Ultrasonic guided wave interpretation for structural health inspections

Structural Health Management (SHM) combines the use of onboard sensors with artificial intelligence algorithms to automatically identify and monitor structural health issues. A fully integrated approach to SHM systems demands an understanding of the sensor output relative to the structure, along with sophisticated prognostic systems that automatically draw conclusions about structural integrity issues. Ultrasonic guided wave methods allow us to examine the interaction of multimode signals within key structural components. Since they propagate relatively long distances within plate- and shell-like structures, guided waves allow inspection of greater areas with fewer sensors, making this technique attractive for a variety of applications.;This dissertation describes the experimental development of automatic guided wave interpretation for three real world applications. Using the guided wave theories for idealized plates we have systematically developed techniques for identifying the mass loading of underwater limpet mines on US Navy ship hulls, characterizing type and bonding of protective coatings on large diameter pipelines, and detecting the thinning effects of corrosion on aluminum aircraft structural stringers. In each of these circumstances the signals received are too complex for interpretation without knowledge of the guided wave physics. We employ a signal processing technique called the Dynamic Wavelet Fingerprint Technique (DFWT) in order to render the guided wave mode information in two-dimensional binary images. The use of wavelets allows us to keep track of both time and scale features from the original signals. With simple image processing we have developed automatic extraction algorithms for features that correspond to the arrival times of the guided wave modes of interest for each of the applications. Due to the dispersive nature of the guided wave modes, the mode arrival times give details of the structure in the propagation path.;For further understanding of how the guided wave modes propagate through the real structures, we have developed parallel processing, 3D elastic wave simulations using the finite integration technique (EFIT). This full field, numeric simulation technique easily examines models too complex for analytical solutions. We have developed the algorithm to handle built up 3D structures as well as layers with different material properties and surface detail. The simulations produce informative visualizations of the guided wave modes in the structures as well as the output from sensors placed in the simulation space to mimic the placement from experiment. Using the previously developed mode extraction algorithms we were then able to compare our 3D EFIT data to their experimental counterparts with consistency

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