The UK Integrated Assessment Model for source apportionment and air pollution policy applications to PM2.5.

Source apportionment and the effect of reducing individual sources is important input for the development of strategies to address air pollution. The UK Integrated Assessment Model, UKIAM, has been developed for this purpose as a flexible framework, combining information from different atmospheric dispersion models to cover different pollutant contributions, and span the range from European to local scale. In this paper we describe the UKIAM as developed for SO2, NOx, NH3, PM2.5 and VOCs. We illustrate its versatility and application with assessment of current PM2.5 concentrations and exposure of the UK population, as a case-study that has been used as the starting point to investigate potential improvement towards attainment of the WHO guideline of 10 µg/m3.

Inorganic nitrogen deposition in arid land ecosystems of Central Asia.

Atmospheric reactive nitrogen (Nr) pollution leads to enhanced Nr deposition. There still big gaps in understanding atmospheric nitrogen deposition because of limited monitoring sites in arid land ecosystems of Central Asia. To determine Nr concentrations and deposition in the study area, we have set up 20 monitoring sites to collect gaseous, particulate, and precipitation samples and measure their Nr components since 2009. Nr concentrations in air showed large spatial variations. Based on the Nr concentrations, dry deposition was calculated using the monthly average Nr concentrations by the corresponding deposition velocities modeled, which was varied between 3.15 and 27.92 kg N ha-1 yr-1 across desert, grassland, desert-grassland, forest, farmland, and city/suburb ecosystems. Ammonia N deposition varied between 0.50 asnd 8.66 kg N ha-1 yr-1, and nitrate N deposition c varied between 0.67 and 4.22 kg N ha-1 yr-1, respectively, in precipitation. Annual N deposition is following the order of desert (4.0) < grassland (6.0) < desert-grassland (7.6) < forest (16.1) < farmland (18.4) < city/suburb (35.4) ecosystems. Dry deposition contributed 52.7, 53.8, 100, 68.2, 73.7, and 78.9% of total N deposition in grassland, desert-grassland, desert, forest, farmland and city/suburb ecosystems, respectively. Reduced nitrogen deposition accounted for 62% of total N deposition in the arid area. Dry NH3 deposition made an important contribution (on average 40%) to total N deposition. Therefore, understanding the characteristics of Nr pollution especially NH3 emission is indispensable to atmospheric pollution control in arid region.

Spatio-temporal patterns of air pollution in China from 2015 to 2018 and implications for health risks.

China has been seriously affected by particulate matter (PM) and gaseous pollutants in the atmosphere. In this study, we systematically analyse the spatio-temporal patterns of PM2.5, PM10, SO2, CO, NO2, and O3 and the associated health risks, using data collected from 1498 national air quality monitoring sites. An analysis of the averaged data from all the sites indicated that, from 2015 to 2018, annual mean concentrations of PM2.5, PM10, SO2 and CO declined by 3.2 µg m-3, 3.7 µg m-3, 3.9 µg m-3, and 0.1 mg m-3, respectively. In contrast, those of NO2 and O3 increased at rates of 0.4 and 3.1 µg m-3, respectively. Except for O3, the annual mean concentrations of all pollutants were generally the highest in North China and lowest in the Tibetan Plateau. The concentrations were generally higher in the north of the country than in the south. In all regions of China, the pollutant concentrations were the highest in winter and lowest in summer, except for O3, which showed an opposite seasonal pattern. Overall, the seasonal mean concentrations of all the pollutants (except for O3) significantly decreased between the same seasons in 2018 and 2015, whereas the seasonal mean O3 concentrations generally significantly increased, and/or remained at stable levels in all four seasons except for winter. Diurnal variations of all pollutants (except for O3) exhibited a bimodal pattern with peaks between 8:00 and 11:00 a.m. and 9:00 and 12:00 p.m., whereas O3 exhibited a unimodal pattern with maximum values between 5:00 and 7:00 p.m. No significant differences in the daily mean concentrations of all pollutants were found between weekdays and weekends in all regions, except for PM2.5 and PM10 in Northeast China. In Northwest China and Southeast China, PM2.5 showed stronger correlations with NO2 relative to SO2, suggesting that NOx emission control may be more effective than SO2 emission control for alleviating PM2.5 formation. Compared with 2015, the total PM2.5-attributable mortality, number of respiratory and cardiovascular diseases, and incidence of chronic bronchitis decreased overall by 23.4%-26.9% in 2018. In contrast, for O3-attributable deaths, there was an increase of 18.9%. Our study not only improves the understanding of the spatial and temporal patterns of air pollutants in China, but also highlights that synchronous control of PM2.5 and O3 pollution should be implemented to achieve dual benefits in protecting human health.

