Mapping the platelet profile for functional genomic studies and demonstration of the effect size of the GP6 locus

BACKGROUND: Evidence suggests the wide variation in platelet response within the population is genetically controlled. Unraveling the complex relationship between sequence variation and platelet phenotype requires accurate and reproducible measurement of platelet response. OBJECTIVE: To develop a methodology suitable for measuring signaling pathway-specific platelet phenotype, to use this to measure platelet response in a large cohort, and to demonstrate the effect size of sequence variation in a relevant model gene. METHODS: Three established platelet assays were evaluated: mobilization of [Ca(2+)](i), aggregometry and flow cytometry, each in response to adenosine 5'-diphosphate (ADP) or the glycoprotein (GP) VI-specific crosslinked collagen-related peptide (CRP). Flow cytometric measurement of fibrinogen binding and P-selectin expression in response to a single, intermediate dose of each agonist gave the best combination of reproducibility and inter-individual variability and was used to measure the platelet response in 506 healthy volunteers. Pathway specificity was ensured by blocking the main subsidiary signaling pathways. RESULTS: Individuals were identified who were hypo- or hyper-responders for both pathways, or who had differential responses to the two agonists, or between outcomes. 89 individuals, retested three months later using the same methodology, showed high concordance between the two visits in all four assays (r(2) = 0.872, 0.868, 0.766 and 0.549); all subjects retaining their phenotype at recall. The effect of sequence variation at the GP6 locus accounted for approximately 35% of the variation in the CRP-XL response. CONCLUSION: Genotyping-phenotype association studies in a well-characterized, large cohort provides a powerful strategy to measure the effect of sequence variation in genes regulating the platelet response.

City futures: exploring urban retrofit and sustainable transitions

Cities are responsible for up to 70% of global carbon emissions and 75% of global energy consumption. By 2050 it is estimated that 70% of the world's population will live in cities. The critical challenge for contemporary urbanism, therefore, is to understand how to develop the knowledge, capacity and capability for public agencies, the private sector and multiple users in city-regions (i.e. the city and its wider hinterland) to re-engineer systemically their built environment and urban infrastructure in response to climate change and resource constraints. To inform transitions to urban sustainability, key stakeholders' perceptions were sought though a participatory backcasting and scenario foresight process in order to illuminate challenging but realistic socio-technical scenarios for the systemic retrofit of core UK city-regions. The challenge of conceptualizing complex urban transitions is explored across multiple socio-technical ‘regimes’ (housing, non-domestic buildings, urban infrastructure), scales (building, neighbourhood, city-region), and domains (energy, water, use of resources) within a participatory process. The development of three archetypal ‘guiding visions’ of retrofit city-regional futures developed through this process are discussed, along with the contribution that such foresight processes might play in ‘opening up’ the governance and strategic navigation of urban sustainability.

Research priorities in observing and modeling urban weather and climate

In 2007, the world reached the unprecedented milestone of half of its people living in cities, and that proportion is projected to be 60% in 2030. The combined effect of global climate change and rapid urban growth, accompanied by economic and industrial development, will likely make city residents more vulnerable to a number of urban environmental problems, including extreme weather and climate conditions, sea-level rise, poor public health and air quality, atmospheric transport of accidental or intentional releases of toxic material, and limited water resources. One fundamental aspect of predicting the future risks and defining mitigation strategies is to understand the weather and regional climate affected by cities. For this reason, dozens of researchers from many disciplines and nations attended the Urban Weather and Climate Workshop.1 Twenty-five students from Chinese universities and institutes also took part. The presentations by the workshop's participants span a wide range of topics, from the interaction between the urban climate and energy consumption in climate-change environments to the impact of urban areas on storms and local circulations, and from the impact of urbanization on the hydrological cycle to air quality and weather prediction.

Syntheses, spectroelectrochemical studies, and molecular and electronic structures of ferrocenyl ene-diynes

The readily available complex 1,1-dibromo-2-ferrocenylethylene provides a convenient entry point for the preparation of a wide range of cross-conjugated 1,1-bis(alkynyl)-2-ferrocenylethenes through simple Pd(0)/Cu(I)-mediated cross-coupling reactions with 1-alkynes. The ferrocene moiety in compounds of the general form FcCHC(CCR)2 is essentially electronically isolated from the cross-conjugated π system, as evidenced by IR and UV−vis spectroelectrochemical experiments and quantum chemical calculations. In contrast to the other examples which give stable ferrocenium derivatives upon electrochemical oxidation, the aniline derivatives [FcCHC(CCC6H4NH2-4)2]+ and [FcCHC(CCC6H4NMe2-4)2]+ proved to be unstable on the time scale of the spectroelectrochemical experiments, leading to passivation of the electrode surface over time. There is no significant thermodynamic stabilization of the radical anion [FcCHC(CCC6H4NO2-4)2]− relative to the neutral and dianionic analogues, although the dianion [FcCHC(CCC6H4NO2- 4)2]2− could be studied as a relatively chemically stable species and is well described in terms of two linked nitrophenyl radicals. The capacity to introduce a relatively isolated point charge at the periphery of the cross-conjugated π system appears to make these complexes useful templates for the construction of electrochemically gated quantum interference transistors.

