Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity

Background: Acquisition of the intestinal microbiota in early life corresponds with the development of the mucosal immune system. Recent work on caesarean-delivered infants revealed that early microbial composition is influenced by birthing method and environment. Furthermore, we have confirmed that early-life environment strongly influences both the adult gut microbiota and development of the gut immune system. Here, we address the impact of limiting microbial exposure after initial colonization on the development of adult gut immunity. Methodology/Principal Findings: Piglets were born in indoor or outdoor rearing units, allowing natural colonization in the immediate period after birth, prior to transfer to high-health status isolators. Strikingly, gut closure and morphological development were strongly affected by isolator-rearing, independent of indoor or outdoor origins of piglets. Isolator-reared animals showed extensive vacuolation and disorganization of the gut epithelium, inferring that normal gut closure requires maturation factors present in maternal milk. Although morphological maturation and gut closure were delayed in isolatorreared animals, these hard-wired events occurred later in development. Type I IFN, IL-22, IL-23 and Th17 pathways were increased in indoor-isolator compared to outdoor-isolator animals during early life, indicating greater immune activation in pigs originating from indoor environments reflecting differences in the early microbiota. This difference was less apparent later in development due to enhanced immune activation and convergence of the microbiota in all isolator-reared animals. This correlated with elevation of Type I IFN pathways in both groups, although T cell pathways were still more affected in indoor-reared animals. Conclusions/Significance: Environmental factors, in particular microbial exposure, influence expression of a large number of immune-related genes. However, the homeostatic effects of microbial colonization in outdoor environments require sustained microbial exposure throughout development. Gut development in high-hygiene environments negatively impacts on normal succession of the gut microbiota and promotes innate immune activation which may impair immune homeostasis.

Toward vicarious calibration of microwave remote-sensing satellites in arid environments

The Soil Moisture and Ocean Salinity (SMOS) satellite marks the commencement of dedicated global surface soil moisture missions, and the first mission to make passive microwave observations at L-band. On-orbit calibration is an essential part of the instrument calibration strategy, but on-board beam-filling targets are not practical for such large apertures. Therefore, areas to serve as vicarious calibration targets need to be identified. Such sites can only be identified through field experiments including both in situ and airborne measurements. For this purpose, two field experiments were performed in central Australia. Three areas are studied as follows: 1) Lake Eyre, a typically dry salt lake; 2) Wirrangula Hill, with sparse vegetation and a dense cover of surface rock; and 3) Simpson Desert, characterized by dry sand dunes. Of those sites, only Wirrangula Hill and the Simpson Desert are found to be potentially suitable targets, as they have a spatial variation in brightness temperatures of <4 K under normal conditions. However, some limitations are observed for the Simpson Desert, where a bias of 15 K in vertical and 20 K in horizontal polarization exists between model predictions and observations, suggesting a lack of understanding of the underlying physics in this environment. Subsequent comparison with model predictions indicates a SMOS bias of 5 K in vertical and 11 K in horizontal polarization, and an unbiased root mean square difference of 10 K in both polarizations for Wirrangula Hill. Most importantly, the SMOS observations show that the brightness temperature evolution is dominated by regular seasonal patterns and that precipitation events have only little impact.

Characterization of energy flux partitioning in urban environments: links with surface seasonal properties

A better understanding of links between the properties of the urban environment and the exchange to the atmosphere is central to a wide range of applications. The numerous measurements of surface energy balance data in urban areas enable intercomparison of observed fluxes from distinct environments. This study analyzes a large database in two new ways. First, instead of normalizing fluxes using net all-wave radiation only the incoming radiative fluxes are used, to remove the surface attributes from the denominator. Second, because data are now available year-round, indices are developed to characterize the fraction of the surface (built; vegetation) actively engaged in energy exchanges. These account for shading patterns within city streets and seasonal changes in vegetation phenology; their impact on the partitioning of the incoming radiation is analyzed. Data from 19 sites in North America, Europe, Africa, and Asia (including 6-yr-long observation campaigns) are used to derive generalized surface–flux relations. The midday-period outgoing radiative fraction decreases with an increasing total active surface index, the stored energy fraction increases with an active built index, and the latent heat fraction increases with an active vegetated index. Parameterizations of these energy exchange ratios as a function of the surface indices [i.e., the Flux Ratio–Active Index Surface Exchange (FRAISE) scheme] are developed. These are used to define four urban zones that characterize energy partitioning on the basis of their active surface indices. An independent evaluation of FRAISE, using three additional sites from the Basel Urban Boundary Layer Experiment (BUBBLE), yields accurate predictions of the midday flux partitioning at each location.