A Biparatopic Antibody That Modulates MET Trafficking Exhibits Enhanced Efficacy Compared with Parental Antibodies in MET-Driven Tumor Models.

PURPOSE: Recent clinical data demonstrate that tumors harboring MET genetic alterations (exon 14 skip mutations and/or gene amplification) respond to small-molecule tyrosine kinase inhibitors, validating MET as a therapeutic target. Although antibody-mediated blockade of the MET pathway has not been successful in the clinic, the failures are likely the result of inadequate patient selection strategies as well as suboptimal antibody design. Thus, our goal was to generate a novel MET blocking antibody with enhanced efficacy. EXPERIMENTAL DESIGN: Here, we describe the activity of a biparatopic MET×MET antibody that recognizes two distinct epitopes in the MET Sema domain. We use a combination of in vitro assays and tumor models to characterize the effect of our antibody on MET signaling, MET intracellular trafficking, and the growth of MET-dependent cells/tumors. RESULTS: In MET-driven tumor models, our biparatopic antibody exhibits significantly better activity than either of the parental antibodies or the mixture of the two parental antibodies and outperforms several clinical-stage MET antibodies. Mechanistically, the biparatopic antibody inhibits MET recycling, thereby promoting lysosomal trafficking and degradation of MET. In contrast to the parental antibodies, the biparatopic antibody fails to activate MET-dependent biological responses, consistent with the observation that it recycles inefficiently and induces very transient downstream signaling. CONCLUSIONS: Our results provide strong support for the notion that biparatopic antibodies are a promising therapeutic modality, potentially having greater efficacy than that predicted from the properties of the parental antibodies.

Impact of long-term nitrogen deposition on the response of dune grassland ecosystems to elevated summer ozone.

Nitrogen deposition and tropospheric ozone are important drivers of vegetation damage, but their interactive effects are poorly understood. This study assessed whether long-term nitrogen deposition altered sensitivity to ozone in a semi-natural vegetation community. Mesocosms were collected from sand dune grassland in the UK along a nitrogen gradient (5-25 kg N/ha/y, including two plots from a long-term experiment), and fumigated for 2.5 months to simulate medium and high ozone exposure. Ozone damage to leaves was quantified for 20 ozone-sensitive species. Soil solution dissolved organic carbon (DOC) and soil extracellular enzymes were measured to investigate secondary effects on soil processes. Mesocosms from sites receiving the highest N deposition showed the least ozone-related leaf damage, while those from the least N-polluted sites were the most damaged by ozone. This was due to differences in community-level sensitivity, rather than species-level impacts. The N-polluted sites contained fewer ozone-sensitive forbs and sedges, and a higher proportion of comparatively ozone-resistant grasses. This difference in the vegetation composition of mesocosms in relation to N deposition conveyed differential resilience to ozone. Mesocosms in the highest ozone treatment showed elevated soil solution DOC with increasing site N deposition. This suggests that, despite showing relatively little leaf damage, the 'ozone resilient' vegetation community may still sustain physiological damage through reduced capacity to assimilate photosynthate, with its subsequent loss as DOC through the roots into the soil. We conclude that for dune grassland habitats, the regions of highest risk to ozone exposure are those that have received the lowest level of long-term nitrogen deposition. This highlights the importance of considering community- and ecosystem-scale impacts of pollutants in addition to impacts on individual species. It also underscores the need for protection of 'clean' habitats from air pollution and other environmental stressors.

