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Atmospheric dimethyl sulfide, DMS, is the main biogenic source of sulfate particles in the Arctic atmosphere. Sulfate particles have a net cooling effect, which can partially offset Arctic warming from absorbing aerosols, such as black carbon. As efficient cloud condensation nuclei (CCN), sulfate particles are also able to influence the cloud’s microphysical properties. DMS production and emission to the atmosphere increase during the Arctic summer, due to a greater ice-free sea surface area and higher biological activity. In the model simulation of a field campaign conducted over the Canadian high Arctic during the summer of 2014 (NETCARE; Abbatt et al. 2019), the inclusion of DMS in the model, GEM-MACH, resulted in a significant increase, up to 100%, in the modelled atmospheric SO2 in some regions of the Canadian Arctic. Analysis of the modelled size-segregated aerosol sulfate indicated that DMS has the most significant impact on particles in the size range of 50 – 200 nm in this case. Simulations have shown that localized regions of high seawater DMS can have a significant impact on atmospheric concentrations.Further investigation of DMS impact on the Arctic summer cloud microphysics was carried out by using a fully coupled version of GEM-MACH. Overall, the model simulations show that the inclusion of DMS in model leads to an increase in cloud droplet number concentrations (CDNC) and a decrease in droplet mean mass diameters (MMD), and has no significant effects on liquid water content (LWC). The impact of DMS on Canadian weather forecasts will be evaluated using operational forecast tools.

This review is part of a series synthesizing peer-reviewed literature from the past decade on environmental monitoring in the oil sands region (OSR) of northeastern Alberta. It focuses on atmospheric emissions, air quality, and deposition in and downwind of the OSR. Most published monitoring and research activities were concentrated in the surface-mineable region in the Athabasca OSR. Substantial progress has been made in understanding oil sands (OS)-related emission sources using multiple approaches: airborne measurements, satellite measurements, source emission testing, deterministic modeling, and source apportionment modeling. These approaches generally yield consistent results, indicating OS-related sources are regional contributors to nearly all air pollutants. Most pollutants exhibit enhanced air concentrations within ~20 km of surface-mining activities, with some enhanced >100 km downwind. Some pollutants (e.g., sulfur dioxide, nitrogen oxides) undergo transformations as they are transported through the atmosphere. Deposition rates of OS-related substances primarily emitted as fugitive dust are enhanced within ~30 km of surface-mining activities, whereas gaseous and fine particulate emissions have a more diffuse deposition enhancement pattern extending hundreds of kilometers downwind. In general, air quality guidelines are not exceeded, although these single-pollutant thresholds are not comprehensive indicators of air quality. Odor events have occurred in communities near OS industrial activities, although it can be difficult to attribute events to specific pollutants or sources. Nitrogen, sulfur, polycyclic aromatic compounds (PACs), and base cations from OS sources occur in the environment, but explicit and deleterious responses of organisms to these pollutants are not as apparent across all study environments; details of biological monitoring are discussed further in other papers in this special series. However, modeling of critical load exceedances suggests that, at continued emission levels, ecological change may occur in future. Knowledge gaps and recommendations for future work to address these gaps are also presented. Integr Environ Assess Manag 2021;00:1-28. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Ash from biofuels and nitrogen fertilizer are increasingly being used as soil amendments. While this can increase tree growth, it can also increase mammalian grazing and competition with vegetation. We applied moderate amounts of ash (1.5 t·ha−1·year−1) and urea (74 kg N·ha−1·year−1) in each of 2 years to a well-drained site in southeastern Manitoba, planted with Pinus banksiana Lamb. Subplots received deer browsing and (or) vegetation control. The ash resulted in an increase in pH in the upper 15 cm of mineral soil from ∼5.7 to 6.6, and the urea created short-term spikes in soil inorganic nitrogen (NH4 and NO3) levels. Urea combined with ash significantly increased seedling relative growth rates in the first 2 years, with seedlings being largest with urea, with or without ash. However, by the fourth year, seedling growth and size did not differ between the amendments. Urea application increased browsing damage to 91%, but only when vegetation was mowed. Browsing guards resulted in seedlings having 1.6 times greater shoot mass by the end of the fourth growing season. These results suggest that on sandy soils in the dry region of central Canada, P. banksiana may get little benefit from ash applications.

Theoretical models of the Earth's atmosphere adhere to an underlying concept of flow driven by radiative transfer and the nature of the surface over which the flow is taking place: heat from the sun and/or anthropogenic sources are the sole sources of energy driving atmospheric constituent transport. However, another source of energy is prevalent in the human environment at the very local scale – the transfer of kinetic energy from moving vehicles to the atmosphere. We show that this source of energy, due to being co-located with combustion emissions, can influence their vertical distribution to the extent of having a significant influence on lower-troposphere pollutant concentrations throughout North America. The effect of vehicle-induced turbulence on freshly emitted chemicals remains notable even when taking into account more complex urban radiative transfer-driven turbulence theories at high resolution. We have designed a parameterization to account for the at-source vertical transport of freshly emitted pollutants from mobile emissions resulting from vehicle-induced turbulence, in analogy to sub-grid-scale parameterizations for plume rise emissions from large stacks. This parameterization allows vehicle-induced turbulence to be represented at the scales inherent in 3D chemical transport models, allowing this process to be represented over larger regions than is currently feasible with large eddy simulation models. Including this sub-grid-scale parameterization for the vertical transport of emitted pollutants due to vehicle-induced turbulence in a 3D chemical transport model of the atmosphere reduces pre-existing North American nitrogen dioxide biases by a factor of 8 and improves most model performance scores for nitrogen dioxide, particulate matter, and ozone (for example, reductions in root mean square errors of 20 %, 9 %, and 0.5 %, respectively).

