On the Ability of the N-O Bond to Support a Stable Stereogenic Axis: Peptide-Catalyzed Atroposelective N-Oxidation.

During studies of atroposelective, peptide-catalyzed N-oxidations of pyridines, we observed lower-than-expected barriers to atropisomerization for these stereodynamic processes under the reaction conditions. Mechanistic studies indicate a hydrogen bond-assisted racemization mechanism intrinsic to both the starting materials and products. We also identified a protonation-dependent barrier to rotation that operates for the starting materials alone. Nonetheless, several substrates were amenable to atroposelective N-oxidations via kinetic resolution, yielding krel values of up to 12.6 and the isolation of one N-oxide with >99:1 er after recrystallization.

Development of Spatio-Temporal Land Use Regression Models for Fine Particulate Matter and Wood-Burning Tracers in Temuco, Chile.

Biomass burning is common in much of the world, and in some areas, residential wood-burning has increased. However, air pollution resulting from biomass burning is an important public health problem. A sampling campaign was carried out between May 2017 and July 2018 in over 64 sites in four sessions, to develop a spatio-temporal land use regression (LUR) model for fine particulate matter (PM) and wood-burning tracers levoglucosan and soluble potassium (Ksol) in a city heavily impacted by wood-burning. The mean (sd) was 46.5 (37.4) µg m-3 for PM2.5, 0.607 (0.538) µg m-3 for levoglucosan, and 0.635 (0.489) µg m-3 for Ksol. LUR models for PM2.5, levoglucosan, and Ksol had a satisfactory performance (LOSOCV R2), explaining 88.8%, 87.4%, and 87.3% of the total variance, respectively. All models included sociodemographic predictors consistent with the pattern of use of wood-burning in homes. The models were applied to predict concentrations surfaces and to estimate exposures for an epidemiological study.

Asymmetric Catalysis Mediated by Synthetic Peptides, Version 2.0: Expansion of Scope and Mechanisms.

Low molecular weight synthetic peptides have been demonstrated to be effective catalysts for an increasingly wide array of asymmetric transformations. In many cases, these peptide-based catalysts have enabled novel multifunctional substrate activation modes and unprecedented selectivity manifolds. These features, along with their ease of preparation, modular and tunable structures, and often biomimetic attributes make peptides well-suited as chiral catalysts and of broad interest. Many examples of peptide-catalyzed asymmetric reactions have appeared in the literature since the last survey of this broad field in Chemical Reviews (Chem. Rev. 2007, 107, 5759-5812). The overarching goal of this new Review is to provide a comprehensive account of the numerous advances in the field. As a corollary to this goal, we survey the many different types of catalytic reactions, ranging from acylation to C-C bond formation, in which peptides have been successfully employed. In so doing, we devote significant discussion to the structural and mechanistic aspects of these reactions that are perhaps specific to peptide-based catalysts and their interactions with substrates and/or reagents.

Ontario Veterinary College First-Year Veterinary Students' Perceptions of Companion Animal Nutrition and Their Own Nutrition: Implications for a Veterinary Nutrition Curriculum.

Extant research shows veterinarians face increasing challenges in discussing nutrition with clients despite receiving professional nutrition education in the veterinary medical curriculum. This article's aim is to elicit student veterinarians' baseline nutrition-related perceptions and nutrition information-seeking behaviors at the time of entering veterinary school. Participants were newly enrolled veterinary students at the Ontario Veterinary College (n = 120). Focus group discussions (n = 19) informed the design of an online questionnaire capturing students' demographics and perceptions of their own and their pets' nutrition. Students reported being influenced by individual factors (e.g., time), social networks (e.g., family), and surrounding environment (e.g., cost, contradictory media messages). Overall, 58% of students considered themselves knowledgeable about pet nutrition when commencing veterinary school, with 71% prioritizing their pets' diets as much as their own. Students' confidence in finding pet nutrition information was correlated with perceived accessibility (r = .76, p = .001) and perceived quantity of information available on pet nutrition (r = .83, p = .001), but not quality of information (r = .13, p = .03). In general, students relied on and trusted veterinarians for nutrition advice. However, 94% of students mistrusted pet food companies' motivations. Our data support that students entering veterinary school have their own perceptions on pet nutrition that impact nutrition education, suggesting this as an important consideration in the design and delivery of a veterinary nutrition curriculum. Veterinary medical faculty should be encouraged to discuss baseline nutrition information and address any misconceptions to prepare students for future consultations with clients.

