Mesoscale acid deposition modeling studies

The work performed in support of the EPA/DOE MADS (Mesoscale Acid Deposition) Project included the development of meteorological data bases for the initialization of chemistry models, the testing and implementation of new planetary boundary layer parameterization schemes in the MASS model, the simulation of transport and precipitation for MADS case studies employing the MASS model, and the use of the TASS model in the simulation of cloud statistics and the complex transport of conservative tracers within simulated cumuloform clouds. The work performed in support of the NASA/FAA Wind Shear Program included the use of the TASS model in the simulation of the dynamical processes within convective cloud systems, the analyses of the sensitivity of microburst intensity and general characteristics as a function of the atmospheric environment within which they are formed, comparisons of TASS model microburst simulation results to observed data sets, and the generation of simulated wind shear data bases for use by the aviation meteorological community in the evaluation of flight hazards caused by microbursts

Profiling of Saharan dust and biomass-burning smoke with multiwavelength polarization Raman lidar at Cape Verde

Published under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported LicenseExtensive lidar measurements of Saharan dust and biomass-burning smoke were performed with one airborne and three ground-based instruments in the framework of the second part of the SAharan Mineral dUst experiMent (SAMUM-2a) during January and February of 2008 at Cape Verde. Further lidar observations with one system only were conducted during May and June of 2008 (SAMUM-2b). The active measurements were supported by Sun photometer observations. During winter, layers of mineral dust from the Sahara and biomass-burning smoke from southern West Africa pass Cape Verde on their way to South America while pure dust layers cross the Atlantic on their way to the Caribbean during summer. The mean 500-nm aerosol optical thickness (AOT) observed during SAMUM-2a was 0.35 +/- 0.18. SAMUM-2a observations showed transport of pure dust within the lowermost 1.5 km of the atmospheric column. In the height range from 1.5 to 5.0 km, mixed dust/smoke layers with mean lidar ratios of 67 +/- 14 sr at 355 and 532 nm, respectively, prevailed. Within these layers, wavelength-independent linear particle depolarization ratios of 0.12-0.18 at 355, 532, and 710 nm indicate a large contribution (30-70%) of mineral dust to the measured optical properties. Angstrom exponents for backscatter and extinction of around 0.7 support this finding. Mean extinction coefficients in the height range between 2 and 4 km were 66 +/- 6 Mm(-1) at 355 nm and 48 +/- 5 Mm(-1) at 532 nm. Comparisons with airborne high-spectral-resolution lidar observations show good agreement within the elevated layers. 3-5 km deep dust layers where observed during SAMUM-2b. These layers showed optical properties similar to the ones of SAMUM-1 in Morocco with a mean 500-nm AOT of 0.4 +/- 0.2. Dust extinction coefficients were about 80 +/- 6 Mm(-1) at 355 and 532 nm. Dust lidar ratios were 53 +/- 10 sr at 355 and 532 nm, respectively. Dust depolarization ratios showed an increase with wavelength from 0.31 +/- 0.10 at 532 nm to 0.37 +/- 0.07 at 710 nm.Peer reviewe

Prime-boost using separate oncolytic viruses in combination with checkpoint blockade improves anti-tumor therapy

The anti-tumor effects associated with oncolytic virus therapy are mediated significantly through immune-mediated mechanisms which depends both on the type of virus and the route of delivery. Here, we show that intra-tumoral (i.t.) oncolysis by Reovirus induced the priming of a CD8+, Th1-type anti-tumor response. In contrast, systemically delivered VSV expressing a cDNA library of melanoma antigens (VSV-ASMEL) promoted a potent anti-tumor CD4+ Th17 response. Therefore, we hypothesised that combining the Reovirus-induced CD8+ T cell response, with the VSV-ASMEL CD4+ Th17 helper response, would produce enhanced anti-tumor activity. Consistent with this, priming with i.t. Reovirus, followed by an intra-venous VSV-ASMEL Th17 boost, significantly improved survival of mice bearing established subcutaneous (s.c.) B16 melanoma tumors. We also show that combination of either therapy alone with anti-PD-1 immune checkpoint blockade augmented both the Th1 response induced by systemically delivered Reovirus in combination with GM-CSF, and also the Th17 response induced by VSV-ASMEL. Significantly, anti-PD-1 also uncovered an anti-tumor Th1 response following VSV-ASMEL treatment that was not seen in the absence of checkpoint blockade. Finally, the combination of all three treatments (priming with systemically delivered Reovirus, followed by double boosting with systemic VSV-ASMEL and anti-PD-1) significantly enhanced survival, with long-term cures, compared to any individual, or double, combination therapies, associated with strong Th1 and Th17 responses to tumor antigens. Our data show that it is possible to generate fully systemic, highly effective anti-tumor immunovirotherapy by combining oncolytic viruses, along with immune checkpoint blockade, to induce complimentary mechanisms of anti-tumor immune responses