"Where am I?" Impact of display and content variables on spatial presence and comprehension in virtual environments

Forgetting immediate physical reality and having awareness of one�s location in the simulated world is critical to enjoyment and performance in virtual environments be it an interactive 3D game such as Quake or an online virtual 3d community space such as Second Life. Answer to the question "where am I?" at two levels, whether the locus is in the immediate real world as opposed to the virtual world and whether one is aware of the spatial co-ordinates of that locus, hold the key to any virtual 3D experience. While 3D environments, especially virtual environments and their impact on spatial comprehension has been studied in disciplines such as architecture, it is difficult to determine the relative contributions of specific attributes such as screen size or stereoscopy towards spatial comprehension since most of them treat the technology as monolith (box-centered). Using a variable-centered approach put forth by Nass and Mason (1990) which breaks down the technology into its component variables and their corresponding values as its theoretical basis, this paper looks at the contributions of five variables (Stereoscopy, screen size, field of view, level of realism and level of detail) common to most virtual environments on spatial comprehension and presence. The variable centered approach can be daunting as the increase in the number of variables can exponentially increase the number of conditions and resources required. We overcome this drawback posed by adoption of such a theoretical approach by the use of a fractional factorial design for the experiment. This study has completed the first wave of data collection and starting the next phase in January 2007 and expected to complete by February 2007. Theoretical and practical implications of the study are discussed.

Natural ventilation assessment in typical open an semi-open urban environments under various wind directions

Semi-open street roofs protect pedestrians from intense sunshine and rains. Their effects on natural ventilation of urban canopy layers (UCL) are less understood. This paper investigates two idealized urban models consisting of 4(2×2) or 16(4×4) buildings under a neutral atmospheric condition with parallel (0°) or non-parallel (15°,30°,45°) approaching wind. The aspect ratio (building height (H) / street width (W)) is 1 and building width is B=3H. Computational fluid dynamic (CFD) simulations were first validated by experimental data, confirming that standard k-ε model predicted airflow velocity better than RNG k-ε model, realizable k–ε model and Reynolds stress model. Three ventilation indices were numerically analyzed for ventilation assessment, including flow rates across street roofs and openings to show the mechanisms of air exchange, age of air to display how long external air reaches a place after entering UCL, and purging flow rate to quantify the net UCL ventilation capacity induced by mean flows and turbulence. Five semi-open roof types are studied: Walls being hung above street roofs (coverage ratio λa=100%) at z=1.5H, 1.2H, 1.1H ('Hung1.5H', 'Hung1.2H', 'Hung1.1H' types); Walls partly covering street roofs (λa=80%) at z=H ('Partly-covered' type); Walls fully covering street roofs (λa=100%) at z=H ('Fully-covered' type).They basically obtain worse UCL ventilation than open street roof type due to the decreased roof ventilation. 'Hung1.1H', 'Hung1.2H', 'Hung1.5H' types are better designs than 'Fully-covered' and 'Partly-covered' types. Greater urban size contains larger UCL volume and requires longer time to ventilate. The methodologies and ventilation indices are confirmed effective to quantify UCL ventilation.

Urban climates and global climate change

Cities and global climate change are closely linked: cities are where the bulk of greenhouse gas emissions take place through the consumption of fossil fuels; they are where an increasing proportion of the world’s people live; and they also generate their own climate – commonly characterized by the urban heat island. In this way, understanding the way cities affect the cycling of energy, water, and carbon to create an urban climate is a key element of climate mitigation and adaptation strategies, especially in the context of rising global temperatures and deteriorating air quality in many cities. As climate models resolve finer spatial-scales, they will need to represent those areas in which more than 50% of the world’s population already live to provide climate projections that are of greater use to planning and decision-making. Finally, many of the processes that are instrumental in determining urban climate are the same factors leading to global anthropogenic climate change, namely regional-scale land-use changes; increased energy use; and increased emissions of climatically-relevant atmospheric constituents. Cities are therefore both a case study for understanding, and an agent in mitigating, anthropogenic climate change. This chapter reviews and summarizes the current state of understanding of the physical basis of urban climates, as well as our ability to represent these in models. We argue that addressing the challenges of managing urban environments in a changing climate requires understanding the energy, water, and carbon balances for an urban landscape and, importantly, their interactions and feedbacks, together with their links to human behaviour and controls. We conclude with some suggestions for where further research is needed.