Understanding Incoming Canadian and US Veterinary Students' Attitudes and Perceptions of Their Dietary Habits and Levels of Physical Activity.

As critical components of individual well-being, nutrition and physical activity have important physical and psychological implications. Veterinary students face demanding schedules and potentially high rates of psychological distress. Though veterinary students' strategies for healthy eating have been explored, factors influencing their ability to achieve a healthy diet are less understood. This study assesses incoming veterinary students' perceived attitudes to their dietary habits and physical activity levels. Incoming students (n = 322) at five Canadian and five randomly selected US veterinary schools completed a questionnaire inquiring about demographic information, dietary attitudes and habits, and activity levels. More than half (58%) of students perceived their diet to be moderately healthy. A desire to feel better and have more energy was the most reported (79%) motivating factor to modifying personal eating habits and was significantly associated with improved odds of having a perceived healthy diet (OR = 2.22, p < .024). A busy lifestyle was perceived as a barrier to changing current eating habits by 92% of respondents. Students reporting a desire to maintain their health (OR = 3.42, p < .001) and moderate (OR = 2.81, p < .003) or high (OR = 2.30, p < .044) routine physical activity levels were also more likely to perceive their diet as healthy. Findings show that incoming veterinary students' perceptions may influence their goals of achieving a healthy lifestyle. An understanding of incoming veterinary students' barriers and motivators could be applied in future research to assist students in achieving personalized goals.

Asymmetric Catalysis upon Helically Chiral Loratadine Analogues Unveils Enantiomer-Dependent Antihistamine Activity.

Analogues of the conformationally dynamic Claritin (loratadine) and Clarinex (desloratadine) scaffolds have been enantio- and chemoselectively N-oxidized using an aspartic acid containing peptide catalyst to afford stable, helically chiral products in up to >99:1 er. The conformational dynamics and enantiomeric stability of the N-oxide products have been investigated experimentally and computationally with the aid of crystallographic data. Furthermore, biological assays show that rigidifying the core structure of loratadine and related analogues through N-oxidation affects antihistamine activity in an enantiomer-dependent fashion. Computational docking studies illustrate the observed activity differences.

Utilization of the Thorpe-Ingold Effect in the Synthesis of Cyclooctanoid Ring Systems via Anionic 6-exo-dig Cyclization/Claisen Rearrangement Sequence.

We demonstrate a facile approach for the synthesis of gem-disubstituted cyclooctanoids, a motif found in several biologically active compounds. Appropriately substituted 1-alkenyl-5-pentyn-1-ols bearing gem-dialkyl substituents at either the C2, C3, or C4 position serve as useful precursors to a number of cyclooct-4-enone derivatives via a tandem, microwave-assisted oxyanionic 6-exo-dig cyclization/Claisen rearrangement reaction. gem-Dialkyl activation is necessary for these reactions to occur, as unactivated 1-alkenyl-5-pentyn-1-ols fail to undergo 6-exo-dig cyclization under the conditions employed. Further application of the methodology to the corresponding gem-dialkoxy system was also explored to facilitate access to more complex carbocycles.

Garbage Burning in South Asia: How Important Is It to Regional Air Quality?

