In the aftermath of thymic negative selection, natural and adaptive regulatory T cells (Tregs) must acknowledge peripheral, “danger-free” self-Ag to ensure their sustained activity. In this paper, we show that natural and adaptive Tregs or T cells transduced with cDNA for Foxp3, just like Th1 cells, express members of the MS4A family of transmembrane molecules. Naive T cells transduced with MS4A4B become able to respond to lower levels of Ag. Using two family members, MS4A4B and MS4A6B, as baits in a yeast split-ubiquitin Treg library screen, we demonstrate their interaction with each other and with GITR, Orai1, and other surface receptors. Interaction of 4B with GITR augments GITR signaling and T cell IL-2 production in response to triggering with GITR ligand or anti-GITR Abs. This interaction provides a mechanism whereby MS4A family members, through lateral coassociation with costimulatory molecules, may amplify Ag signals. We propose that T cells preoccupied with immune defense use this MS4A family to enhance sensitivity to extrinsic Ag stimulation, ensuring its elimination, while Tregs use these adaptors to allow low level Ag signals to sustain regulatory function.
The novel coronavirus SARS-CoV2 emerged in December 2019 and is now pandemic. Initial analysis suggests that 5% of infected patients will require critical care, and that respiratory failure requiring intubation is associated with high mortality.Sick patients are geographically dispersed: most patients will remain in situ until they are in need of critical care. Additionally, there are likely to be patients who require retrieval for other reasons but who are co-incidentally infected with SARS-CoV-2 or shedding virus.The COVID-19 pandemic therefore poses a challenge to critical care retrieval systems, which often depend on small teams of specialists who live and work together closely. The infection or quarantining of a small absolute number of these staff could catastrophically compromise service delivery.Avoiding occupational exposure to COVID-19, and thereby ensuring service continuity, is the primary objective of aeromedical retrieval services during the pandemic. In this discussion paper we collaborated with helicopter emergency medical services(HEMS) worldwide to identify risks in retrieving COVID-19 patients, and develop strategies to mitigate these.Simulation involving the whole aeromedical retrieval team ensures that safety concerns can be addressed during the development of a standard operating procedure. Some services tested personal protective equipment and protocols in the aeromedical environment with simulation. We also incorporated experiences, standard operating procedures and approaches across several HEMS services internationally.As a result of this collaboration, we outline an approach to the safe aeromedical retrieval of a COVID-19 patient, and describe how this framework can be used to develop a local standard operating procedure.
The Sugar Creek Wind Project is a 57-turbine wind farm in Logan County, Illinois, with a capacity of up to 202 megawatts. Preconstruction sound modeling of the final Project layout was conducted in July 2019. Following construction of the Project, postconstruction attended sound measurements were made at 38 sites in the vicinity of Project turbines in September, October, and November 2021. Measured postconstruction sound levels were compared to the octave band sound level limits applicable under the Project’s Conditional Use Permit. A comparison of the modeled and background-adjusted measured octave band sound levels for the Project indicate that with the proper modeling parameters, octave band sound levels can be conservatively predicted.
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