Showing papers by "Pompeu Fabra University published in 2000"

Image inpainting

Abstract: Inpainting, the technique of modifying an image in an undetectable form, is as ancient as art itself. The goals and applications of inpainting are numerous, from the restoration of damaged paintings and photographs to the removal/replacement of selected objects. In this paper, we introduce a novel algorithm for digital inpainting of still images that attempts to replicate the basic techniques used by professional restorators. After the user selects the regions to be restored, the algorithm automatically fills-in these regions with information surrounding them. The fill-in is done in such a way that isophote lines arriving at the regions' boundaries are completed inside. In contrast with previous approaches, the technique here introduced does not require the user to specify where the novel information comes from. This is automatically done (and in a fast way), thereby allowing to simultaneously fill-in numerous regions containing completely different structures and surrounding backgrounds. In addition, no limitations are imposed on the topology of the region to be inpainted. Applications of this technique include the restoration of old photographs and damaged film; removal of superimposed text like dates, subtitles, or publicity; and the removal of entire objects from the image like microphones or wires in special effects.

The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells.

Abstract: The adhesion protein E-cadherin plays a central part in the process of epithelial morphogenesis. Expression of this protein is downregulated during the acquisition of metastatic potential at late stages of epithelial tumour progression. There is evidence for a transcriptional blockage of E-cadherin gene expression in this process. Here we show that the transcription factor Snail, which is expressed by fibroblasts and some E-cadherin-negative epithelial tumour cell lines, binds to three E-boxes present in the human E-cadherin promoter and represses transcription of E-cadherin. Inhibition of Snail function in epithelial cancer cell lines lacking E-cadherin protein restores the expression of the E-cadherin gene.

A simple adaptive procedure leading to correlated equilibrium

Abstract: We propose a new and simple adaptive procedure for playing a game: ‘‘regret-matching.’’ In this procedure, players may depart from their current play with probabilities that are proportional to measures of regret for not having used other strategies in the past. It is shown that our adaptive procedure guarantees that, with probability one, the empirical distributions of play converge to the set of correlated equilibria of the game.

Y chromosome sequence variation and the history of human populations

Abstract: Binary polymorphisms associated with the non-recombining region of the human Y chromosome (NRY) preserve the paternal genetic legacy of our species that has persisted to the present, permitting inference of human evolution, population affinity and demographic history 1 . We used denaturing highperformance liquid chromatography (DHPLC; ref. 2) to identify 160 of the 166 bi-allelic and 1 tri-allelic site that formed a parsimonious genealogy of 116 haplotypes, several of which display distinct population affinities based on the analysis of 1062 globally representative individuals. A minority of contemporary East Africans and Khoisan represent the descendants of the most ancestral patrilineages of anatomically modern humans that left Africa between 35,000 and 89,000 years ago.

Scaled and Adjusted Restricted Tests in Multi-Sample Analysis of Moment Structures

Abstract: Moment structure analysis is widely used in behavioural, social and economic studies to analyse structural relations between variables, some of which may be latent (i.e., unobservable); see, for example, Bollen (1989), Yuan and Bentler (1997), and references therein. Commercial computer programs to carry out such analysis, for a general class of structural equation models, are available, for example, LISREL of Joreskog and Sorbom (1994) and EQS of Bentler (1995). In multi-sample analysis, data from several samples are combined into one analysis, making it possible, among other features, to test for across-group invariance of specific model parameters. One issue which is central in moment structure analysis is the goodness-of-fit test of the model and the test of restrictions on parameters.

Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses

Abstract: The role of the opioid system in controlling pain, reward and addiction is well established, but its role in regulating other emotional responses is poorly documented in pharmacology. The mu-, delta- and kappa- opioid receptors (encoded by Oprm, Oprd1 and Oprk1, respectively) mediate the biological activity of opioids. We have generated Oprd1-deficient mice and compared the behavioural responses of mice lacking Oprd1, Oprm (ref. 6) and Oprk1 (ref. 7) in several models of anxiety and depression. Our data show no detectable phenotype in Oprk1-/- mutants, suggesting that kappa-receptors do not have a role in this aspect of opioid function; opposing phenotypes in Oprm-/- and Oprd1-/- mutants which contrasts with the classical notion of similar activities of mu- and delta-receptors; and consistent anxiogenic- and depressive-like responses in Oprd1-/- mice, indicating that delta-receptor activity contributes to improvement of mood states. We conclude that the Oprd1-encoded receptor, which has been proposed to be a promising target for the clinical management of pain, should also be considered in the treatment of drug addiction and other mood-related disorders.

Y-Chromosomal Diversity in Europe Is Clinal and Influenced Primarily by Geography, Rather than by Language

Abstract: Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.

Involvement of the extracellular signal-regulated kinase cascade for cocaine-rewarding properties.

Abstract: A central feature of drugs of abuse is to induce gene expression in discrete brain structures that are critically involved in behavioral responses related to addictive processes. Although extracellular signal-regulated kinase (ERK) has been implicated in several neurobiological processes, including neuronal plasticity, its role in drug addiction remains poorly understood. This study was designed to analyze the activation of ERK by cocaine, its involvement in cocaine-induced early and long-term behavioral effects, as well as in gene expression. We show, by immunocytochemistry, that acute cocaine administration activates ERK throughout the striatum, rapidly but transiently. This activation was blocked when SCH 23390 [a specific dopamine (DA)-D1 antagonist] but not raclopride (a DA-D2 antagonist) was injected before cocaine. Glutamate receptors of NMDA subtypes also participated in ERK activation, as shown after injection of the NMDA receptor antagonist MK 801. The systemic injection of SL327, a selective inhibitor of the ERK kinase MEK, before cocaine, abolished the cocaine-induced ERK activation and decreased cocaine-induced hyperlocomotion, indicating a role of this pathway in events underlying early behavioral responses. Moreover, the rewarding effects of cocaine were abolished by SL327 in the place-conditioning paradigm. Because SL327 antagonized cocaine-induced c-fos expression and Elk-1 hyperphosphorylation, we suggest that the ERK intracellular signaling cascade is also involved in the prime burst of gene expression underlying long-term behavioral changes induced by cocaine. Altogether, these results reveal a new mechanism to explain behavioral responses of cocaine related to its addictive properties.

A Parameter-Free Elicitation of the Probability Weighting Function in Medical Decision Analysis

Abstract: An important reason why people violate expected utility theory is probability weighting. Previous studies on the probability weighting function typically assume a specific parametric form, exclude heterogeneity in individual preferences, and exclusively consider monetary decision making. This study presents a method to elicit the probability weighting function in rank-dependent expected utility theory that makes no prior assumptions about the functional form of the probability weighting function. We use both aggregate and individual subject data, thereby allowing for heterogeneity of individual preferences, and we examine probability weighting in a new domain, medical decision making. There is significant evidence of probability weighting both at the aggregate and at the individual subject level. The modal probability weighting function is inverse S-shaped, displaying both lower subadditivity and upper subadditivity. Probability weighting is in particular relevant at the boundaries of the unit interval. Compared to studies involving monetary outcomes, we generally find more elevation of the probability weighting function. The robustness of the empirical findings on probability weighting indicates its importance. Ignoring probability weighting in modeling decision under risk and in utility measurement is likely to lead to descriptively invalid theories and distorted elicitations.

How do types of employment relate to health indicators? Findings from the Second European Survey on Working Conditions

Abstract: Study objective—To investigate the associations of various types of employment with six self reported health indicators, taking into account the part played by demographic variables, individual working conditions and four ecological indicators at the country level. Design—Cross sectional survey (structured interview) of a sample of the active population of 15 European countries aged 15 years or over. Main independent variables were nine types of employment categorised as follows: small employers, full and part time permanent employees, full and part time fixed term employees, full and part time sole traders and full and part time temporary contracts. Main outcome measures were three self reported health related outcomes (job satisfaction, health related absenteeism, and stress) and three self reported health problems (overall fatigue, backache, and muscular pains). Logistic regression and multilevel models were used in the analyses. Setting—15 countries of the European Union. Participants—15 146 employed persons aged 15 or over.