Increasing air pollution in South Asia has serious consequences for air quality and human/ecosystem health within the region. South Asia, including India and Nepal, suffers from severe air pollution, including high concentrations of aerosols, as well as gaseous pollutants. One of the often-neglected sources contributing to the regional air pollution is garbage burning. It is mostly related to numerous yet small, open, uncontrolled fires burning diverse fuels, making it difficult to quantify activity and emissions. In this study, we attempted to quantify the total emissions due to garbage burning and its contribution to regional air quality, using new observational data, a new inventory, and a regional chemical transport model. We implemented the newly available emission factors (EFs) from a recent field campaign, Nepal Ambient Monitoring and Source Testing Experiment (NAMaSTE), which took place in April 2015. Using a chemical transport model-Weather Research and Forecasting model coupled with Chemistry version 3.5 (WRF-Chem)-and three emission scenarios, we assessed the impact of open garbage burning emissions on regional air quality. Our results show that garbage burning emissions could increase PM2.5 concentrations by nearly 30% in India and Nepal, and result in ∼300 000 premature deaths from chronic obstructive pulmonary disease in the two countries.

Relating Structure and Ice Nucleation of Mixed Surfactant Systems Relevant to Sea Spray Aerosol.

Ice nucleating particles (INPs) influence weather and climate by their effect on cloud phase state. Fatty alcohols present within aerosol particles confer a potentially important source of ice nucleation activity to sea spray aerosol produced in oceanic regions. However, their interactions with other aerosol components and the influence on freezing were previously largely unknown. Here, we report quantitative measurements of fatty alcohols in model sea spray aerosol and examine the relationships between the composition and structure of the surfactants and subphase in the context of these measurements. Deposited mixtures of surfactants retain the ability to nucleate ice, even in fatty acid-dominant compositions. Strong refreezing effects are also observed, where previously frozen water-surfactant samples nucleate more efficiently. Structural sources of refreezing behavior are identified as either kinetically trapped film states or three-dimensional (3D) solid surfactant particles. Salt effects are especially important for surfactant INPs, where high salt concentrations suppress freezing. A simple water uptake model suggests that surfactant-containing aerosol requires either very low salt content or kinetic trapping as solid particles to act as INPs in the atmosphere. These types of INPs could be identified through comparison of different INP instrument responses.

Secondary Organic Aerosols from Aromatic Hydrocarbons and their Contribution to Fine Particulate Matter in Atlanta, Georgia.

Tracers of secondary organic aerosols (SOA) from thirteen aromatic hydrocarbons were quantified in laboratory smog chamber experiments. Class-specific SOA tracers emerged, including 2,3-dihydroxy-4-oxo-pentatonic acid (DHOPA) from monoaromatic volatile organic compounds (VOCs), phthalic acid from naphthalene and 1-methylnaphthalene, and methyl-nitrocatechol isomers from o,m,p-cresol oxidation. Organic carbon mass fractions (fSOC) for these and other tracers were determined and extend the SOA tracer method widely used to apportion biogenic SOC. The extended SOA tracer model was applied to evaluate the sources of SOC in Atlanta, GA during summer 2015 and winter 2016 after modifying the chamber-derived fSOC values to reflect SOA yields and local VOC levels (fSOC'). Monoaromatic, diaromatic, and cresol SOC contributed an average of 24%, 8%, and 0.12% of organic carbon (OC) mass during summer and 17%, 5%, and 0.27% during winter, respectively. Cresol SOC peaked during winter and was highly correlated with levoglucosan (r=0.83, p<0.001), consistent with it originating from biomass burning. Together, aromatic, biogenic, and biomass burning derived SOC accounted for an average of 77% and 28% of OC in summer and winter, respectively. The new understanding of SOA composition from aromatic VOCs advances the tracer-based method by including important precursors of SOC and enables a better understanding of the sources of atmospheric aerosol.

Catalytic Enantioselective Pyridine N-Oxidation.

