CARFMAP: A Curated Pathway Map of Cardiac Fibroblasts

The adult mammalian heart contains multiple cell types that work in unison under tightly regulated conditions to maintain homeostasis. Cardiac fibroblasts are a significant and unique population of non-muscle cells in the heart that have recently gained substantial interest in the cardiac biology community. To better understand this renaissance cell, it is essential to systematically survey what has been known in the literature about the cellular and molecular processes involved. We have built CARFMAP (http://visionet.erc.monash.edu.au/CARFMAP), an interactive cardiac fibroblast pathway map derived from the biomedical literature using a software-assisted manual data collection approach. CARFMAP is an information-rich interactive tool that enables cardiac biologists to explore the large body of literature in various creative ways. There is surprisingly little overlap between the cardiac fibroblast pathway map, a foreskin fibroblast pathway map, and a whole mouse organism signalling pathway map from the REACTOME database. Among the use cases of CARFMAP is a common task in our cardiac biology laboratory of identifying new genes that are (1) relevant to cardiac literature, and (2) differentially regulated in high-throughput assays. From the expression profiles of mouse cardiac and tail fibroblasts, we employed CARFMAP to characterise cardiac fibroblast pathways. Using CARFMAP in conjunction with transcriptomic data, we generated a stringent list of six genes that would not have been singled out using bioinformatics analyses alone. Experimental validation showed that five genes (Mmp3, Il6, Edn1, Pdgfc and Fgf10) are differentially regulated in the cardiac fibroblast. CARFMAP is a powerful tool for systems analyses of cardiac fibroblasts, facilitating systems-level cardiovascular research

Using schedulers to test probabilistic distributed systems

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s00165-012-0244-5. Copyright © 2012, British Computer Society.Formal methods are one of the most important approaches to increasing the confidence in the correctness of software systems. A formal specification can be used as an oracle in testing since one can determine whether an observed behaviour is allowed by the specification. This is an important feature of formal testing: behaviours of the system observed in testing are compared with the specification and ideally this comparison is automated. In this paper we study a formal testing framework to deal with systems that interact with their environment at physically distributed interfaces, called ports, and where choices between different possibilities are probabilistically quantified. Building on previous work, we introduce two families of schedulers to resolve nondeterministic choices among different actions of the system. The first type of schedulers, which we call global schedulers, resolves nondeterministic choices by representing the environment as a single global scheduler. The second type, which we call localised schedulers, models the environment as a set of schedulers with there being one scheduler for each port. We formally define the application of schedulers to systems and provide and study different implementation relations in this setting

Cooperative secretions facilitate host range expansion in bacteria

The majority of emergent human pathogens are zoonotic in origin, that is, they can transmit to humans from other animals. Understanding the factors underlying the evolution of pathogen host range is therefore of critical importance in protecting human health. There are two main evolutionary routes to generalism: organisms can tolerate multiple environments or they can modify their environments to forms to which they are adapted. Here we use a combination of theory and a phylogenetic comparative analysis of 191 pathogenic bacterial species to show that bacteria use cooperative secretions that modify their environment to extend their host range and infect multiple host species. Our results suggest that cooperative secretions are key determinants of host range in bacteria, and that monitoring for the acquisition of secreted proteins by horizontal gene transfer can help predict emerging zoonoses

The migration-sustainability paradox: transformations in mobile worlds

This is the final version. Available from Elsevier via the DOI in this record. Migration represents a major transformation of the lives of those involved and has been transformative of societies and economies globally. Yet models of sustainability transformations do not effectively incorporate the movement of populations. There is an apparent migration-sustainability paradox: migration plays a role as a driver of unsustainability as part of economic globalisation, yet simultaneously represents a transformative phenomenon and potential force for sustainable development. We propose criteria by which migration represents an opportunity for sustainable development: increasing aggregate well-being; reduced inequality leading to diverse social benefits; and reduced aggregate environmental burden. We detail the dimensions of the transformative potential of migration and develop a generic framework for migration-sustainability linkages based on environmental, social, and economic dimensions of sustainability, highlighting identity and social transformation dimensions of migration. Such a model overcomes the apparent paradox by explaining the role of societal mobility in achieving sustainable outcomes.Economic and Social Research Council (ESRC)European Research CouncilUniversity of Exeter European Network Fun

The Migration-Sustainability Paradox: Transformations in Mobile Worlds

Migration represents a major transformation of the lives of those involved and has been transformative of societies and economies globally. Yet models of sustainability transformations do not effectively incorporate the movement of populations. There is an apparent migration-sustainability paradox: migration plays a role as a driver of unsustainability as part of economic globalisation, yet simultaneously represents a transformative phenomenon and potential force for sustainable development. We propose criteria by which migration represents an opportunity for sustainable development: increasing aggregate well-being; reduced inequality leading to diverse social benefits; and reduced aggregate environmental burden. We detail the dimensions of the transformative potential of migration and develop a generic framework for migration-sustainability linkages based on environmental, social, and economic dimensions of sustainability, highlighting identity and social transformation dimensions of migration. Such a model overcomes the apparent paradox by explaining the role of societal mobility in achieving sustainable outcomes

Implications of unitarity and analyticity for the D\pi form factors

We consider the vector and scalar form factors of the charm-changing current responsible for the semileptonic decay D\rightarrow \pi l \nu. Using as input dispersion relations and unitarity for the moments of suitable heavy-light correlators evaluated with Operator Product Expansions, including O(\alpha_s^2) terms in perturbative QCD, we constrain the shape parameters of the form factors and find exclusion regions for zeros on the real axis and in the complex plane. For the scalar form factor, a low energy theorem and phase information on the unitarity cut are also implemented to further constrain the shape parameters. We finally propose new analytic expressions for the $D\pi$ form factors, derive constraints on the relevant coefficients from unitarity and analyticity, and briefly discuss the usefulness of the new parametrizations for describing semileptonic data.Comment: 10 pages, 7 figures, uses EPJ style files: expanded version of v1 with extended discussion, additional analysis, explanation, figure and references; corresponds to EPJA versio

Secondary Chromosomal Attachment Site and Tandem Integration of the Mobilizable Salmonella Genomic Island 1

The Salmonella genomic island 1 is an integrative mobilizable element (IME) originally identified in epidemic multidrug-resistant Salmonella enterica serovar Typhimurium (S. Typhimurium) DT104. SGI1 contains a complex integron, which confers various multidrug resistance phenotypes due to its genetic plasticity. Previous studies have shown that SGI1 integrates site-specifically into the S. enterica, Escherichia coli, or Proteus mirabilis chromosome at the 3′ end of thdF gene (attB site)