De-novo design of complementary (antisense) peptide mini-receptor inhibitor of interleukin 18 (IL-18).

Complementary (antisense) peptide mini-receptor inhibitors are complementary peptides designed to be receptor-surrogates that act by binding to selected surface features of biologically important proteins thereby inhibiting protein-cognate receptor interactions and subsequent biological effects. Previously, we described a complementary peptide mini-receptor inhibitor of interleukin-1beta (IL-1beta) that was designed to bind to an external surface loop (beta-bulge) of IL-1beta (Boraschi loop) clearly identified in the X-ray crystal structure of this cytokine. Here, we report the de-novo design and rational development of a complementary peptide mini-receptor inhibitor of cytokine interleukin-18 (IL-18), a protein for which there is no known X-ray crystal structure. Using sequence homology comparisons with IL-1beta, putative IL-18 surface loops are identified and used as a starting point for design, including a loop region 1 thought to be equivalent with the Boraschi loop of IL-1beta. Only loop region 1 complementary peptides are found to be promising leads as mini-receptor inhibitors of IL-18 but these are prevented from being properly successful owing to solubility problems. The application of "M-I pair mutagenesis" and inclusion of a C-terminal arginine residue are then sufficient to solve this problem and convert one lead peptide into a functional complementary peptide mini-receptor inhibitor of IL-18. This suggests that the biophysical and biological properties of complementary peptides can be improved in a rational and logical manner where appropriate, further strengthening the potential importance of complementary peptides as inhibitors of protein-protein interactions, even when X-ray crystal structural information is not readily available

Medium-term performance and maintenance of SUDS:a case-study of Hopwood Park Motorway Service Area, UK

One of the main barriers to implementing SUDS is concern about performance and maintenance costs since there are few well-documented case-studies. This paper summarizes studies conducted between 2000 and 2008 of the performance and maintenance of four SUDS management trains constructed in 1999 at the Hopwood Park Motorway Service Area, central England. Assessments were made of the wildlife value and sedimentation in the SUDS ponds, the hydraulic performance of the coach park management train, water quality in all management trains, and soil/sediment composition in the grass filter strip, interceptor and ponds. Maintenance procedures and costs were also reviewed. Results demonstrate the benefits of a management train approach over individual SUDS units for flow attenuation, water treatment, spillage containment and maintenance. Peak flows, pond sediment depth and contaminant concentrations in sediment and water decreased through the coach park management train. Of the 2007 annual landscape budget of £15,000 for the whole site, the maintenance costs for SUDS only accounted for £2,500 compared to £4,000 for conventional drainage structures. Furthermore, since sediment has been attenuated in the management trains, the cost of sediment removal after the recommended period of three years was only £554 and, if the design is not compromised, less frequent removal will be required in future

Land-Use Regression Modelling of Intra-Urban Air Pollution Variation in China: Current Status and Future Needs

Rapid urbanization in China is leading to substantial adverse air quality issues, particularly for NO2 and particulate matter (PM). Land-use regression (LUR) models are now being applied to simulate pollutant concentrations with high spatial resolution in Chinese urban areas. However, Chinese urban areas differ from those in Europe and North America, for example in respect of population density, urban morphology and pollutant emissions densities, so it is timely to assess current LUR studies in China to highlight current challenges and identify future needs. Details of twenty-four recent LUR models for NO2 and PM2.5/PM10 (particles with aerodynamic diameters <2.5 µm and <10 µm) are tabulated and reviewed as the basis for discussion in this paper. We highlight that LUR modelling in China is currently constrained by a scarcity of input data, especially air pollution monitoring data. There is an urgent need for accessible archives of quality-assured measurement data and for higher spatial resolution proxy data for urban emissions, particularly in respect of traffic-related variables. The rapidly evolving nature of the Chinese urban landscape makes maintaining up-to-date land-use and urban morphology datasets a challenge. We also highlight the importance for Chinese LUR models to be subject to appropriate validation statistics. Integration of LUR with portable monitor data, remote sensing, and dispersion modelling has the potential to enhance derivation of urban pollution maps

Evidence of traffic-related pollutant control in soil-based Sustainable Urban Drainage Systems (SUDS)

SUDS are being increasingly employed to control highway runoff and have the potential to protect groundwater and surface water quality by minimising the risks of both point and diffuse sources of pollution. While these systems are effective at retaining polluted solids by filtration and sedimentation processes, less is known of the detail of pollutant behaviour within SUDS structures. This paper reports on investigations carried out as part of a co-ordinated programme of controlled studies and field measurements at soft-engineered SUDS undertaken in the UK, observing the accumulation and behaviour of traffic-related heavy metals, oil and PAHs. The field data presented were collected from two extended detention basins serving the M74 motorway in the south-west of Scotland. Additional data were supplied from an experimental lysimeter soil core leaching study. Results show that basin design influences pollutant accumulation and behaviour in the basins. Management and/or control strategies are discussed for reducing the impact of traffic-related pollutants on the aqueous environment