The catalytic, enantioselective N-oxidation of substituted pyridines is described. The approach is predicated on a biomolecule-inspired catalytic cycle wherein high levels of asymmetric induction are provided by aspartic-acid-containing peptides as the aspartyl side chain shuttles between free acid and peracid forms. Desymmetrizations of bis(pyridine) substrates bearing a remote pro-stereogenic center substituted with a group capable of hydrogen bonding to the catalyst are demonstrated. Our approach presents a new entry into chiral pyridine frameworks in a heterocycle-rich molecular environment. Representative functionalizations of the enantioenriched pyridine N-oxides further document the utility of this approach. Demonstration of the asymmetric N-oxidation in two venerable drug-like scaffolds, Loratadine and Varenicline, show the likely generality of the method for highly variable and distinct chiral environments, while also revealing that the approach is applicable to both pyridines and 1,4-pyrazines.

Water-Soluble Brown Carbon in Atmospheric Aerosols from Godavari (Nepal), a Regional Representative of South Asia.

Brown carbon (BrC) has recently emerged as an important light-absorbing aerosol. This study provides interannual and seasonal variations in light absorption properties, chemical composition, and sources of water-soluble BrC (WS-BrC) based on PM10 samples collected in Godavari, Nepal, from April 2012 to May 2014. The mass absorption efficiency of WS-BrC at 365 nm (MAE365) shows a clear seasonal variability, with the highest MAE365 of 1.05 ± 0.21 m2 g-1 in premonsoon season and the lowest in monsoon season (0.59 ± 0.16 m2 g-1). The higher MAE365 values in nonmonsoon seasons are associated with fresh biomass burning emissions. This is further substantiated by a strong correlation ( r = 0.79, P < 0.01) between Abs365 (light absorption coefficient at 365 nm) and levoglucosan. We found, using fluorescence techniques, that humic-like and protein-like substances are the main chromophores in WS-BrC and responsible for 80.2 ± 4.1% and 19.8 ± 4.1% of the total fluorescence intensity, respectively. BrC contributes to 8.78 ± 3.74% of total light absorption over the 300-700 nm wavelength range. Considering the dominant contribution of biomass burning to BrC over Godavari, this study suggests that reduction in biomass burning emission may be a practical method for climate change mitigation in South Asia.

Response of the Aerodyne Aerosol Mass Spectrometer to Inorganic Sulfates and Organosulfur Compounds: Applications in Field and Laboratory Measurements.

Organosulfur compounds are important components of secondary organic aerosols (SOA). While the Aerodyne high-resolution time-of-flight aerosol mass spectrometer (AMS) has been extensively used in aerosol studies, the response of the AMS to organosulfur compounds is not well-understood. Here, we investigated the fragmentation patterns of organosulfurs and inorganic sulfates in the AMS, developed a method to deconvolve total sulfate into components of inorganic and organic origins, and applied this method in both laboratory and field measurements. Apportionment results from laboratory isoprene photooxidation experiment showed that with inorganic sulfate seed, sulfate functionality of organic origins can contribute ∼7% of SOA mass at peak growth. Results from measurements in the Southeastern U.S. showed that 4% of measured sulfate is from organosulfur compounds. Methanesulfonic acid was estimated for measurements in the coastal and remote marine boundary layer. We explored the application of this method to unit mass-resolution data, where it performed less well due to interferences. Our apportionment results demonstrate that organosulfur compounds could be a non-negligible source of sulfate fragments in AMS laboratory and field data sets. A reevaluation of previous AMS measurements over the full range of atmospheric conditions using this method could provide a global estimate/constraint on the contribution of organosulfur compounds.

Sea spray aerosol chemical composition: elemental and molecular mimics for laboratory studies of heterogeneous and multiphase reactions.

