The minimax distortion redundancy in empirical quantizer design

We obtain minimax lower and upper bounds for the expected distortionredundancy of empirically designed vector quantizers. We show that the meansquared distortion of a vector quantizer designed from $n$ i.i.d. datapoints using any design algorithm is at least $\Omega (n^{-1/2})$ awayfrom the optimal distortion for some distribution on a bounded subset of${\cal R}^d$. Together with existing upper bounds this result shows thatthe minimax distortion redundancy for empirical quantizer design, as afunction of the size of the training data, is asymptotically on the orderof $n^{1/2}$. We also derive a new upper bound for the performance of theempirically optimal quantizer.

The challenge of representative design in psychology and economics

The demands of representative design, as formulated by Egon Brunswik (1956), set a high methodological standard. Both experimental participants and the situations with which they are faced should be representative of the populations to which researchers claim to generalize results. Failure to observe the latter has led to notable experimental failures in psychology from which economics could learn. It also raises questions about the meaning of testing economic theories in abstract environments. Logically, abstract tests can only be generalized to abstract realities and these may or may not have anything to do with the empirical realities experienced by economic actors.

Expanding molecular modeling and design tools to non-natural sidechains.

Protein-protein interactions encode the wiring diagram of cellular signaling pathways and their deregulations underlie a variety of diseases, such as cancer. Inhibiting protein-protein interactions with peptide derivatives is a promising way to develop new biological and therapeutic tools. Here, we develop a general framework to computationally handle hundreds of non-natural amino acid sidechains and predict the effect of inserting them into peptides or proteins. We first generate all structural files (pdb and mol2), as well as parameters and topologies for standard molecular mechanics software (CHARMM and Gromacs). Accurate predictions of rotamer probabilities are provided using a novel combined knowledge and physics based strategy. Non-natural sidechains are useful to increase peptide ligand binding affinity. Our results obtained on non-natural mutants of a BCL9 peptide targeting beta-catenin show very good correlation between predicted and experimental binding free-energies, indicating that such predictions can be used to design new inhibitors. Data generated in this work, as well as PyMOL and UCSF Chimera plug-ins for user-friendly visualization of non-natural sidechains, are all available at http://www.swisssidechain.ch. Our results enable researchers to rapidly and efficiently work with hundreds of non-natural sidechains.

Genomewide association study using a high-density single nucleotide polymorphism array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase.

Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37-1.73]; combined P=2.58 · 10(-13)). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25-1.44; P=1.032 · 10(-14)). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16-3.66) for systolic and 1.40 (95% CI: 0.25-2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.

La société sénégalaise et les enfants de la rue : approche socio-anthropologique des dynamiques d'exclusion et de survie : étude de cas à Dakar

Résumé : La société sénégalaise traverse une crise profonde qui touche tous les secteurs de la vie. Cette crise à la fois structurelle et conjoncturelle crée à son tour une sorte de société de la crise qui touche les populations les plus vulnérables. Le phénomène des enfants de la rue est l'expression parfaite de cette société de la crise. Le rythme dans lequel il se développe est la traduction de la dynamique d'exclusion qui sévit en milieu urbain sénégalais en général et dans la région de Dakar en particulier. Dans cette région, l'urbanisation s'est accompagnée de la montée des inégalités qui placent la société dans une sorte de dualisation entre centre et périphérie. A la ville de Dakar qui s'est constituée selon les normes de la planification urbaine, s'oppose les principales banlieues de Pikine, Guédiawaye et Rufisque qui offrent le visage de marges sociales urbaines. D'une certaine manière, la montée des inégalités remet en cause les politiques sociales, de la bonne gouvernance et de la redistribution des richesses. Ces banlieues constituent les principaux milieux d'accueil de la masse de migrants ruraux qui fuient la misère des villages. D'une part, l'hétérogénéité sociale de ces banlieues ne favorise pas l'émergence d'une conscience collective fondée sur l'appartenance à un fonds historique commun. Par contre, elle renforce l'anonymat et l'indifférence propres à la ville. D'autre part, les difficultés économiques et la précarité des conditions de vie conjuguées à l'explosion démographique et ses conséquences affaiblissent les systèmes de solidarité entraînant ainsi la montée de l'individualisme et la philosophie du chacun pour soi. Ce qui met en cause l'éducation des enfants qui devient difficile pour les parents d'assumer. En outre, la place importante accordée à l'imaginaire social dans la société sénégalaise explique le recours aux forces surnaturelles par l'intercession des marabouts, sorciers, devins, etc. D'autre part, la place accordée aux offrandes et aux sacrifices de même que le "besoin de donner" alimente et pérennise la pratique de la mendicité en général et celle des enfants en particulier. En outre, l'instrumentalisation de la mendicité par certains marabouts qui se traduit par une sorte de "business talibé" ou de "marché de l'aumône", rapproche les enfants de l'univers de là rue qui devient pour eux une sorte d'échappatoire face aux conditions de vie que leur imposent ces marabouts. Ainsi, pour eux, la rue remplit une fonction de socialisation. En effet, dans cet univers social, les enfants se forgent une personnalité, développent des compétences et des activités qui leur permettent de survivre, créent des repères et des codes collectifs qui leur permettent de mener une existence que la société assimile strictement à la déviance. Mots clé : crise, école, éducation, enfants de la rue, exclusion, inégalités, migration, pauvreté, socialisation, stratégies de survie, uibanisation.