The dry deposition process refers to flux loss of an atmospheric pollutant due to uptake of the pollutant by the Earth's surfaces, including vegetation, underlying soil, and any other surface types. In chemistry transport models (CTMs), the dry deposition flux of a chemical species is typically calculated as the product of its surface layer concentration and its dry deposition velocity (Vd); the latter is a variable that needs to be highly empirically parameterized due to too many meteorological, biological, and chemical factors affecting this process. The gaseous dry deposition scheme of Zhang et al. (2003) parameterizes Vd for 31 inorganic and organic gaseous species. The present study extends the scheme of Zhang et al. (2003) to include an additional 12 oxidized volatile organic compounds (oVOCs) and hydrogen cyanide (HCN), while keeping the original model structure and formulas, to meet the demand of CTMs with increasing complexity. Model parameters for these additional chemical species are empirically chosen based on their physicochemical properties, namely the effective Henry's law constants and oxidizing capacities. Modeled Vd values are compared against field flux measurements over a mixed forest in the southeastern US during June 2013. The model captures the basic features of the diel cycles of the observed Vd. Modeled Vd values are comparable to the measurements for most of the oVOCs at night. However, modeled Vd values are mostly around 1 cm s−1 during daytime, which is much smaller than the observed daytime maxima of 2–5 cm s−1. Analysis of the individual resistance terms and uptake pathways suggests that flux divergence due to fast atmospheric chemical reactions near the canopy was likely the main cause of the large model–measurement discrepancies during daytime. The extended dry deposition scheme likely provides conservative Vd values for many oVOCs. While higher Vd values and bidirectional fluxes can be simulated by coupling key atmospheric chemical processes into the dry deposition scheme, we suggest that more experimental evidence of high oVOC Vd values at additional sites is required to confirm the broader applicability of the high values studied here. The underlying processes leading to high measured oVOC Vd values require further investigation.

Formation of indium deposited coverage on (001) surface of InTe layered semiconductor crystal due to solid state dewetting process was studied by STM/STS in UHV. The initial surface was characteriz...

The present work focuses on improving zaleplon (ZAP) performance through nanosizing its insoluble particles which were then delivered intranasally in powder form. Since nanopowders have an exceptio...

Introduction and objectives Selenium supplementation has been shown to have therapeutic value in chronic liver disease. We aimed to investigate the association between serum selenium, severity of liver fibrosis, and mortality in patients with Nonalcoholic Fatty Liver Disease (NAFLD). Patients or material and methods A total of 33,944 patients were identified from the Third National Health and Nutrition Examination Survey. NAFLD was diagnosed by hepatic ultrasound after the exclusion of other forms of liver diseases. The severity of liver fibrosis was determined by NAFLD Fibrosis Score >0.676. Multivariate logistic regression analysis was used to investigate the relationship between serum selenium level and liver fibrosis. Association between serum selenium and all-cause mortality in NAFLD patients was also evaluated. Results Multivariate logistic regression analysis demonstrated odds ratio of advanced liver fibrosis (NFS > 0.676) was significantly reduced with increasing serum selenium levels; OR 0.55, [95% CI 0.32−0.94] in the highest selenium quartile. On stratification analysis, the following populations had a significantly reduced risk of advanced liver fibrosis: non-Hispanic white = OR 0.41 [0.24,0.68]; female = OR 0.32 [0.15−0.66] and age >47 = OR 0.47 [0.28−0.79]. The relationship was significant regardless of BMI as noted by BMI ≤ 30 Kg/m2= OR 0.42 [0.19−0.91] and BMI > 30 Kg/m2=OR 0.52 [0.28−0.97]. Hazard ratio for all-cause mortality was HR 0.72 [0.56−0.95]. Conclusions The risk of advanced liver fibrosis is inversely associated with serum selenium levels, particularly in older patients, Caucasians, and females. All-cause mortality decreased with increased selenium levels. Selenium may play a role in the prevention of liver fibrosis in NAFLD.

Autophagosomes are vital organelles required to facilitate the lysosomal degradation of cytoplasmic cargo, thereby playing an important role in maintaining cellular homeostasis. A number of autophagy-related (ATG) protein complexes are recruited to the site of autophagosome biogenesis where they act to facilitate membrane growth and maturation. Regulated recruitment of ATG complexes to autophagosomal membranes is essential for their autophagic activities and is required to ensure the efficient engulfment of cargo destined for lysosomal degradation. In this review, we discuss our current understanding of the spatiotemporal hierarchy between ATG proteins, examining the mechanisms underlying their recruitment to membranes. A particular focus is placed on the relevance of phosphatidylinositol 3-phosphate and the extent to which the core autophagy players are reliant on this lipid for their localisation to autophagic membranes. In addition, open questions and potential future research directions regarding the membrane recruitment and displacement of ATG proteins are discussed here.

