The Advantage of Arriving First: Characteristic Times in Finite Size Populations of Error-Prone Replicators

We study the evolution of a finite size population formed by mutationally isolated lineages of error-prone replicators in a two-peak fitness landscape. Computer simulations are performed to gain a stochastic description of the system dynamics. More specifically, for different population sizes, we compute the probability of each lineage being selected in terms of their mutation rates and the amplification factors of the fittest phenotypes. We interpret the results as the compromise between the characteristic time a lineage takes to reach its fittest phenotype by crossing the neutral valley and the selective value of the sequences that form the lineages. A main conclusion is drawn: for finite population sizes, the survival probability of the lineage that arrives first to the fittest phenotype rises significantly

Upstream A-tracts increase bacterial promoter activity through interactions with the RNA polymerase α subunit

Upstream A-tracts stimulate transcription from a variety of bacterial promoters, and this has been widely attributed to direct effects of the intrinsic curvature of A-tract-containing DNA. In this work we report experiments that suggest a different mechanism for the effects of upstream A-tracts on transcription. The similarity of A-tract-containing sequences to the adenine- and thymine-rich upstream recognition elements (UP elements) found in some bacterial promoters suggested that A-tracts might increase promoter activity by interacting with the α subunit of RNA polymerase (RNAP). We found that an A-tract-containing sequence placed upstream of the Escherichia coli lac or rrnB P1 promoters stimulated transcription both in vivo and in vitro, and that this stimulation required the C-terminal (DNA-binding) domain of the RNAP α subunit. The A-tract sequence was protected by wild-type RNAP but not by α-mutant RNAPs in footprints. The effect of the A-tracts on transcription was not as great as that of the most active UP elements, consistent with the degree of similarity of the A-tract sequence to the UP element consensus. A-tracts functioned best when positioned close to the −35 hexamer rather than one helical turn farther upstream, similar to the positioning optimal for UP element function. We conclude that A-tracts function as UP elements, stimulating transcription by providing binding site(s) for the RNAP αCTD, and we suggest that these interactions could contribute to the previously described wrapping of promoter DNA around RNAP.

Mutations in the MSH3 gene preferentially lead to deletions within tracts of simple repetitive DNA in Saccharomyces cerevisiae.

Eukaryotic genomes contain tracts of DNA in which a single base or a small number of bases are repeated (microsatellites). Mutations in the yeast DNA mismatch repair genes MSH2, PMS1, and MLH1 increase the frequency of mutations for normal DNA sequences and destabilize microsatellites. Mutations of human homologs of MSH2, PMS1, and MLH1 also cause microsatellite instability and result in certain types of cancer. We find that a mutation in the yeast gene MSH3 that does not substantially affect the rate of spontaneous mutations at several loci increases microsatellite instability about 40-fold, preferentially causing deletions. We suggest that MSH3 has different substrate specificities than the other mismatch repair proteins and that the human MSH3 homolog (MRP1) may be mutated in some tumors with microsatellite instability.

Structures, Systems and Organizational Communication Processes in Franchises in times of crisis: the Spanish case

Current economic crisis together with the Internet revolution has had direct impacts on the franchise sector of Spain: in particular on its unique communication network. The aim of this research is to analyse how Spanish franchise companies have adapted to these changes through its corporate communications management. We want to determine whether the management of communications is ideal to the growth and consolidation of companies in the market. Corporate communications plans and organizational structures were analyzed to verify whether or not information technology (i.e. the use of the Internet) is maximized: the communications aspect being a critical area of company growth. We found that most franchise companies surveyed had adapted well to the changes in information technology, despite economic challenges. The Internet as a communications tool has been limited to its utility as a “bulletin board” for information. The marketing advantage of Internet communication, or its use as an avenue for customer exchange and exchange of goods and services has yet to be maximized. Future research may look into the details of how companies are able to maximize the communications-marketing advantage that Online/Internet can contribute to the franchise sector.

Health inequality between immigrants and natives in Spain: the loss of the healthy immigrant effect in times of economic crisis

