Event-related potential analyses via single-subject topographic classification.

Introduction: Responses to external stimuli are typically investigated by averaging peri-stimulus electroencephalography (EEG) epochs in order to derive event-related potentials (ERPs) across the electrode montage, under the assumption that signals that are related to the external stimulus are fixed in time across trials. We demonstrate the applicability of a single-trial model based on patterns of scalp topographies (De Lucia et al, 2007) that can be used for ERP analysis at the single-subject level. The model is able to classify new trials (or groups of trials) with minimal a priori hypotheses, using information derived from a training dataset. The features used for the classification (the topography of responses and their latency) can be neurophysiologically interpreted, because a difference in scalp topography indicates a different configuration of brain generators. An above chance classification accuracy on test datasets implicitly demonstrates the suitability of this model for EEG data. Methods: The data analyzed in this study were acquired from two separate visual evoked potential (VEP) experiments. The first entailed passive presentation of checkerboard stimuli to each of the four visual quadrants (hereafter, "Checkerboard Experiment") (Plomp et al, submitted). The second entailed active discrimination of novel versus repeated line drawings of common objects (hereafter, "Priming Experiment") (Murray et al, 2004). Four subjects per experiment were analyzed, using approx. 200 trials per experimental condition. These trials were randomly separated in training (90%) and testing (10%) datasets in 10 independent shuffles. In order to perform the ERP analysis we estimated the statistical distribution of voltage topographies by a Mixture of Gaussians (MofGs), which reduces our original dataset to a small number of representative voltage topographies. We then evaluated statistically the degree of presence of these template maps across trials and whether and when this was different across experimental conditions. Based on these differences, single-trials or sets of a few single-trials were classified as belonging to one or the other experimental condition. Classification performance was assessed using the Receiver Operating Characteristic (ROC) curve. Results: For the Checkerboard Experiment contrasts entailed left vs. right visual field presentations for upper and lower quadrants, separately. The average posterior probabilities, indicating the presence of the computed template maps in time and across trials revealed significant differences starting at ~60-70 ms post-stimulus. The average ROC curve area across all four subjects was 0.80 and 0.85 for upper and lower quadrants, respectively and was in all cases significantly higher than chance (unpaired t-test, p<0.0001). In the Priming Experiment, we contrasted initial versus repeated presentations of visual object stimuli. Their posterior probabilities revealed significant differences, which started at 250ms post-stimulus onset. The classification accuracy rates with single-trial test data were at chance level. We therefore considered sub-averages based on five single trials. We found that for three out of four subjects' classification rates were significantly above chance level (unpaired t-test, p<0.0001). Conclusions: The main advantage of the present approach is that it is based on topographic features that are readily interpretable along neurophysiologic lines. As these maps were previously normalized by the overall strength of the field potential on the scalp, a change in their presence across trials and between conditions forcibly reflects a change in the underlying generator configurations. The temporal periods of statistical difference between conditions were estimated for each training dataset for ten shuffles of the data. Across the ten shuffles and in both experiments, we observed a high level of consistency in the temporal periods over which the two conditions differed. With this method we are able to analyze ERPs at the single-subject level providing a novel tool to compare normal electrophysiological responses versus single cases that cannot be considered part of any cohort of subjects. This aspect promises to have a strong impact on both basic and clinical research.

Mutations inducing divergent shifts of constitutive activity reveal different modes of binding among catecholamine analogues to the beta(2)-adrenergic receptor.

1. We compared the changes in binding energy generated by two mutations that shift in divergent directions the constitutive activity of the human beta(2) adrenergic receptor (beta(2)AR). 2. A constitutively activating mutant (CAM) and the double alanine replacement (AA mutant) of catechol-binding serines (S204A, S207A) in helix 5 were stably expressed in CHO cell lines, and used to measure the binding affinities of more than 40 adrenergic ligands. Moreover, the efficacy of the same group of compounds was determined as intrinsic activity for maximal adenylyl cyclase stimulation in wild-type beta(2)AR. 3. Although the two mutations had opposite effects on ligand affinity, the extents of change were in both cases largely correlated with the degree of ligand efficacy. This was particularly evident if the extra loss of binding energy due to hydrogen bond deletion in the AA mutant was taken into account. Thus the data demonstrate that there is an overall linkage between the configuration of the binding pocket and the intrinsic equilibrium between active and inactive receptor forms. 4. We also found that AA mutation-induced affinity changes for catecholamine congeners gradually lacking ethanolamine substituents were linearly correlated to the loss of affinity that such modifications of the ligand cause for wild-type receptor. This indicates that the strength of bonds between catechol ring and helix 5 is critically dependent on the rest of interactions of the beta-ethanolamine tail with other residues of the beta(2)-AR binding pocket.

