Ab initio modeling and molecular dynamics simulation of the alpha 1b-adrenergic receptor activation.

This work describes the ab initio procedure employed to build an activation model for the alpha 1b-adrenergic receptor (alpha 1b-AR). The first version of the model was progressively modified and complicated by means of a many-step iterative procedure characterized by the employment of experimental validations of the model in each upgrading step. A combined simulated (molecular dynamics) and experimental mutagenesis approach was used to determine the structural and dynamic features characterizing the inactive and active states of alpha 1b-AR. The latest version of the model has been successfully challenged with respect to its ability to interpret and predict the functional properties of a large number of mutants. The iterative approach employed to describe alpha 1b-AR activation in terms of molecular structure and dynamics allows further complications of the model to allow prediction and interpretation of an ever-increasing number of experimental data.

Numerical simulation of combined heat transfer phenomena (conduction, convection, and radiation). Application to he optimisation of thermal systems

Thermal systems interchanging heat and mass by conduction, convection, radiation (solar and thermal ) occur in many engineering applications like energy storage by solar collectors, window glazing in buildings, refrigeration of plastic moulds, air handling units etc. Often these thermal systems are composed of various elements for example a building with wall, windows, rooms, etc. It would be of particular interest to have a modular thermal system which is formed by connecting different modules for the elements, flexibility to use and change models for individual elements, add or remove elements without changing the entire code. A numerical approach to handle the heat transfer and fluid flow in such systems helps in saving the full scale experiment time, cost and also aids optimisation of parameters of the system. In subsequent sections are presented a short summary of the work done until now on the orientation of the thesis in the field of numerical methods for heat transfer and fluid flow applications, the work in process and the future work.

Analyse des risques d'extinction des populations naturelles

A review of extinction risk analysis and viability methods is presented. The importance of environmental, demographic and genetic uncertainties, as well as the role of catastrophes are successively considered, and different approaches aiming at the integration of these risk factors in predictive population dynamic models are discussed.

L' Aprenentatge basat en problemes a través de casos clínics simulats. Una proposta metodològica de disseny i avaluació docent