Smoke from wildfires is a significant source of air pollution, which can adversely impact air quality and ecosystems downwind. With the recently increasing intensity and severity of wildfires, the threat to air quality is expected to increase. Satellite-derived biomass burning emissions can fill in gaps in the absence of aircraft or ground-based measurement campaigns and can help improve the online calculation of biomass burning emissions as well as the biomass burning emissions inventories that feed air quality models. This study focuses on satellite-derived NOx emissions using the high-spatial-resolution TROPOspheric Monitoring Instrument (TROPOMI) NO2 dataset. Advancements and improvements to the satellite-based determination of forest fire NOx emissions are discussed, including information on plume height and effects of aerosol scattering and absorption on the satellite-retrieved vertical column densities. Two common top-down emission estimation methods, (1) an exponentially modified Gaussian (EMG) and (2) a flux method, are applied to synthetic data to determine the accuracy and the sensitivity to different parameters, including wind fields, satellite sampling, noise, lifetime, and plume spread. These tests show that emissions can be accurately estimated from single TROPOMI overpasses. The effect of smoke aerosols on TROPOMI NO2 columns (via air mass factors, AMFs) is estimated, and these satellite columns and emission estimates are compared to aircraft observations from four different aircraft campaigns measuring biomass burning plumes in 2018 and 2019 in North America. Our results indicate that applying an explicit aerosol correction to the TROPOMI NO2 columns improves the agreement with the aircraft observations (by about 10 %–25 %). The aircraft- and satellite-derived emissions are in good agreement within the uncertainties. Both top-down emissions methods work well; however, the EMG method seems to output more consistent results and has better agreement with the aircraft-derived emissions. Assuming a Gaussian plume shape for various biomass burning plumes, we estimate an average NOx e-folding time of 2 ±1 h from TROPOMI observations. Based on chemistry transport model simulations and aircraft observations, the net emissions of NOx are 1.3 to 1.5 times greater than the satellite-derived NO2 emissions. A correction factor of 1.3 to 1.5 should thus be used to infer net NOx emissions from the satellite retrievals of NO2.

Breast cancer, a most common malignancy in women, was known to be associated with steroid hormone estrogen. The discovery of estrogen receptor (ER) gave us not only a powerful predictive and prognostic marker, but also an efficient target for the treatment of hormone-dependent breast cancer with various estrogen ligands. ER consists of two subtypes i.e. ERα and ERβ, that are mostly G-protein-coupled receptors and activated by estrogen, specially 17β-estradiol. The activation is followed by translocation into the nucleus and binding with DNA to modulate activities of different genes. ERs can manage synthesis of RNA through genomic actions without directly binding to DNA. Receptors are tethered by protein-protein interactions to a transcription factor complex to communicate with DNA. Estrogens also exhibit nongenomic actions, a characteristic feature of steroid hormones, which are so rapid to be considered by the activation of RNA and translation. These are habitually related to stimulation of different protein kinase cascades. Majority of post-menopausal breast cancer is estrogen dependent, mostly potent biological estrogen (E2) for continuous growth and proliferation. Estrogen helps in regulating the differentiation and proliferation of normal breast epithelial cells. In this review we have investigated the important role of ER in development and progression of breast cancer, which is complicated by receptor's interaction with co-regulatory proteins, cross-talk with other signal transduction pathways and development of treatment strategies viz. selective estrogen receptor modulators (SERMs), selective estrogen receptor down regulators (SERDs), aromatase and sulphatase inhibitors.

In May 2016, the Horse River wildfire led to the evacuation of ∼ 88 000 people from Fort McMurray and surrounding areas and consumed ∼ 590 000 ha of land in Northern Alberta and Saskatchewan. Within the plume, satellite instruments measured elevated values of CO, NH3, and NO2. CO was measured by two Infrared Atmospheric Sounding Interferometers (IASI-A and IASI-B), NH3 by IASI-A, IASI-B, and the Cross-track Infrared Sounder (CrIS), and NO2 by the Ozone Monitoring Instrument (OMI). Daily emission rates were calculated from the satellite measurements using fire hotspot information from the Moderate Resolution Imaging Spectroradiometer (MODIS) and wind information from the European Centre for Medium-Range Weather Forecasts (ECMWF) ERA5 reanalysis, combined with assumptions on lifetimes and the altitude range of the plume. Sensitivity tests were performed and it was found that uncertainties of emission estimates are more sensitive to the plume shape for CO and to the lifetime for NH3 and NOx. The satellite-derived emission rates were ∼ 50–300 kt d−1 for CO, ∼ 1–7 kt d−1 for NH3, and ∼ 0.5–2 kt d−1 for NOx (expressed as NO) during the most active fire periods. The daily satellite-derived emission estimates were found to correlate fairly well (R∼0.4–0.7) with daily output from the ECMWF Global Fire Assimilation System (GFAS) and the Environment and Climate Change Canada (ECCC) FireWork models, with agreement within a factor of 2 for most comparisons. Emission ratios of NH3∕CO, NOx∕CO, and NOx∕NH3 were calculated and compared against enhancement ratios of surface concentrations measured at permanent surface air monitoring stations and by the Alberta Environment and Parks Mobile Air Monitoring Laboratory (MAML). For NH3∕CO, the satellite emission ratios of ∼ 0.02 are within a factor of 2 of the model emission ratios and surface enhancement ratios. For NOx∕CO satellite-measured emission ratios of ∼0.01 are lower than the modelled emission ratios of 0.033 for GFAS and 0.014 for FireWork, but are larger than the surface enhancement ratios of ∼0.003, which may have been affected by the short lifetime of NOx. Total emissions from the Horse River fire for May 2016 were calculated and compared against total annual anthropogenic emissions for the province of Alberta in 2016 from the ECCC Air Pollutant Emissions Inventory (APEI). Satellite-measured emissions of CO are ∼1500 kt for the Horse River fire and exceed the total annual Alberta anthropogenic CO emissions of 992.6 kt for 2016. The satellite-measured emissions during the Horse River fire of ∼30 kt of NH3 and ∼7 kt of NOx (expressed as NO) are approximately 20 % and 1 % of the magnitude of total annual Alberta anthropogenic emissions, respectively.