iLOGP: A Simple, Robust, and Efficient Description of n-Octanol/Water Partition Coefficient for Drug Design Using the GB/SA Approach.

The n-octanol/water partition coefficient (log Po/w) is a key physicochemical parameter for drug discovery, design, and development. Here, we present a physics-based approach that shows a strong linear correlation between the computed solvation free energy in implicit solvents and the experimental log Po/w on a cleansed data set of more than 17,500 molecules. After internal validation by five-fold cross-validation and data randomization, the predictive power of the most interesting multiple linear model, based on two GB/SA parameters solely, was tested on two different external sets of molecules. On the Martel druglike test set, the predictive power of the best model (N = 706, r = 0.64, MAE = 1.18, and RMSE = 1.40) is similar to six well-established empirical methods. On the 17-drug test set, our model outperformed all compared empirical methodologies (N = 17, r = 0.94, MAE = 0.38, and RMSE = 0.52). The physical basis of our original GB/SA approach together with its predictive capacity, computational efficiency (1 to 2 s per molecule), and tridimensional molecular graphics capability lay the foundations for a promising predictor, the implicit log P method (iLOGP), to complement the portfolio of drug design tools developed and provided by the SIB Swiss Institute of Bioinformatics.

Design effect and interviewer effects: Evidence from the Spanish ESS3-2006 Data

In 2007 the first Quality Enhancement Meeting on sampling in the European SocialSurvey (ESS) took place. The discussion focused on design effects and inteviewereffects in face-to-face interviews. Following the recomendations of this meeting theSpanish ESS team studied the impact of interviewers as a new element in the designeffect in the response s variance using the information of the correspondent SampleDesign Data Files. Hierarchical multilevel and cross-classified multilevel analysis areconducted in order to estimate the amount of responses variation due to PSU and tointerviewers for different questions in the survey. Factor such as the age of theinterviewer, gender, workload, training and experience and respondent characteristicssuch as age, gender, renuance to participate and their possible interactions are alsoincluded in the analysis of some specific questions like trust in politicians and trustin legal system . Some recomendations related to future sampling designs and thecontents of the briefing sessions are derived from this initial research.

O Estereótipo na Publicidade em Cabo verde Estudo de Caso das Publicidades produzidas pela Design Comunicação e Imagem (DECO)

O presente trabalho monográfico intitulado “O estereótipo na publicidade em Cabo Verde – Estudo de Caso das Publicidades Produzida pela Design Comunicação e Imagem”, enquadra-se no âmbito do curso de licenciatura em Ciências da Comunicação, vertente Publicidade realizado pela universidade Jean Piaget de Cabo Verde. O presente trabalho visa apresentar as noções conceptuais do estereótipo e a sua dinâmica na publicidade e argumentar sobre alguns efeitos que este elemento pode promover no discurso publicitário. Assim, propôs-se como estudo de caso as publicidades criadas pela empresa DECO: O objectivo é, essencialmente, caracterizar a publicidade que se faz em Cabo Verde, verificando se os publicitários cabo-verdianos estão a explorar os recursos de que dispõem, designadamente os valores, os estilos de vida, estereótipos, etc., para chegar aos seus consumidores. Com a realização deste trabalho, chegou-se a conclusão que, o estereótipo faz parte da vida do homem para o bem ou para o mal. Sem a sua presença seria muito complicado perceber ou descodificar alguns fenómenos que acontecem na sociedade. O estereótipo ajuda na compreensão de informações que a primeira seria complexo de interpretar, tornando-a fácil.

