INVESTIGATION BY MASS SPECTROMETRY OF THE UBIQUITOME AND PROTEIN CARGO OF EXOSOMES DERIVED FROM MYELOID-DERIVED SUPPRESSOR CELLS

Exosomes released by myeloid-derived suppressor cells (MDSC) are 30 nm in diameter extracellular vesicles that have been shown to carry biologically active proteins as well as ubiquitin molecules. Ubiquitin is known to have many functions, including involvement in the formation of exosomes, although the exact role is highly contested. In the study reported here, the proteome and ubiquitome of MDSC exosomes has been investigated by bottom-up proteomics techniques. This report identifies more than 1000 proteins contained in the MDSC exosome cargo and 489 sites of ubiquitination in more than 300 ubiquitinated proteins based on recognition of glycinylglycine tagged peptides without antibody enrichment. This has allowed extensive chemical and biological characterization of the ubiquitinated cohort compared to that of the entire protein cargo to support hypotheses on the role of ubiquitin in exosomes.

MULTI-UNIT ACCIDENT CONTRIBUTIONS TO U.S. NUCLEAR REGULATORY COMMISSION QUANTITATIVE HEALTH OBJECTIVES: A SAFETY GOAL POLICY ANALYSIS USING MODELS FROM STATE-OF-THE-ART REACTOR CONSEQUENCE ANALYSES

The U.S. Nuclear Regulatory Commission implemented a safety goal policy in response to the 1979 Three Mile Island accident. This policy addresses the question “How safe is safe enough?” by specifying quantitative health objectives (QHOs) for comparison with results from nuclear power plant (NPP) probabilistic risk analyses (PRAs) to determine whether proposed regulatory actions are justified based on potential safety benefit. Lessons learned from recent operating experience—including the 2011 Fukushima accident—indicate that accidents involving multiple units at a shared site can occur with non-negligible frequency. Yet risk contributions from such scenarios are excluded by policy from safety goal evaluations—even for the nearly 60% of U.S. NPP sites that include multiple units. This research develops and applies methods for estimating risk metrics for comparison with safety goal QHOs using models from state-of-the-art consequence analyses to evaluate the effect of including multi-unit accident risk contributions in safety goal evaluations.