Chemical compositions of fog and precipitation at Sejila Mountain in the southeast Tibetan Plateau, China.

Chemical compositions of fog and rain water were measured between July 2017 and September 2018 at Sejila Mountain, southeast Tibet, where fog events frequently occurred in original fir forests at altitude 3950 m. Fog water samples were collected using a Caltech Active Strand Cloud Collector (CASCC), and rain samples were collected using a precipitation gauge. Differences were observed between fog water and rain composition for most analyzed ions. Ion abundance in fog water was Ca2+ > Cl- > Na+ > SO42- > Mg2+ > NH4+ >K+ > NO3- whereas an order of Ca2+ > Na+ > Cl- > Mg2+ > SO42- > NO3- > K+ > NH4+ was observed for rain water. All ion concentrations were higher in fog water than in rain water. Additionally, Ca2+ was the dominant cation in both fog and rain samples, accounting for more than half of all measured cations. NH4+ and SO42- concentrations were notable for being higher in fog than rain water when compared with other ions. For trace elements, Al, As, Mn and Se were the most abundant elements in fog water; only Al and As were detected in rain water. Seventy-two hour back-trajectory analysis showed that air masses during fog and/or rain events mainly came from the south of Sejila Mountain. Spearman correlation analysis and source contribution calculations indicated that both marine and terrestrial sources contributed to the observed ion concentrations. Considering the higher concentrations of NH4+ and higher ratio of NH4+/NO3- measured in fog than in rain, we suggest that quantification of fog nitrogen deposition and its ecological effect in this area should be given more attention.

Assessing Contributions of Agricultural and Nonagricultural Emissions to Atmospheric Ammonia in a Chinese Megacity.

Ammonia (NH3) is the predominant alkaline gas in the atmosphere contributing to formation of fine particles-a leading environmental cause of increased morbidity and mortality worldwide. Prior findings suggest that NH3 in the urban atmosphere derives from a complex mixture of agricultural (mainly livestock production and fertilizer application) and nonagricultural (e.g., urban waste, fossil fuel-related emissions) sources; however, a citywide holistic assessment is hitherto lacking. Here we show that NH3 from nonagricultural sources rivals agricultural NH3 source contributions in the Shanghai urban atmosphere. We base our conclusion on four independent approaches: (i) a full-year operation of a passive NH3 monitoring network at 14 locations covering urban, suburban, and rural landscapes; (ii) model-measurement comparison of hourly NH3 concentrations at a pair of urban and rural supersites; (iii) source-specific NH3 measurements from emission sources; and (iv) localized isotopic signatures of NH3 sources integrated in a Bayesian isotope mixing model to make isotope-based source apportionment estimates of ambient NH3. Results indicate that nonagricultural sources and agricultural sources are both important contributors to NH3 in the urban atmosphere. These findings highlight opportunities to limit NH3 emissions from nonagricultural sources to help curb PM2.5 pollution in urban China.

What is the most ecologically-meaningful metric of nitrogen deposition?

Nitrogen (N) deposition poses a severe risk to global terrestrial ecosystems, and managing this threat is an important focus for air pollution science and policy. To understand and manage the impacts of N deposition, we need metrics which accurately reflect N deposition pressure on the environment, and are responsive to changes in both N deposition and its impacts over time. In the UK, the metric typically used is a measure of total N deposition over 1-3 years, despite evidence that N accumulates in many ecosystems and impacts from low-level exposure can take considerable time to develop. Improvements in N deposition modelling now allow the development of metrics which incorporate the long-term history of pollution, as well as current exposure. Here we test the potential of alternative N deposition metrics to explain vegetation compositional variability in British semi-natural habitats. We assembled 36 individual datasets representing 48,332 occurrence records in 5479 quadrats from 1683 sites, and used redundancy analyses to test the explanatory power of 33 alternative N metrics based on national pollutant deposition models. We find convincing evidence for N deposition impacts across datasets and habitats, even when accounting for other large-scale drivers of vegetation change. Metrics that incorporate long-term N deposition trajectories consistently explain greater compositional variance than 1-3 year N deposition. There is considerable variability in results across habitats and between similar metrics, but overall we propose that a thirty-year moving window of cumulative deposition is optimal to represent impacts on plant communities for application in science, policy and management.

