From SNPs to pathways: integration of functional effect of sequence variations on models of cell signalling pathways

Background: Single nucleotide polymorphisms (SNPs) are the most frequent type of sequence variation between individuals, and represent a promising tool for finding genetic determinants of complex diseases and understanding the differences in drug response. In this regard, it is of particular interest to study the effect of non-synonymous SNPs in the context of biological networks such as cell signalling pathways. UniProt provides curated information about the functional and phenotypic effects of sequence variation, including SNPs, as well as on mutations of protein sequences. However, no strategy has been developed to integrate this information with biological networks, with the ultimate goal of studying the impact of the functional effect of SNPs in the structure and dynamics of biological networks. Results: First, we identified the different challenges posed by the integration of the phenotypic effect of sequence variants and mutations with biological networks. Second, we developed a strategy for the combination of data extracted from public resources, such as UniProt, NCBI dbSNP, Reactome and BioModels. We generated attribute files containing phenotypic and genotypic annotations to the nodes of biological networks, which can be imported into network visualization tools such as Cytoscape. These resources allow the mapping and visualization of mutations and natural variations of human proteins and their phenotypic effect on biological networks (e.g. signalling pathways, protein-protein interaction networks, dynamic models). Finally, an example on the use of the sequence variation data in the dynamics of a network model is presented. Conclusion: In this paper we present a general strategy for the integration of pathway and sequence variation data for visualization, analysis and modelling purposes, including the study of the functional impact of protein sequence variations on the dynamics of signalling pathways. This is of particular interest when the SNP or mutation is known to be associated to disease. We expect that this approach will help in the study of the functional impact of disease-associated SNPs on the behaviour of cell signalling pathways, which ultimately will lead to a better understanding of the mechanisms underlying complex diseases.

Bilinear models for spatio-temporal point distribution analysis: application to extrapolation of left ventricular, biventricular and whole heart cardiac dynamics

In this work we describe the usage of bilinear statistical models as a means of factoring the shape variability into two components attributed to inter-subject variation and to the intrinsic dynamics of the human heart. We show that it is feasible to reconstruct the shape of the heart at discrete points in the cardiac cycle. Provided we are given a small number of shape instances representing the same heart atdifferent points in the same cycle, we can use the bilinearmodel to establish this. Using a temporal and a spatial alignment step in the preprocessing of the shapes, around half of the reconstruction errors were on the order of the axial image resolution of 2 mm, and over 90% was within 3.5 mm. From this, weconclude that the dynamics were indeed separated from theinter-subject variability in our dataset.

La variació en termes matemàtics

La idea predominant és que una ciència exacta que es caracteritza per la precisió, la concisió i la no-ambigüitat, i que s'expressa amb l'ajuda de formalismes de manera molt freqüent, difícilment pot presentar variació. En aquest article, es vol demostrar que en el llenguatge de les matemàtiques existeix variació perquè és llenguatge, i perquè la variació és una de les característiques intrínseques del llenguatge. A banda d'això, fa un primer esbós dels tipus de variació que s'hi produeixen amb l'anàlisi de textos reals.

Fading models and metrics for contemporary wireless systems

The purpose of this paper is to examine (1) some of the models commonly used to represent fading,and (2) the information-theoretic metrics most commonly used to evaluate performance over those models. We raise the question of whether these models and metrics remain adequate in light of the advances that wireless systems haveundergone over the last two decades. Weaknesses are pointedout, and ideas on possible fixes are put forth.

Political mobilisation and models of trade unionism : Southern Europe in comparative perspective

The relationship between union membership and political mobilization has been studied under many perspectives, but quantitative cross-national analyses have been hampered by the absence of international comparable survey data until the first round of the European Social Survey (ESS-2002) was made available. Using different national samples from this survey in four moments of time (2002, 2004 and 2006), our paper provides evidence of cross-country divergence in the empirical association between political mobilisation and trade union membership. Cross-national differences in union members’ political mobilization, we argue, can be explained by the existence of models of unionism that in turn differ with respect to two decisive factors: the institutionalisation of trade union activity and the opportunities left-wing parties have available for gaining access to executive power.

