License renewal demonstration program: NRC observations and lessons learned

This report summarizes the Nuclear Regulatory Commission staff`s observations and lessons learned from the five License Renewal Demonstration Program (LRDP) site visits performed by the staff from March 25, 1996, through August 16, 1996. The LRDP was a Nuclear Energy Institute (NEI) program intended to assess the effectiveness of the guidance provided by NEI 95-10, Revision 0, {open_quotes}Industry Guideline for Implementing the Requirements of 10 CFR Part 54 - The License Renewal Rule,{close_quotes} to implement the requirements of Title 10 of the Code of Federal Regulations, Part 54 (10 CFR Part 54), {open_quotes}Requirements for Renewal of Operating Licenses for Nuclear Power Plants.{close_quotes} In general, NEI 95-10 appeared to contain the basic guidance needed for scoping, screening, identifying aging effects, developing aging management programs, and performing time-limited aging analyses. However, inconsistent implementation of this guidance in some areas was an indication that clarification of existing guidance and/or the inclusion-of some new guidance may be needed for applicants to develop a license renewal program that is consistent with the intent of the rule

Genome Characterization of a Novel Wastewater Bacteroides fragilis Bacteriophage (vB_BfrS_23) and its Host GB124

Bacteroides spp. are part of the human intestinal microbiota but can under some circumstances become clinical pathogens. Phages are a potentially valuable therapeutic treatment option for many pathogens, but phage therapy for pathogenic Bacteroides spp. including Bacteroides fragilis is currently limited to three genome-sequenced phages. Here we describe the isolation from sewage wastewater and genome of a lytic phage, vB_BfrS_23, that infects and kills B. fragilis strain GB124. Transmission electron microscopy identified this phage as a member of the Siphoviridae family. The phage is stable when held at temperatures of 4 and 60°C for 1 h. It has a very narrow host range, only infecting one host from a panel of B. fragilis strains (n = 8). Whole-genome sequence analyses of vB_BfrS_23 determined it is double-stranded DNA phage and is circularly permuted, with a genome of 48,011 bp. The genome encodes 73 putative open reading frames. We also sequenced the host bacterium, B. fragilis GB124 (5.1 Mb), which has two plasmids of 43,923 and 4,138 bp. Although this phage is host specific, its isolation together with the detailed characterization of the host B. fragilis GB124 featured in this study represent a useful starting point from which to facilitate the future development of highly specific therapeutic agents. Furthermore, the phage could be a novel tool in determining water (and water reuse) treatment efficacy, and for identifying human fecal transmission pathways within contaminated environmental waters and foodstuffs

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn's disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.Cellular mechanisms in basic and clinical gastroenterology and hepatolog