The integration of proteomics and systems approaches to map regulatory mechanisms underpinning platelet function.

Platelets in the circulation are triggered by vascular damage to activate, aggregate and form a thrombus that prevents excessive blood loss. Platelet activation is stringently regulated by intracellular signalling cascades, which when activated inappropriately lead to myocardial infarction and stroke. Strategies to address platelet dysfunction have included proteomics approaches which have lead to the discovery of a number of novel regulatory proteins of potential therapeutic value. Global analysis of platelet proteomes may enhance the outcome of these studies by arranging this information in a contextual manner that recapitulates established signalling complexes and predicts novel regulatory processes. Platelet signalling networks have already begun to be exploited with interrogation of protein datasets using in silico methodologies that locate functionally feasible protein clusters for subsequent biochemical validation. Characterization of these biological systems through analysis of spatial and temporal organization of component proteins is developing alongside advances in the proteomics field. This focused review highlights advances in platelet proteomics data mining approaches that complement the emerging systems biology field. We have also highlighted nucleated cell types as key examples that can inform platelet research. Therapeutic translation of these modern approaches to understanding platelet regulatory mechanisms will enable the development of novel anti-thrombotic strategies.

Harringtonian virtue: Harrington, Machiavelli, and the method of the 'Moment'

This article presents a reinterpretation of James Harrington's writings. It takes issue with J. G. A. Pocock's reading, which treats him as importing into England a Machiavellian ‘language of political thought’. This reading is the basis of Pocock's stress on the republicanism of eighteenth-century opposition values. Harrington's writings were in fact a most implausible channel for such ideas. His outlook owed much to Stoicism. Unlike the Florentine, he admired the contemplative life; was sympathetic to commerce; and was relaxed about the threat of ‘corruption’ (a concept that he did not understand). These views can be associated with his apparent aims: the preservation of a national church with a salaried but politically impotent clergy; and the restoration of the royalist gentry to a leading role in English politics. Pocock's hypothesis is shown to be conditioned by his method; its weaknesses reflect some difficulties inherent in the notion of ‘languages of thought’.

Recent advances in global electric circuit coupling between the space environment and the troposphere

The global atmospheric electric circuit is driven by thunderstorms and electrified rain/shower clouds and is also influenced by energetic charged particles from space. The global circuit maintains the ionosphere as an equipotential at∼+250 kV with respect to the good conducting Earth (both land and oceans). Its “load” is the fair weather atmosphere and semi-fair weather atmosphere at large distances from the disturbed weather “generator” regions. The main solar-terrestrial (or space weather) influence on the global circuit arises from spatially and temporally varying fluxes of galactic cosmic rays (GCRs) and energetic electrons precipitating from the magnetosphere. All components of the circuit exhibit much variability in both space and time. Global circuit variations between solar maximum and solar minimum are considered together with Forbush decrease and solar flare effects. The variability in ion concentration and vertical current flow are considered in terms of radiative effects in the troposphere, through infra-red absorption, and cloud effects, in particular possible cloud microphysical effects from charging at layer cloud edges. The paper identifies future research areas in relation to Task Group 4 of the Climate and Weather of the Sun-Earth System (CAWSES-II) programme.

Numerical modelling of the energy and water cycle of the Baltic Sea

This paper will introduce the Baltex research programme and summarize associated numerical modelling work which has been undertaken during the last five years. The research has broadly managed to clarify the main mechanisms determining the water and energy cycle in the Baltic region, such as the strong dependence upon the large scale atmospheric circulation. It has further been shown that the Baltic Sea has a positive water balance, albeit with large interannual variations. The focus on the modelling studies has been the use of limited area models at ultra-high resolution driven by boundary conditions from global models or from reanalysis data sets. The programme has further initiated a comprehensive integration of atmospheric, land surface and hydrological modelling incorporating snow, sea ice and special lake models. Other aspects of the programme include process studies such as the role of deep convection, air sea interaction and the handling of land surface moisture. Studies have also been undertaken to investigate synoptic and sub-synoptic events over the Baltic region, thus exploring the role of transient weather systems for the hydrological cycle. A special aspect has been the strong interests and commitments of the meteorological and hydrological services because of the potentially large societal interests of operational applications of the research. As a result of this interests special attention has been put on data-assimilation aspects and the use of new types of data such as SSM/I, GPS-measurements and digital radar. A series of high resolution data sets are being produced. One of those, a 1/6 degree daily precipitation climatology for the years 1996–1999, is such a unique contribution. The specific research achievements to be presented in this volume of Meteorology and Atmospheric Physics is the result of a cooperative venture between 11 European research groups supported under the EU-Framework programmes.