TROPOMI, on-board the Sentinel-5 Precursor satellite is a nadir-viewing spectrometer measuring reflected sunlight in the ultraviolet, visible, near-infrared, and shortwave infrared spectral range. From these spectra several important air quality and climate-related atmospheric constituents are retrieved at an unprecedented high spatial resolution, including nitrogen dioxide (NO(2)). We present the first retrievals of TROPOMI NO(2) over the Canadian Oil Sands, contrasting them with observations from the OMI satellite instrument, and demonstrate its ability to resolve individual plumes and highlight its potential for deriving emissions from individual mining facilities. Further, the first TROPOMI NO(2) validation is presented, consisting of aircraft and surface in-situ NO(2) observations, as well as ground-based remote-sensing measurements between March and May 2018. Our comparisons show that the TROPOMI NO(2) vertical column densities are highly correlated with the aircraft and surface in-situ NO(2) observations, and the ground-based remote-sensing measurements with a low bias (15–30 %) over the Canadian Oil Sands. PLAIN LANGUAGE SUMMARY: Nitrogen dioxide (NO(2)) is a pollutant that is linked to respiratory health issues and has negative environmental impacts such as soil and water acidification. Near the surface the most significant sources of NO(2) are fossil fuel combustion and biomass burning. With a recently launched satellite instrument (TROPOspheric Monitoring Instrument; TROPOMI) NO(2) can be measured with an unprecedented combination of accuracy, spatial coverage, and resolution. This work presents the first TROPOMI NO(2) measurements near the Canadian Oil Sands and shows that these measurements have an outstanding ability to detect NO(2) on a very high horizontal resolution that is unprecedented for satellite NO(2) observations. Further, these satellite measurements are in excellent agreement with aircraft and ground-based measurements.

We present in this technical note the research protocol for phase 4 of the Air Quality Model Evaluation International Initiative (AQMEII4). This research initiative is divided into two activities, collectively having three goals: (i) to define the current state of the science with respect to representations of wet and especially dry deposition in regional models, (ii) to quantify the extent to which different dry deposition parameterizations influence retrospective air pollutant concentration and flux predictions, and (iii) to identify, through the use of a common set of detailed diagnostics, sensitivity simulations, model evaluation, and reduction of input uncertainty, the specific causes for the current range of these predictions. Activity 1 is dedicated to the diagnostic evaluation of wet and dry deposition processes in regional air quality models (described in this paper), and Activity 2 to the evaluation of dry deposition point models against ozone flux measurements at multiple towers with multiyear observations (to be described in future submissions as part of the special issue on AQMEII4). The scope of this paper is to present the scientific protocols for Activity 1, as well as to summarize the technical information associated with the different dry deposition approaches used by the participating research groups of AQMEII4. In addition to describing all common aspects and data used for this multi-model evaluation activity, most importantly, we present the strategy devised to allow a common process-level comparison of dry deposition obtained from models using sometimes very different dry deposition schemes. The strategy is based on adding detailed diagnostics to the algorithms used in the dry deposition modules of existing regional air quality models, in particular archiving diagnostics specific to land use–land cover (LULC) and creating standardized LULC categories to facilitate cross-comparison of LULC-specific dry deposition parameters and processes, as well as archiving effective conductance and effective flux as means for comparing the relative influence of different pathways towards the net or total dry deposition. This new approach, along with an analysis of precipitation and wet deposition fields, will provide an unprecedented process-oriented comparison of deposition in regional air quality models. Examples of how specific dry deposition schemes used in participating models have been reduced to the common set of comparable diagnostics defined for AQMEII4 are also presented.

Smoke from wildfires are a significant source of air pollution, which can adversely impact ecosystems and the air quality in downwind populated areas. With increasing severity of wildfires over the years, these are a significant threat to air quality in densely populated areas. Emissions from wildfires are most commonly estimated by a bottom-up approach, using proxies such fuel type, burn area, and emission factors. Emissions are also commonly derived with a top-down approach, using satellite observed Fire Radiative Power. Furthermore, wildfire emissions can also be estimated directly from satellite-borne measurements.Here, we present advancements and improvements of direct emission estimates of forest fire NOx emissions by using TROPOMI (Tropospheric Monitoring Instrument) high-resolution satellite datasets, including NO2 vertical column densities (VCDs) and information on plume height and aerosol scattering. The effect of smoke aerosols on the sensitivity of TROPOMI to NO2 (via air mass factors) is estimated with recalculated VCDs, and validated with aircraft observations. Different top-down emission estimation methods are tested on synthetic data to determine the accuracy, and the sensitivity to parameters, such as wind fields, satellite sampling, instrument noise, NO2:NOx conversion ratio, species atmosphere lifetime and plume spread. Lastly, the top-down, bottom-up and direct emission estimates of fire emissions are quantitatively compared.