RESUM Les exigències actuals de la professió de d’infermeria requereixen que la docència vagi orientada a interrelacionar els diferents rols a desenvolupar enla pràctica diària, per adquirir experiència en l’aprenentatge i així augmentar la qualitat de les cures d’infermeria. Per assolir aquest objectiu és important l’aprenentatge basat enproblemes. Aquest pretén en primer lloc que els estudiants aprenguin allò que permet desenvolupar-se enla vida professional de la manera més natural possible a partir d’una idea clara i profunda de l’evidència sobre la que s’ha d’actuar. Amb aquesta finalitat es vandissenyar casos clínics amb uns objectius que requerien la integració de coneixements, actituds i valors, en diferents fases a desenvolupar en un període de temps predeterminat. També ens vam proposar una estratègia docent que permetés a l’estudiant incorporar el coneixement científic que dóna suport a la pràctica assistencial per aproximar teoria i pràctica. Es pretén que els estudiants busquin una resposta basada en la millor evidència científica disponible, per prendre una decisió respecte a les cures del pacient. Els objectius de l’estudi són: Avaluar globalment l’aprenentatge basat en la simulació de casos Avaluar com els estudiants valoren la integració del model d’infermeria i del procés d’atenció en l’aprenentatge basat en la simulació de casos. Valorar les sensacions percebudes per l’estudiant durant la simulació del cas. Valorar l’actitud d el’estudiant en relació a la incorporació de l’evidència científica per una millora en la pràctica clínica. Avaluar el grau de dificultat manifestat per l’estudiant en relació al procés de documentació. Avaluar la idonietat de l’argumentació i la decisió de l’estudiant a la pregunta formulada en el cas clínic. Metodologia: L’assignatura d’Infermeria Medicoquirúrgica. Adult I del Departament d’Infermeria de la Universitat de Vic, va iniciar una experiència d’aprenentatge basat en la resolució de problemes, amb estudiants de 2on curs. Les professores responsables dels seminaris van realitzar una avaluació de l’experiència a través d’una enquesta. Aquesta es responia al cap d’un mes de la simulació al laboratori, quan es contrastaven els resultats obtinguts en aquesta entre professores i estudiants després de visualitzar la gravació feta durant el mateix. En el context del seminari de simulació de casos, es va introduir una pregunta/problema, a partir de la que els estudiants, en grup, havien de documentar-se amb el suport d’una guia. Per valorar l’actitud davant aquesta pregunta/problema es va dissenyar un qustionari tipus Likert. L’avaluació del grau de dificultat s’ha registrat a través d’unes escales de puntuació. Per a l’avaluació de la decisió presa, es van valorar les síntesis resum entregades en els treballs escrits pels diferents grups. Resultats: La realització de la simulació en el laboratori va ser avaluada per un alt percentatge d’estudiants (68,8%) amb puntuacions entre 6 i 8 mentre que un 26,6% la van situar en tre 9 i 10, només un 4,7 % la van puntuar amb 5. La integració del model d’infermeria va ser valorada pel 86% amb una puntuació entre 7 i 10. La valoració global de la simulació va ser qualificada pels estudiants amb una puntuació de 8 (34,4%) seguida d’un 28,1% amb una consideració de 7. Un 7,2% van puntuar entre 9 i 10. El 93,3% van assegurar que conèixer les fonts documentals els serviria per millorar l’assistència, el 86,7% esperen obtenir arguments sòlids respecte les seves desicions si la documentació consultada és de qualitat. Un 77,8% dels estudiants consideren estar més satisfets al saber incorporar la presa de decisions basada en evidències. Respecte el grau de dificultat en el procés de documentació la dificultat més gran la presenten en com buscar en les bases de dades de referències bibliogràfiques. Conclusions: L’aprenentatge dels estudiants a través de la simulació de casos és una estratègia vàlida que l’estudiant valora positivament al mateix temps que permet desenvolupar habilitats per a la pràctica professional. L’estratègia docent dissenyada per integrar les evidències en la presa de decisions es considera positiva, no obstant, després d’analitzar els resultats, s’han de modificar alguns aspectes per a la seva millora; tutoritzar per a millorar el procés de documentació i incidir més en la crítica i reflexió, de manera que les troballes de la investigació siguin canalitzades cap a la pràctica.

Effort, reward and self-reported mental health: a simulation study on negative affectivity bias.

Background : In the present article, we propose an alternative method for dealing with negative affectivity (NA) biases in research, while investigating the association between a deleterious psychosocial environment at work and poor mental health. First, we investigated how strong NA must be to cause an observed correlation between the independent and dependent variables. Second, we subjectively assessed whether NA can have a large enough impact on a large enough number of subjects to invalidate the observed correlations between dependent and independent variables.Methods : We simulated 10,000 populations of 300 subjects each, using the marginal distribution of workers in an actual population that had answered the Siegrist's questionnaire on effort and reward imbalance (ERI) and the General Health Questionnaire (GHQ).Results : The results of the present study suggested that simulated NA has a minimal effect on the mean scores for effort and reward. However, the correlations between the effort and reward imbalance (ERI) ratio and the GHQ score might be important, even in simulated populations with a limited NA.Conclusions : When investigating the relationship between the ERI ratio and the GHQ score, we suggest the following rules for the interpretation of the results: correlations with an explained variance of 5% and below should be considered with caution; correlations with an explained variance between 5% and 10% may result from NA, although this effect does not seem likely; and correlations with an explained variance of 10% and above are not likely to be the result of NA biases. [Authors]

Stock market integration between new EU member states and the Euro-zone

This paper measures the degree in stock market integration between five Eastern European countries and the Euro-zone. A potentially gradual transition in correlations is accommodated by smooth transition conditional correlation models. We find that the correlation between stock markets has increased from 2001 to 2007. In particular, the Czech and Polish markets show a higher correlation to the Euro-zone. However, this is not a broad-based phenomenon across Eastern Europe. We also find that the increase in correlations is not a reflection of a world-wide phenomenon of financial integration but appears to be specific to the European market. JEL classifications: C32; C51; F36; G15 Keywords: Multivariate GARCH; Smooth Transition Conditional Correlation; Stock Return Comovement; New EU Members.