Community engagement and social organization: introducing concepts, policy and practical applications

This chapter provides an introductory overview of how the term ‘community’ has been conceptualized in sociological literatures, noting that there remains considerable uncertainty with regard to the way in which communities could or should be defined. The chapter examines the salience of underlying concepts of social organization that can shape and influence the extent to which programmes of engagement are likely to be successful. Drawing on recent empirical work some of the key opportunities and challenges for local government in translating the concepts into practice are considered.

Variation in genome organization of the plant pathogenic fungus Colletotrichum lindemuthianum

The genome structure of Colletotrichum lindemuthianum in a set of diverse isolates was investigated using a combination of physical and molecular approaches. Flow cytometric measurement of genome size revealed significant variation between strains, with the smallest genome representing 59% of the largest. Southern-blot profiles of a cloned fungal telomere revealed a total chromosome number varying from 9 to 12. Chromosome separations using pulsed-field gel electrophoresis (PFGE) showed that these chromosomes belong to two distinct size classes: a variable number of small (< 2.5 Mb) polymorphic chromosomes and a set of unresolved chromosomes larger than 7 Mb. Two dispersed repeat elements were shown to cluster on distinct polymorphic minichromosomes. Single-copy flanking sequences from these repeat-containing clones specifically marked distinct small chromosomes. These markers were absent in some strains, indicating that part of the observed variability in genome organization may be explained by the presence or absence, in a given strain, of dispensable genomic regions and/or chromosomes.

The European storm Kyrill in January 2007: synoptic evolution, meteorological impacts and some considerations with respect to climate change

The synoptic evolution and some meteorological impacts of the European winter storm Kyrill that swept across Western, Central, and Eastern Europe between 17 and 19 January 2007 are investigated. The intensity and large storm damage associated with Kyrill is explained based on synoptic and mesoscale environmental storm features, as well as on comparisons to previous storms. Kyrill appeared on weather maps over the US state of Arkansas about four days before it hit Europe. It underwent an explosive intensification over the Western North Atlantic Ocean while crossing a very intense zonal polar jet stream. A superposition of several favourable meteorological conditions west of the British Isles caused a further deepening of the storm when it started to affect Western Europe. Evidence is provided that a favourable alignment of three polar jet streaks and a dry air intrusion over the occlusion and cold fronts were causal factors in maintaining Kyrill's low pressure very far into Eastern Europe. Kyrill, like many other strong European winter storms, was embedded in a pre-existing, anomalously wide, north-south mean sea-level pressure (MSLP) gradient field. In addition to the range of gusts that might be expected from the synoptic-scale pressure field, mesoscale features associated with convective overturning at the cold front are suggested as the likely causes for the extremely damaging peak gusts observed at many lowland stations during the passage of Kyrill's cold front. Compared to other storms, Kyrill was by far not the most intense system in terms of core pressure and circulation anomaly. However, the system moved into a pre-existing strong MSLP gradient located over Central Europe which extended into Eastern Europe. This fact is considered determinant for the anomalously large area affected by Kyrill. Additionally, considerations of windiness in climate change simulations using two state-of-the-art regional climate models driven by ECHAM5 indicate that not only Central, but also Eastern Central Europe may be affected by higher surface wind speeds at the end of the 21st century. These changes are partially associated with the increased pressure gradient over Europe which is identified in the ECHAM5 simulations. Thus, with respect to the area affected, as well as to the synoptic and mesoscale storm features, it is proposed that Kyrill may serve as an interesting study case to assess future storm impacts.

