Earthquake-induced ground failure hazards in the Reno-Sparks region, Washoe County, Nevada

Online access for this thesis was created in part with support from the Institute of Museum and Library Services (IMLS) administered by the Nevada State Library, Archives and Public Records through the Library Services and Technology Act (LSTA). To obtain a high quality image or document please contact the DeLaMare Library at https://unr.libanswers.com/ or call: 775-784-6945.Earthquake-induced ground failure hazards associated with liquefaction and landsliding are identified and mapped throughout the urbanized and developing areas of the Reno- Sparks region. Separate maps, produced at 1:62,500 scale, identify areas susceptible to liquefaction and landsliding. Liquefaction susceptibility mapping is based on a compilation of more than 500 bore holes. Where bore hole density is sufficient, the critical acceleration to cause liquefaction during a M 7.5 earthquake, values were contoured to yield the map pattern. The critical accelerations refer to acceleration at the ground surface, not bedrock accelerations. The potential for liquefaction at a site is strongly influenced by the properties of the soil underlying the site and resonance effects. The influence of these local site conditions are not included in this study. Where data density is sparse or nonexistent, liquefaction susceptibility mapping is based on published geology and groundwater conditions. Landslide hazards addressed in this study include: 1) rockfall, 2) rotational rock slides and 3) shallow soil slides. These three slide types are considered the most pertinent to discussions involving earthquake induced slides given the geologic, climatic and geomorphic conditions of the Reno-Sparks region

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival