institutional innovation from the bottom up?

A sustainable economy fulfills societal needs in a fundamentally different way to the current economic system. Improvements to the efficiency of existing technologies or practices appear insufficient for achieving sustainable development within the planetary boundaries. Disruptive, systemic and transformational changes appear necessary in order to replace existing technologies and practices to establish a sustainable economy. Such innovations often start out in niches; however, the scaling up and the ultimate replacement of current socio-technical systems requires governance to allow for the coordination of actors, the reorganization of socio-technical systems and the mobilization and allocation of resources. As governmental institutions are part of the current (non-sustainable) systems and thereby fail to provide coherent, integrated and transformative governance, we explore whether institutional innovation from non-state actors can step in to provide governance of transformation processes. Based on explorative qualitative case studies of networks in the food sector, city planning and reporting tools, we analyze the potential of bottom-up institutional innovations to coordinate actors in transformation processes

Wireless Neurosensor for Full-Spectrum Electrophysiology Recordings during Free Behavior

SummaryBrain recordings in large animal models and humans typically rely on a tethered connection, which has restricted the spectrum of accessible experimental and clinical applications. To overcome this limitation, we have engineered a compact, lightweight, high data rate wireless neurosensor capable of recording the full spectrum of electrophysiological signals from the cortex of mobile subjects. The wireless communication system exploits a spatially distributed network of synchronized receivers that is scalable to hundreds of channels and vast environments. To demonstrate the versatility of our wireless neurosensor, we monitored cortical neuron populations in freely behaving nonhuman primates during natural locomotion and sleep-wake transitions in ecologically equivalent settings. The interface is electrically safe and compatible with the majority of existing neural probes, which may support previously inaccessible experimental and clinical research

Measurements of ψ(2S) and X(3872) → J/ψπ+π− production in pp collisions at √s=8 TeV with the ATLAS detector

Differential cross sections are presented for the prompt and non-prompt production of the hidden-charm states X(3872) and ψ(2S), in the decay mode J/ψπ+π−, measured using 11.4 fb−1 of pp collisions at √s=8 TeV by the ATLAS detector at the LHC. The ratio of cross-sections X(3872)/ψ(2S) is also given, separately for prompt and non-prompt components, as well as the non-prompt fractions of X(3872) and ψ(2S). Assuming independent single effective lifetimes for non-prompt X(3872) and ψ(2S) production gives RB=B(B→X(3872)+any)B(X(3872)→J/ψπ+π−)B(B→ψ(2S)+any)B(ψ(2S)→J/ψπ+π−)=(3.95±0.32(stat)±0.08(sys))×10−2RB=B(B→X(3872)+any)B(X(3872)→J/ψπ+π−)B(B→ψ(2S)+any)B(ψ(2S)→J/ψπ+π−)=(3.95±0.32(stat)±0.08(sys))×10−2 separating short- and long-lived contributions, assuming that the short-lived component is due to Bc decays, gives RB = (3.57 ± 0.33(stat) ± 0.11(sys)) × 10−2, with the fraction of non-prompt X(3872) produced via Bc decays for pT(X(3872)) > 10 GeV being (25 ± 13(stat) ± 2(sys) ± 5(spin))%. The distributions of the dipion invariant mass in the X(3872) and ψ(2S) decays are also measured and compared to theoretical predictions

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