Precursors to potential severe core damage accidents: 1994, a status report. Volume 22: Appendix I

Nine operational events that affected eleven commercial light-water reactors (LWRs) during 1994 and that are considered to be precursors to potential severe core damage are described. All these events had conditional probabilities of subsequent severe core damage greater than or equal to 1.0 {times} 10{sup {minus}6}. These events were identified by computer-screening the 1994 licensee event reports from commercial LWRs to identify those that could be potential precursors. Candidate precursors were then selected and evaluated in a process similar to that used in previous assessments. Selected events underwent engineering evaluation that identified, analyzed, and documented the precursors. Other events designated by the Nuclear Regulatory Commission (NRC) also underwent a similar evaluation. Finally, documented precursors were submitted for review by licensees and NRC headquarters and regional offices to ensure that the plant design and its response to the precursor were correctly characterized. This study is a continuation of earlier work, which evaluated 1969--1981 and 1984--1993 events. The report discusses the general rationale for this study, the selection and documentation of events as precursors, and the estimation of conditional probabilities of subsequent severe core damage for events. This document is bound in two volumes: Vol. 21 contains the main report and Appendices A--H; Vol. 22 contains Appendix 1

Precursors to potential severe core damage accidents: 1994, a status report. Volume 21: Main report and appendices A--H

Nine operational events that affected eleven commercial light-water reactors (LWRs) during 1994 and that are considered to be precursors to potential severe core damage are described. All these events had conditional probabilities of subsequent severe core damage greater than or equal to 1.0 {times} 10{sup {minus}6}. These events were identified by computer-screening the 1994 licensee event reports from commercial LWRs to identify those that could be potential precursors. Candidate precursors were then selected and evaluated in a process similar to that used in previous assessments. Selected events underwent engineering evaluation that identified, analyzed, and documented the precursors. Other events designated by the Nuclear Regulatory Commission (NRC) also underwent a similar evaluation. Finally, documented precursors were submitted for review by licensees and NRC headquarters and regional offices to ensure that the plant design and its response to the precursor were correctly characterized. This study is a continuation of earlier work, which evaluated 1969--1981 and 1984--1993 events. The report discusses the general rationale for this study, the selection and documentation of events as precursors, and the estimation of conditional probabilities of subsequent severe core damage for events. This document is bound in two volumes: Vol. 21 contains the main report and Appendices A--H; Vol. 22 contains Appendix 1

The First Extrasolar Planet Discovered with a New Generation High Throughput Doppler Instrument

We report the detection of the first extrasolar planet, ET-1 (HD 102195b), using the Exoplanet Tracker (ET), a new generation Doppler instrument. The planet orbits HD 102195, a young star with solar metallicity that may be part of the local association. The planet imparts radial velocity variability to the star with a semiamplitude of $63.4\pm2.0$ m s$^{-1}$ and a period of 4.11 days. The planetary minimum mass ($m \sin i$) is $0.488\pm0.015$ $M_J$.Comment: 42 pages, 11 figures and 5 tables, Accepted for publication in Ap

CDK-Mediated Regulation of Cell Functions via c-Jun Phosphorylation and AP-1 Activation

Cyclin-dependent kinases (CDKs) and their targets have been primarily associated with regulation of cell-cycle progression. Here we identify c-Jun, a transcription factor involved in the regulation of a broad spectrum of cellular functions, as a newly recognized CDK substrate. Using immune cells from mouse and human, and several complementary in vitro and in vivo approaches including dominant negative protein expression, pharmacologic inhibitors, kinase assays and CDK4 deficient cells, we demonstrate the ability of CDK4 to phosphorylate c-Jun. Additionally, the activity of AP-1, a ubiquitous transcription factor containing phosphorylated c-Jun as a subunit, was inhibited by abrogating CDK4. Surprisingly, the regulation of c-Jun phosphorylation by CDK4 occurred in non-dividing cells, indicating that this pathway is utilized for cell functions that are independent of proliferation. Our studies identify a new substrate for CDK4 and suggest a mechanism by which CDKs can regulate multiple cellular activation functions, not all of which are directly associated with cell cycle progression. These findings point to additional roles of CDKs in cell signaling and reveal potential implications for therapeutic manipulations of this kinase pathway

Comparative Analysis of Gene Regulation by the Transcription Factor PPARα between Mouse and Human

Studies in mice have shown that PPARalpha is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPARalpha in human liver. Here we set out to compare the function of PPARalpha in mouse and human hepatocytes via analysis of target gene regulation

Effect of Synthetic Dietary Triglycerides: A Novel Research Paradigm for Nutrigenomics

The effect of dietary fats on human health and disease are likely mediated by changes in gene expression. Several transcription factors have been shown to respond to fatty acids, including SREBP-1c, NF-kappaB, RXRs, LXRs, FXR, HNF4alpha, and PPARs. However, it is unclear to what extent these transcription factors play a role in gene regulation by dietary fatty acids in vivo

