A CD123-specific chimeric antigen receptor augments anti-acute myeloid leukemia activity of Vγ9Vδ2 T cells.

Aim: To investigate whether anti-CD123 chimeric antigen receptor (CAR)-expressing Vγ9Vδ2 T cells could be an alternative for acute myeloid leukemia (AML) treatment. Materials & methods:Ex vivo expanded Vγ9Vδ2 T cells were electroporated with anti-CD123 CAR-encoding mRNA. The effector function and specificity of the modified Vγ9Vδ2 T cells were examined by in vitro cytotoxicity, degranulation and cytokine release level. The in vivo function was analyzed using the xenograft KG1-luc model with NOD-SCID-γc-/- mice. Results: The modified Vγ9Vδ2 T cells exhibited significantly improved effector activities against both AML cell lines and primary AML cells in vitro. In the xenograft mouse model, the modified Vγ9Vδ2 cells displayed an enhanced tumor control potency. Conclusion: Anti-CD123 CAR-expressing Vγ9Vδ2 T cells may serve as an alternative way to target AML.

Examining global electricity supply vulnerability to climate change using a high-fidelity hydropower dam model.

An important and plausible impact of a changing global climate is altered power generation from hydroelectric dams. Here we project 21st century global hydropower production by forcing a coupled, global hydrological and dam model with three General Circulation Model (GCM) projections run under two emissions scenarios. Dams are simulated using a detailed model that accounts for plant specifications, storage dynamics, reservoir bathymetry and realistic, optimized operations. We show that the inclusion of these features can have a non-trivial effect on the simulated response of hydropower production to changes in climate. Simulation results highlight substantial uncertainty in the direction of change in globally aggregated hydropower production (~-5 to +5% change in mean global production by the 2080s under a high emissions scenario, depending on GCM). Several clearly impacted hotspots are identified, the most prominent of which encompasses the Mediterranean countries in southern Europe, northern Africa and the Middle East. In this region, hydropower production is projected to be reduced by approximately 40% on average by the end of the century under a high emissions scenario. After accounting for each country's dependence on hydropower for meeting its current electricity demands, the Balkans countries emerge as the most vulnerable (~5-20% loss in total national electricity generation depending on country). On the flipside, a handful of countries in Scandinavia and central Asia are projected to reap a significant increase in total electrical production (~5-15%) without investing in new power generation facilities.