The Integrability of Pauli System in Lorentz Violating Background

We systematically analyze the integrability of a Pauli system in Lorentz violating background at the non-relativistic level both in two- and three-dimensions. We consider the non-relativistic limit of the Dirac equation from the QED sector of the so-called Standard Model Extension by keeping only two types of background couplings, the vector a_mu and the axial vector b_mu. We show that the spin-orbit interaction comes as a higher order correction in the non-relativistic limit of the Dirac equation. Such an interaction allows the inclusion of spin degree non-trivially, and if Lorentz violating terms are allowed, they might be comparable under special circumstances. By including all possible first-order derivative terms and considering the cases a\ne 0, b\ne 0, and b_0\ne 0 one at a time, we determine the possible forms of constants of motion operator, and discuss the existence or continuity of integrability due to Lorentz violating background.Comment: 19 page

Evaluation of the pathways of tropospheric nitrophenol formation using a multiphase model

International audiencePhenols are a major class of volatile organic compounds (VOC) whose reaction within, and partitioning between, the gas and liquid phases affects their lifetime within the atmosphere, the local oxidising capacity, and the extent of production of nitrophenols, which are toxic chemicals. In this work, a zero-dimension box model was constructed to quantify the relative nitration pathways, and partitioning into the liquid phase, of mono-aromatic compounds in order to help elucidate the formation pathways of 2- and 4-nitrophenol in the troposphere. The liquid phase contributed significantly to the production of nitrophenols for liquid water content (Lc) values exceeding 3×10-9, and for a range of assumed liquid droplet diameter, even though the resultant equilibrium partitioning to the liquid phase was much lower. For example, in a ''typical'' model scenario, with Lc=3×10-7, 58% of nitrophenol production occurred in the liquid phase but only 2% of nitrophenol remained there, i.e. a significant proportion of nitrophenol observed in the gas phase may actually be produced via the liquid phase. The importance of the liquid phase was enhanced at lower temperatures, by a factor ~1.5?2 at 278 K cf. 298 K. The model showed that nitrophenol production was particularly sensitive to the values of the rate coefficients for the liquid phase reactions between phenol and OH or NO3 reactions, but insensitive to the rate coefficient for the reaction between benzene and OH, thus identifying where further experimental data are required

Chemical climatology: a case study for ozone

In 1872 Scottish chemist Robert Angus Smith established the basis of ‘chemical climatology’ explicitly designed to assess the human health impact of the ‘man-made climates’ in cities. Since then usage of chemical climatology has been sporadic. However with large volumes of atmospheric composition datasets available from campaign measurements, monitoring and modelling, as well as pollutant impact studies, an updated framework based on Angus Smith’s principles would be useful as a resource for both scientists and policy makers. Through analogy with the use of the term climate in other areas (e.g. meteorological or political) a modern chemical climatology framework is described, highlighting impact-focused principles. To derive the chemical climatology the impact of atmospheric composition is first identified (e.g. damage to human health) The impact is linked to the state of atmospheric composition in time and space (e.g. ozone concentrations in the UK 1990 -2010). Finally the drivers of the state are assessed (e.g. emissions, chemical background, chemical precursors, meteorology). Two chemical climates are presented: O3-human health and ozone-vegetation. The chemical climates are derived from measurements at the two UK European Monitoring and Evaluation Programme (EMEP) monitoring ‘supersites’: Auchencorth Moss and Harwell. The impacts of O3 on human health and on vegetation are assessed using the SOMO35 and AOT40 metrics respectively. Drivers of significant spatial variation in these impacts across the UK, and temporal changes at Harwell between 1990 and 2011 are discussed, as well as the relative importance of hemispheric, regional and local O3 chemical processing and its precursors. The individual site assessments are placed in regional context through the statistical evaluation of O3 variation across Europe. The chemical climatology framework allows integration of individual scientific studies focussing on specific processes within the impact-state and driver space into a synthesised and more general understanding. This approach provides opportunities for developing understanding of multiple impacts are considered for each chemical component allow identification of common drivers of impacts, and potentially holistically considered mitigation strategies

Rigidity analysis of HIV-1 protease

We present a rigidity analysis on a large number of X-ray crystal structures of the enzyme HIV-1 protease using the 'pebble game' algorithm of the software FIRST. We find that although the rigidity profile remains similar across a comprehensive set of high resolution structures, the profile changes significantly in the presence of an inhibitor. Our study shows that the action of the inhibitors is to restrict the flexibility of the beta-hairpin flaps which allow access to the active site. The results are discussed in the context of full molecular dynamics simulations as well as data from NMR experiments.Comment: 4 pages, 3 figures. Conference proceedings for CMMP conference 2010 which was held at the University of Warwic