Sea spray aerosol particles (SSA), formed through wave breaking at the ocean surface, contribute to natural aerosol particle concentrations in remote regions of Earth's atmosphere, and alter the direct and indirect effects of aerosol particles on Earth's radiation budget. In addition, sea spray aerosol serves as suspended surface area that can catalyze trace gas reactions. It has been shown repeatedly that sea spray aerosol is heavily enriched in organic material compared to the surface ocean. The selective enrichment of organic material complicates the selection of representative molecular mimics of SSA for laboratory or computational studies. In this review, we first provide a short introduction to SSA formation processes and discuss chemical transformations of SSA that occur in polluted coastal regions and remote pristine air. We then focus on existing literature of the chemical composition of nascent SSA generated in controlled laboratory experiments and field investigations. We combine the evidence on the chemical properties of nascent SSA with literature measurements of SSA water uptake to assess SSA molecular composition and liquid water content. Efforts to speciate SSA organic material into molecular classes and specific molecules have led to the identification of saccharides, alkanes, free fatty acids, anionic surfactants, dicarboxylic acids, amino acids, proteinaceous matter, and other large macromolecules. However to date, less than 25% of the organic mass of nascent SSA has been quantified at a molecular level. As discussed here, quantitative measurements of size resolved elemental ratios, combined with determinations of water uptake properties, provides unique insight on the concentration of ions within SSA as a function of particle size, pointing to a controlling role for relative humidity and the hygroscopicity of SSA organic material at small particle diameters.

Parameterization and Analysis of Peptide-Based Catalysts for the Atroposelective Bromination of 3-Arylquinazolin-4(3H)-ones.

We report the development of a method to parameterize and predict the performance of structurally flexible ß-turn-containing peptide catalysts, using the atroposelective bromination of 3-arylquinazolin-4(3H)-ones as a case study. The multivariate correlations obtained for tetrapeptides of two ß-turn types, type I' pre-helical and type II' ß-hairpin, indicate that although one conformer may be associated with a more dominant contribution to the observed enantioselectivity, it is possible that multiple conformers contribute to a complex transition state ensemble.

Airway surface liquid from smokers promotes bacterial growth and biofilm formation via iron-lactoferrin imbalance.

BACKGROUND: Smoking is a leading cause of respiratory infections worldwide. Tobacco particulate matter disrupts iron homeostasis in the lungs and increases the iron content in the airways of smokers. The airway epithelia secrete lactoferrin to quench iron required for bacteria to proliferate and cause lung infections. We hypothesized that smokers would have increased bacterial growth and biofilm formation via iron lactoferrin imbalance. METHODS: We collected bronchoalveolar lavage (BAL) samples from non-smokers and smokers. We challenged these samples using a standard inoculum of Staphylococcus aureus and Pseudomonas aeruginosa and quantified bacterial growth and biofilm formation. We measured both iron and lactoferrin in the samples. We investigated the effect of supplementing non-smoker BAL with cigarette smoke extract (CSE) or ferric chloride and the effect of supplementing smoker BAL with lactoferrin on bacterial growth and biofilm formation. RESULTS: BAL from smokers had increased bacterial growth and biofilm formation compared to non-smokers after both S. aureus and P. aeruginosa challenge. In addition, we found that samples from smokers had a higher iron to lactoferrin ratio. Supplementing the BAL of non-smokers with cigarette smoke extract and ferric chloride increased bacterial growth. Conversely, supplementing the BAL of smokers with lactoferrin had a concentration-dependent decrease in bacterial growth and biofilm formation. CONCLUSION: Cigarette smoking produces factors which increase bacterial growth and biofilm formation in the BAL. We propose that smoking disrupts the iron-to-lactoferrin in the airways. This finding offers a new avenue for potential therapeutic interventions to prevent respiratory infections in smokers.

Milestone Educational Planning Initiatives in Veterinary Medical Education: Progress and Pitfalls.

Three milestone educational planning initiatives engaged the veterinary medical profession in the United States and Canada between 1987 and 2011, namely the Pew National Veterinary Education Program, the Foresight Project, and the North American Veterinary Medical Education Consortium. In a quantitative study, we investigated the impact of these initiatives on veterinary medical education through a survey of academic leaders (deans, previous deans, and associate deans for academics from veterinary medical schools that are members of the Association of American Veterinary Medical Colleges) to assess their perspectives on the initiatives and eight recommendations that were common to all three initiatives. Two of the recommendations have in effect been implemented: enable students to elect in-depth instruction and experience within a practice theme or discipline area (tracking), and increase the number of graduating veterinarians. For three of the recommendations, awareness of the issues has increased but substantial progress has not been made: promote diversity in the veterinary profession, develop a plan to reduce student debt, and develop a North American strategic plan. Lastly, three recommendations have not been accomplished: emphasize use of information more than fact recall, share educational resources to enable a cost-effective education, and standardize core admissions requirements. The educational planning initiatives did provide collaborative opportunities to discuss and determine what needs to change within veterinary medical education. Future initiatives should explore how to avoid and overcome obstacles to successful implementation.