Background: The immigrant population living in Spain grew exponentially in the early 2000s but has been particularly affected by the economic crisis. This study aims to analyse health inequalities between immigrants born in middle- or low-income countries and natives in Spain, in 2006 and 2012, taking into account gender, year of arrival and socioeconomic exposures. Methods: Study of trends using two cross-sections, the 2006 and 2012 editions of the Spanish National Health Survey, including residents in Spain aged 15–64 years (20 810 natives and 2950 immigrants in 2006, 14 291 natives and 2448 immigrants in 2012). Fair/poor self-rated health, poor mental health (GHQ-12 > 2), chronic activity limitation and use of psychotropic drugs were compared between natives and immigrants who arrived in Spain before 2006, adjusting robust Poisson regression models for age and socioeconomic variables to obtain prevalence ratios (PR) and 95% confidence interval (CI). Results: Inequalities in poor self-rated health between immigrants and natives tend to increase among women (age-adjusted PR2006 = 1.39; 95% CI: 1.24–1.56, PR2012 = 1.56; 95% CI: 1.33–1.82). Among men, there is a new onset of inequalities in poor mental health (PR2006 = 1.10; 95% CI: 0.86–1.40, PR2012 = 1.34; 95% CI: 1.06–1.69) and an equalization of the previously lower use of psychotropic drugs (PR2006 = 0.22; 95% CI: 0.11–0.43, PR2012 = 1.20; 95% CI: 0.73–2.01). Conclusions: Between 2006 and 2012, immigrants who arrived in Spain before 2006 appeared to worsen their health status when compared with natives. The loss of the healthy immigrant effect in the context of a worse impact of the economic crisis on immigrants appears as potential explanation. Employment, social protection and re-universalization of healthcare would prevent further deterioration of immigrants’ health status.

The life and times of Anne Royall

by Sarah Harvey Porter.

The climatic changes of later geological times : a discussion based on observations made in the Cordilleras of North America / by J. D. Whitney.

v.7:no.2 (1882)

Talking with the “pouvoir constituant” in times of constitutional reform: The European Court of Justice on Private Applicants’ Access to Justice. Research Paper in Law 3/2003

[From the Introduction]. European lawyers, at least those dealing predominantly with institutional matters, are living particularly interesting times since the setting-up of the “European Convention on the Future of Europe” in December 2001.1 As the Convention’s mandate, spelled out in rather broad terms in the European Council’s declaration of Laeken,2 is potentially unlimited, and as the future constitution of the European Union (EU) will be ultimately adopted by the subsequent Intergovernmental Conference (IGC), there appears to be a great possibility to clarify, to simplify and also to reform many of the more controversial elements in the European legal construction. The present debate on the future of the European constitution also highlights the relationship between the pouvoir constituant3 and the European Courts, the Court of Justice (ECJ) and its Court of First Instance (CFI), who have to interpret the basic rules and principles of the EU.4 In that light, the present article will focus on a classic theme of the Court’s case law: the relationship between judges and pouvoir constituant. In the EU, this relationship has traditionally been marked by the ECJ’s role as driving force in the “constitutionalisation” of the EC Treaties – which has, to a large extent, been accepted and even codified by the Member States in subsequent treaty revisions. However, since 1994, the ECJ appears to be more reluctant to act as a “law-maker.”5 The recent judgment in Unión de Pequeños Agricultores (UPA)6 – an important decision by which the ECJ refused to liberalize individuals’ access to the Community Courts – is also interesting in this context. UPA may be seen as another proof of judicial restraint - or even as indicator of the beginning of a new phase in the “constitutional dialogue” between the ECJ and the “Masters of the Treaties.”

National Parliaments and their Role in European Integration: The EU’s Democratic Deficit in Times of Economic Hardship and Political Insecurity. Bruges Political Research Paper 28/2013

The article describes and assesses the role of national parliaments in EU legislation considering the reforms introduced by the Lisbon Treaty. This is closely connected with the understanding and (political) application of the principle of subsidiarity. After an analysis of the possibilities and limitations of the relevant legal regulations in the post-Lisbon age, alternative ways for participation of national legislators on the European level are being scrutinized and proposed. The issue of democratic legitimization is also interconnected with the current political reforms being discussed in order to overcome the Euro Crisis. Finally, the authors argue that it does not make sense to include national parliaments in the existing legislative triangle of the EU, but instead to promote the creation of a new kind of supervisory body.

Partnership in times of crisis: challenges for the Eastern European countries' integration with Europe. OSW Point of View Number 36, July 2013

Over the four years since its launch, the Eastern Partnership initiative has created frameworks and mechanisms for the integration of Eastern Partnership countries with the European Union. Despite this, the partner countries have so far made little meaningful progress in modernisation, implementation of reforms or integration with the EU.Since the European Neighbourhood Policy was launched in 2004, the situation in areas of key importance for the EU, such as democratisation, free-market transformations, European integration, political stability and regional security, has not improved significantly. In this context, it is legitimate to ask questions about the extent to which the European Neighbourhood Policy and the Eastern Partnership have brought the Union closer to achieving its declared objectives in the relations with eastern neighbours. What is the underlying cause of the dwindling involvement and declining interest in achieving real progress in integration? How may the events that have been dominating the political agenda – i.e. the EU’s financial crisis, the debate on the future of the Union, but also the political processes taking place within the partner countries – affect the future of mutual relations?