Quantitative ventilation assessments of idealized urban canopy layers with various urban layouts and the same building packing density

This paper investigates urban canopy layers (UCL) ventilation under neutral atmospheric condition with the same building area density (λp=0.25) and frontal area density (λf=0.25) but various urban sizes, building height variations, overall urban forms and wind directions. Turbulent airflows are first predicted by CFD simulations with standard k-ε model evaluated by wind tunnel data. Then air change rates per hour (ACH) and canopy purging flow rate (PFR) are numerically analyzed to quantify the rate of air exchange and the net ventilation capacity induced by mean flows and turbulence. With a parallel approaching wind (θ=0o), the velocity ratio first decreases in the adjustment region, followed by the fully-developed region where the flow reaches a balance. Although the flow quantities macroscopically keep constant, however ACH decreases and overall UCL ventilation becomes worse if urban size rises from 390m to 5km. Theoretically if urban size is infinite, ACH may reach a minimum value depending on local roof ventilation, and it rises from 1.7 to 7.5 if the standard deviation of building height variations increases (0% to 83.3%). Overall UCL ventilation capacity (PFR) with a square overall urban form (Lx=Ly=390m) is better as θ=0o than oblique winds (θ=15o, 30o, 45o), and it exceeds that of a staggered urban form under all wind directions (θ=0o to 45o), but is less than that of a rectangular urban form (Lx=570m, Ly=270m) under most wind directions (θ=30o to 90o). Further investigations are still required to quantify the net ventilation efficiency induced by mean flows and turbulence.

Development of the Surface Urban Energy and Water balance Scheme (SUEWS) for cold climate cities

The Surface Urban Energy and Water Balance Scheme (SUEWS) is developed to include snow. The processes addressed include accumulation of snow on the different urban surface types: snow albedo and density aging, snow melting and re-freezing of meltwater. Individual model parameters are assessed and independently evaluated using long-term observations in the two cold climate cities of Helsinki and Montreal. Eddy covariance sensible and latent heat fluxes and snow depth observations are available for two sites in Montreal and one in Helsinki. Surface runoff from two catchments (24 and 45 ha) in Helsinki and snow properties (albedo and density) from two sites in Montreal are also analysed. As multiple observation sites with different land-cover characteristics are available in both cities, model development is conducted independent of evaluation. The developed model simulates snowmelt related runoff well (within 19% and 3% for the two catchments in Helsinki when there is snow on the ground), with the springtime peak estimated correctly. However, the observed runoff peaks tend to be smoother than the simulated ones, likely due to the water holding capacity of the catchments and the missing time lag between the catchment and the observation point in the model. For all three sites the model simulates the timing of the snow accumulation and melt events well, but underestimates the total snow depth by 18–20% in Helsinki and 29–33% in Montreal. The model is able to reproduce the diurnal pattern of net radiation and turbulent fluxes of sensible and latent heat during cold snow, melting snow and snow-free periods. The largest model uncertainties are related to the timing of the melting period and the parameterization of the snowmelt. The results show that the enhanced model can simulate correctly the exchange of energy and water in cold climate cities at sites with varying surface cover.

Atmospheric electric field measurements in urban environment and the pollutant aerosol weekly dependence

The weekly dependence of pollutant aerosols in the urban environment of Lisbon (Portugal) is inferred from the records of atmospheric electric field at Portela meteorological station (38°47′N,9°08′W). Measurements were made with a Bendorf electrograph. The data set exists from 1955 to 1990, but due to the contaminating effect of the radioactive fallout during 1960 and 1970s, only the period between 1980 and 1990 is considered here. Using a relative difference method a weekly dependence of the atmospheric electric field is found in these records, which shows an increasing trend between 1980 and 1990. This is consistent with a growth of population in the Lisbon metropolitan area and consequently urban activity, mainly traffic. Complementarily, using a Lomb–Scargle periodogram technique the presence of a daily and weekly cycle is also found. Moreover, to follow the evolution of theses cycles, in the period considered, a simple representation in a colour surface plot representation of the annual periodograms is presented. Further, a noise analysis of the periodograms is made, which validates the results found. Two datasets were considered: all days in the period, and fair-weather days only.