An evaluation of new parsimony-based versus parametric inference methods in biogeography: a case study using the globally distributed plant family Sapindaceae

Aim  Recently developed parametric methods in historical biogeography allow researchers to integrate temporal and palaeogeographical information into the reconstruction of biogeographical scenarios, thus overcoming a known bias of parsimony-based approaches. Here, we compare a parametric method, dispersal-extinction-cladogenesis (DEC), against a parsimony-based method, dispersal-vicariance analysis (DIVA), which does not incorporate branch lengths but accounts for phylogenetic uncertainty through a Bayesian empirical approach (Bayes-DIVA). We analyse the benefits and limitations of each method using the cosmopolitan plant family Sapindaceae as a case study.Location  World-wide.Methods  Phylogenetic relationships were estimated by Bayesian inference on a large dataset representing generic diversity within Sapindaceae. Lineage divergence times were estimated by penalized likelihood over a sample of trees from the posterior distribution of the phylogeny to account for dating uncertainty in biogeographical reconstructions. We compared biogeographical scenarios between Bayes-DIVA and two different DEC models: one with no geological constraints and another that employed a stratified palaeogeographical model in which dispersal rates were scaled according to area connectivity across four time slices, reflecting the changing continental configuration over the last 110 million years.Results  Despite differences in the underlying biogeographical model, Bayes-DIVA and DEC inferred similar biogeographical scenarios. The main differences were: (1) in the timing of dispersal events - which in Bayes-DIVA sometimes conflicts with palaeogeographical information, and (2) in the lower frequency of terminal dispersal events inferred by DEC. Uncertainty in divergence time estimations influenced both the inference of ancestral ranges and the decisiveness with which an area can be assigned to a node.Main conclusions  By considering lineage divergence times, the DEC method gives more accurate reconstructions that are in agreement with palaeogeographical evidence. In contrast, Bayes-DIVA showed the highest decisiveness in unequivocally reconstructing ancestral ranges, probably reflecting its ability to integrate phylogenetic uncertainty. Care should be taken in defining the palaeogeographical model in DEC because of the possibility of overestimating the frequency of extinction events, or of inferring ancestral ranges that are outside the extant species ranges, owing to dispersal constraints enforced by the model. The wide-spanning spatial and temporal model proposed here could prove useful for testing large-scale biogeographical patterns in plants.

Després de l’ESO què : eleccions i restriccions dels i les joves d’origen immigrant

En el projecte s’analitzarà, des d’una perspectiva biogràfica, la construcció d’aquests itineraris, amb les seves potencialitats i limitacions, oportunitats i problemàtiques; el moment especialment rellevant d’estudi serà en la transició després de l’ensenyament obligatori, bé sigui a les diferents vies formatives postobligatòries o bé al mercat de treball. El final de l’ESO és un moment de bifurcació i d’elecció, d’oportunitats més tancades o més obertes. En el nostre treball empíric, analitzarem els itineraris escolars d’un territori concret, en el qual hi trobem una alta concentració de persones immigrants. A partir d’aquest entorn determinat i específic, s’intentarà analitzar elements tant “sistèmics” com “comunitaris”. Els elements sistèmics seran: institució escolar, mercat laboral i polítiques públiques. Específicament, també es tindrà en compte: l’estructura d’oportunitats (segmentació laboral i geogràfica), la configuració de l’oferta formativa i les polítiques locals d’acollida. Els elements comunitaris seran: ètnia, classe, i gènere; família i grup d’iguals i pràctiques de lleure i de consum. Específicament, també es tindrà en compte: la genealogia de la “història de contacte”, la percepció de l’estructura d’oportunitats, la distància cultural, així com problemàtiques educatives específiques (llengua i escolarització en origen), A partir de l’anàlisi d’aquests elements estructurals, el treball pretén fer una aproximació multiestratègica (quantitativa i qualitativa) als itineraris formatius i laborals dels i les joves d’origen immigrant; i fer-ho des de la pròpia perspectiva i veu dels joves, per captar les seves experiències i analitzar les lògiques de pressa de decisions que configuren els seus itineraris.

Dual-wavelength digital holographic microscopy with sub-nanometer axial accuracy

We present dual-wavelength Digital Holographic Microscopy (DHM) measurements on a certified 8.9 nm high Chromium thin step sample and demonstrate sub-nanometer axial accuracy. We introduce a modified DHM Reference Calibrated Hologram (RCH) reconstruction algorithm taking into account amplitude contributions. By combining this with a temporal averaging procedure and a specific dual-wavelength DHM arrangement, it is shown that specimen topography can be measured with an accuracy, defined as the axial standard deviation, reduced to at least 0.9 nm. Indeed, it is reported that averaging each of the two wavefronts recorded with real-time dual-wavelength DHM can provide up to 30% spatial noise reduction for the given configuration, thanks to their non-correlated nature. ©2008 COPYRIGHT SPIE