Multiplex Immuno-Liquid Chromatography-Mass Spectrometry-Parallel Reaction Monitoring (LC-MS-PRM) Quantitation of CD8A, CD4, LAG3, PD1, PD-L1, and PD-L2 in Frozen Human Tissues.

The immune status of tumors critically influences their responsiveness to PD1 blockades and other immune-based therapies. Programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) is a clinically validated predictive biomarker of response to checkpoint-inhibitor therapy in a limited number of clinical settings but is poorly predictive in most. With emerging evidence that multiple pathways and immune-checkpoint proteins may coordinately contribute to the adaptive immune resistance, the identification and quantitation of multiple immune markers in tumor tissue could help identify the controlling pathways in a given patient, guide the selection of optimal therapy, and monitor response to treatment. We developed and validated a sensitive and robust immuno-liquid chromatography-parallel reaction monitoring assay to simultaneously quantify the expression levels of six immune markers (CD8A, CD4, LAG3, PD1, PD-L1, and PD-L2) using as little as 1-2 mg of fresh frozen tissue. The lower limit of quantitation ranged from 0.07 ng/mg protein for PD1 to 1.0 ng/mg protein for CD4. The intrabatch accuracy was within -16.6% to 15.0% for all proteins at all concentrations, and the variation ranged from 0.8% to 14.7%, while interbatch accuracy was within -6.3% to 8.6%, and the variation ranged from 1.3% to 12.8%. The validated assay was then applied to quantify all six biomarkers in different tissues and was confirmed to have sufficient sensitivity (0.07-1.00 ng/mg protein) and reproducibility (variation ranged from 4.3 to 12.0%). In an analysis of 26 cervical tumors, CD8A and CD4 were detected in all tumors, followed by PD-L1 in 85%, LAG-3 in 65%, PD1 in 50%, and PD-L2 in 35%. The strongest correlations were observed between CD8A and CD4 ( r = 0.88) and CD8A and LAG-3 ( r = 0.86). PD1 was not significantly correlated with any of the other proteins tested. This method can be applied to survey the immune signatures across tumor types and tailored to incorporate additional markers as needed.

Impact of two centuries of intensive agriculture on soil carbon, nitrogen and phosphorus cycling in the UK.

This paper describes an agricultural model (Roth-CNP) that estimates carbon (C), nitrogen (N) and phosphorus (P) pools, pool changes, their balance and the nutrient fluxes exported from arable and grassland systems in the UK during 1800-2010. The Roth-CNP model was developed as part of an Integrated Model (IM) to simulate C, N and P cycling for the whole of UK, by loosely coupling terrestrial, hydrological and hydro-chemical models. The model was calibrated and tested using long term experiment (LTE) data from Broadbalk (1843) and Park Grass (1856) at Rothamsted. We estimated C, N and P balance and their fluxes exported from arable and grassland systems on a 5km×5km grid across the whole of UK by using the area of arable of crops and livestock numbers in each grid and their management. The model estimated crop and grass yields, soil organic carbon (SOC) stocks and nutrient fluxes in the form of NH4-N, NO3-N and PO4-P. The simulated crop yields were compared to that reported by national agricultural statistics for the historical to the current period. Overall, arable land in the UK have lost SOC by -0.18, -0.25 and -0.08MgCha-1y-1 whereas land under improved grassland SOC stock has increased by 0.20, 0.47 and 0.24MgCha-1y-1 during 1800-1950, 1950-1970 and 1970-2010 simulated in this study. Simulated N loss (by leaching, runoff, soil erosion and denitrification) increased both under arable (-15, -18 and -53kgNha-1y-1) and grass (-18, -22 and -36kgNha-1y-1) during different time periods. Simulated P surplus increased from 2.6, 10.8 and 18.1kgPha-1y-1 under arable and 2.8, 11.3 and 3.6kgPha-1y-1 under grass lands 1800-1950, 1950-1970 and 1970-2010.

