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

Cold and moderate ambient temperatures effects on expansive pressure develop-ment in soundless chemical demolition agents

This paper explores cool and moderate temperature (2–19 °C) impacts on hydration heat and expansive pressure development in two commercial soundless chemical demolition agents (SCDAs). Experimental results showed (1) product-specific, linear relationships between the ambient temperature and time to peak hydration heat; (2) peak hydration heats to be consistently 1.5 times the ambient temperatures at 10–19 °C; outside of this range the factor was greater; (3) a linear relationship between peak hydration heat time and the onset of expansive pressure development; (4) a largely proportional relationship between ambient temperature and volumetric expansion of 1.1–1.4 times the original volume.European Research CouncilScience Foundation Ireland2018-05-02 JG: .docx converted to PDF at author's reques

CERCOM - Development of an Analytic Software Tool for the Evaluation of Innovative Infrastructure Maintenance Methods in the Move Towards Circularity

Implementation of the circular economy and resource efficiency has the potential to significantly tackle the root causes of global challenges such as climate change, biodiversity loss and pollution whilst at the same time providing regenerative design for generations to come. The CEDR funded CERCOM project facilitates a move towards circular public procurement of national road infrastructure. A flexible and stable approach using ranked interpolation is used to generate KPI values for various criterion, where the user can specify the desired level of complexity based on scheme requirements and data available. The framework considers technical, economic, environmental and social criteria, as well as circularity, while assessing the change in risks in moving from a linear to a circular economy. National Road Authorities (NRAs) are at different maturity levels in relation to circularity. The developed framework caters for this, allowing flexibility for NRAs to tailor their application of the framework to suit their maturity level and the scheme under consideration. The outcome is a user-friendly intuitive tool with a step-by-step approach to enable informed decision making around adoption of the principles of circular economy in the maintenance of highway infrastructure.Pavement Engineerin

The University of Texas: Looking Forward; Research Libraries in the 21st Century

The Research Library in the 21st Century symposium was held at The University of Texas at Austin over the course of two days, September 11-12, 2006. The idea behind the symposium was to begin shaping a strategy for the future of academic research libraries. We invited some of the best minds in the field and representatives from leading institutions to explore the future of the research library and new developments in scholarly communication. Dr. Fred Heath, Vice Provost and Director of the University of Texas Libraries, prepared a subsequent report – "The University of Texas: Looking Forward; Research Libraries in the 21st Century" – that presents an overview of the principle themes and trends identified over the course of the symposium, with particular attention to their relevance to libraries at the University of Texas. This white paper is available, along with complete transcripts of the symposium presentations, as well as audio files (MP3 format) of the presentations.UT Librarie