Scenario and modelling uncertainty in global mean temperature change derived from emission-driven global climate models

We compare future changes in global mean temperature in response to different future scenarios which, for the first time, arise from emission-driven rather than concentration-driven perturbed parameter ensemble of a global climate model (GCM). These new GCM simulations sample uncertainties in atmospheric feedbacks, land carbon cycle, ocean physics and aerosol sulphur cycle processes. We find broader ranges of projected temperature responses arising when considering emission rather than concentration-driven simulations (with 10–90th percentile ranges of 1.7 K for the aggressive mitigation scenario, up to 3.9 K for the high-end, business as usual scenario). A small minority of simulations resulting from combinations of strong atmospheric feedbacks and carbon cycle responses show temperature increases in excess of 9 K (RCP8.5) and even under aggressive mitigation (RCP2.6) temperatures in excess of 4 K. While the simulations point to much larger temperature ranges for emission-driven experiments, they do not change existing expectations (based on previous concentration-driven experiments) on the timescales over which different sources of uncertainty are important. The new simulations sample a range of future atmospheric concentrations for each emission scenario. Both in the case of SRES A1B and the Representative Concentration Pathways (RCPs), the concentration scenarios used to drive GCM ensembles, lies towards the lower end of our simulated distribution. This design decision (a legacy of previous assessments) is likely to lead concentration-driven experiments to under-sample strong feedback responses in future projections. Our ensemble of emission-driven simulations span the global temperature response of the CMIP5 emission-driven simulations, except at the low end. Combinations of low climate sensitivity and low carbon cycle feedbacks lead to a number of CMIP5 responses to lie below our ensemble range. The ensemble simulates a number of high-end responses which lie above the CMIP5 carbon cycle range. These high-end simulations can be linked to sampling a number of stronger carbon cycle feedbacks and to sampling climate sensitivities above 4.5 K. This latter aspect highlights the priority in identifying real-world climate-sensitivity constraints which, if achieved, would lead to reductions on the upper bound of projected global mean temperature change. The ensembles of simulations presented here provides a framework to explore relationships between present-day observables and future changes, while the large spread of future-projected changes highlights the ongoing need for such work.

On Hamiltonian balanced dynamics and the slowest invariant manifold

The concept of a slowest invariant manifold is investigated for the five-component model of Lorenz under conservative dynamics. It is shown that Lorenz's model is a two-degree-of-freedom canonical Hamiltonian system, consisting of a nonlinear vorticity-triad oscillator coupled to a linear gravity wave oscillator, whose solutions consist of regular and chaotic orbits. When either the Rossby number or the rotational Froude number is small, there is a formal separation of timescales, and one can speak of fast and slow motion. In the same regime, the coupling is weak, and the Kolmogorov–Arnold-Moser theorem is shown to apply. The chaotic orbits are inherently unbalanced and are confined to regions sandwiched between invariant tori consisting of quasi-periodic regular orbits. The regular orbits generally contain free fast motion, but a slowest invariant manifold may be geometrically defined as the set of all slow cores of invariant tori (defined by zero fast action) that are smoothly related to such cores in the uncoupled system. This slowest invariant manifold is not global; in fact, its structure is fractal; but it is of nearly full measure in the limit of weak coupling. It is also nonlinearly stable. As the coupling increases, the slowest invariant manifold shrinks until it disappears altogether. The results clarify previous definitions of a slowest invariant manifold and highlight the ambiguity in the definition of “slowness.” An asymptotic procedure, analogous to standard initialization techniques, is found to yield nonzero free fast motion even when the core solutions contain none. A hierarchy of Hamiltonian balanced models preserving the symmetries in the original low-order model is formulated; these models are compared with classic balanced models, asymptotically initialized solutions of the full system and the slowest invariant manifold defined by the core solutions. The analysis suggests that for sufficiently small Rossby or rotational Froude numbers, a stable slowest invariant manifold can be defined for this system, which has zero free gravity wave activity, but it cannot be defined everywhere. The implications of the results for more complex systems are discussed.