Effects of elevated ozone concentration and nitrogen addition on ammonia stomatal compensation point in a poplar clone.

The stomatal compensation point of ammonia (χs) is a key factor controlling plant-atmosphere NH3 exchange, which is dependent on the nitrogen (N) supply and varies among plant species. However, knowledge gaps remain concerning the effects of elevated atmospheric N deposition and ozone (O3) on χs for forest species, resulting in large uncertainties in the parameterizations of NH3 incorporated into atmospheric chemistry and transport models (CTMs). Here, we present leaf-scale measurements of χs for hybrid poplar clone '546' (Populusdeltoides cv. 55/56 x P. deltoides cv. Imperial) growing in two N treatments (N0, no N added; N50, 50 kg N ha-1 yr-1 urea fertilizer added) and two O3 treatments (CF, charcoal-filtered air; E-O3, non-filtered air plus 40 ppb) for 105 days. Our results showed that χs was significantly reduced by E-O3 (41%) and elevated N (19%). The interaction of N and O3 was significant, and N can mitigate the negative effects of O3 on χs. Elevated O3 significantly reduced the light-saturated photosynthetic rate (Asat) and chlorophyll (Chl) content and significantly increased intercellular CO2 concentrations (Ci), but had no significant effect on stomatal conductance (gs). By contrast, elevated N did not significantly affect all measured photosynthetic parameters. Overall, χs was significantly and positively correlated with Asat, gs and Chl, whereas a significant and negative relationship was observed between χs and Ci. Our results suggest that O3-induced changes in Asat, Ci and Chl may affect χs. Our findings provide a scientific basis for optimizing parameterizations of χs in CTMs in response to environmental change factors (i.e., elevated N deposition and/or O3) in the future.

Atmospheric nitrogen deposition in the Yangtze River basin: Spatial pattern and source attribution.

The Yangtze River basin is one of the world's hotspots for nitrogen (N) deposition and likely plays an important role in China's riverine N output. Here we constructed a basin-scale total dissolved inorganic N (DIN) deposition (bulk plus dry) pattern based on published data at 100 observational sites between 2000 and 2014, and assessed the relative contributions of different reactive N (Nr) emission sectors to total DIN deposition using the GEOS-Chem model. Our results show a significant spatial variation in total DIN deposition across the Yangtze River basin (33.2 kg N ha-1 yr-1 on average), with the highest fluxes occurring mainly in the central basin (e.g., Sichuan, Hubei and Hunan provinces, and Chongqing municipality). This indicates that controlling N deposition should build on mitigation strategies according to local conditions, namely, implementation of stricter control of Nr emissions in N deposition hotspots but moderate control in the areas with low N deposition levels. Total DIN deposition in approximately 82% of the basin area exceeded the critical load of N deposition for semi-natural ecosystems along the basin. On the basin scale, the dominant source of DIN deposition is fertilizer use (40%) relative to livestock (11%), industry (13%), power plant (9%), transportation (9%), and others (18%, which is the sum of contributions from human waste, residential activities, soil, lighting and biomass burning), suggesting that reducing NH3 emissions from improper fertilizer (including chemical and organic fertilizer) application should be a priority in curbing N deposition. This, together with distinct spatial variations in emission sector contributions to total DIN deposition also suggest that, in addition to fertilizer, major emission sectors in different regions of the basin should be considered when developing synergistic control measures.

Ambient concentrations and deposition rates of selected reactive nitrogen species and their contribution to PM2.5 aerosols at three locations with contrasting land use in southwest China.