atellite-derived and reported sulphur dioxide (SO2) emissions from the Canadian oil sands are shown to have been consistent up to 2013. Post-2013, these sources of emissions data diverged, with reported emissions dropping by a factor of two, while satellite-derived emissions for the region remained relatively constant, with the discrepancy (satellite-derived emissions minus reported emissions) peaking at 50 kT(SO2) yr-1 around 2016. The 2013-2014 period corresponds to when new flue-gas desulphurization units came on-line. Previous work has established a high level of consistency between at-stack SO2 emissions observations and satellite estimates, and surface monitoring network SO2 concentrations over the same multi-year period show similar trends as the satellite data, with a slight increase in concentrations post-2013. No clear explanation for this discrepancy currently exists. The implications of the discrepancy towards estimated total sulphur deposition to downwind ecosystems were estimated relative to 2013 emissions levels, with the satellite-derived values leaving the area of regional critical load exceedances of aquatic ecosystems largely unchanged from 2013 values, 335,000 km2, and reported values potentially decreasing this area to 185,000 km2.

Surface-level ozone (O3) continues to be a significant health risk in the Greater Toronto Hamilton Area (GTHA) of Canada even though precursor emissions in the area have decreased significantly over the past two decades. In July 2015, Environment and Climate Change Canada (ECCC) led an intensive field study coincident with Toronto hosting the 2015 Pan American Games. During the field study, the daily 1-h maximum O3 standard (80 ppbv) was exceeded twice at a measurement site in North Toronto, once on July 12 and again on July 28. In this study, ECCC&rsquo, s 2.5-km configuration of the Global Environmental Multi-scale (GEM) meteorological model was combined with the Modelling Air-quality and CHemistry (MACH) on-line atmospheric chemistry model and the Town Energy Balance (TEB) urban surface parameterization to create a new urban air quality modelling system. In general, the model results showed that the nested 2.5-km grid-spaced urban air quality model performed better in statistical scores compared to the piloting 10-km grid-spaced GEM-MACH model without TEB. Model analyses were performed with GEM-MACH-TEB for the two exceedance periods. The local meteorology for both cases consisted of light winds with the highest O3 predictions situated along lake-breeze fronts. For the July 28 case, O3 production sensitivity analysis along the trajectory of the lake-breeze circulation showed that the region of most efficient O3 production occurred in the updraft region of the lake-breeze front, as the precursors to O3 formation underwent vertical mixing. In this updraft region, the ozone production switches from volatile organic compound (VOC)-sensitive to NOx-sensitive, and the local net O3 production rate reaches a maximum. This transition in the chemical regime is a previously unidentified factor for why O3 surface-level mixing ratios maximize along the lake-breeze front. For the July 12 case, differences between the model and observed Lake Ontario water temperature and the strength of lake-breeze opposing wind flow play a role in differences in the timing of the lake-breeze, which impacts the predicted location of the O3 maximum north of Toronto.

Benzene and polycyclic aromatic hydrocarbons (PAHs) are toxic air pollutants that have long been associated with motor vehicle emissions, though the importance of such emissions has never been quantified over an extended domain using a chemical transport model. Herein we present the first application of such a model (GEM-MACH-PAH) to examine the contribution of motor vehicles to benzene and PAHs in ambient air. We have applied the model over a region that is centred on Toronto, Canada, and includes much of southern Ontario and the northeastern United States. The resolution (2.5 km) was the highest ever employed by a model for these compounds in North America, and the model domain was the largest at this resolution in the world to date. Using paired model simulations that were run with vehicle emissions turned on and off (while all other emissions were left on), we estimated the absolute and relative contributions of motor vehicles to ambient pollutant concentrations. Our results provide estimates of motor vehicle contributions that are realistic as a result of the inclusion of atmospheric processing, whereas assessing changes in benzene and PAH emissions alone would neglect effects caused by shifts in atmospheric oxidation and particle–gas partitioning. A secondary benefit of our scenario approach is in its utility in representing a fleet of zero-emission vehicles (ZEVs), whose adoption is being encouraged in a variety of jurisdictions. Our simulations predicted domain-average on-road vehicle contributions to benzene and PAH concentrations of 4 %–21 % and 14 %–24 % in the spring–summer and fall–winter periods, respectively, depending on the aromatic compound. Contributions to PAH concentrations up to 50 % were predicted for the Greater Toronto Area, and the domain maximum was simulated to be 91 %. Such contributions are substantially higher than those reported at the national level in Canadian emissions inventories, and they also differ from inventory estimates at the subnational scale in the US. Our model has been run at a finer spatial scale than reported in those inventories, and furthermore includes physico-chemical processing that alters pollutant concentrations after their release. The removal of on-road vehicle emissions generally led to decreases in benzene and PAH concentrations during both periods that were studied, though atmospheric processing (such as chemical reactions and changes to particle–gas partitioning) contributed to non-linear behaviour at some locations or times of year. Such results demonstrate the added value associated with regional air quality modelling relative to examinations of emissions inventories alone. We also found that removing on-road vehicle emissions reduced spring–summertime surface O3 volume mixing ratios and fall–wintertime PM10 concentrations each by ∼10 % in the model domain, providing further air quality benefits. Toxic equivalents contributed by vehicle emissions of PAHs were found to be substantial (20 %–60 % depending on location), and this finding is particularly relevant to the study of public health in the urban areas of our model domain where human population, ambient concentrations, and traffic volumes tend to be high.

