derived from R1 mouse embryonic stem cells restore blood glucose concentrations to normal when they are transplanted into streptozotocin-induced diabetic animals. These results show that diabetes could be among the first applications of stem cell therapy. [Diabetologia (2001) 44: 407–415]

Color image enhancement via chromaticity diffusion

Abstract: A novel approach for color image denoising is proposed in this paper. The algorithm is based on separating the color data into chromaticity and brightness, and then processing each one of these components with partial differential equations or diffusion flows. In the proposed algorithm, each color pixel is considered as an n-dimensional vector. The vectors' direction, a unit vector, gives the chromaticity, while the magnitude represents the pixel brightness. The chromaticity is processed with a system of coupled diffusion equations adapted from the theory of harmonic maps in liquid crystals. This theory deals with the regularization of vectorial data, while satisfying the intrinsic unit norm constraint of directional data such as chromaticity. Both isotropic and anisotropic diffusion flows are presented for this n-dimensional chromaticity diffusion flow. The brightness is processed by a scalar median filter or any of the popular and well established anisotropic diffusion flows for scalar image enhancement. We present the underlying theory, a number of examples, and briefly compare with the current literature.

Interbank Market Integration Under Asymmetric Information

Abstract: While domestic interbank markets are often considered to work in an efficient way, cross-country bank lending appears to be subject to market imperfections leading to persistent interest rate differentials. In a model where banks need to cope with liquidity shocks by borrowing or by liquidating assets, we study the scope for international interbank market integration with unsecured lending when cross-country information is noisy. We find that an equilibrium with integrated markets need not always exist, and that it coexists with one characterized by segmentation. A repo market reduces interest rate spreads and improves upon the segmentation equilibrium. However, it may destroy the unsecured integrated equilibrium, since it reduces the liquidity imbalances and thus the gains from unsecured market integration. The introduction of other transnational institutional arrangements, such as multinational banking, correspondent banking and the existence of "too-big-to-fail" banks may reduce cross country interest spreads and provide more insurance against country wide liquidity shocks. Still, multinational banking, as the introduction of repos, may threaten the integrated interbank market equilibrium.

Origins and Divergence of the Roma (Gypsies)

Abstract: The identification of a growing number of novel Mendelian disorders and private mutations in the Roma (Gypsies) points to their unique genetic heritage. Linguistic evidence suggests that they are of diverse Indian origins. Their social structure within Europe resembles that of the jatis of India, where the endogamous group, often defined by profession, is the primary unit. Genetic studies have reported dramatic differences in the frequencies of mutations and neutral polymorphisms in different Romani populations. However, these studies have not resolved ambiguities regarding the origins and relatedness of Romani populations. In this study, we examine the genetic structure of 14 well-defined Romani populations. Y-chromosome and mtDNA markers of different mutability were analyzed in a total of 275 individuals. Asian Y-chromosome haplogroup VI-68, defined by a mutation at the M82 locus, was present in all 14 populations and accounted for 44.8% of Romani Y chromosomes. Asian mtDNA-haplogroup M was also identified in all Romani populations and accounted for 26.5% of female lineages in the sample. Limited diversity within these two haplogroups, measured by the variation at eight short-tandem-repeat loci for the Y chromosome, and sequencing of the HVS1 for the mtDNA are consistent with a small group of founders splitting from a single ethnic population in the Indian subcontinent. Principal-components analysis and analysis of molecular variance indicate that genetic structure in extant endogamous Romani populations has been shaped by genetic drift and differential admixture and correlates with the migrational history of the Roma in Europe. By contrast, social organization and professional group divisions appear to be the product of a more recent restitution of the caste system of India.