The fast economic development of southwest China has resulted in significant increases in the concentrations of reactive nitrogen (Nr) in the atmosphere. In this study, an urban (Chengdu, CD), suburban (Shifang, SF) and agriculture (Yanting, YT) - dominated location in the Sichuan Province, southwest China, were selected to investigate the atmospheric composition of Nr, their concentrations and deposition rates. We measured Nr concentrations in precipitation (NH4+, NO3- and organic N (DON)), the gas phase (NH3 and NO2), and the aerosol particles (PM2.5), and calculated their fluxes over a two year period (2014-2016). Total annual N deposition rates were 49.2, 44.7 and 19.8 kg N ha-1 yr-1 at CD, SF and YT, respectively. Ammonia concentrations were larger at the urban and suburban sites than the agricultural site (12.2, 14.9, and 4.9 µg N m-3 at CD, SF and YT, respectively). This is consistent with the multitude of larger sources of NH3, including city garbage, livestock and traffic, in the urban and suburban areas. Monthly NO2 concentrations were lower in warmer compared to the colder months, but seasonal differences were insignificant. Daily PM2.5 concentrations ranged from 7.7 to 236.0, 5.0-210.4 and 4.2-128.4 µg m-3 at CD, SF and YT, respectively, and showed significant correlations with fine particulate NH4+ and NO3- concentrations. Ratios of reduced to oxidized N were in the range of 1.6-2.7. This implies that the control of reduced Nr especially in urban environments is needed to improve local air quality.

Bulk deposition of organic and inorganic nitrogen in southwest China from 2008 to 2013.

China is regarded as one of the nitrogen deposition hotspots in the world. Measurements to-date have focused mainly on the North China Plain, ignoring the fact that atmospheric chemical and physical properties vary across the country and that there may be other hotspots regions that should be investigated. For this reason we have conducted a six year study, measuring the bulk deposition of reduced (NH4-N), oxidized (NO3-N), and dissolved organic nitrogen (DON) at three contrasting sites in the Sichuan province, southwest China. The study sites were a high altitude forest in the Gongga Mountains (GG), an agriculture dominated region in Yanting (YT) and an urban site in the mega city Chengdu (CD). The annual average bulk deposition fluxes of total dissolved nitrogen (TDN) were 7.4, 23.1 and 36.6 kg N ha-1 yr-1 at GG, YT and CD sites, respectively, during the study period 2008 to 2013. The contributions of NH4-N, NO3-N and DON to the TDN were in the range of 48.4-57.8%, 28.8-43.7%, and 8.0-15.6%, respectively. DON bulk deposition was mainly dominated by agricultural activities. TDN bulk deposition fluxes showed increasing trends at the agricultural and urban sites from 2008 to 2013, but there was little change at the remote forest (GG) site. While reduced N dominated bulk N deposition at all the three sites, its contribution showed a decreasing trend, suggesting a gradual increase in the importance of oxidized N. These results reveal the value of long term monitoring in detecting changes in the atmospheric chemical composition of this rapidly changing region, and their inclusion in the policy debate regarding which sources should be controlled in order to reduce the long term impacts of N deposition, especially for southwest China, where there are few measurements of N deposition.

Myostatin deficiency but not anti-myostatin blockade induces marked proteomic changes in mouse skeletal muscle.

Pharmacologic blockade of the myostatin (Mstn)/activin receptor pathway is being pursued as a potential therapy for several muscle wasting disorders. The functional benefits of blocking this pathway are under investigation, in particular given the findings that greater muscle hypertrophy results from Mstn deficiency arising from genetic ablation compared to post-developmental Mstn blockade. Using high-resolution MS coupled with SILAC mouse technology, we quantitated the relative proteomic changes in gastrocnemius muscle from Mstn knockout (Mstn(-/-) ) and mice treated for 2-weeks with REGN1033, an anti-Mstn antibody. Relative to wild-type animals, Mstn(-/-) mice had a two-fold greater muscle mass and a >1.5-fold change in expression of 12.0% of 1137 quantified muscle proteins. In contrast, mice treated with REGN1033 had minimal changes in muscle proteome (0.7% of 1510 proteins >1.5-fold change, similar to biological difference 0.5% of 1310) even though the treatment induced significant 20% muscle mass increase. Functional annotation of the altered proteins in Mstn(-/-) mice corroborates the mutiple physiological changes including slow-to-fast fiber type switch. Thus, the proteome-wide protein expression differs between Mstn(-/-) mice and mice subjected to specific Mstn blockade post-developmentally, providing molecular-level insights to inform mechanistic hypotheses to explain the observed functional differences.

