There is strong evidence of an association between fine particulate matter less than 2.5 μm (PM2.... more There is strong evidence of an association between fine particulate matter less than 2.5 μm (PM2.5) in aerodynamic diameter and adverse health outcomes. This study analyzes the global excess mortality attributable to the aviation sector in the present (2006) and in the future (three 2050 scenarios) using the integrated exposure response model that was also used in the 2010 Global Burden of Disease assessment. The PM2.5 concentrations for the present and future scenarios were calculated using aviation emission inventories developed by the Volpe National Transportation Systems Center and a global chemistry-climate model. We found that while excess mortality due to the aviation sector emissions is greater in 2050 compared to 2006, improved fuel policies (technology and operations improvements yielding smaller increases in fuel burn compared to 2006, and conversion to fully sustainable fuels) in 2050 could lead to 72% fewer deaths for adults 25 years and older than a 2050 scenario with ...
Dual target inhibitors against COX-2 and LTA(4)H were designed by adding functional groups from a... more Dual target inhibitors against COX-2 and LTA(4)H were designed by adding functional groups from a marketed COX-2 inhibitor, Nimesulide, to an existing LTA(4)H inhibitor 1-(2-(4-phenoxyphenoxy) ethyl) pyrrolidine. A series of phenoxyphenyl pyrrolidine compounds were synthesized and tested for their inhibition activities using enzyme assays and human whole blood assay. Introduction of small electron withdrawing groups like NO(2) and CF(3) in the ortho-position of the terminal phenyl ring was found to change the original single target LTA(4)H inhibitor to dual target LTA(4)H and COX-2 inhibitors. Compound 5a and 5m showed dual LTA(4)H and COX-2 inhibition activities in the enzyme assays and the HWB assay with IC(50) values in the micromolar to submicromolar range. As their activities in HWB assay were comparable to the two starting single target inhibitors, the two compounds are promising for further studies. The strategy used in the current study may be generally applicable to other dual target drug designs.
Environmental health : a global access science source, 2015
A warming climate will affect future temperature-attributable premature deaths. This analysis is ... more A warming climate will affect future temperature-attributable premature deaths. This analysis is the first to project these deaths at a near national scale for the United States using city and month-specific temperature-mortality relationships. We used Poisson regressions to model temperature-attributable premature mortality as a function of daily average temperature in 209 U.S. cities by month. We used climate data to group cities into clusters and applied an Empirical Bayes adjustment to improve model stability and calculate cluster-based month-specific temperature-mortality functions. Using data from two climate models, we calculated future daily average temperatures in each city under Representative Concentration Pathway 6.0. Holding population constant at 2010 levels, we combined the temperature data and cluster-based temperature-mortality functions to project city-specific temperature-attributable premature deaths for multiple future years which correspond to a single reportin...
There is strong evidence of an association between fine particulate matter less than 2.5 μm (PM2.... more There is strong evidence of an association between fine particulate matter less than 2.5 μm (PM2.5) in aerodynamic diameter and adverse health outcomes. This study analyzes the global excess mortality attributable to the aviation sector in the present (2006) and in the future (three 2050 scenarios) using the integrated exposure response model that was also used in the 2010 Global Burden of Disease assessment. The PM2.5 concentrations for the present and future scenarios were calculated using aviation emission inventories developed by the Volpe National Transportation Systems Center and a global chemistry-climate model. We found that while excess mortality due to the aviation sector emissions is greater in 2050 compared to 2006, improved fuel policies (technology and operations improvements yielding smaller increases in fuel burn compared to 2006, and conversion to fully sustainable fuels) in 2050 could lead to 72% fewer deaths for adults 25 years and older than a 2050 scenario with ...
Dual target inhibitors against COX-2 and LTA(4)H were designed by adding functional groups from a... more Dual target inhibitors against COX-2 and LTA(4)H were designed by adding functional groups from a marketed COX-2 inhibitor, Nimesulide, to an existing LTA(4)H inhibitor 1-(2-(4-phenoxyphenoxy) ethyl) pyrrolidine. A series of phenoxyphenyl pyrrolidine compounds were synthesized and tested for their inhibition activities using enzyme assays and human whole blood assay. Introduction of small electron withdrawing groups like NO(2) and CF(3) in the ortho-position of the terminal phenyl ring was found to change the original single target LTA(4)H inhibitor to dual target LTA(4)H and COX-2 inhibitors. Compound 5a and 5m showed dual LTA(4)H and COX-2 inhibition activities in the enzyme assays and the HWB assay with IC(50) values in the micromolar to submicromolar range. As their activities in HWB assay were comparable to the two starting single target inhibitors, the two compounds are promising for further studies. The strategy used in the current study may be generally applicable to other dual target drug designs.
Environmental health : a global access science source, 2015
A warming climate will affect future temperature-attributable premature deaths. This analysis is ... more A warming climate will affect future temperature-attributable premature deaths. This analysis is the first to project these deaths at a near national scale for the United States using city and month-specific temperature-mortality relationships. We used Poisson regressions to model temperature-attributable premature mortality as a function of daily average temperature in 209 U.S. cities by month. We used climate data to group cities into clusters and applied an Empirical Bayes adjustment to improve model stability and calculate cluster-based month-specific temperature-mortality functions. Using data from two climate models, we calculated future daily average temperatures in each city under Representative Concentration Pathway 6.0. Holding population constant at 2010 levels, we combined the temperature data and cluster-based temperature-mortality functions to project city-specific temperature-attributable premature deaths for multiple future years which correspond to a single reportin...
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