Inflation Dynamics: A Structural Econometric Analysis

Abstract: We develop and estimate a structural model of inflation that allows for a fraction of firms that use a backward looking rule to set prices. The model nests the purely forward looking New Keynesian Phillips curve as a particular case. We use measures of arginal cost as the relevant determinant of inflation, as the theory suggests, instead of an ad-hoc output gap. Real marginal costs are a significant and quantitatively important determinant of inflation. Backward looking price setting, while statistically significant, is not quantitatively important. Thus, we conclude that the New Keynesian Phillips curve provides a good first approximation to the dynamics of inflation.

GeneID in Drosophila

Abstract: GeneID is a program to predict genes in anonymous genomic sequences designed with a hierarchical structure. In the first step, splice sites, and start and stop codons are predicted and scored along the sequence using position weight matrices (PWMs). In the second step, exons are built from the sites. Exons are scored as the sum of the scores of the defining sites, plus the log-likelihood ratio of a Markov model for coding DNA. In the last step, from the set of predicted exons, the gene structure is assembled, maximizing the sum of the scores of the assembled exons. In this paper we describe the obtention of PWMs for sites, and the Markov model of coding DNA in Drosophila melanogaster. We also compare other models of coding DNA with the Markov model. Finally, we present and discuss the results obtained when GeneID is used to predict genes in the Adh region. These results show that the accuracy of GeneID predictions compares currently with that of other existing tools but that GeneID is likely to be more efficient in terms of speed and memory usage.

Model Selection and Error Estimation

Abstract: We study model selection strategies based on penalized empirical loss minimization. We point out a tight relationship between error estimation and data-based complexity penalization: any good error estimate may be converted into a data-based penalty function and the performance of the estimate is governed by the quality of the error estimate. We consider several penalty functions, involving error estimates on independent test data, empirical VC dimension, empirical VC entropy, and margin-based quantities. We also consider the maximal difference between the error on the first half of the training data and the second half, and the expected maximal discrepancy, a closely related capacity estimate that can be calculated by Monte Carlo integration. Maximal discrepancy penalty functions are appealing for pattern classification problems, since their computation is equivalent to empirical risk minimization over the training data with some labels flipped.

Calcineurin: from structure to function.

Abstract: Publisher Summary The use of the calcineurin inhibitors—namely, FK506 and CsA, together with yeast genetics and the overexpression of calcineurin by transgenic mice, has established the critical roles of calcineurin in the regulation of many cellular processes that are induced by changes in the concentration of intracellular Ca 2+ in response to external signals. None of the physiological roles of calcineurin is better documented than the regulation of gene expression mediated by the broadly distributed NFAT family of transcription factors in mammalian cells. Equally well documented is the role of calcineurin in the regulation of expression of many genes that are under the control of the TCNI/CRZl transcription factor in yeast. Calcineurim was originally identified as a major calmodulin-binding protein in the brain and later shown to be the only Ca 2+ /calmodulin-regulated serine/threonine protein phosphatase. Since then, this enzyme has been shown to be expressed in every tissue and to be highly conserved phylogenetically.

Hot vs. Cold: Sequential Responses and Preference Stability in Experimental Games

Abstract: In experiments with two-person sequential games we analyze whether responses to favorable and unfavorable actions depend on the elicitation procedure. In our “hot” treatment the second player responds to the first player's observed action while in our “cold” treatment we follow the “strategy method” and have the second player decide on a contingent action for each and every possible first player move, without first observing this move. Our analysis centers on the degree to which subjects deviate from the maximization of their pecuniary rewards, as a response to others' actions. Our results show no difference in behavior between the two treatments. We also find evidence of the stability of subjects' preferences with respect to their behavior over time and to the consistency of their choices as first and second mover.

