Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

Massive Science with VO and Grids

There is a growing need for massive computational resources for the analysis of new astronomical datasets. To tackle this problem, we present here our first steps towards marrying two new and emerging technologies; the Virtual Observatory (e.g, AstroGrid) and the computa- tional grid (e.g. TeraGrid, COSMOS etc.). We discuss the construction of VOTechBroker, which is a modular software tool designed to abstract the tasks of submission and management of a large number of compu- tational jobs to a distributed computer system. The broker will also interact with the AstroGrid workflow and MySpace environments. We discuss our planned usages of the VOTechBroker in computing a huge number of n–point correlation functions from the SDSS data and mas- sive model-fitting of millions of CMBfast models to WMAP data. We also discuss other applications including the determination of the XMM Cluster Survey selection function and the construction of new WMAP maps.

Statistical computations with AstroGrid and the Grid

We outline our first steps towards marrying two new and emerging technologies; the Virtual Observatory (e.g, Astro- Grid) and the computational grid. We discuss the construction of VOTechBroker, which is a modular software tool designed to abstract the tasks of submission and management of a large number of computational jobs to a distributed computer system. The broker will also interact with the AstroGrid workflow and MySpace environments. We present our planned usage of the VOTechBroker in computing a huge number of n–point correlation functions from the SDSS, as well as fitting over a million CMBfast models to the WMAP data.

Committed terrestrial ecosystem changes due to climate change

Targets for stabilizing climate change are often based on considerations of the impacts of different levels of global warming, usually assessing the time of reaching a particular level of warming. However, some aspects of the Earth system, such as global mean temperatures1 and sea level rise due to thermal expansion2 or the melting of large ice sheets3, continue to respond long after the stabilization of radiative forcing. Here we use a coupled climate–vegetation model to show that in turn the terrestrial biosphere shows significant inertia in its response to climate change. We demonstrate that the global terrestrial biosphere can continue to change for decades after climate stabilization. We suggest that ecosystems can be committed to long-term change long before any response is observable: for example, we find that the risk of significant loss of forest cover in Amazonia rises rapidly for a global mean temperature rise above 2 °C. We conclude that such committed ecosystem changes must be considered in the definition of dangerous climate change, and subsequent policy development to avoid it.

A time-series method to identify and correct range sidelobes in meteorological radar data

The use of pulse compression techniques to improve the sensitivity of meteorological radars has become increasingly common in recent years. An unavoidable side-effect of such techniques is the formation of ‘range sidelobes’ which lead to spreading of information across several range gates. These artefacts are particularly troublesome in regions where there is a sharp gradient in the power backscattered to the antenna as a function of range. In this article we present a simple method for identifying and correcting range sidelobe artefacts. We make use of the fact that meteorological targets produce an echo which fluctuates at random, and that this echo, like a fingerprint, is unique to each range gate. By cross-correlating the echo time series from pairs of gates therefore we can identify whether information from one gate has spread into another, and hence flag regions of contamination. In addition we show that the correlation coefficients contain quantitative information about the fraction of power leaked from one range gate to another, and we propose a simple algorithm to correct the corrupted reflectivity profile.

Tangeretin regulates platelet function through inhibition of phosphoinositide 3-Kinase and cyclic nucleotide signaling

OBJECTIVE: Dietary flavonoids have long been appreciated in reducing cardiovascular disease risk factors, but their mechanisms of action are complex in nature. In this study, the effects of tangeretin, a dietary flavonoid, were explored on platelet function, signaling, and hemostasis. APPROACH AND RESULTS: Tangeretin inhibited agonist-induced human platelet activation in a concentration-dependent manner. It inhibited agonist-induced integrin αIIbβ3 inside-out and outside-in signaling, intracellular calcium mobilization, and granule secretion. Tangeretin also inhibited human platelet adhesion and subsequent thrombus formation on collagen-coated surfaces under arterial flow conditions in vitro and reduced hemostasis in mice. Further characterization to explore the mechanism by which tangeretin inhibits platelet function revealed distinctive effects of platelet signaling. Tangeretin was found to inhibit phosphoinositide 3-kinase-mediated signaling and increase cGMP levels in platelets, although phosphodiesterase activity was unaffected. Consistent with increased cGMP levels, tangeretin increased the phosphorylation of vasodilator-stimulated phosphoprotein at S239. CONCLUSIONS: This study provides support for the ability and mechanisms of action of dietary flavonoids to modulate platelet signaling and function, which may affect the risk of thrombotic disease.

Toward seamless prediction: calibration of climate change projections using seasonal forecasts

The CWRF is developed as a climate extension of the Weather Research and Forecasting model (WRF) by incorporating numerous improvements in the representation of physical processes and integration of external (top, surface, lateral) forcings that are crucial to climate scales, including interactions between land, atmosphere, and ocean; convection and microphysics; and cloud, aerosol, and radiation; and system consistency throughout all process modules. This extension inherits all WRF functionalities for numerical weather prediction while enhancing the capability for climate modeling. As such, CWRF can be applied seamlessly to weather forecast and climate prediction. The CWRF is built with a comprehensive ensemble of alternative parameterization schemes for each of the key physical processes, including surface (land, ocean), planetary boundary layer, cumulus (deep, shallow), microphysics, cloud, aerosol, and radiation, and their interactions. This facilitates the use of an optimized physics ensemble approach to improve weather or climate prediction along with a reliable uncertainty estimate. The CWRF also emphasizes the societal service capability to provide impactrelevant information by coupling with detailed models of terrestrial hydrology, coastal ocean, crop growth, air quality, and a recently expanded interactive water quality and ecosystem model. This study provides a general CWRF description and basic skill evaluation based on a continuous integration for the period 1979– 2009 as compared with that of WRF, using a 30-km grid spacing over a domain that includes the contiguous United States plus southern Canada and northern Mexico. In addition to advantages of greater application capability, CWRF improves performance in radiation and terrestrial hydrology over WRF and other regional models. Precipitation simulation, however, remains a challenge for all of the tested models.

The mirror of consumption: celebritization, developmental consumption and the shifting cultural politics of fair trade

This paper explores the shifting cultural politics of development as expressed in the changing narratives and discursive transparencies of fair trade marketing tactics in the UK. Pursued through what I call ‘developmental consumption’ and the increasing celebritization of development, it is now through the global media mega-star that the subaltern speaks. After a more general discussion of the implications of the celebritization of development, specific analysis focuses on two parallel processes complicit in the ‘mainstreaming’ of fair trade markets and the desire to develop fair trade as a product of ‘quality’. The first involves improving the taste of fair trade commodities through alterations in their material supply chains while the second involves novel marketing narratives designed to invoke these conventions of quality through highly meaningful discursive and visual means. The later process is conceptualized through the theoretical device of the shifting ‘embodiments’ of fair trade which have moved from small farmers’ livelihoods, to landscapes of ‘quality’, to increasing congeries of celebrities such as Chris Martin from the UK band Coldplay. These shifts encapsulate what is referred to here as fair trade’s Faustian Bargain and its ambiguous results: the creation of increasing economic returns and, thus, more development through the movement of fair trade goods into mainstream retail markets at the same time there is a de-centering of the historical discursive transparency at the core of fair trade’s moral economy. Here, then, the celebritization of fair trade has the potential to create ‘the mirror of consumption’, whereby, our gaze is reflected back upon ourselves in the form of ‘the rich and famous’ Northern celebrity muddling the ethics of care developed by connecting consumers to fair trade farmers and their livelihoods. The paper concludes with a consideration of development and fair trade politics in the context of their growing aestheticization and celebritization.