A Greenhouse-Gas Information System: Monitoring and Validating Emissions Reporting and Mitigation

This study and report focus on attributes of a greenhouse-gas information system (GHGIS) needed to support MRV&V needs. These needs set the function of such a system apart from scientific/research monitoring of GHGs and carbon-cycle systems, and include (not exclusively): the need for a GHGIS that is operational, as required for decision-support; the need for a system that meets specifications derived from imposed requirements; the need for rigorous calibration, verification, and validation (CV&V) standards, processes, and records for all measurement and modeling/data-inversion data; the need to develop and adopt an uncertainty-quantification (UQ) regimen for all measurement and modeling data; and the requirement that GHGIS products can be subjected to third-party questioning and scientific scrutiny. This report examines and assesses presently available capabilities that could contribute to a future GHGIS. These capabilities include sensors and measurement technologies; data analysis and data uncertainty quantification (UQ) practices and methods; and model-based data-inversion practices, methods, and their associated UQ. The report further examines the need for traceable calibration, verification, and validation processes and attached metadata; differences between present science-/research-oriented needs and those that would be required for an operational GHGIS; the development, operation, and maintenance of a GHGIS missions-operations center (GMOC); and the complex systems engineering and integration that would be required to develop, operate, and evolve a future GHGIS

Rational steering of insulin binding specificity by intra-chain chemical crosslinking

Insulin is a key hormone of human metabolism with major therapeutic importance for both types of diabetes. New insulin analogues with more physiological profiles and better glycemic control are needed, especially analogues that preferentially bind to the metabolic B-isoform of insulin receptor (IR-B). Here, we aimed to stabilize and modulate the receptor-compatible conformation of insulin by covalent intra-chain crosslinking within its B22-B30 segment, using the Cu I -catalyzed Huisgen 1,3-dipolar cycloaddition reaction of azides and alkynes. This approach resulted in 14 new, systematically crosslinked insulin analogues whose structures and functions were extensively characterized and correlated. One of the analogues, containing a B26-B29 triazole bridge, was highly active in binding to both IR isoforms, with a significant preference for IR-B. Our results demonstrate the potential of chemistry-driven modulation of insulin function, also shedding new light on the functional importance of hormones B-chain C-terminus for its IR-B specificity