Zara : elecció i distribució òptima

Zara és una marca relativament jove, molt coneguda i que encara està en expansió! Podria ser Vic una població de negoci interessant per la marca? Compleix les característiques demandades per una multinacional d’aquestes característiques? Manifesta la població interès vers la marca? Aquestes són algunes de les preguntes que ens varem plantejar inicialment.El nostre treball tracta de l’obertura d’una tenda Zara a la ciutat de Vic. Aquest projecte consta de dues grans parts; una primera fase teòrica basada en la recerca d’informació realitzada mitjançant diverses fonts per tal de familiaritzar-nos amb la multinacional Inditex i, més concretament, amb Zara. D’aquesta manera detectar els requisits i necessitats de la marca, així com també les preferències dels habitants de Vic envers la possible obertura d’una nova botiga. D’altra banda, una segona part de tipus més pràctica on identificarem el local adient segons les conclusions extretes i en realitzarem la distribució.Pel que fa a la part teòrica hem utilitzat tres fonts d’informació per tal de poder-les contrastar i extreure’n la millor conclusió possible. En primer lloc ens hem basat en la observació empírica de diferents centres Zara i aquest mètode ens ha servit per extreure les característiques més comunes dels establiments observats. Així, hem obtingut una idea dels requisits que haurà de complir el nostre projecte. Cal destacar que aquesta font informativa l’hem complementat amb una entrevista telefònica a la Sra. Isabel Catoira, membre del departament de comunicació del grup Inditex, que ens ha respòs a algunes qüestions que ens han estat de gran ajuda, tot i que hem de deixar constància que l’empresa no ens ha proporcionat la informació desitjada per motius de confidencialitat i hem hagut d’optar per altres mecanismes. En segon lloc, hem confeccionat una enquesta a una mostra aleatòria de 120 persones que es trobaven en diferents zones de la ciutat de Vic, a partir de la qual hem extret informació sobre les preferències de la gent i hem pogut reafirmar la nostra hipòtesi inicial; Zara és la botiga més sol·licitada de les absents a Vic actualment.Pel que fa a la part pràctica, que tracta del muntatge de Zara al local comercial idoni de Vic, consisteix en l’elecció del local òptim dins les possibilitats disponibles a partir de la informació extreta en la primera part. Una vegada triat el local comercial, hem realitzat el muntatge i distribució de les diferents parts de les que ha de constar la tenda i, posteriorment, hem realitzat un breu anàlisi dels costos de muntatge.Finalment, hem presentat el plànol de distribució i muntatge en forma bidimensional i hem adjuntat una presentació virtual per tal de donar-li al treball un toc més de realitat.

Measurement with Some Theory: a New Approach to Evaluate Business Cycle Models

We propose a method to evaluate cyclical models which does not require knowledge of the DGP and the exact empirical specification of the aggregate decision rules. We derive robust restrictions in a class of models; use some to identify structural shocks and others to evaluate the model or contrast sub-models. The approach has good size and excellent power properties, even in small samples. We show how to examine the validity of a class of models, sort out the relevance of certain frictions, evaluate the importance of an added feature, and indirectly estimate structural parameters.

Prime Property Institutions for a Subprime Era: Exploring Innovative Models of Residential Development and Finance

This paper breaks new ground toward contractual and institutional innovation in models of homeownership, equity building, and mortgage enforcement. Inspired by recent developments in the affordable housing sector and in other types of public financing schemes, this paper suggests extending institutional and financial strategies such as timeand place-based division of property rights, conditional subsidies, and credit mediation to alleviate the systemic risks of mortgage foreclosure. Alongside a for-profit shared equity scheme that would be led by local governments, we also outline a private market shared equity model, one of bootstrapping home buying with purchase options.

Ethics Outside, Within, or Beyond OR Models

Since ethical concerns are calling for more attention within Operational Research, we present three approaches to combine Operational Research models with ethics. Our intention is to clarify the trade-offs faced by the OR community, in particular the tension between the scientific legitimacy of OR models (ethics outside OR models) and the integration of ethics within models (ethics within OR models). Presenting and discussing an approach that combines OR models with the process of OR (ethics beyond OR models), we suggest rigorous ways to express the relation between ethics and OR models. As our work is exploratory, we are trying to avoid a dogmatic attitude and call for further research. We argue that there are interesting avenues for research at the theoretical, methodological and applied levels and that the OR community can contribute to an innovative, constructive and responsible social dialogue about its ethics.

Panel index VAR models: Specification, Estimation, Testing and Leading Indicators

This paper proposes a method to conduct inference in panel VAR models with cross unit interdependencies and time variations in the coefficients. The approach can be used to obtain multi-unit forecasts and leading indicators and to conduct policy analysis in a multiunit setups. The framework of analysis is Bayesian and MCMC methods are used to estimate the posterior distribution of the features of interest. The model is reparametrized to resemble an observable index model and specification searches are discussed. As an example, we construct leading indicators for inflation and GDP growth in the Euro area using G-7 information.

Communication, Coordination, and Efficiency in Evolutionary One-population Models

We analyze the role of commitment in pre-play communication for ensuring efficient evolutionarily stable outcomes in coordination games. All players are a priori identical as they are drawn from the same population. In games where efficient outcomes can be reached by players coordinating on the same action we find commitment to be necessary to enforce efficiency. In games where efficienct outcomes only result from play of different actions, communication without commitment is most effective although efficiency can no longer be guaranteed. Only when there are many messages then inefficient outcomes are negligible as their basins of attraction become very small.

Business Cycles, Unemployment Insurance, and the Calibration of Matching Models

This paper points out an empirical puzzle that arises when an RBC economy with a job matching function is used to model unemployment. The standard model can generate sufficiently large cyclical fluctuations in unemployment, or a sufficiently small response of unemployment to labor market policies, but it cannot do both. Variable search and separation, finite UI benefit duration, efficiency wages, and capital all fail to resolve this puzzle. However, both sticky wages and match-specific productivity shocks help the model reproduce the stylized facts: both make the firm's flow of surplus more procyclical, thus making hiring more procyclical too.

Incorporating waiting time in competitive location models: formulations and heuristics

In this paper we propose a metaheuristic to solve a new version of the Maximum Capture Problem. In the original MCP, market capture is obtained by lower traveling distances or lower traveling time, in this new version not only the traveling time but also the waiting time will affect the market share. This problem is hard to solve using standard optimization techniques. Metaheuristics are shown to offer accurate results within acceptable computing times.