Comments on 'Balance and the slow quasimanifold: some explicit results'

The concept of slow vortical dynamics and its role in theoretical understanding is central to geophysical fluid dynamics. It leads, for example, to “potential vorticity thinking” (Hoskins et al. 1985). Mathematically, one imagines an invariant manifold within the phase space of solutions, called the slow manifold (Leith 1980; Lorenz 1980), to which the dynamics are constrained. Whether this slow manifold truly exists has been a major subject of inquiry over the past 20 years. It has become clear that an exact slow manifold is an exceptional case, restricted to steady or perhaps temporally periodic flows (Warn 1997). Thus the concept of a “fuzzy slow manifold” (Warn and Ménard 1986) has been suggested. The idea is that nearly slow dynamics will occur in a stochastic layer about the putative slow manifold. The natural question then is, how thick is this layer? In a recent paper, Ford et al. (2000) argue that Lighthill emission—the spontaneous emission of freely propagating acoustic waves by unsteady vortical flows—is applicable to the problem of balance, with the Mach number Ma replaced by the Froude number F, and that it is a fundamental mechanism for this fuzziness. They consider the rotating shallow-water equations and find emission of inertia–gravity waves at O(F2). This is rather surprising at first sight, because several studies of balanced dynamics with the rotating shallow-water equations have gone beyond second order in F, and found only an exponentially small unbalanced component (Warn and Ménard 1986; Lorenz and Krishnamurthy 1987; Bokhove and Shepherd 1996; Wirosoetisno and Shepherd 2000). We have no technical objection to the analysis of Ford et al. (2000), but wish to point out that it depends crucially on R 1, where R is the Rossby number. This condition requires the ratio of the characteristic length scale of the flow L to the Rossby deformation radius LR to go to zero in the limit F → 0. This is the low Froude number scaling of Charney (1963), which, while originally designed for the Tropics, has been argued to be also relevant to mesoscale dynamics (Riley et al. 1981). If L/LR is fixed, however, then F → 0 implies R → 0, which is the standard quasigeostrophic scaling of Charney (1948; see, e.g., Pedlosky 1987). In this limit there is reason to expect the fuzziness of the slow manifold to be “exponentially thin,” and balance to be much more accurate than is consistent with (algebraic) Lighthill emission.

EU membership of the WTO: international trade disputes and judicial protection of individuals by EU Courts

The European Union (EU) is embedded in a pluralistic legal context because of the EU and its Member States’ treaty memberships and domestic laws. Where EU conduct has implications for both the EU’s international trade relations and the legal position of individual traders, it possibly affects EU and its Member States’ obligations under the law of the World Trade Organization (WTO law) as well as the Union’s own multi-layered constitutional legal order. The present paper analyses the way in which the European Court of Justice (ECJ) accommodates WTO and EU law in the context of international trade disputes triggered by the EU. Given the ECJ’s denial of direct effect of WTO law in principle, the paper focuses on the protection of rights and remedies conferred by EU law. It assesses the implications of the WTO Dispute Settlement Understanding (DSU) – which tolerates the acceptance of retaliatory measures constraining traders’ activities in sectors different from those subject to the original trade dispute (Bananas and Hormones cases) – for the protection of ‘retaliation victims’. The paper concludes that governmental discretion conferred by WTO law has not affected the applicability of EU constitutional law but possibly shapes the actual scope of EU rights and remedies where such discretion is exercised in the EU’s general interest.

Globalization and the evolution of international retailing: a comment on Alexander’s ‘British Overseas Retailing, 1900-1960'

Nicholas Alexander's (2011. British overseas retailing, 1900–60: International firm characteristics, market selections and entry modes. Business History, 53, 530–556) survey of British overseas retailers from 1900 to 1960 provides pathbreaking new evidence of international retailing activity during the first globalisation boom. The article surveys this and other recent evidence, and confirms that international retailing was far more significant up to 1929 than previously thought. This activity was overwhelmingly undertaken by non-retailers, however, and hence by multinationals whose advantages in retailing were fundamentally unsustainable over the long run. Even the department store format, the principal retail innovation of the period, was not internationalised primarily by multinationals. Rather it was diffused via indigenous entrepreneurs, driven by a rapidly growing global demand for western style fashion and dress.