Chronic ingestion of licorice is known to cause numerous metabolic and electrolyte disturbances. Severe hyponatremia, hypertension, and hypokalemia as well as metabolic alkalosis are amongst the most common consequences of chronic ingestion resulting in an apparent mineralocorticoid excess (AME). Treatment predominantly consists of cessation of licorice ingestion, potassium replenishment and aldosterone antagonists. Given the potentially lethal effects of chronic licorice ingestion, clinicians should be made aware of the presentation of AME and the proper management. We present the rare case of a 62-year-old male with licorice-induced apparent mineralocorticoid excess secondary to excessive licorice tea intake. Initial presentation included severe hypokalemia of 2.2mmol/L and hypertension of 180/110mmHg, while eunatremic (Na, 144meq/L).

Cancer is one of the leading causes of death among various noncommunicable diseases. The proteases, involved in tumor progression and metastasis, are the attractive targets for anticancer therapy. This chapter presents a collective view on the structure and ligand-based drug design for the inhibition of aspartate proteases (APs). It also highlights the structural aspects of various APs. Interestingly, all APs share structural similarities but certain significantly distinct structural features may be vital to design their selective inhibitors. The chapter also introduces the readers with different classes of APs inhibitors i.e., HIV-1 proteases, cathepsin D, endothelin converting enzyme, γ-secretase and β-secretase inhibitors, etc.

In an effort to develop new therapeutic agents to treat Alzheimer's disease, a series of donepezil-based analogs were designed, synthesized using an environmentally friendly route, and biologically evaluated for their inhibitory activity against electric eel acetylcholinesterase (AChE) enzyme. In vitro studies revealed that the phenyl moiety of donepezil can be successfully replaced with a pyridine ring leading to equally potent inhibitors of electric eel AChE. Further kinetic evaluations of the most potent inhibitor showed a dual-binding (mixed inhibition) mode, similar to donepezil. Molecular modeling studies suggest that several additional residues could be involved in the binding of this inhibitor in the human AChE enzyme active site compared to donepezil.

Environment and Climate Change Canada's online air quality forecasting model, GEM-MACH, was extended to simulate atmospheric concentrations of benzene and seven polycyclic aromatic hydrocarbons (PAHs): phenanthrene, anthracene, fluoranthene, pyrene, benz(a)anthracene, chrysene, and benzo(a)pyrene. In the expanded model, benzene and PAHs are emitted from major point, area, and mobile sources, with emissions based on recent emission factors. Modelled PAHs undergo gas–particle partitioning (whereas benzene is only in the gas phase), atmospheric transport, oxidation, cloud processing, and dry and wet deposition. To represent PAH gas–particle partitioning, the Dachs–Eisenreich scheme was used, and we have improved gas–particle partitioning parameters based on an empirical analysis to get significantly better gas–particle partitioning results than the previous North American PAH model, AURAMS-PAH. Added process parametrizations include the particle phase benzo(a)pyrene reaction with ozone via the Kwamena scheme and gas-phase scavenging of PAHs by snow via vapour sorption to the snow surface. The resulting GEM-MACH-PAH model was used to generate the first online model simulations of PAH emissions, transport, chemical transformation, and deposition for a high-resolution domain (2.5 km grid cell spacing) in North America, centred on the PAH data-rich region of southern Ontario, Canada and the northeastern US. Model output for two seasons was compared to measurements from three monitoring networks spanning Canada and the US Average spring–summertime model results were found to be statistically unbiased from measurements of benzene and all seven PAHs. The same was true for the fall–winter seasonal mean, except for benzo(a)pyrene, which had a statistically significant positive bias. We present evidence that the benzo(a)pyrene results may be ameliorated via further improvements to particulate matter and oxidant processes and transport. Our analysis focused on four key components to the prediction of atmospheric PAH levels: spatial variability, sensitivity to mobile emissions, gas–particle partitioning, and wet deposition. Spatial variability of PAHs ∕ PM2.5 at a 2.5 km resolution was found to be comparable to measurements. Predicted ambient surface concentrations of benzene and the PAHs were found to be critically dependent on mobile emission factors, indicating the mobile emissions sector has a significant influence on ambient PAH levels in the study region. PAH wet deposition was overestimated due to additive precipitation biases in the model and the measurements. Our overall performance evaluation suggests that GEM-MACH-PAH can provide seasonal estimates for benzene and PAHs and is suitable for emissions scenario simulations.

Low molecular weight heparins (LMWHs) are used for a variety of indications. The most common type of hypersensitivity reactions to LMWHs are delayed-type hypersensitivity reactions (DHR). Immediate-type hypersensitivity reactions (IHR) occur only sporadically. Cross-reactivity of different LMWHs is a common and unpredictable problem. We present 2 cases of patients who developed DHR to nadroparin and enoxaparin, respectively. The third case presents a patient who developed IHR to nadroparin. Skin tests confirmed the hypersensitivity in all cases. In the cases of DHR, a skin test negative LMWH was identified and was tolerated in a challenge test. In the IHR case, cross-reactivity to all tested LMWHs was established. We hypothesize that the degree of cross-reactivity might depend on the type of hypersensitivity reaction with immediate reactions linked to more extensive cross-reactivity than delayed reactions. This is important to consider because, at least in some cases, a safe alternative LMWH can be identified.