Yeast Cdc42 GTPase and Ste20 PAK‐like kinase regulate Sho1‐dependent activation of the Hog1 MAPK pathway

Abstract: The adaptive response to hyperosmotic stress in yeast, termed the high osmolarity glycerol (HOG) response, is mediated by two independent upstream pathways that converge on the Pbs2 MAP kinase kinase (MAPKK), leading to the activation of the Hog1 MAP kinase. One branch is dependent on the Sho1 transmembrane protein, whose primary role was found to be the binding and translocation of the Pbs2 MAPKK to the plasma membrane, and specifically to sites of polarized growth. The yeast PAK homolog Ste20 is essential for the Sho1-dependent activation of the Hog1 MAP kinase in response to severe osmotic stress. This function of Ste20 in the HOG pathway requires binding of the small GTPase Cdc42. Overexpression of Cdc42 partially complements the osmosensitivity of ste20Δ mutants, perhaps by activating another PAK-like kinase, while a dominant-negative Cdc42 mutant inhibited signaling through the SHO1 branch of the HOG pathway. Since activated Cdc42 translocates Ste20 to sites of polarized growth, the upstream and downstream elements of the HOG pathway are brought together through the membrane targeting function of Sho1 and Cdc42.

Geographic Patterns of mtDNA Diversity in Europe

Abstract: Genetic diversity in Europe has been interpreted as a reflection of phenomena occurring during the Paleolithic (∼45,000 years before the present [BP]), Mesolithic (∼18,000 years BP), and Neolithic (∼10,000 years BP) periods. A crucial role of the Neolithic demographic transition is supported by the analysis of most nuclear loci, but the interpretation of mtDNA evidence is controversial. More than 2,600 sequences of the first hypervariable mitochondrial control region were analyzed for geographic patterns in samples from Europe, the Near East, and the Caucasus. Two autocorrelation statistics were used, one based on allele-frequency differences between samples and the other based on both sequence and frequency differences between alleles. In the global analysis, limited geographic patterning was observed, which could largely be attributed to a marked difference between the Saami and all other populations. The distribution of the zones of highest mitochondrial variation (genetic boundaries) confirmed that the Saami are sharply differentiated from an otherwise rather homogeneous set of European samples. However, an area of significant clinal variation was identified around the Mediterranean Sea (and not in the north), even though the differences between northern and southern populations were insignificant. Both a Paleolithic expansion and the Neolithic demic diffusion of farmers could have determined a longitudinal cline of mtDNA diversity. However, additional phenomena must be considered in both models, to account both for the north-south differences and for the greater geographic scope of clinal patterns at nuclear loci. Conversely, two predicted consequences of models of Mesolithic reexpansion from glacial refugia were not observed in the present study.

Cocaine, but not morphine, induces conditioned place preference and sensitization to locomotor responses in CB1 knockout mice

Abstract: The involvement of cannabinoid CB1 receptors in morphine and cocaine motivational effects was investigated using CB1 knockout mice For this purpose, we evaluated the rewarding effects in the place conditioning paradigm and the sensitization to the locomotor responses induced by these drugs The hyperlocomotion induced by acute morphine administration (15 mg/kg, sc) was preserved, but the sensitization to this locomotor response induced by chronic morphine treatment was abolished in CB1 mutant mice Morphine (5 mg/kg, sc) induced conditioned place preference in wild-type mice but failed to produce any response in knockout mice, indicating the inability of morphine to induce rewarding effects in the absence of CB1 cannabinoid receptors When the aversive effects of morphine withdrawal were investigated using the place aversion paradigm, no differences between genotypes were observed Acute cocaine (10 mg/kg, ip) induced hyperlocomotor responses in wild-type and knockout mice and a chronic cocaine treatment produced a similar sensitization to this response in both genotypes In the conditioning place preference paradigm, cocaine (20 mg/kg, ip) produced rewarding responses in both wild-type and knockout mice These results demonstrate that CB1 receptors are essential for adaptive responses produced by chronic morphine but not by chronic cocaine treatment