Progress Towards to Equity Market Integration in Eastern Europe

The advent of the European Union has decreased the diversification benefits available from country based equity market indices in the region. This paper measures the increase in stock integration between the three largest new EU members (Hungary, the Czech Republic and Poland who joined in May 2004) and the Euro-zone. A potentially gradual transition in correlations is accommodated in a single VAR model by embedding smooth transition conditional correlation models with fat tails, spillovers, volatility clustering, and asymmetric volatility effects. At the country market index level all three Eastern European markets show a considerable increase in correlations in 2006. At the industry level the dates and transition periods for the correlations differ, and the correlations are lower although also increasing. The results show that sectoral indices in Eastern European markets may provide larger diversification opportunities than the aggregate market. JEL classifications: C32; C51; F36; G15 Keywords: Multivariate GARCH; Smooth Transition Conditional Correlation; Stock Return Comovement; Sectoral correlations; New EU Members

Why the EU does not Have an Independent Competition Agency: French Interests and Transaction Costs in Early European Integration

A major achievement of new institutionalism in economics and political science is the formalisation of the idea that certain policies are more efficient when administered by a politically independent organisation. Based on this insight, several policy actors and scholars criticise the European Community for relying too much on a multi-task, collegial, and politicised organisation, the European Commission. This raises important questions, some constitutional (who should be able to change the corresponding procedural rules?) and some political-economic (is Europe truly committed to free and competitive markets?). Though acknowledging the relevance of legal and normative arguments, this paper contributes to the debate with a positive political-scientific perspective. Based on the view that institutional equilibria raise the question of equilibrium institutions, it shows that collegiality was (a) an equilibrium institution during the Paris negotiations of 1950-51; and (b) an institutional equilibrium for the following 50 years. The conclusion points to some recent changes in the way that European competition policy is implemented, and discusses how these affect the “constitutional” principle of collegial European governance.

Political Risk, Economic Integration, and the Foreign Direct Investment Decision

In this paper we analyse the impact of policy uncertainty on foreign direct investment strategies. We also consider the impact of economic integration upon FDI decisions. The paper follows the real options approach, which allows investigating the value to a firm of waiting to invest and/or disinvest, when payoffs are stochastic due to political uncertainty and investments are partially reversible. Across the board we find that political uncertainty can be very detrimental to FDI decisions while economic integration leads to an increasing benefit of investing abroad.

Labour Market Imperfections, International Integration and Selection

Although a large body of literature has focused on the effects of intra-firm differences on export performance, relatively little attention has been devoted to the interaction between firms' selection and international performance and labour market institutions - in contrast with the centrality of the latter to current policy and public debates on the implications of economic globalisation for national policies and institutions. In this paper, we study the effects of labour market unionisation on the process of competitive selection between heterogeneous firms and analyse how the interaction between the two is affected by trade liberalisation between countries with different unionisation patterns.

The role of attention in multisensory integration processes

Report for the scientific sojourn at the University of Queensland, Australia, between June to October 2007. The integration of sensory information coming from different modalities is a subjectively effortless and automatic process. However, recent findings converge on the idea that there might be some limitations on how much multisensory information can our brains integrate at a given moment. The overall objective of this research visit was to expand and reinforce our current line of research addressing the role that attention plays on the mechanisms responsible for multisensory integration. There is also a critical review of the literature as well as a list of research questions of potential interest in the area of the neuropsychology of multisensory attention.

Microsatellites can be misleading: an empirical and simulation study.

It has been long recognized that highly polymorphic genetic markers can lead to underestimation of divergence between populations when migration is low. Microsatellite loci, which are characterized by extremely high mutation rates, are particularly likely to be affected. Here, we report genetic differentiation estimates in a contact zone between two chromosome races of the common shrew (Sorex araneus), based on 10 autosomal microsatellites, a newly developed Y-chromosome microsatellite, and mitochondrial DNA. These results are compared to previous data on proteins and karyotypes. Estimates of genetic differentiation based on F- and R-statistics are much lower for autosomal microsatellites than for all other genetic markers. We show by simulations that this discrepancy stems mainly from the high mutation rate of microsatellite markers for F-statistics and from deviations from a single-step mutation model for R-statistics. The sex-linked genetic markers show that all gene exchange between races is mediated by females. The absence of male-mediated gene flow most likely results from male hybrid sterility.

