One million indents, a hardness (and modulus) story

Advances in nanomechanical testing have progressed to a point where high-speed mapping and large data sets have become achievable. An Edisonian approach to indentation spacing and rate determines the experimental parameters that are then applied to a modern Damascene steel. One million indents were then performed over a period of less than 6 days thereby mapping out an area of 1mm x 1mm with a spacing of 1µm. To make sense of the data, artificial intelligence algorithms are used to provide an analysis of the hardness and modulus data. Please click Additional Files below to see the full abstract

Shear slitting of aluminum webs using block knives

C Shear slitting of two aluminum webs, namely 1050 H18 of 0.28 mm thick and 5182 H19 of 0.20 mm thick, using block knives are investigated through experiments using a laboratory slitter. This investigation focused on two aspects of shear slitting using block knives, appropriate for relatively thick webs. They are: (1) tangential shear slitting at zero rake angle, i.e., traditional shear slitting with a pair of block knives. In this aspect, the effects of major slitting parameters on the burr height at the slit edge were investigated. These include the clearance, overlap, overdrive and cant angle. The critical clearances for both webs have been determined; and (2) slitting at a rake angle, a new method for edge trimming when the two blades are not necessarily in contact. The top blade geometry was modified for slitting with a rake angle of -15o to allow slitting of an aluminum web, up to 1 mm thick in this investigation. This new method of edge trimming using block knives was found to be very effective and robust over a (relatively) very wide range of slitting parameters. Very good slit edge was produced, and the burr height was found to be independent of slitting parameters over a relatively large range of slitting parameters. Because two blades do not have to be in contact in slitting so that the blade wear is much less than in the case of traditional shear slitting, this new method is expected to extend significantly the block knife service life while producing consistently high quality slit edges.Mechanical and Aerospace Engineerin

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