Inverse association of colorectal cancer prevalence to serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in a large Appalachian population

Background Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are persistent environmental contaminants that affect metabolic regulation, inflammation, and other factors implicated in the development and progression of colorectal cancer (CRC). However, the link between these compounds and CRC remains unknown. In this cross-sectional study, we investigated the association of CRC diagnosis to PFOA and PFOS blood levels in a large Appalachian population. Methods Participants were 47,359 adults ≥ 21 years of age and residing in six PFOA-contaminated water districts in the mid-Ohio Valley (N = 47,151 cancer-free adults, 208 cases of primary CRC). All participants completed a comprehensive health survey between 2005 and 2006; serum levels of PFOA, PFOS, and a range of other blood markers were also measured. Medical history was assessed via self report and cancer diagnosis confirmed via chart review. Results CRC showed a strong inverse, dose–response association with PFOS serum levels (odds ratio (OR) adjusted for potential confounders = 0.2, 95% confidence interval (CI) 0.2,0.3) for highest vs. lowest quartile of PFOS, P-trend \u3c 0.00001) and a significant, but more modest inverse association with PFOA (adjusted OR = 0.6 (CI 0.4, 0.9) for highest vs. lowest quartile, P-trend = 0.001). These inverse associations were stronger in those diagnosed within the previous 6 years and resident in the same water district for a minimum of 10–15 years preceding assessment. The relationship between PFOA and CRC was also more pronounced in men and leaner adults, and showed a stronger linear trend at lower exposure levels. Conclusions In this large cross-sectional study, we found a strong, inverse association between PFOS and likelihood of CRC diagnosis and a significant, although more modest inverse association between PFOA and CRC. If confirmed in prospective investigations, these findings may aid in identifying new strategies for CRC prevention and treatment and inform future studies regarding mechanisms underlying CRC pathogenesis

Ectopic expression of the homeobox gene Cux-1 rescues calcineurin inhibition in mouse embryonic kidney cultures

Cux-1 is a murine homeobox gene structurally related to Drosophila cut. Cux-1 is highly expressed in the nephrogenic zone of the developing kidney, where its expression coincides with cell proliferation. Cux-1 functions as a transcriptional repressor of the cyclin kinase inhibitors (CKI) p21 and p27. Cux-1 DNA binding activity is negatively regulated by phosphorylation, and dephosphorylation of Cux-1 results in increased DNA binding. Transgenic mice ectopically expressing Cux-1 develop renal hyperplasia associated with the down-regulation of the CKI p27. Calcineurin A (CnA) α (-/-) mice display renal hypoplasia associated with the ectopic expression of p27. CnA is a serine/threonine phosphatase activated by intracellular calcium. Inhibiting CnA with cyclosporin A (CsA) leads to nephron deficit in rat metanephric organ cultures and apoptosis in various renal cell lines. To determine whether the ectopic expression of p27 in CnA-α -/- kidneys results from the down-regulation of Cux-1, metanephrol from embryonic Cux-1 transgenic and wild-type mice were harvested and cultured with CsA for 5 days. CsA treatment significantly inhibited growth of wild-type metanephrol. In contrast, CsA-treated Cux-1 transgenic kidney cultures were not growth inhibited, but showed high levels of cell proliferation in the nephrogenic zone. Moreover, in CsA-treated Cux-1 transgenic kidney cultures, p27 was not expressed in the nephrogenic zone, but only up-regulated in maturing glomeruli and tubules. Taken together, our results demonstrate that ectopic expression of Cux-1 can rescue the effects of CsA inhibition of CnA and suggest that Cux-1 may be regulated by calcineurin A. © 2006 Wiley-Liss, Inc

Peer groups and operational cycle enhancements to the performance indicator report

Accurate performance evaluation and plant trending by the performance indicator program are integral parts of monitoring the operation of commercial nuclear power plants. The presentations of the NRC/AEOD performance indicator program have undergone a number of enhancements. The diversity of the commercial nuclear plants, coupled with continued improvements in the performance indicator program, has resulted in the evaluation of plants in logical peer groups and highlighted the need to evaluate the impact of plant operational conditions on the performance indicators. These enhancements allow a more-meaningful evaluation of operating commercial nuclear power plant performance. This report proposes methods to enhance the presentation of the performance indicator data by analyzing the data in logical peer groups and displaying the performance indicator data based on the operational status of the plants. Previously, preliminary development of the operational cycle displays of the performance indicator data was documented. This report extends the earlier findings and presents the continued development of the peer groups and operational cycle trend and deviation data and displays. This report describes the peer groups and enhanced PI data presentations by considering the operational cycle phase breakdowns, calculation methods, and presentation methods