Aspergillus fumigatus causes invasive disease in severely immunocompromised hosts but is readily cleared when host innate defenses are intact. Animal models for evaluation of therapeutic strategies to combat invasive aspergillosis that closely mimic human disease are desirable. We determined optimal dosing regimens for neutrophil depletion and evaluated the course of infection following aerosol infection in mice by determining survival, organ fungal burden, and histopathology in mice in which neutropenia was induced by three methods, administration of granulocyte-depleting monoclonal antibody RB6-8C5 (MAb RB6), administration of cyclophosphamide, and administration of both agents. Administration of either individual agent resulted in a requirement for relatively high conidial inocula to achieve 100% mortality in both BALB/c and C57BL/6 mice, although the infection appeared to be somewhat more lethal in C57BL/6 mice. Death following induction of neutropenia with MAb RB6 occurred when a relatively low fungal burden was present in the lung and may have been related to the inflammatory response associated with neutrophil recovery. In contrast, administration of both agents reduced the lethal inoculum in each mouse strain by approximately 1 log 10 , and C57BL/6 mice that received both agents had a higher fungal burden and less inflammation in the lung at the time of death than BALB/c mice or mice of either strain that received MAb RB6 alone. Our data suggest that the relationship among fungal burden, inflammation, and death is complex and can be influenced by the immunosuppression regimen, the mouse strain, and the inoculum.

No abstract

Adoption of hydrogen infrastructure and hydrogen fuel cell vehicles (HFCVs) to replace gasoline internal combustion engine (ICE) vehicles has been proposed as a strategy to reduce criteria pollutant and greenhouse gas (GHG) emissions from the transportation sector and transition to fuel independence. However, it is uncertain (1) to what degree the reduction in criteria pollutants will impact urban air quality, and (2) how the reductions in pollutant emissions and concomitant urban air quality impacts compare to ultralow emission gasoline-powered vehicles projected for a future year (e.g., 2060). To address these questions, the present study introduces a "spatially and temporally resolved energy and environment tool" (STREET) to characterize the pollutant and GHG emissions associated with a comprehensive hydrogen supply infrastructure and HFCVs at a high level of geographic and temporal resolution. To demonstrate the utility of STREET, two spatially and temporally resolved scenarios for hydrogen infrastructure are evaluated in a prototypical urban airshed (the South Coast Air Basin of California) using geographic information systems (GIS) data. The well-to-wheels (WTW) GHG emissions are quantified and the air quality is established using a detailed atmospheric chemistry and transport model followed by a comparison to a future gasoline scenario comprised of advanced ICE vehicles. One hydrogen scenario includes more renewable primary energy sources for hydrogen generation and the other includes more fossil fuel sources. The two scenarios encompass a variety of hydrogen generation, distribution, and fueling strategies. GHG emissions reductions range from 61 to 68% for both hydrogen scenarios in parallel with substantial improvements in urban air quality (e.g., reductions of 10 ppb in peak 8-h-averaged ozone and 6 µg/m 3 in 24-h-averaged particulate matter concentrations, particularly in regions of the airshed where concentrations are highest for the gasoline scenario).

Emissions of criteria pollutants increase or decrease, depending on the hydrogen deployment scenario, when compared to an evolution of the existing paradigm of conventional vehicles and fuels. For all scenarios, pipeline distribution from a centrally located generation source reduces criteria pollutant emissions when compared to distribution by truck. With one qualification, greenhouse gas emissions are reduced for the scenarios considered with the extent of reduction increasing in proportion to the renewable sources of hydrogen. When natural gas is utilized as a source for hydrogen, leakage of methane from the U.S. natural gas infrastructure is a significant contributor to the greenhouse gases associated with a hydrogen economy. For all scenarios considered, the WTW energy efficiency improves whereas the consumption of water (and the associated energy) increases.