Jeune dans sa tête. Une histoire critique du cerveau adolescent

Les recherches visant à élucider les bases neurales de l'adolescence ont émergé au cours des années 1990 pour s'imposer cette dernière décennie. Il est aujourd'hui accepté dans le champ des neurosciences cognitives et du développement que le cerveau continue à se développer après la 10eme année de vie et qu'il atteint un stade de maturation similaire à l'adulte seulement vers 25 ans. La configuration structurelle et fonctionnelle du cerveau spécifique à la période de l'adolescence impliquerait un manque de contrôle émotionnel, favorisant des comportements dits de prise de risques qui à la fois permettent l'acquisition de l'indépendance et provoquent des situations de mise en danger du jeune individu et de son entourage. Ses mêmes comportements, dans leur acception négative - consommation d'alcool et de stupéfiants, conduite en état d'ivresse, rapports sexuels non-protégés, port d'arme, etc. - mobilisent les politiques de prévention et de santé publique relatives à l'adolescence et à la jeunesse. Cette thèse qui retrace l'histoire du cerveau adolescent de la fin des années 1950 à nos jours se situe à l'intersection de ces deux thèmes d'intérêt scientifique et public. A partir d'une perspective d'histoire culturelle et sociale des sciences, elle approche les éléments expérimentaux, institutionnels et contextuels qui ont contribué à la construction d'une adolescence définie par son immaturité cérébrale, associée à des comportements dits à risque. Plus précisément, elle met en évidence, sous l'angle privilégié du genre, selon quelles modalités et quelles temporalités l'histoire des recherches scientifiques sur le développement cérébral humain à l'adolescence et celle du façonnage d'un type d'adolescent-e impulsif/ve et preneur/euse de risques - c'est-à-dire potentiellement délinquant, dépendant, invalide ou malade chronique, constitué en problème de politique et de santé publique - sont amenées à converger. L'argument développé est que le genre et le sexe sont des catégories actives dans la construction d'un cerveau adolescent idéalement unisexe. En d'autres termes, bien que le cerveau adolescent qualifie des individus en regard de leur âge, sans distinction apparente de sexe et de genre, les conditions de sa production et les critères de sa définition sont constitutivement genrés, notamment par des comportements à risque qui concernent une majorité de garçons. Il s'agit d'analyser comment du sexe et du genre peuvent produire de l'âge, a priori unisexe, et d'interroger les enjeux scientifiques, sociaux et politiques qui participent de cette invisibilisation des catégories de sexe et de genre. Le but est de considérer la manière dont l'adolescence cérébrale reconfigure la gestion des questions liées à l'adolescence et à la jeunesse, en termes de problèmes sanitaires et de délinquance, mais aussi en termes de reproduction des normes sociales, de ce qu'implique devenir un homme ou une femme.

Genometrics as an essential tool for the assembly of whole genome sequences: the example of the chromosome of Bifidobacterium longum NCC2705.

BACKGROUND: Analysis of the first reported complete genome sequence of Bifidobacterium longum NCC2705, an actinobacterium colonizing the gastrointestinal tract, uncovered its proteomic relatedness to Streptomyces coelicolor and Mycobacterium tuberculosis. However, a rapid scrutiny by genometric methods revealed a genome organization totally different from all so far sequenced high-GC Gram-positive chromosomes. RESULTS: Generally, the cumulative GC- and ORF orientation skew curves of prokaryotic genomes consist of two linear segments of opposite slope: the minimum and the maximum of the curves correspond to the origin and the terminus of chromosome replication, respectively. However, analyses of the B. longum NCC2705 chromosome yielded six, instead of two, linear segments, while its dnaA locus, usually associated with the origin of replication, was not located at the minimum of the curves. Furthermore, the coorientation of gene transcription with replication was very low. Comparison with closely related actinobacteria strongly suggested that the chromosome of B. longum was misassembled, and the identification of two pairs of relatively long homologous DNA sequences offers the possibility for an alternative genome assembly proposed here below. By genometric criteria, this configuration displays all of the characters common to bacteria, in particular to related high-GC Gram-positives. In addition, it is compatible with the partially sequenced genome of DJO10A B. longum strain. Recently, a corrected sequence of B. longum NCC2705, with a configuration similar to the one proposed here below, has been deposited in GenBank, confirming our predictions. CONCLUSION: Genometric analyses, in conjunction with standard bioinformatic tools and knowledge of bacterial chromosome architecture, represent fast and straightforward methods for the evaluation of chromosome assembly.