Hypoglycémie: approche diagnostique

Hypoglycaemia can occur if the endogenous liver glucose output is lower than the glucose uptake in insulin-sensitive and insulin-insensitive tissues. The onset of hypoglycaemia induces the production of counterregulatory hormones such as glucagon, epinephrine, growth hormone and cortisol, and symptoms of neuroglycopenia. The correlation between biological hypoglycaemia and the symptoms associated with low blood sugar is particularly poor in diabetic patients and in patients with suspected postprandial hypoglycaemia. It is important to discriminate between fasting and postprandial hypoglycaemia. Idiopathic postprandial hypoglycaemia should be diagnosed clinically without further laboratory assessment, whereas the etiology of a fasting hypoglycaemia needs to be clarified further by laboratory testing, as it is potentially life-threatening.

Design of new promoters and of a dual-bioreporter based on cross-activation by the two regulatory proteins XylR and HbpR.

The HbpR protein is the sigma54-dependent transcription activator for 2-hydroxybiphenyl degradation in Pseudomonas azelaica. The ability of HbpR and XylR, which share 35% amino acid sequence identity, to cross-activate the PhbpC and Pu promoters was investigated by determining HbpR- or XylR-mediated luciferase expression and by DNA binding assays. XylR measurably activated the PhbpC promoter in the presence of the effector m-xylene, both in Escherichia coli and Pseudomonas putida. HbpR weakly stimulated the Pu promoter in E. coli but not in P. azelaica. Poor HbpR-dependent activation from Pu was caused by a weak binding to the operator region. To create promoters efficiently activated by both regulators, the HbpR binding sites on PhbpC were gradually changed into the XylR binding sites of Pu by site-directed mutagenesis. Inducible luciferase expression from mutated promoters was tested in E. coli on a two plasmid system, and from mono copy gene fusions in P. azelaica and P. putida. Some mutants were efficiently activated by both HbpR and XylR, showing that promoters can be created which are permissive for both regulators. Others achieved a higher XylR-dependent transcription than from Pu itself. Mutants were also obtained which displayed a tenfold lower uninduced expression level by HbpR than the wild-type PhbpC, while keeping the same maximal induction level. On the basis of these results, a dual-responsive bioreporter strain of P. azelaica was created, containing both XylR and HbpR, and activating luciferase expression from the same single promoter independently with m-xylene and 2-hydroxybiphenyl.

Approche multidimensionnelle des jeux de hasard et d'argent - Représentations, dépistages et prévalences du jeu problématique.

Ce rapport présente plusieurs axes relatifs aux jeux de hasard et d'argent et au jeu problématique. Comment comprendre l'évolution de ce type de problématique dans une société? C'est au travers d'une analyse sur les représentations sociales en Suisse romande que ce travail propose une piste de réflexion et ceci dans le but de dresser un état des lieux de ces thématiques telles qu'elles existent dans les consciences collectives. Les représentations sociales ont fait l'objet de nombreuses études en Amérique du Nord mais sont par contre plutôt rares en Suisse. Nous avons pu constater au fil de ce travail que les représentations sont teintées de prudence; la population générale sollicitée ne semble pas ignorer quels sont les écueils pouvant être générés par ces pratiques; mais, en revanche, d'autres résultats nous ont permis de comprendre que le jeu problématique n'est pas encore intégré par l'ensemble de la population puisque 42.6% n'en ont jamais entendu parler. Il y a donc une brèche à exploiter en la matière tant d'un point de vue préventif que scientifique. Afin d'apporter une réalité supplémentaire et concrète à ces considérations d'ordre subjectif, nous avons agrémenté ce rapport d'analyses propres à l'épidémiologie du jeu en Suisse, et ceci au travers des données relatives aux Enquêtes suisses sur la santé 2002 et 2007. Finalement, un certain nombre d'outils de mesure et de dépistage à l'égard du jeu pathologique ont été sélectionnés dans la littérature internationale, et ceci dans le but de mieux comprendre quels sont les critères privilégiés permettant de déterminer ou diagnostiquer un joueur à risque. Le présent rapport offre donc un éventail de ce que sont les jeux et de ce qu'ils représentent dans notre société et délivre des informations diverses sur leurs appréhensions tant au niveau individuel que médical et social.