Purpose: Triple solid dispersion adsorbates (TSDads) and spherical agglomerates (SA) present new techniques that extensively enhance dissolution of poorly soluble drugs. The aim of the present study is to hasten the onset of hypoglycemic effect of glimepiride through enhancing its rate of release from tablet formulation prepared from either technique. Methods: Drug release from TSDads or SA tablets with different added excipients was explored. Scanning electron microscopy (SEM) and effect of compression on dissolution were illustrated. Pharmacodynamic evaluation was performed on optimized tablets. Results: TSDads & SA tablets with Cross Povidone showed least disintegration times of 1.48 and 0.5 min. respectively. Kinetics of drug release recorded least half-lives (54.13 and 59.83min for both techniques respectively). Cross section in tablets displayed an organized interconnected matrix under SEM, accounting for the rapid access of dissolution media to the tablet core. Components of tablets filled into capsules showed a similar release profile to that of tablets after compression as indicated by similarity factor. The onset time of maximum reduction in blood glucose in male albino rabbits was hastened to 2h instead of 3h for commercial tablets. Conclusion: After optimization of tablet excipients that interacted differently with respect to their effect on drug release, we could conclude that both amorphisation and spheronization were equally successful in promoting in vitro dissolution enhancement as well as providing a more rapid onset time for drug action in vivo.

In this report we have presented synthesis of a new air stable bidentate selenium ligand (L1) by the reaction of 1,8-bis(2-(chloromethyl)phenoxy)octane with sodium salt of diphenyl diselenide. The reaction of bidentate selenium ligand (L1) with Pd(CH3CN)2Cl2 in acetonitrile under reflux conditions resulted nineteen membered ring macrocyclic palladium(II) complex. The structure of ligand precursors, ligand, and macrocyclic palladium(II) complex were authenticated by using 1H, 13C{1H} NMR spectroscopy and elemental analysis. The repeated attempts to obtain single crystals of macrocyclic palladium(II) complex were unsuccessful probably due to long flexible aliphatic chain in the molecule. The air and moisture stable, thermally robust macrocyclic palladium(II) complex was employed as catalyst to catalyze the regioselective arylation reaction of imidazole derivatives. The reaction works efficiently without any need of inert atmosphere. The current protocol works under mild reaction conditions with exclusive C-5 regioselectivity. Excellent yields (~73–95%) were obtained by using only 1.5 mol% of C1, with wide range of derivatives and large functional group tolerance. Homogeneous nature of catalysis process was confirmed with the help of mercury and triphenylphosphine poisoning tests. Further, the catalyst can be reused with significant loss (22%) in the efficiency.

The theory of cartographic projections is a tool which can present the convex surface of the Earth on the plane. Of the many types of maps, thematic maps perform an important function due to the wide possibilities of adapting their content to current needs. The limitation of classic maps is their two-dimensional nature. In the era of rapidly growing methods of mass acquisition of spatial data, the use of flat images is often not enough to reveal the level of complexity of certain objects. In this case, it is necessary to use visualization in three-dimensional space. The motivation to conduct the study was the use of cartographic projections methods, spatial transformations, and the possibilities offered by thematic maps to create thematic three-dimensional map imaging (T3DMI). The authors presented a practical verification of the adopted methodology to create a T3DMI visualization of the marina of the National Sailing Centre of the Gdańsk University of Physical Education and Sport (Poland). The profiled characteristics of the object were used to emphasize the key elements of its function. The results confirmed the increase in the interpretative capabilities of the T3DMI method, relative to classic two-dimensional maps. Additionally, the study suggested future research directions of the presented solution.

This article deals with the question of the influence of preparations that contain pharmacological doses of iodine on the functional activity of the thyroid gland. In the practice of a cardiologist amiodarone and x-ray contrasting substances are often used that may induce thyroid disorders in many ways, followed by hypothyroidism and thyrotoxicosis development.

Thioredoxin (Trx) is one of the two major thiol antioxidants, playing essential roles in redox homeostasis and signaling. Despite its importance, there is a lack of methods for monitoring Trx redox dynamics in live cells, hindering a better understanding of physiological and pathological roles of the Trx redox system. In this work, we developed the first genetically encoded fluorescent biosensor for Trx redox by engineering a redox relay between the active-site cysteines of human Trx1 and rxRFP1, a redox-sensitive red fluorescent protein. We used the resultant biosensor-TrxRFP1-to selectively monitor perturbations of Trx redox in various mammalian cell lines. We subcellularly localized TrxRFP1 to image compartmentalized Trx redox changes. We further combined TrxRFP1 with a green fluorescent Grx1-roGFP2 biosensor to simultaneously monitor Trx and glutathione redox dynamics in live cells in response to chemical and physiologically relevant stimuli.

Global distribution of hepatocellular carcinomas (HCCs) is dominated by its incidence in developing countries, accounting for >700,000 estimated deaths per year, with dietary exposures to aflatoxin (AFB1) and subsequent DNA adduct formation being a significant driver. Genetic variants that increase individual susceptibility to AFB1-induced HCCs are poorly understood. Herein, it is shown that the DNA base excision repair (BER) enzyme, DNA glycosylase NEIL1, efficiently recognizes and excises the highly mutagenic imidazole ring-opened AFB1-deoxyguanosine adduct (AFB1-Fapy-dG). Consistent with this in vitro result, newborn mice injected with AFB1 show significant increases in the levels of AFB1-Fapy-dG in Neil1-/- vs. wild-type liver DNA. Further, Neil1-/- mice are highly susceptible to AFB1-induced HCCs relative to WT controls, with both the frequency and average size of hepatocellular carcinomas being elevated in Neil1-/- The magnitude of this effect in Neil1-/- mice is greater than that previously measured in Xeroderma pigmentosum complementation group A (XPA) mice that are deficient in nucleotide excision repair (NER). Given that several human polymorphic variants of NEIL1 are catalytically inactive for their DNA glycosylase activity, these deficiencies may increase susceptibility to AFB1-associated HCCs.