Veterinarians at the Connaught Medical Research Laboratories, 1931-72.

This study traces the changing mission of the University of Toronto's Connaught Medical Research Laboratories regarding the health of animals. We argue that the early work of Connaught's veterinarians in the 1930s and 1940s focused on the care for experimental animals as well as lending veterinary knowledge to problems in human medicine and public health. This gave way to a more direct focus on veterinary products after the Second World War. Connaught was motivated to enter the veterinary field in part to capitalize upon the growing market for veterinary medicines. It met with mixed success in this endeavour. Work was initially focused on livestock medicines and later expanded into products for companion animals, reflecting broader shifts in the veterinary profession and the economic value of animals during the 20th century.

Desymmetrization of Diarylmethylamido Bis(phenols) through Peptide-Catalyzed Bromination: Enantiodivergence as a Consequence of a 2 amu Alteration at an Achiral Residue within the Catalyst.

Diarylmethylamido bis(phenols) have been subjected to peptide-catalyzed, enantioselective bromination reactions. Desymmetrization of compounds in this class has been achieved such that enantioenriched products may be isolated with up to 97:3 er. Mechanistically, the observed enantioselectivity was shown to be primarily a function of differential functionalization of enantiotopic arenes, although additional studies unveiled a contribution from secondary kinetic resolution of the product (to afford the symmetrical dibromide) under the reaction conditions. Variants of the tetrapeptide catalyst were also evaluated and revealed a striking observation-enantiodivergent catalysis is observed upon changing the achiral amino acid residue in the catalyst (at the i+2 position) from an aminocyclopropane carboxamide residue (97:3 er) to an aminoisobutyramide residue (33:67 er) under a common set of conditions. An expanded set of catalysts was also evaluated, enabling structure/selectivity correlations to be considered in a mechanistic light.

Water Uptake and Hygroscopic Growth of Organosulfate Aerosol.

Organosulfates (OS) are important components of secondary organic aerosol (SOA) that have been identified in numerous field studies. This class of compounds within SOA can potentially affect aerosol physicochemical properties such as hygroscopicity because of their polar and hydrophilic nature as well as their low volatility. Currently, there is a dearth of information on how aerosol particles that contain OS interact with water vapor in the atmosphere. Herein we report a laboratory investigation on the hygroscopic properties of a structurally diverse set of OS salts at varying relative humidity (RH) using a Hygroscopicity-Tandem Differential Mobility Analyzer (H-TDMA). The OS studied include the potassium salts of glycolic acid sulfate, hydroxyacetone sulfate, 4-hydroxy-2,3-epoxybutane sulfate, and 2-butenediol sulfate and the sodium salts of benzyl sulfate, methyl sulfate, ethyl sulfate, and propyl sulfate. In addition, mixtures of OS and sodium chloride were also studied. The results showed gradual deliquescence of these aerosol particles characterized by continuous uptake and evaporation of water in both hydration and dehydration processes for the OS, while the mixture showed prompt deliquescence and effloresce transitions, albeit at a lower relative humidity relative to pure sodium chloride. Hygroscopic growth of these OS at 85% RH were also fit to parameterized functional forms. This new information provided here has important implications about the atmospheric lifetime, light scattering properties, and the role of OS in cloud formation. Moreover, results of these studies can ultimately serve as a basis for the development and evaluation of thermodynamic models for these compounds in order to consider their impact on the atmosphere.