Corporate Finance and the Monetary Transmission Mechanism

Abstract: This Paper analyses the transmission mechanisms of monetary policy in a general equilibrium model of securities markets and banking with asymmetric information. Banks' optimal asset/liability policy is such that in equilibrium capital adequacy constraints are always binding. Asymmetric information about banks' net worth adds a cost to outside equity capital, which limits the extent to which banks can relax their capital constraint. In this context monetary policy does not affect bank lending through changes in bank liquidity. Rather, it has the effect of changing the aggregate composition of financing by firms. The model also produces multiple equilibria, one of which displays all the features of a 'credit crunch'. Thus, monetary policy can also have large effects when it induces a shift between equilibria.

Restless bandits, partial conservation laws and indexability

Abstract: We show that if performance measures in a general stochastic scheduling problem satisfy partial conservation laws (PCL), which extend the generalized conservation laws (GCL) introduced by Bertsimas and Nino-Mora (1996), then the problem is solved optimally by a priority-index policy under a range of admissible linear performance objectives, with both this range and the optimal indices being determined by a one-pass adaptive-greedy algorithm that extends Klimov’s: we call such scheduling problems PCL-indexable. We further apply the PCL framework to investigate the indexability property of restless bandits (two-action finite-state Markov decision chains) introduced by Whittle, obtaining the following results: (i) we present conditions on model parameters under which a single restless bandit is PCL-indexable, and hence indexable; membership ofthe class of PCL-indexable bandits is tested through a single run ofthe adaptive-greedy algorithm, which further computes the Whittle indices when the test is positive; this provides a tractable sufficient condition for indexability; (ii) we further introduce the subclass of GCL-indexable bandits (including classical bandits), which are indexable under arbitrary linear rewards. Our analysis is based on the achievable region approach to stochastic optimization, as the results follow from deriving and exploiting a new linear programming reformulation for single restless bandits.

Impairment of mossy fiber long-term potentiation and associative learning in pituitary adenylate cyclase activating polypeptide type I receptor-deficient mice.

Abstract: The pituitary adenylate cyclase activating polypeptide (PACAP) type I receptor (PAC1) is a G-protein-coupled receptor binding the strongly conserved neuropeptide PACAP with 1000-fold higher affinity than the related peptide vasoactive intestinal peptide. PAC1-mediated signaling has been implicated in neuronal differentiation and synaptic plasticity. To gain further insight into the biological significance of PAC1-mediated signaling in vivo, we generated two different mutant mouse strains, harboring either a complete or a forebrain-specific inactivation of PAC1. Mutants from both strains show a deficit in contextual fear conditioning, a hippocampus-dependent associative learning paradigm. In sharp contrast, amygdala-dependent cued fear conditioning remains intact. Interestingly, no deficits in other hippocampus-dependent tasks modeling declarative learning such as the Morris water maze or the social transmission of food preference are observed. At the cellular level, the deficit in hippocampus-dependent associative learning is accompanied by an impairment of mossy fiber long-term potentiation (LTP). Because the hippocampal expression of PAC1 is restricted to mossy fiber terminals, we conclude that presynaptic PAC1-mediated signaling at the mossy fiber synapse is involved in both LTP and hippocampus-dependent associative learning.

Connected components of sets of finite perimeter and applications to image processing

Abstract: This paper contains a systematic analysis of a natural measure theoretic notion of connectedness for sets of finite perimeter in ℝN, introduced by H. Federer in the more general framework of the theory of currents. We provide a new and simpler proof of the existence and uniqueness of the decomposition into the so-called M-connected components. Moreover, we study carefully the structure of the essential boundary of these components and give in particular a reconstruction formula of a set of finite perimeter from the family of the boundaries of its components. In the two dimensional case we show that this notion of connectedness is comparable with the topological one, modulo the choice of a suitable representative in the equivalence class. Our strong motivation for this study is a mathematical justification of all those operations in image processing that involve connectedness and boundaries. As an application, we use this weak notion of connectedness to provide a rigorous mathematical basis to a large class of denoising filters acting on connected components of level sets. We introduce a natural domain for these filters, the space WBV(Ω) of functions of weakly bounded variation in Ω, and show that these filters are also well behaved in the classical Sobolev and BV spaces.