The surface modification of spherical melamine-formaldehyde particles during their levitation in a dusty plasma as a part of plasma–dust structures in a trap formed in strata in a neon glow discharge has been investigated using scanning electron microscopy. The dependence of the particle size on the time of plasma exposure has been found and measured, and the modification of the surface structure has been studied. The source of the observed modification has been interpreted.

The wealth of air quality information provided by satellite infrared observations of ammonia (NH3), carbon monoxide (CO), formic acid (HCOOH), and methanol (CH3OH) is currently being explored and used for a number of applications, especially at regional or global scales. These applications include air quality monitoring, trend analysis, emissions, and model evaluation. This study provides one of the first direct validations of Tropospheric Emission Spectrometer (TES) satellite-retrieved profiles of NH3, CH3OH, and HCOOH through comparisons with coincident aircraft profiles. The comparisons are performed over the Canadian oil sands region during the intensive field campaign (August–September, 2013) in support of the Joint Canada–Alberta Implementation Plan for Oil Sands Monitoring (JOSM). The satellite/aircraft comparisons over this region during this period produced errors of (i) +0.08 ± 0.25 ppbv for NH3, (ii) +7.5 ± 23 ppbv for CO, (iii) +0.19 ± 0.46 ppbv for HCOOH, and (iv) −1.1 ± 0.39 ppbv for CH3OH. These values mostly agree with previously estimated retrieval errors; however, the relatively large negative bias in CH3OH and the significantly greater positive bias for larger HCOOH and CO values observed during this study warrant further investigation. Satellite and aircraft ammonia observations during the field campaign are also used in an initial effort to perform preliminary evaluations of Environment Canada's Global Environmental Multi-scale – Modelling Air quality and CHemistry (GEM-MACH) air quality modelling system at high resolution (2.5 × 2.5 km2). These initial results indicate a model underprediction of ~ 0.6 ppbv (~ 60 %) for NH3, during the field campaign period. The TES/model CO comparison differences are ~ +20 ppbv (~ +20 %), but given that under these conditions the TES/aircraft comparisons also show a small positive TES CO bias indicates that the overall model underprediction of CO is closer to ~ 10 % at 681 hPa (~ 3 km) during this period.

Drug discovery and development have gained momentum due to the rational drug design by engaging computational tools and bioinformatics methodologies. Bioisosteric replacements and hybrid molecular approaches are the other inventive processes, used by medicinal chemists for the desired modifications of leads for clinical drug candidates. SERMs, ought to produce inhibitory activity in breast, uterus and agonist activity in other tissues, are beneficial for estrogen-like actions. ER subtypes α and β are hormone dependent modulators of intracellular signaling and gene expression, and development of ER selective ligands could be an effective approach for treatment of breast cancer. This report has critically investigated the possible designing considerations of SERMs, their in silico interactions, and potent pharmacophore generation approaches viz. indole, restricted benzothiophene [3, 2-b] indole, carborane, xanthendione, combretastatin A-4, organometallic heterocycles, OBHS-SAHA hybrids, benzopyranones, tetrahydroisoquinolines, Dig G derivatives and their specifications in drug design and development, to rationally improve the understanding in drug discovery. This also includes various strategies for the development of dual inhibitors for the management of antiestrogenic resistance.

Background: Antipsychotic-induced weight gain and metabolic abnormalities are one of the major challenges in the treatment of psychosis, contributing to the morbidity, mortality and treatment non-adherence. Different approaches were used to counteract these side effects but showed only limited or short-term effects. This study aims to analyse the effects of a long-term multimodal treatment program for first episode psychosis on antipsychotic-induced metabolic changes. ----- Methods: We enrolled 71 patients with first episode psychosis treated at the Zagreb University Hospital Centre from 2016 until 2018. Participants were assigned to one of the two groups: day hospital program vs. treatment as usual (TAU). Outcomes were: body weight, blood glucose, lipids and cholesterol, psychopathology and global level of functioning during the 18-months follow-up. ----- Results: Although the TAU group gained more weight and had higher increase of blood glucose, while the day hospital group had a higher increase in total cholesterol at 18th month follow-up, after the adjustment for age, gender and baseline measures, the type of treatment was not significantly associated with any of the primary outcome measures. Patients' psychopathology measures significantly decreased and their functional level significantly increased at month 18th in both groups. ----- Conclusion: While both types of treatment were effective in reducing psychopathology and restoring the patients' level of functioning, both were relatively ineffective in counteracting antipsychotic-induced metabolic abnormalities and antipsychotic-induced weight gain.

Ocular involvement in hemolytic uremic syndrome is rare and in most cases presents with retinal ischemia, hemorrhages, and neovascularization. The authors describe the progression of retinal involvement as a rare complication of typical hemolytic uremic syndrome in a 2-year-old boy. Progression of retinal findings were demonstrated with serial fundus photographs. All children who develop hemolytic uremic syndrome have an early ocular consultation and regular ophthalmic follow-up. Early and regular ophthalmic examinations will be useful to expand the understanding of this rare ocular complication and to guide treatment options. [ J Pediatr Ophthalmol Strabismus . 2018;55:e49–e51.]