MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype

Integrated analysis of miRNA expression and genomic changes in human breast tumors allows the classification of tumor subtypes

Dynamics of photodissociation of XeF2 in organic solvents

This article explores photodissociation of XeF2 in solution, using femtosecond pump probe spectroscopy to follow the fates of photoproducts following cleavage of one Xe–F bond.</p

The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

The spatio-relational nature of urban innovation systems: Universities, knowledge intensive business service firms, and collaborative networks

The need to better identify the spatio-relational nature of urban innovation systems and spaces is increasingly acknowledged. The aim of this paper, therefore, is to provide an enhanced understanding of the knowledge networks existing between urban Knowledge Intensive Business Services firms (KIBS) and universities, which are often key components of such systems and spaces. Drawing on an analysis of urban KIBS firms and universities in the UK, it is found that the nature of firms, the location in which they are based, and the research intensity of their university partners are important determinants of the spatiality and localisation of the networks they form. The results show that the smallest urban KIBS firms have the highest propensity to engage in local links with universities, suggesting that they rely most significantly on their own urban innovation system for collaborative network ties. Keywords : innovation systems; urban innovation spaces; knowledge-based development; proximity; networks; KIBS; universities

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

The United Kingdom and British Empire: A Figurational Approach

Drawing upon the work of Norbert Elias and the process [figurational] sociology perspective, this article examines how state formation processes are related to, and, affected by, expanding and declining chains of international interdependence. In contrast to civic and ethnic conceptions, this approach focuses on the emergence of the nation/nation-state as grounded in broader processes of historical and social development. In doing so, state formation processes within the United Kingdom are related to the expansion and decline of the British Empire. That is, by focusing on the functional dynamics that are embedded in collective groups, one is able to consider how the UK’s ‘state’ and ‘imperial’ figurations were interdependently related to changes in both the UK and the former British Empire. Consequently, by locating contemporary UK relations in the historical context of former imperial relationships, nationalism studies can go ‘beyond’ the nation/nation-state in order to include broader processes of imperial expansion and decline. Here, the relationship between empire and nationalism can offer a valuable insight into contemporary political movements, especially within former imperial groups

A re-randomisation design for clinical trials

Background: Recruitment to clinical trials is often problematic, with many trials failing to recruit to their target sample size. As a result, patient care may be based on suboptimal evidence from underpowered trials or non-randomised studies. Methods: For many conditions patients will require treatment on several occasions, for example, to treat symptoms of an underlying chronic condition (such as migraines, where treatment is required each time a new episode occurs), or until they achieve treatment success (such as fertility, where patients undergo treatment on multiple occasions until they become pregnant). We describe a re-randomisation design for these scenarios, which allows each patient to be independently randomised on multiple occasions. We discuss the circumstances in which this design can be used. Results: The re-randomisation design will give asymptotically unbiased estimates of treatment effect and correct type I error rates under the following conditions: (a) patients are only re-randomised after the follow-up period from their previous randomisation is complete; (b) randomisations for the same patient are performed independently; and (c) the treatment effect is constant across all randomisations. Provided the analysis accounts for correlation between observations from the same patient, this design will typically have higher power than a parallel group trial with an equivalent number of observations. Conclusions: If used appropriately, the re-randomisation design can increase the recruitment rate for clinical trials while still providing an unbiased estimate of treatment effect and correct type I error rates. In many situations, it can increase the power compared to a parallel group design with an equivalent number of observations