A importância do sector microcrédito e o perfil do microempresário: Ilha de Santo Antão Cabo Verde

As microempresas desempenham um papel fundamental na promoção do emprego, na inovação, na criação de rendimentos e no desenvolvimento económico e social. Para os países em vias de desenvolvimento, crê-se que a dinamização das microempresas pode ser um instrumento privilegiado de promoção e combate à pobreza, na medida em que esta poderá ser a via para incentivar as camadas mais pobres das populações rurais e urbanas a criarem os seus próprios negócios e a providenciarem os seus próprios rendimentos. A criação e o crescimento das microempresas estão, todavia, condicionados por vários constrangimentos. A inexistência de capital inicial (Start-Up Capital) é apontada na literatura financeira como uma das mais relevantes. O recurso ao capital externo, como fonte de financiamento, dependerá, por sua vez, de vários factores. O presente estudo foi realizado em Santo Antão, a ilha mais a norte e a mais montanhosa do Arquipélago de Cabo Verde. O sector micro crédito chama atenção pelo facto de ser um instrumento de importância primordial para Cabo Verde e, particularmente, para a ilha de Santo Antão que possui uma estrutura económica e social muito vulnerável o que nos leva a compreender melhor, o funcionamento das microempresas, instaladas nos três municípios da Ilha (Paul, Ribeira Grande e Porto Novo). Ao longo do estudo definimos o perfil sócio económico do micro empresário Santantonense, com o objectivo de compreender e quantificar o contributo do sector para o desenvolvimento empresarial da ilha, sem esquecer os constrangimentos e dificuldades que se colocam aos micros empresários na procura de financiamento. O processo de recolha de informação foi efectuado com recurso a pesquisas de campo, a partir da elaboração e aplicação de entrevistas de uma forma semi-estruturada, no sentido de identificar as principais características/perfil do empresário. Os dados recolhidos pelas entrevistas têm por base uma apreciação crítica da gestão para melhor compreender e comparar as fragilidades existentes e analisar a capacidade de sucesso dos micros empresários. A configuração da actividade económica foi feita com base na análise quantitativa e qualitativa, dos dados obtidos na aplicação dos questionários. De igual modo, analisamos e comparamos os casos de sucesso e insucesso nas microempresas em estudo, casos de sucesso no que diz respeito aos benefícios de micro créditos para a redução da pobreza e do desemprego, de criação do auto-emprego, e da formação/informação aos micros empresários santantonenses. Nos casos de insucesso analisamos as causas que estiveram na sua origem assim como as consequências daí advenientes. Uma das constatações do estudo, como se verá pela análise dos dados, é que o micro empresário Santantonense, possui um baixo nível de escolaridade e que na sua maioria são mulheres. Um outro resultado evidenciado pelo estudo, é que há uma necessidade da política pública de desenvolvimento no sentido de definição de incentivos à criação e à promoção de micro negócios, atendendo às características demográficas e às necessidades específicas dos beneficiários. Micro enterprises perform a fundamental component in promoting employment, innovation, and earnings-generation and in socio-economic development. For countries en route to development, the belief is that the dynamic engine of the micro enterprises could be a privileged instrument to promote in the battle against poverty, in the hope that this could be the venue to incentivize the poorest of the rural and urban populations to create their own businesses and forecast their own earnings. The creation and the growth of micro enterprises is, however, conditional upon various constraints. The inexistence of initial capital is cited in financial literature as one of the more important. To resort to external capital as a financing source, is itself dependent on various factors. The current study was conducted in Santo Antão, the most northern and mountainous island in the Archipelago of Cape Verde. The micro credit´s sector calls attention to the fact that it is an essential instrument in Cape Verde, particularly in the island of Santo Antão which has an economic and social structure extremely vulnerable, leading us to a better understanding of how micro enterprises operate in the three municipalities of the Island (Paul, Ribeira Grande and Porto Novo). During the course of the study we defined the socio-economic character of the micro entrepreneur Santantonense, with the goal of understanding and quantifying the sector´s contribution to the Island´s entrepreneurial development, keeping in mind the contraints and difficulties that confront the entrepreneurs when seeking financing. The process for gathering the information was performed through field research, beginning with elaboration and application of interviews, designed to identify the entrepreneur´s major characteristics and the importance of micro credit for the island of Santo Antão. The data gathered through the interviews have un underlying basic and critic appreciation of management for a better understanding and comparing the existing fragilities and for analyzing the micro entrepreneurs´ capacity to succeed. The configuration of economic activities was designed based on quantitative and qualitative analysis from data obtained from the questionnaires. Likewise, we analyzed and compared the success and non-success cases of the micro enterprises in the study, success cases with respect to the benefits of micro credit in reducing poverty and unemployment, creation of self-employment, and the education/information for the micro entrepreneurs of Santo Antão. In the non-success cases we analyzed the original causes as well as the impending consequences. One of the study´s contentions, as the data analysis shows, is that micro entrepreneur of Santo Antão has a low level of education with the majority of them being women. In addition the study shows that there is a need for a public discourse in terms of defining and developing incentives for creating and promoting micro businesses given the demographic characteristics and the specific necessities of the beneficiaries.