Characteristics of ammonia, acid gases, and PM2.5 for three typical land-use types in the North China Plain.

Air pollution is one of the most serious environmental problems in China due to its rapid economic development alongside a very large consumption of fossil fuel, particularly in the North China Plain (NCP). During the period 2011-2014, we integrated active and passive sampling methods to perform continuous measurements of NH3, HNO3, NO2, and PM2.5 at two urban, one suburban, and two rural sites in the NCP. The annual average concentrations of NH3, NO2, and HNO3 across the five sites were in the ranges 8.5-23.0, 22.2-50.5, and 5.5-9.7 µg m(-3), respectively, showing no significant spatial differences for NH3 and HNO3 but significantly higher NO2 concentration at the urban sites. At each site, annual average concentrations of NH3 and NO2 showed increasing and decreasing trends, respectively, while there was no obvious trend in annual HNO3 concentrations. Daily PM2.5 concentrations ranged from 11.8 to 621.0 µg m(-3) at the urban site, from 19.8 to 692.9 µg m(-3) at the suburban site, and from 23.9 to 754.5 µg m(-3) at the two rural sites, with more than 70% of sampling days exceeding 75 µg m(-3). Concentrations of water-soluble ions in PM2.5 ranked differently between the non-rural and rural sites. The three dominant ions were NH4(+), NO3(-), and SO4(2-) and mainly existed as (NH4)2SO4, NH4HSO4, and NH4NO3, and their concentrations averaged 48.6 ± 44.9, 41.2 ± 40.8, and 49.6 ± 35.9 µg m(-3) at the urban, suburban, and rural sites, respectively. Ion balance calculations indicated that PM2.5 was neutral at the non-rural sites but acidic at the rural sites. Seasonal variations of the gases and aerosols exhibited different patterns, depending on source emission strength and meteorological conditions. Our results suggest that a feasible pathway to control PM2.5 pollution in the NCP should target ammonia and acid gases together.

Human Excreta as a Stable and Important Source of Atmospheric Ammonia in the Megacity of Shanghai.

Although human excreta as a NH3 source has been recognized globally, this source has never been quantitatively determined in cities, hampering efforts to fully assess the causes of urban air pollution. In the present study, the exhausts of 15 ceiling ducts from collecting septic tanks in 13 buildings with 6 function types were selected to quantify NH3 emission rates in the megacity of Shanghai. As a comparison, the ambient NH3 concentrations across Shanghai were also measured at 13 atmospheric monitoring sites. The concentrations of NH3 in the ceiling ducts (2809(-2661)(+5803) µg m(-3)) outweigh those of the open air (~10 µg m(-3)) by 2-3 orders of magnitude, and there is no significant difference between different seasons. δ15N values of NH3 emitted from two ceiling ducts are also seasonally consistent, suggesting that human excreta may be a stable source of NH3 in urban areas. The NH3 concentration levels were variable and dependent on the different building types and the level of human activity. NH3 emission rates of the six residential buildings (RBNH3) were in agreement with each other. Taking occupation time into account, we confined the range of the average NH3 emission factor for human excreta to be 2-4 times (with the best estimate of 3 times) of the averaged RBNH3 of 66.0±58.9 g NH3 capita(-1) yr(-1). With this emission factor, the population of ~21 million people living in the urban areas of Shanghai annually emitted approximately 1386 Mg NH3, which corresponds to over 11.4% of the total NH3 emissions in the Shanghai urban areas. The spatial distribution of NH3 emissions from human excreta based on population data was calculated for the city of Shanghai at a high-resolution (100×100 m). Our results demonstrate that human excreta should be included in official ammonia emission inventories.