Oxidized alginate hydrogels as niche environments for corneal epithelial cells

Chemical and biochemical modification of hydrogels is one strategy to create physiological constructs that maintain cell function. The aim of this study was to apply oxidised alginate hydrogels as a basis for development of a biomimetic niche for limbal epithelial stem cells that may be applied to treating corneal dysfunction. The stem phenotype of bovine limbal epithelial cells (LEC) and the viability of corneal epithelial cells (CEC) were examined in oxidised alginate gels containing collagen IV over a 3-day culture period. Oxidation increased cell viability (P

Cost effectiveness of mitigation measures for water security and water quality in the River Thames catchment: impacts of changing climate, land use and water scarcity

The catchment of the River Thames, the principal river system in southern England, provides the main water supply for London but is highly vulnerable to changes in climate, land use and population. The river is eutrophic with significant algal blooms with phosphorus assumed to be the primary chemical indicator of ecosystem health. In the Thames Basin, phosphorus is available from point sources such as wastewater treatment plants and from diffuse sources such as agriculture. In order to predict vulnerability to future change, the integrated catchments model for phosphorus (INCA-P) has been applied to the river basin and used to assess the cost-effectiveness of a range of mitigation and adaptation strategies. It is shown that scenarios of future climate and land-use change will exacerbate the water quality problems, but a range of mitigation measures can improve the situation. A cost-effectiveness study has been undertaken to compare the economic benefits of each mitigation measure and to assess the phosphorus reductions achieved. The most effective strategy is to reduce fertilizer use by 20% together with the treatment of effluent to a high standard. Such measures will reduce the instream phosphorus concentrations to close to the EU Water Framework Directive target for the Thames.

Economic forecasting in a changing world

This article explains the basis for a theory of economic forecasting developed over the past decade by the authors. The research has resulted in numerous articles in academic journals, two monographs, Forecasting Economic Time Series, 1998, Cambridge University Press, and Forecasting Nonstationary Economic Time Series, 1999, MIT Press, and three edited volumes, Understanding Economic Forecasts, 2001, MIT Press, A Companion to Economic Forecasting, 2002, Blackwells, and the Oxford Bulletin of Economics and Statistics, 2005. The aim here is to provide an accessible, non-technical, account of the main ideas. The interested reader is referred to the monographs for derivations, simulation evidence, and further empirical illustrations, which in turn reference the original articles and related material, and provide bibliographic perspective.

Models of human behaviour in social-ecological systems

Environmental change research often relies on simplistic, static models of human behaviour in social-ecological systems. This limits understanding of how social-ecological change occurs. Integrative, process-based behavioural models, which include feedbacks between action, and social and ecological system structures and dynamics, can inform dynamic policy assessment in which decision making is internalised in the model. These models focus on dynamics rather than states. They stimulate new questions and foster interdisciplinarity between and within the natural and social sciences.

Flavonoid inhibitory pharmacodynamics on platelet function in physiological environments

The complex relationship between flavonoid-based nutrition and cardiovascular disease may be dissected by understanding the activities of these compounds in biological systems. The aim of the present study was to explore a hierarchy for the importance of dietary flavonoids on cardiovascular health by examining the structural basis for inhibitory effects of common, dietary flavonoids (quercetin, apigenin, and naringenin) and the plasma metabolite, tamarixetin. Understanding flavonoid effects on platelets in vivo can be informed by investigations of the ability of these compounds to attenuate the function of these cells. Inhibition of platelet function in whole blood and plasma was structure-dependent. The order of potency was apigenin > tamarixetin > quercetin = naringenin indicating that in vivo, important functional groups are potentially a methylated B ring, and a non-hydroxylated, planar C ring. Apigenin and the methylated metabolite of quercetin, tamarixetin significantly reduced thrombus volume at concentrations (5 μM) that suggested their reported physiological levels (0.1-1 μM) may exert low levels of inhibition. Flavonoid interactions with erythrocytes, leukocytes and human serum albumin in whole blood reduce their inhibitory activities against platelet function. The diminished inhibitory activity of flavonoids that we observed in whole blood and plasma indicated that these interactions do not overcome the attenuating effects of these compounds. Furthermore, inhibition of platelet aggregation by flavonoids was enhanced with increases in exposure time, indicating the potential for measurable inhibitory effects during resident plasma times. We conclude that flavonoid structures may be a major influence of their activities in vivo with methylated metabolites and those of flavones being more potent than those of flavonols and flavanones.

Sustaining growth and profits in a rapidly changing world - a Chinese perspective

The aim of this paper is to stimulate discussion about how Chinese construction and professional service companies can best equip themselves and grow sustainably and profitably in a rapidly changing world. It identifies some of the issues and risks faced by Chinese construction and professional service companies operating domestically and overseas. China has experienced a period of rapid economic growth which is also reflected in the annual construction output. China’s population is the largest in the world, but the demographic profile is changing with an ageing population and a changing dependency ratio. The population is urbanising at a fast rate, putting pressure on housing, and infrastructure. The government must plan for the future and the construction sector must be involved in that planning. The paper considers the drivers shaping China’s construction market, how companies are responding by embracing change and internationalising by seeking to exploit their skills overseas. The drivers are globalisation, urbanisation, demographic change, sustainability, safety and health, and the evolution of professional services as a core part of construction activity. Clients/owners are driving change by demanding more certainty and more sustainable projects.