Effects of urban density on carbon dioxide exchanges: observations of dense urban, suburban and woodland areas of southern England

Anthropogenic and biogenic controls on the surface–atmosphere exchange of CO2 are explored for three different environments. Similarities are seen between suburban and woodland sites during summer, when photosynthesis and respiration determine the diurnal pattern of the CO2 flux. In winter, emissions from human activities dominate urban and suburban fluxes; building emissions increase during cold weather, while traffic is a major component of CO2 emissions all year round. Observed CO2 fluxes reflect diurnal traffic patterns (busy throughout the day (urban); rush-hour peaks (suburban)) and vary between working days and non-working days, except at the woodland site. Suburban vegetation offsets some anthropogenic emissions, but 24-h CO2 fluxes are usually positive even during summer. Observations are compared to estimated emissions from simple models and inventories. Annual CO2 exchanges are significantly different between sites, demonstrating the impacts of increasing urban density (and decreasing vegetation fraction) on the CO2 flux to the atmosphere.

Surface Urban Energy and Water Balance Scheme (SUEWS): development and evaluation at two UK sites

The Surface Urban Energy and Water Balance Scheme (SUEWS) is evaluated at two locations in the UK: a dense urban site in the centre of London and a residential suburban site in Swindon. Eddy covariance observations of the turbulent fluxes are used to assess model performance over a twoyear period (2011-2013). The distinct characteristics of the sites mean their surface energy exchanges differ considerably. The model suggests the largest differences can be attributed to surface cover (notably the proportion of vegetated versus impervious area) and the additional energy supplied by human activities. SUEWS performs better in summer than winter, and better at the suburban site than the dense urban site. One reason for this is the bias towards suburban summer field campaigns in observational data used to parameterise this (and other) model(s). The suitability of model parameters (such as albedo, energy use and water use) for the UK sites is considered and, where appropriate, alternative values are suggested. An alternative parameterisation for the surface conductance is implemented, which permits greater soil moisture deficits before evaporation is restricted at non-irrigated sites. Accounting for seasonal variation in the estimation of storage heat flux is necessary to obtain realistic wintertime fluxes.

Implications of climate change for expanding cities worldwide

This paper analyses the trends of the changing environmental effects within growing megacities as their diameters exceed 50–100 km and their populations rise beyond 30 million people. The authors consider how these effects are influenced by climate change, to which urban areas themselves contribute, caused by their increasing greenhouse gas emissions associated with rapidly expanding energy use. Other environmental and social factors are assessed, quantitatively and qualitatively, using detailed modelling of urban mesoscale meteorology, which shows how these factors can lead to large conurbations becoming more vulnerable to climatic and environmental hazards. The paper discusses the likely changes in meteorological and hydrological hazards in urban areas, both as the climate changes and the sizes of urban areas grow. Examples are given of how these risks are being reduced through innovations in warning and response systems, planning and infrastructure design, which should include refuges against extreme natural disasters. Policies are shown to be more effective when they are integrated and based on substantial community involvement. Some conclusions are drawn regarding how policies for the natural and artificial environment and for reducing many kinds of climate and hazard risk are related to future designs and planning of infrastructure and open spaces.

"Ever-growing Amman", Jordan: Urban expansion, social polarisation and contemporary urban planning issues

Amman the primate capital city of the Hashemite Kingdom of Jordan currently has a population in excess of 2 million, but in 1924 it consisted of little more than a collection of dwellings and some 2000-3000 inhabitants. The present paper sets out to document and explain the phenomenal expansion of "ever-growing Amman". The physical geography of the urban region and the early growth of the city are considered at the outset and this leads directly to consideration of the highly polarised social structuring that characterises contemporary Amman. In doing this, original data derived from the recent Greater Amman Municipality's Geographical Information System are presented. In this respect, the essential modernity of the city is exemplified. The employment and industrial bases of the city and a range of pressing contemporary issues are then considered, including transport and congestion, the provision of urban water under conditions of water stress and privatisation, and urban and regional development planning for the city. The paper concludes by emphasizing the growing regional and international geopolitical salience of the city of Amman at the start of the 21st century. (C) 2008 Elsevier Ltd. All rights reserved.

Resilience planning, economic change and the politics of post-recession development in London and Hong Kong

For much of the 1990s and 2000s, the emphasis of urban policy in many global cities was on managing and mitigating the social and environmental effects of rapid economic growth. The credit crunch of 2008 and the subsequent recession have undermined some of the core assumptions on which such policies were based. It is in this context that the concept of resilience planning has taken on a new significance. Drawing on contemporary research in London and Hong Kong, the paper shows how resilience and recovery planning has become a key area of political debate. It examines what is meant by conservative and radical interpretations of resilience and how conservative views have come to dominate ‘recovery’ thinking, with élite groups unwilling to accept the limits to the neo-liberal orthodoxies that helped to precipitate the economic crisis. The paper explores the implications of such thinking for the politics of urban development.