17 research outputs found

    TMI-2 - A Case Study for PWR Instrumentation Performance during a Severe Accident

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    The accident at the Three Mile Island Unit 2 (TMI-2) reactor provided a unique opportunity to evaluate sensors exposed to severe accident conditions. Conditions associated with the release of coolant and the hydrogen burn that occurred during this accident exposed instrumentation to harsh conditions, including direct radiation, radioactive contamination, and high humidity with elevated temperatures and pressures. As part of a program initiated in 2012 by the Department of Energy Office of Nuclear Energy (DOE-NE), a review was completed to gain insights from prior TMI-2 sensor survivability and data qualification efforts. This new effort focussed upon a set of sensors that provided critical data to TMI-2 operators for assessing the condition of the plant and the effects of mitigating actions taken by these operators. In addition, the effort considered sensors providing data required for subsequent accident simulations. Over 100 references related to instrumentation performance and post-accident evaluations of TMI-2 sensors and measurements were reviewed. Insights gained from this review are summarized within this report. For each sensor, a description is provided with the measured data and conclusions related to the sensor’s survivability, and the basis for conclusions about its survivability. As noted within this document, several techniques were invoked in the TMI-2 post-accident evaluation program to assess sensor status, including comparisons with data from other sensors, analytical calculations, laboratory testing, and comparisons with sensors subjected to similar conditions in large-scale integral tests and with sensors that were similar in design but more easily removed from the TMI-2 plant for evaluations. Conclusions from this review provide important insights related to sensor survivability and enhancement options for improving sensor performance. In addition, this document provides recommendations related to the sensor survivability and data evaluation process that could be implemented in upcoming Fukushima Daiichi recovery efforts

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

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    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
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