An Assessment of Gene Prediction Accuracy in Large DNA Sequences

Abstract: One of the first useful products from the human genome will be a set of predicted genes. Besides its intrinsic scientific interest, the accuracy and completeness of this data set is of considerable importance for human health and medicine. Though progress has been made on computational gene identification in terms of both methods and accuracy evaluation measures, most of the sequence sets in which the programs are tested are short genomic sequences, and there is concern that these accuracy measures may not extrapolate well to larger, more challenging data sets. Given the absence of experimentally verified large genomic data sets, we constructed a semiartificial test set comprising a number of short single-gene genomic sequences with randomly generated intergenic regions. This test set, which should still present an easier problem than real human genomic sequence, mimics the approximately 200kb long BACs being sequenced. In our experiments with these longer genomic sequences, the accuracy of GENSCAN, one of the most accurate ab initio gene prediction programs, dropped significantly, although its sensitivity remained high. Conversely, the accuracy of similarity-based programs, such as GENEWISE, PROCRUSTES, and BLASTX was not affected significantly by the presence of random intergenic sequence, but depended on the strength of the similarity to the protein homolog. As expected, the accuracy dropped if the models were built using more distant homologs, and we were able to quantitatively estimate this decline. However, the specificities of these techniques are still rather good even when the similarity is weak, which is a desirable characteristic for driving expensive follow-up experiments. Our experiments suggest that though gene prediction will improve with every new protein that is discovered and through improvements in the current set of tools, we still have a long way to go before we can decipher the precise exonic structure of every gene in the human genome using purely computational methodology.

A behavioural model to reveal place preference to Δ9-tetrahydrocannabinol in mice

Abstract: Rationale: The rewarding properties of Δ9- tetrahydrocannabinol (THC) are difficult to demonstrate in rodents using standard procedures. Objective: To evaluate the motivational responses of THC in the place conditioning paradigm in mice after minimizing the dysphoric effects of the first drug exposure and/or the consequences of its pharmacokinetic properties. Methods: Mice were conditioned to THC (1 or 5 mg/kg) using an unbiased procedure with an elevated number of pairings and long conditioning time. Results: A place aversion was observed with 5 mg/kg THC using a standard protocol. Similar results were obtained when the CB-1 receptor antagonist SR 141716A (1 mg/kg) was administered immediately after each THC conditioning period. However, mice receiving a priming THC injection and conditioned 24 h later showed a place preference with 1 mg/kg THC and no effect with 5 mg/kg THC. Conclusion: THC produces a clear place preference in mice by using a long period of conditioning and avoiding the possible dysphoric consequences of the first drug exposure.

A sharp concentration inequality with application

Abstract: We derive a new general concentration-of-measure inequality. The concentration inequality applies, among others, to configuration functions as defined by Talagrand and also to combinatorial entropies such as the logarithm of the number of increasing subsequences in a random permutation and to Vapnik-Chervonenkis (VC) entropies. The results find direct applications in statistical learning theory, substantiating the possibility to use the empirical VC entropy in penalization techniques. © 2000 John Wiley & Sons, Inc. Random Struct. Alg., 16: 277–292, 2000

Contractual Allocation of Decision Rights and Incentives: The Case of Automobile Distribution

Abstract: We analyze empirically the allocation of rights and monetary incentives in automobile franchise contracts. All of these contracts substantially restrict the decision rights of dealers and grant manufacturers extensive rights to specify and enforce dealers' duties. The allocation of decision rights and incentive intensity differs across brands, however. This variation is explained by the incidence of moral hazard. In particular, when the cost of dealer moral hazard is higher and the risk of manufacturer opportunism is lower, manufacturers hold more rights to determine the performance required from their dealers and to use mechanisms such as monitoring, termination and monetary incentives to ensure that such performance is provided.

Responsibility and effort in an experimental labor market

Abstract: Previous indirect evidence suggests that impulses towards pro-social behavior are diminished when an external authority is responsible for an outcome. The responsibility-alleviation effect states that a shift of responsibility to an external authority dampens internal impulses toward honesty, loyalty, or generosity. In a gift-exchange experiment, we find that subjects respond with more generosity (higher effort) when wages are determined by a random process than when assigned by a third party, indicating that even a slight shift in perceived responsibility for the final payoffs can change behavior. Responsibility-alleviation can be a factor in economic environments featuring substantial personal interaction.

The health-damaging potential of new types of flexible employment: a challenge for public health researchers.

Abstract: 1316 American Journal of Public Health Department of Health Services, Boston University School of Public Health, and the New England Regional Spinal Cord Injury Center, Boston, Mass. Dr Meyers died while this report was in press. Requests for reprints should be sent to Rachel H. Tanenhaus, MPH, Boston University School of Public Health, Department of Health Services , 715 Albany St, T–3W, Boston, MA 02118 (e-mail: tivka@bu.edu). Note. This paper reflects only the authors’ opinions and does not necessarily reflect the official positions of the Centers for Disease Control and Prevention, the National Institute on Disability and Rehabilitation Research, Boston University, or the Boston Medical Center.

Alu insertion polymorphisms in NW Africa and the Iberian Peninsula: evidence for a strong genetic boundary through the Gibraltar Straits.

Abstract: An analysis of 11 Alu insertion polymorphisms (ACE, TPA25, PV92, APO, FXIIIB, D1, A25, B65, HS2.43, HS3.23, and HS4.65) has been performed in several NW African (Northern, Western, and Southeastern Moroccans; Saharawi; Algerians; Tunisians) and Iberian (Basques, Cata- lans, and Andalusians) populations. Genetic distances and principal component analyses show a clear differentiation of NW African and Iberian groups of samples, suggesting a strong genetic barrier matching the geographical Mediter- ranean Sea barrier. The restriction to gene flow may be at- tributed to the navigational hazards across the Straits, but cultural factors must also have played a role. Some degree of gene flow from sub-Saharan Africa can be detected in the southern part of North Africa and in Saharawi and South- eastern Moroccans, as a result of a continuous gene flow across the Sahara desert that has created a south-north cline of sub-Saharan Africa influence in North Africa. Iberian samples show a substantial degree of homogeneity and fall within the cluster of European-based genetic diversity.

Patients hospitalized for COPD have a high prevalence of modifiable risk factors for exacerbation (EFRAM study)

Abstract: There is little information available concerning the extent to which chronic obstructive pulmonarv disease (COPD) patients are satisfactorily managed, especially, regards factors supposedly related to COPD exacerbation. The present study assessed the prevalence rates of potentially modifiable risk factors of COPD exacerbation in patients hospitalized for this reason. A systematic sample of one out of two patients admitted for COPD exacerbation, during 1 yr, in four tertiary hospitals in the Barcelona area, Spain, was performed. Patients answered a questionnaire and underwent anthropometric measurements, spirometric tests and arterial blood gas sampling. Prevalence rates and 95% confidence intervals (95% CI) for risk factors were obtained, and the generalized estimating equation (GEE) method was used to allow for patients to provide information on different admissions. The study recruited 353 patients (29 female) with a total of 404 admissions age (mean+/-SD) 69+/-9, median forced expiratory volume in one second (FEV1) 31% of predicted and mean partial pressure of oxygen (PO2) 63+/-13 mmHg. Of these, 28% had not received an influenza vaccination; a high number (86%) did not attend rehabilitation programmes; 28% of patients with PO2 < or =55 mmHg were not using long-term oxygen therapy (LTOT); among LTOT users, 18% used it <15 h a day; 43% of the total failed in some of the essential inhaler manoeuvres; 26% were current smokers; 21% of noncurrent smokers were exposed to passive smoking at home; current occupational exposure was low (5%). In summary, the authors found a moderate to high prevalence of potentially modifiable risk factors in a large representative sample of patients hospitalized for a chronic obstructive pulmonary disease exacerbation, suggesting unsatisfactory features in their management.