Nonlinear fiber-optic strain sensor based on four-wave mixing in microstructured optical fiber

We demonstrate a nonlinear fiber-optic strain sensor, which uses the shifts of four-wave mixing Stokes and anti-Stokes peaks caused by the strain-induced changes in the structure and refractive index of a microstructured optical fiber. The sensor thus uses the inherent nonlinearity of the fiber and does not require any advanced post-processing of the fiber. Strain sensitivity of -0.23 pm/mu epsilon is achieved experimentally and numerical simulations reveal that for the present fiber the sensitivity can be increased to -4.46 pm/mu epsilon by optimizing the pump wavelength and power. (C) 2012 Optical Society of Americ

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

Ultrasonic stress relief on TC4 titanium alloy subjected to laser surface irradiation

The ultrasonic stress relief was introduced to relieve the residual stress in TC4 titanium alloy subjected to the laser surface irradiation. The experiments for the laser surface irradiation were carried out based on the CO2 laser machine and the hole-drilling method was used to evaluate the residual stress in the TC4 titanium alloy. The results show that the larger tensile residual stress induced by the high-energy laser can be effectively relieved by the ultrasonic stress relief. In addition, the effect of the ultrasonic stress relief can be improved by increasing the ultrasonic vibration energy imposed into the TC4 titanium alloy. The findings confirm that the ultrasonic stress relief is promising to be used to relieve the residual stress in TC4 titanium alloy during the processing and manufacturing process

Application of high-energy oscillating electric current pulse to relieve pulsed-laser surface irradiation induced residual stress in AISI 1045 steel

The high-energy oscillating electric current pulse (ECP) technology was introduced to relieve the residual stresses in the small AISI 1045 steel specimens treated by the pulsed-laser surface irradiation. The high-energy oscillating ECP stress relief experiments were conducted to study the effectiveness of the high-energy oscillating ECP technology. In addition, the electroplasticity framework was developed based on the thermal activation theory to reveal the mechanism of the high-energy oscillating ECP stress relief. The results show that the high-energy oscillating ECP stress relief has good effects on eliminating the residual stress. Furthermore, the residual stress relieving mechanism of the high-energy oscillating ECP stress relief can be attributed to the electric softening effect and the dynamic stress effect. The findings confirm that the significant effects of high-energy oscillating ECP on metal plasticity and provide a basis to understand the underlying mechanism of the high-energy oscillating ECP stress relief

Gene therapy for colorectal cancer by an oncolytic adenovirus that targets loss of the insulin-like growth factor 2 imprinting system

Abstract Background Colorectal cancer is one of the most common malignant tumors worldwide. Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) gene is an epigenetic abnormality observed in human colorectal neoplasms. Our aim was to investigate the feasibility of using the IGF2 imprinting system for targeted gene therapy of colorectal cancer. Results We constructed a novel oncolytic adenovirus, Ad315-E1A, and a replication-deficient recombinant adenovirus, Ad315-EGFP, driven by the IGF2 imprinting system by inserting the H19 promoter, CCCTC binding factor, enhancer, human adenovirus early region 1A (E1A) and enhanced green fluorescent protein (EGFP) reporter gene into a pDC-315 shuttle plasmid. Cell lines with IGF2 LOI (HCT-8 and HT-29), which were infected with Ad315-EGFP, produced EGFP. However, no EGFP was produced in cell lines with maintenance of imprinting (HCT116 and GES-1). We found that Ad315-E1A significantly decreased cell viability and induced apoptosis only in LOI cell lines in vitro. In addition, mice bearing HCT-8-xenografted tumors, which received intratumoral administration of the oncolytic adenovirus, showed significantly reduced tumor growth and enhanced survival. Conclusions Our recombinant oncolytic virus targeting the IGF2 LOI system inhibits LOI cell growth in vitro and in vivo, and provides a novel approach for targeted gene therapy.</p