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The need for (nearly) Zero Energy Buildings (nZEBs) in the Netherlands becomes increasingly important due to climate change, increasing energy prices, scarcity of fossil fuels and increasing geopolitical conflicts. In line with the EU EPBD, from January 2021 new buildings, including hospital and university buildings, have to fulfill more strict energy requirements. Besides that, also the energy requirements for existing buildings will become stricter to realize an energy neutral built environment by 2050. On request of the Dutch Universities (WO) and the Dutch Academic Medical Centre’s (UMC), the Netherlands Enterprise Agency (RVO) assigned Royal HaskoningDHV to study the effect of the nZEB requirements on this real estate of the sector. The feasibility of the final nZEB requirements has been assessed for eight representative, recently designed and realized university buildings. The results show that: · Compared to the provisional nZEB requirements it has become less difficult to fulfil the final nZEB requirements and sometimes even less difficult than using the former method (NEN 7120) and requirements (EPC); · Five of eight university buildings comply with all nZEB requirements and three buildings do not comply with the nZEB requirement on primary energy (BENG 2); · Effective and necessary measures in general are: good thermal isolation, energy efficient lighting with daylight and occupancy control, ventilation with heat recovery and CO2/occupancy control, Aquifer Thermal Energy Storage with Heat Pumps and local PV solar panels. Although the nZEB requirements are feasible, organizations should keep in mind that fulfilling these requirements for only their new buildings is not enough to meet the 95% CO2 emission reduction target in line with the Paris Climate agreement in 2050. A roadmap with all measures to reach this target, including the existing buildings, should prevail when making design and energy transition decisions for the campus energy infrastructure and each building., CLIMA 2022 conference, 2022: CLIMA 2022 The 14th REHVA HVAC World Congress

Serine protease cascades regulate important insect immune responses, including melanization and Toll pathway activation. In the context of melanization, central components of these cascades are clip domain serine proteases (CLIPs) including the catalytic, clip domain serine proteases (cSPs) and their non-catalytic homologs (cSPHs). Here, we define partially the structural hierarchy of An. gambiae cSPs of the CLIPB family, central players in melanization, and characterize their relative contributions to bacterial melanization and to mosquito susceptibility to bacterial infections. Using in vivo genetic analysis we show that the protease cascade branches downstream of the cSPs CLIPB4 and CLIPB17 into two branches one converging on CLIPB10 and the second on CLIPB8. We also show that the contribution of key cSPHs to melanization in vivo in response to diverse microbial challenges is more significant than any of the individual cSPs, possibly due to partial functional redundancy among the latter. Interestingly, we show that the key cSPH CLIPA8 which is essential for the efficient activation cleavage of CLIPBs in vivo is efficiently cleaved itself by several CLIPBs in vitro , suggesting that cSPs and cSPHs regulate signal amplification and propagation in melanization cascades by providing positive reinforcement upstream and downstream of each other., Competing Interests: Declaration of Competing interest The authors have no conflicts of interest to declare

Insect humoral immune responses are regulated in part by protease cascades, whose components circulate as zymogens in the hemolymph. In mosquitoes, these cascades consist of clip domain serine proteases (cSPs) and/or their non-catalytic homologs (cSPHs), which form a complex network, whose molecular make-up is not fully understood. Using a systems biology approach, based on a co-expression network of gene family members that function in melanization and co-immunoprecipitation using the serine protease inhibitor (SRPN)2, a key negative regulator of the melanization response in mosquitoes, we identify the cSP CLIPB4 from the African malaria mosquito Anopheles gambiae as a central node in this protease network. CLIPB4 is tightly co-expressed with SRPN2 and forms protein complexes with SRPN2 in the hemolymph of immune-challenged female mosquitoes. Genetic and biochemical approaches validate our network analysis and show that CLIPB4 is required for melanization and antibacterial immunity, acting as a prophenoloxidase (proPO)-activating protease, which is inhibited by SRPN2. In addition, we provide novel insight into the structural organization of the cSP network in An. gambiae, by demonstrating that CLIPB4 is able to activate proCLIPB8, a cSP upstream of the proPO-activating protease CLIPB9. These data provide the first evidence that, in mosquitoes, cSPs provide branching points in immune protease networks and deliver positive reinforcement in proPO activation cascades.