Doing more harm than good? Community based natural resource management and the neglect of local institutions in policy development

Approaches to natural resource management emphasise the importance of involving local people and institutions in order to build capacity, limit costs, and achieve environmental sustainability. Governments worldwide, often encouraged by international donors, have formulated devolution policies and legal instruments that provide an enabling environment for devolved natural resource management. However, implementation of these policies reveals serious challenges. This article explores the effects of limited involvement of local people and institutions in policy development and implementation. An in-depth study of the Forest Policy of Malawi and Village Forest Areas in the Lilongwe district provides an example of externally driven policy development which seeks to promote local management of natural resources. The article argues that policy which has weak ownership by national government and does not adequately consider the complexity of local institutions, together with the effects of previous initiatives on them, can create a cumulative legacy through which destructive resource use practices and social conflict may be reinforced. In short, poorly developed and implemented community based natural resource management policies can do considerably more harm than good. Approaches are needed that enable the policy development process to embed an in-depth understanding of local institutions whilst incorporating flexibility to account for their location-specific nature. This demands further research on policy design to enable rigorous identification of positive and negative institutions and ex-ante exploration of the likely effects of different policy interventions.

Modelling fire and the terrestrial carbon balance

Four CO2 concentration inversions and the Global Fire Emissions Database (GFED) versions 2.1 and 3 are used to provide benchmarks for climate-driven modeling of the global land-atmosphere CO2 flux and the contribution of wildfire to this flux. The Land surface Processes and exchanges (LPX) model is introduced. LPX is based on the Lund-Potsdam-Jena Spread and Intensity of FIRE (LPJ-SPITFIRE) model with amended fire probability calculations. LPX omits human ignition sources yet simulates many aspects of global fire adequately. It captures the major features of observed geographic pattern in burnt area and its seasonal timing and the unimodal relationship of burnt area to precipitation. It simulates features of geographic variation in the sign of the interannual correlations of burnt area with antecedent dryness and precipitation. It simulates well the interannual variability of the global total land-atmosphere CO2 flux. There are differences among the global burnt area time series from GFED2.1, GFED3 and LPX, but some features are common to all. GFED3 fire CO2 fluxes account for only about 1/3 of the variation in total CO2 flux during 1997–2005. This relationship appears to be dominated by the strong climatic dependence of deforestation fires. The relationship of LPX-modeled fire CO2 fluxes to total CO2 fluxes is weak. Observed and modeled total CO2 fluxes track the El Niño–Southern Oscillation (ENSO) closely; GFED3 burnt area and global fire CO2 flux track the ENSO much less so. The GFED3 fire CO2 flux-ENSO connection is most prominent for the El Niño of 1997–1998, which produced exceptional burning conditions in several regions, especially equatorial Asia. The sign of the observed relationship between ENSO and fire varies regionally, and LPX captures the broad features of this variation. These complexities underscore the need for process-based modeling to assess the consequences of global change for fire and its implications for the carbon cycle.

Changes in gene expression in Arabidopsis shoots during phosphate starvation and the potential for developing smart plants

Our aim was to generate and prove the concept of "smart" plants to monitor plant phosphorus (P) status in Arabidopsis. Smart plants can be genetically engineered by transformation with a construct containing the promoter of a gene up-regulated specifically by P starvation in an accessible tissue upstream of a marker gene such as beta-glucuronidase (GUS). First, using microarrays, we identified genes whose expression changed more than 2.5-fold in shoots of plants growing hydroponically when P, but not N or K, was withheld from the nutrient solution. The transient changes in gene expression occurring immediately (4 h) after P withdrawal were highly variable, and many nonspecific, shock-induced genes were up-regulated during this period. However, two common putative cis-regulatory elements (a PHO-like element and a TATA box-like element) were present significantly more often in the promoters of genes whose expression increased 4 h after the withdrawal of P compared with their general occurrence in the promoters of all genes represented on the microarray. Surprisingly, the expression of only four genes differed between shoots of P-starved and -replete plants 28 h after P was withdrawn. This lull in differential gene expression preceded the differential expression of a new group of 61 genes 100 h after withdrawing P. A literature survey indicated that the expression of many of these "late" genes responded specifically to P starvation. Shoots had reduced P after 100 h, but growth was unaffected. The expression of SQD1, a gene involved in the synthesis of sulfolipids, responded specifically to P starvation and was increased 100 h after withdrawing P. Leaves of Arabidopsis bearing a SQD1::GUS construct showed increased GUS activity after P withdrawal, which was detectable before P starvation limited growth. Hence, smart plants can monitor plant P status. Transferring this technology to crops would allow precision management of P fertilization, thereby maintaining yields while reducing costs, conserving natural resources, and preventing pollution.