Directed integration of new insulated lentiviral vectors to heterochromatin towards safer gene transfer to stem cells

The need for better gene transfer systems towards improved risk=benefit balance for patients remains a major challenge in the clinical translation of gene therapy (GT). We have investigated the improvement of integrating vectors safety in combining (i) new short synthetic genetic insulator elements (GIE) and (ii) directing genetic integration to heterochromatin. We have designed SIN-insulated retrovectors with two candidate GIEs and could identify a specific combination of insulator 2 repeats which translates into best functional activity, high titers and boundary effect in both gammaretro (p20) and lentivectors (DCaro4) (see Duros et al, abstract ibid). Since GIEs are believed to shield the transgenic cassette from inhibitory effects and silencing, DCaro4 has been further tested with chimeric HIV-1 derived integrases which comprise C-ter chromodomains targeting heterochromatin through either histone H3 (ML6chimera) or methylatedCpGislands (ML10). With DCaro4 only and both chimeras, a homogeneous expression is evidenced in over 20% of the cells which is sustained over time. With control lentivectors, less than 2% of cells express GFP as compared to background using a control double-mutant in both catalytic and ledgf binding-sites; in addition, a two-times increase of expression can be induced with histone deacetylase inhibitors. Our approach could significantly reduce integration into open chromatin sensitive sites in stem cells at the time of transduction, a feature which might significantly decrease subsequent genotoxicity, according to X-SCIDs patients data.Work performed with the support of EC-DG research within the FP6-Network of Excellence, CLINIGENE: LSHB-CT-2006-018933

Sex biased spatial strategies relying on the integration of multimodal cues in a rat model of schizophrenia: impairment in predicting future context?

Male and female Wistar rats were treated postnatally (PND 5-16) with BSO (l-buthionine-(S,R)-sulfoximine) to provide a rat model of schizophrenia based on transient glutathione deficit. In the watermaze, BSO-treated male rats perform very efficiently in conditions where a diversity of visual information is continuously available during orientation trajectories [1]. Our hypothesis is that the treatment impairs proactive strategies anticipating future sensory information, while supporting a tight visual adjustment on memorized snapshots, i.e. compensatory reactive strategies. To test this hypothesis, BSO rats' performance was assessed in two conditions using an 8-arm radial maze task: a semi-transparent maze with no available view on the environment from maze centre [2], and a modified 2-parallel maze known to induce a neglect of the parallel pair in normal rats [3-5]. Male rats, but not females, were affected by the BSO treatment. In the semi-transparent maze, BSO males expressed a higher error rate, especially in completing the maze after an interruption. In the 2-parallel maze shape, BSO males, unlike controls, expressed no neglect of the parallel arms. This second result was in accord with a reactive strategy using accurate memory images of the contextual environment instead of a representation based on integrating relative directions. These results are coherent with a treatment-induced deficit in proactive decision strategy based on multimodal cognitive maps, compensated by accurate reactive adaptations based on the memory of local configurations. Control females did not express an efficient proactive capacity in the semi-transparent maze, neither did they show the significant neglect of the parallel arms, which might have masked the BSO induced effect. Their reduced sensitivity to BSO treatment is discussed with regard to a sex biased basal cognitive style.

Unionisation, International Integration and Selection

We study how unionisation affects competitive selection between heterogeneous firms when wage negotiations can occur at the rm or at the profit-centre level. With productivity specific wages, an increase in union power has: (i) a selection-softening; (ii) a counter-competitive; (iii) a wage-inequality; and (iv) a variety effect. In a two-country asymmetric setting, stronger unions soften competition for domestic firms and toughen it for exporters. With profit-centre bargaining, we show how trade liberalisation can affect wage inequality among identical workers both across firms (via its effects on competitive selection) and within firms (via wage discrimination across destination markets).