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

Resources, Trade, and Debt

The paper studies a two-region economy that has two sectors and three factors of production: oil, capital, and labor. The South exports oil in exchange for industrial goods from the North. There is a net capital inflow to the South. This equals the difference between its export revenues and import costs, and represents the South's indebtedness. This overseas borrowing finances the development of the oil sector: increased borrowing leads to &her oil supplies, to new levels of consumption and a new distribution of income in the South, and to new levels of industrial exports from the North. The paper studies the macro impacts of changes in the values of the debt on both the borrowing and the lending regions

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

"Building back better": seeking an equitable return to sport-for-development in the wake of COVID-19

The COVID-19 pandemic affected sport programming by restricting in-person activities. Concurrently, global outcry for racial justice for Black and racialized communities promoted calls-to-action to assess equitable practices in sport, including Sport for Development (SfD). This study critically examined SfD ‘return to play’ programming to include perspectives from racialized persons’ lived experiences. We present findings based on data collected from MLSE Foundation’s Change the Game (CtG) research, which explored questions of sport inequity to ‘build back better’. Outcomes further SfD discourses challenging (potentially) harmful structures affecting participants, including under reported effects of racialization. The study used a mixed-method methodology with quantitative analysis of survey data, and thematic analysis of personal experience within an anti-racist, anti-oppressive, and decolonial conceptual framework

Evaluation of global EMEP MSC-W (rv4.34)-WRF (v3.9.1.1) model surface concentrations and wet deposition of reactive N and S with measurements

Atmospheric pollution has many profound effects on human health, ecosystems, and the climate. Of concern are high concentrations and deposition of reactive nitrogen (Nr) species, especially of reduced N (gaseous NH3, particulate NH4+). Atmospheric chemistry and transport models (ACTMs) are crucial to understanding sources and impacts of Nr chemistry and its potential mitigation. Here we undertake the first evaluation of the global version of the EMEP MSC-W ACTM driven by WRF meteorology (1∘×1∘ resolution), with a focus on surface concentrations and wet deposition of N and S species relevant to investigation of atmospheric Nr and secondary inorganic aerosol (SIA). The model–measurement comparison is conducted both spatially and temporally, covering 10 monitoring networks worldwide. Model simulations for 2010 compared use of both HTAP and ECLIPSEE (ECLIPSE annual total with EDGAR monthly profile) emissions inventories; those for 2015 used ECLIPSEE only. Simulations of primary pollutants are somewhat sensitive to the choice of inventory in places where regional differences in primary emissions between the two inventories are apparent (e.g. China) but are much less sensitive for secondary components. For example, the difference in modelled global annual mean surface NH3 concentration using the two 2010 inventories is 18 % (HTAP: 0.26 µg m−3; ECLIPSEE: 0.31 µg m−3) but is only 3.5 % for NH4+ (HTAP: 0.316 µg m−3; ECLIPSEE: 0.305 µg m−3). Comparisons of 2010 and 2015 surface concentrations between the model and measurements demonstrate that the model captures the overall spatial and seasonal variations well for the major inorganic pollutants NH3, NO2, SO2, HNO3, NH4+, NO3−, and SO42− and their wet deposition in East Asia, Southeast Asia, Europe, and North America. The model shows better correlations with annual average measurements for networks in Southeast Asia (mean R for seven species: R7¯¯¯¯=0.73), Europe (R7¯¯¯¯=0.67), and North America (R7¯¯¯¯=0.63) than in East Asia (R5¯¯¯¯=0.35) (data for 2015), which suggests potential issues with the measurements in the latter network. Temporally, both model and measurements agree on higher NH3 concentrations in spring and summer and lower concentrations in winter. The model slightly underestimates annual total precipitation measurements (by 13 %–45 %) but agrees well with the spatial variations in precipitation in all four world regions (0.65–0.94 R range). High correlations between measured and modelled NH4+ precipitation concentrations are also observed in all regions except East Asia. For annual total wet deposition of reduced N, the greatest consistency is in North America (0.75–0.82 R range), followed by Southeast Asia (R=0.68) and Europe (R=0.61). Model–measurement bias varies between species in different networks; for example, bias for NH4+ and NO3− is largest in Europe and North America and smallest in East Asia and Southeast Asia. The greater uniformity in spatial correlations than in biases suggests that the major driver of model–measurement discrepancies (aside from differing spatial representativeness and uncertainties and biases in measurements) are shortcomings in absolute emissions rather than in modelling the atmospheric processes. The comprehensive evaluations presented in this study support the application of this model framework for global analysis of current and potential future budgets and deposition of Nr and SIA

Chemical Mixing Study for the Hanford TWRS Supporting Facilities (U)

This Engineering Calculation addresses consequences of mixing any two hazardous chemicals contained in the same section of TWRS supporting facilities, as screened in accordance with `Westinghouse Savannah River Company Engineering and Construction Services Division Guidelines and Methods.

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

An empirical model approach for assessing soil organic carbon stock changes following biomass crop establishment in Britain

Land-use change (LUC) is a major influence on soil organic carbon (SOC) stocks and the global carbon cycle. LUC from conventional agricultural to biomass crops has increased in Britain but there is limited understanding of the effects on SOC stocks. Results from paired plot studies investigating site-specific effects document both increasing and decreasing SOC stocks over time. Such variation demonstrates the sensitivity of SOC to many factors including environmental conditions. Using a chronosequence of 93 biomass crop sites in England and Wales, mainly of 1–14 y age, empirical models were developed of SOC trajectory following LUC from arable and grassland to short rotation coppice (SRC) willow and Miscanthus production. SOC stocks were calculated for each site using a fixed sampling depth of 30 cm and changes were estimated by comparing with typical pre-conversion SOC stocks. Most LUCs had no demonstrable net effect on SOC stocks. An estimated net SOC loss of 45.2 ± 24.1 tonnes per hectare (±95% confidence intervals) occurred after 14 y following LUC from grassland to SRC willow. Soil texture and climate data for each site were included in multivariable models to assess the influence of different environmental conditions on SOC trajectory. In most cases the addition of explanatory variables improved the model fit. These models may provide some preliminary estimates of more region-specific changes in SOC following LUC. However, the model fit did not improve sufficiently as to provide a basis for adopting a more targeted LUC strategy for lignocellulosic biomass crop production