Best-in-Class Global Bumper Reinforcement Beam

Modern bumper systems are governed by laws and regulations imposed separately by various countries. Today, the regulations in China, North America, and Europe are becoming more similar, but there is not a widely accepted bumper reinforcement that meets the requirements of all markets around the globe. A universal bumper reinforcement beam incorporating Plug-n-Play techniques was developed to meet and exceed all testing requirements and performance standards of each country. These Plug-n-Play techniques consist of adding energy absorbing attachments to the front of a base bumper beam. Simple beam analysis and FEA were the primary analysis tools in the development of the bumper beam system. Plug & Play techniques were utilized to increase the performance of the universal bumper across all markets

The Social Case as a Business Case: Making Sense of Social Entrepreneurship from an Ordonomic Perspective

This article discusses how the theoretical perspective of ordonomics provides a framework for better understanding and advancing the practice of social entrepreneurship. From an ordonomic perspective, the concept of social entrepreneurship offers a semantic innovation (at the ideas level) whose potential for social innovation can be fully reaped only if it is used as a heuristics for social structural change (on the institutions level). Social entrepreneurs recognize relevant social problems, interpret them as an entrepreneurial challenge, and succeed in turning what was a social case into a business case in a broader sense. Using the real-life example of a successful eco-social entrepreneur, the article demonstrates that such win-win solutions can be reconstructed as the sophisticated management of social dilemmas. It sketches a strategy matrix for the practice of social entrepreneurship and distinguishes four paradigmatic strategies social entrepreneurs can employ to create win-win scenarios by changing the rules of the game to overcome undesirable social dilemmas. The article concludes by discussing social entrepreneurship in the context of new governance processes and highlights key similarities and differences to the concept of corporate citizenship.Dieser Artikel nutzt die theoretische Perspektive der Ordonomik, um einen konzeptionellen Beitrag zum Verständnis von Social Entrepreneurship zu entwickeln. Aus ordonomischer Sicht verbindet sich mit dem Konzept von Social Entrepreneurship eine semantische Innovation (auf der Ebene der Ideen), deren Potential für gesellschaftlichen Wandel jedoch daran geknüpft ist, sozialstrukturellen Wandel (also Reformen auf der Ebene der Institutionen) heuristisch anzuleiten. Social Entrepreneurs identifizieren relevante gesellschaftliche Probleme, interpretieren sie als unternehmerische Herausforderungen und vermögen es, einen „social case“ in einen „business case“ im weiteren Sinne zu transformieren. Am Beispiel eines realen Öko-Sozialunternehmers wird gezeigt, dass derartige Win-Win-Lösungen als das differenzierte Management sozialer Dilemmata rekonstruiert werden können. Der Beitrag entwirft eine Strategiematrix für Social Entrepreneurship und unterscheidet vier paradigmatische Strategien, wie Social Entrepreneurs Win-Win-Potentiale erschließen können, indem sie durch Bindungen unerwünschte soziale Dilemmata überwinden. Abschließend verortet der Artikel das Phänomen Social Entrepreneurship im Kontext von New Governance und diskutiert Unterschiede und Gemeinsamkeiten zum Konzept von Corporate Citizenship

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