Identification of renal Cd36 as a determinant of blood pressure and risk for hypertension

To identify renally expressed genes that influence risk for hypertension, we integrated expression quantitative trait locus (QTL) analysis of the kidney with genome-wide correlation analysis of renal expression profiles and blood pressure in recombinant inbred strains derived from the spontaneously hypertensive rat (SHR). This strategy, together with renal transplantation studies in SHR progenitor, transgenic and congenic strains, identified deficient renal expression of Cd36 encoding fatty acid translocase as a genetically determined risk factor for spontaneous hypertension.     

Biodiversity as a barrier to ecological invasion

Biological invasions are a pervasive and costly environmental problem that has been the focus of intense management and research activities over the past half century. Yet accurate predictions of community susceptibility to invasion remain elusive. The diversity resistance hypothesis, which argues that diverse communities are highly competitive and readily resist invasion, is supported by both theory and experimental studies conducted at small spatial scales. However, there is also convincing evidence that the relationship between the diversity of native and invading species is positive when measured at regional scales. Although this latter relationship may arise from extrinsic factors, such as resource heterogeneity, that covary with diversity of native and invading species at large scales, the mechanisms conferring greater invasion resistance to diverse communities at local scales remain unknown. Using neighbourhood analyses, a technique from plant competition studies, we show here that species diversity in small experimental grassland plots enhances invasion resistance by increasing crowding and species richness in localized plant neighbourhoods. Both the establishment (number of invaders) and success (proportion of invaders that are large) of invading plants are reduced. These results suggest that local biodiversity represents an important line of defence against the spread of invaders.     

The promotion of mining and the advancement of science: the chemical revolution of mineralogy

This paper explores the origins of the analytical definition of simple substance, a concept whose central importance in the new chemistry of Lavoisier and his colleagues is now widely recognized. I argue that this notion derived from the practical activities of metallurgists and mineral assayers, and that the theoretical elaboration necessary for the analytical concept to be understood as relevant to chemistry was inspired by the efforts of enlightened rulers in Sweden and Germany to turn chemical science to the benefit of mining—and thus of the various state treasuries. The involvement of chemically-literate mineralogists in the mining industry led them to adopt the principle that analytically-determined composition was a far more essential aspect of minerals than any mere congeries of properties. The same men who pioneered the analytical notion of simple substance also inaugurated the attempt to define a nomenclature for chemistry based exclusively on composition, as determined in the laboratory.     

Structural basis of West Nile virus neutralization by a therapeutic antibody

West Nile virus is a mosquito-borne flavivirus closely related to the human epidemic-causing dengue, yellow fever and Japanese encephalitis viruses. In establishing infection these icosahedral viruses undergo endosomal membrane fusion catalysed by envelope glycoprotein rearrangement of the putative receptor-binding domain III (DIII) and exposure of the hydrophobic fusion loop. Humoral immunity has an essential protective function early in the course of West Nile virus infection. Here, we investigate the mechanism of neutralization by the E16 monoclonal antibody that specifically binds DIII. Structurally, the E16 antibody Fab fragment engages 16 residues positioned on four loops of DIII, a consensus neutralizing epitope sequence conserved in West Nile virus and distinct in other flaviviruses. The E16 epitope protrudes from the surface of mature virions in three distinct environments, and docking studies predict Fab binding will leave five-fold clustered epitopes exposed. We also show that E16 inhibits infection primarily at a step after viral attachment, potentially by blocking envelope glycoprotein conformational changes. Collectively, our results suggest that a vaccine strategy targeting the dominant DIII epitope may elicit safe and effective immune responses against flaviviral diseases.     

Forecasting interest rate swap spreads using domestic and international risk factors: evidence from linear and non‐linear models

This paper explores the ability of factor models to predict the dynamics of US and UK interest rate swap spreads within a linear and a non‐linear framework. We reject linearity for the US and UK swap spreads in favour of a regime‐switching smooth transition vector autoregressive (STVAR) model, where the switching between regimes is controlled by the slope of the US term structure of interest rates. We compare the ability of the STVAR model to predict swap spreads with that of a non‐linear nearest‐neighbours model as well as that of linear AR and VAR models. We find some evidence that the non‐linear models predict better than the linear ones. At short horizons, the nearest‐neighbours (NN) model predicts better than the STVAR model US swap spreads in periods of increasing risk conditions and UK swap spreads in periods of decreasing risk conditions. At long horizons, the STVAR model increases its forecasting ability over the linear models, whereas the NN model does not outperform the rest of the models. Copyright © 2007 John Wiley & Sons, Ltd.     

On the Virtues and Disadvantage of Quantification for Democratic Life

In this paper, a response to Ed Levy's discussion of medical quantification, I reflect on the ambitions of my book Trust in Numbers. I explore the idealized method of randomized clinical trials, revealed in his case study, as a social technology, one endowed with a persuasive scientific rationale but shaped also by political and social demands. The scholarly study of quantification requires not a choice between blind admiration and sweeping rejection, but a nuanced understanding. This should take into account not only the cognitive aspects of science, but also its role in relation to institutions and customs, examined with some specificity. While history is narrowed and distorted when it is written to support a position on some present issue, historical and social studies of science should at least provide tools of criticism. For this, the historian of science must look beyond narrow communities of specialists, and seek a wider perspective on science as an administrative tool and a bearer of cultural and political values.