Comparison of the Current Center of Site Annual Neshap Dose Modeling at the Savannah River Site with Other Assessment Methods.

The U.S. Environmental Protection Agency (EPA) requires the use of the model CAP88 to estimate the total effective dose (TED) to an offsite maximally exposed individual (MEI) for demonstrating compliance with 40 CFR 61, Subpart H: The National Emission Standards for Hazardous Air Pollutants (NESHAP) regulations. For NESHAP compliance at the Savannah River Site (SRS), the EPA, the U.S. Department of Energy (DOE), South Carolina's Department of Health and Environmental Control, and SRS approved a dose assessment method in 1991 that models all radiological emissions as if originating from a generalized center of site (COS) location at two allowable stack heights (0 m and 61 m). However, due to changes in SRS missions, radiological emissions are no longer evenly distributed about the COS. An area-specific simulation of the 2015 SRS radiological airborne emissions was conducted to compare to the current COS method. The results produced a slightly higher dose estimate (2.97 × 10 mSv vs. 2.22 × 10 mSv), marginally changed the overall MEI location, and noted that H-Area tritium emissions dominated the dose. Thus, an H-Area dose model was executed as a potential simplification of the area-specific simulation by adopting the COS methodology and modeling all site emissions from a single location in H-Area using six stack heights that reference stacks specific to the tritium production facilities within H-Area. This "H-Area Tritium Stacks" method produced a small increase in TED estimates (3.03 × 10 mSv vs. 2.97 × 10 mSv) when compared to the area-specific simulation. This suggests that the current COS method is still appropriate for demonstrating compliance with NESHAP regulations but that changing to the H-Area Tritium Stacks assessment method may now be a more appropriate representation of operations at SRS.

Dose Comparisons for a Site-specific Representative Person Using the Age-dependent Dose Coefficients in CAP88-PC Version 4.

Most U.S. Department of Energy (DOE) facilities with radiological airborne releases use the U.S. Environmental Protection Agency's (EPA) environmental dosimetry code CAP88-PC to demonstrate compliance with regulations in 40CFR61, subpart H [National Emission Standards for Hazardous Air Pollutants: Radiological (NESHAP)]. In 2015, EPA released Version 4 of CAP88-PC, which included significant modifications that improved usability and age-dependent dose coefficients and usage factors for six age groups (infant, 1 y, 5 y, 10 y, 15 y, and adult). However, EPA has not yet provided specific guidance on how to use these age-dependent factors. For demonstrating compliance with DOE public dose regulations, the Savannah River Site (SRS) recently changed from using the maximally exposed individual (MEI) concept (adult male) to the representative person concept (age- and gender-averaged reference person). In this study, dose comparisons are provided between the MEI and a SRS-specific representative person using the age-specific dose coefficients and usage factors in CAP88-PC V.4. Dose comparisons also are provided for each of the six age groups using five radionuclides of interest at SRS (tritium oxide, Cs, Sr, Pu, and I). In general, the total effective dose increases about 11% for the representative person as compared to the current NESHAP MEI because of the inclusion of the more radiosensitive age groups.

Hsp90 inhibition suppresses NF-κB transcriptional activation via Sirt-2 in human lung microvascular endothelial cells.

The ability of anti-heat shock protein 90 (Hsp90) drugs to attenuate NF-κB-mediated transcription is the major basis for their anti-inflammatory properties. While the molecular mechanisms underlying this effect are not clear, they appear to be distinct in human endothelial cells. We now show for the first time that type 2 sirtuin (Sirt-2) histone deacetylase binds human NF-κB target gene promoter and prevents the recruitment of NF-κB proteins and subsequent assembly of RNA polymerase II complex in human lung microvascular endothelial cells. Hsp90 inhibitors stabilize the Sirt-2/promoter interaction and impose a "transcriptional block," which is reversed by either inhibition or downregulation of Sirt-2 protein expression. Furthermore, this process is independent of NF-κB (p65) Lysine 310 deacetylation, suggesting that it is distinct from known Sirt-2-dependent mechanisms. We demonstrate that Sirt-2 is recruited to NF-κB target gene promoter via interaction with core histones. Upon inflammatory challenge, chromatin remodeling and core histone H3 displacement from the promoter region removes Sirt-2 and allows NF-κB/coactivator recruitment essential for RNA Pol II-dependent mRNA induction. This novel mechanism may have important implications in pulmonary inflammation.