A multiyear assessment of air quality benefits from China's emerging shale gas revolution: Urumqi as a case study.

China is seeking to unlock its shale gas in order to curb its notorious urban air pollution, but robust assessment of the impact on PM2.5 pollution of replacing coal with natural gas for winter heating is lacking. Here, using a whole-city heating energy shift opportunity offered by substantial reductions in coal combustion during the heating periods in Urumqi, northwest China, we conducted a four-year study to reveal the impact of replacing coal with natural gas on the mass concentrations and chemical components of PM2.5. We found a significant decline in PM2.5, major soluble ions and metal elements in PM2.5 in January of 2013 and 2014 compared with the same periods in 2012 and 2011, reflecting the positive effects on air quality of using natural gas as a heating fuel throughout the city. This occurred following complete replacement with natural gas for heating energy in October 2012. The weather conditions during winter did not show any significant variation over the four years of the study. Our results indicate that China and other developing nations will benefit greatly from a change in energy source, that is, increasing the contribution of either natural gas or shale gas to total energy consumption with a concomitant reduction in coal consumption.

Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice.

Mice genetically engineered to be humanized for their Ig genes allow for human antibody responses within a mouse background (HumAb mice), providing a valuable platform for the generation of fully human therapeutic antibodies. Unfortunately, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which their genetic humanization was carried out. Heretofore, HumAb mice have been generated by disrupting the endogenous mouse Ig genes and simultaneously introducing human Ig transgenes at a different and random location; KO-plus-transgenic humanization. As we describe in the companion paper, we attempted to make mice that more efficiently use human variable region segments in their humoral responses by precisely replacing 6 Mb of mouse Ig heavy and kappa light variable region germ-line gene segments with their human counterparts while leaving the mouse constant regions intact, using a unique in situ humanization approach. We reasoned the introduced human variable region gene segments would function indistinguishably in their new genetic location, whereas the retained mouse constant regions would allow for optimal interactions and selection of the resulting antibodies within the mouse environment. We show that these mice, termed VelocImmune mice because they were generated using VelociGene technology, efficiently produce human:mouse hybrid antibodies (that are rapidly convertible to fully human antibodies) and have fully functional humoral immune systems indistinguishable from those of WT mice. The efficiency of the VelocImmune approach is confirmed by the rapid progression of 10 different fully human antibodies into human clinical trials.

Quantifying missing annual emission sources of heavy metals in the United Kingdom with an atmospheric transport model.

An atmospheric chemical transport model was adapted to simulate the concentration and deposition of heavy metals (arsenic, cadmium, chromium, copper, lead, nickel, selenium, vanadium, and zinc) in the United Kingdom. The model showed that wet deposition was the most important process for the transfer of metals from the atmosphere to the land surface. The model achieved a good correlation with annually averaged measurements of metal concentrations in air. The correlation with measurements of wet deposition was less strong due to the complexity of the atmospheric processes involved in the washout of particulate matter which were not fully captured by the model. The measured wet deposition and air concentration of heavy metals were significantly underestimated by the model for all metals (except vanadium) by factors between 2 and 10. These results suggest major missing sources of annual heavy metal emissions which are currently not included in the official inventory. Primary emissions were able to account for only 9%, 21%, 29%, 21%, 36%, 7% and 23% of the measured concentrations for As, Cd, Cr, Cu, Ni, Pb and Zn. A likely additional contribution to atmospheric heavy metal concentrations is the wind driven re-suspension of surface dust still present in the environment from the legacy of much higher historic emissions. Inclusion of two independent estimates of emissions from re-suspension in the model was found to give an improved agreement with measurements. However, an accurate estimate of the magnitude of re-suspended emissions is restricted by the lack of measurements of metal concentrations in the re-suspended surface dust layer.