Faculty Bibliography

There are about 75,000 pedestrian crashes in the United States each year. Approximately 5000 of these crashes are fatal, accounting for 12% of all roadway deaths. On college campuses, pedestrian exposure and crash-risk can be quite high. Therefore, we analyzed pedestrian crashes on the campus of the University of North Carolina at Chapel Hill (UNC) as a test case for our spatially-oriented prototype tool that combines perceived-risk (survey) data with police-reported crash data to obtain a more complete picture of pedestrian crash-risk. We use spatial analysis techniques combined with regression models to understand factors associated with risk. The spatial analysis is based on comparing two distributions, i.e. the locations of perceived-risk with police-reported crash locations. The differences between the two distributions are statistically significant, implying that certain locations on campus are perceived as dangerous, though pedestrian crashes have not yet occurred there, and there are actual locations of police-reported crashes that are not perceived to be dangerous by pedestrians or drivers. Furthermore, we estimate negative binomial regression models to combine pedestrian and automobile exposure with roadway characteristics and spatial/land use information. The models show that high exposure, incomplete sidewalks and high crosswalk density are associated with greater observed and perceived pedestrian crash-risk. Additionally, we found that people perceive a lower risk near university libraries, stadiums, and academic buildings, despite the occurrence of crashes.

The timing of the terrible events of September 11, 2001 (9-11), and an ongoing randomized clinical trial of case monitoring have allowed a prospective examination of the effects of trauma upon the relapse rates of a group of clients following alcohol detoxification. The clients studied in this report were enrolled in case monitoring prior to 9-11. Case monitoring consists of telephone contacts on a tapering schedule designed to help clients avoid relapses, reduce the severity of relapses that do occur, and get clients back into treatment, at less intense levels, than would occur without case monitoring. For those clients completing a telephone contact before and a telephone contact after 9-11, none of the clients drank between detox discharge and 9-11, while 42% drank by the first telephone contact after 9-11. Data from another study were analyzed and results counter the rival hypothesis that the case monitoring study results reflect an annual seasonal effect. Results suggest that terrorist events may lead to a greater likelihood of relapse for those in alcohol recovery. These effects may be ameliorated by public education and outreach.

Hepatitis B virus (HBV) infects more than 300 million people and is a leading cause of liver cancer and disease. The HBV HBx protein is essential for infection; HBx activation of Src is important for HBV DNA replication. In our study, HBx activated cytosolic calcium-dependent proline-rich tyrosine kinase-2 (Pyk2), a Src kinase activator. HBx activation of HBV DNA replication was blocked by inhibiting Pyk2 or calcium signaling mediated by mitochondrial calcium channels, which suggests that HBx targets mitochondrial calcium regulation. Reagents that increased cytosolic calcium substituted for HBx protein in HBV DNA replication. Thus, alteration of cytosolic calcium was a fundamental requirement for HBV replication and was mediated by HBx protein

Numerous studies have demonstrated that the hepatitis B virus HBx protein stimulates signal transduction pathways and may bind to certain transcription factors, particularly the cyclic AMP response element binding protein, CREB. HBx has also been shown to promote early cell cycle progression, possibly by functionally replacing the TATA-binding protein-associated factor 250 (TAF(II)250), a transcriptional coactivator, and/or by stimulating cytoplasmic signal transduction pathways. To understand the basis for early cell cycle progression mediated by HBx, we characterized the molecular mechanism by which HBx promotes deregulation of the G(0) and G(1) cell cycle checkpoints in growth-arrested cells. We demonstrate that TAF(II)250 is absolutely required for HBx activation of the cyclin A promoter and for promotion of early cell cycle transit from G(0) through G(1). Thus, HBx does not functionally replace TAF(II)250 for transcriptional activity or for cell cycle progression, in contrast to a previous report. Instead, HBx is shown to activate the cyclin A promoter, induce cyclin A-cyclin-dependent kinase 2 complexes, and promote cycling of growth-arrested cells into G(1) through a pathway involving activation of Src tyrosine kinases. HBx stimulation of Src kinases and cyclin gene expression was found to force growth-arrested cells to transit through G(1) but to stall at the junction with S phase, which may be important for viral replication

The AU-rich element (AUUUA)n, found in the 3' noncoding region of many short-lived cytokine and proto-oncogene mRNAs, is sufficient to specifically target these mRNAs for rapid degradation in mammalian cells. The mechanism by which the AU-rich element promotes rapid mRNA decay is not known. Previous studies have shown that release of intracellular stored calcium by ionophore treatment of thymocytes and mast cells inhibits the rapid turnover of AU-rich interleukin mRNAs. Increased cytoplasmic half-life of interleukin mRNAs was linked to calcium-induced activation of the N-terminal c-Jun kinase. In this report we have characterized the calcium-induced stabilization of AU-rich mRNAs. We show that calcium induces stabilization of mRNAs with canonical AU-rich elements in all cell types tested. These results indicate that short-lived mRNA stabilization by calcium is not unique to immune cells nor interleukin mRNAs, but is a widespread default response that includes generic AU-rich mRNAs. Stabilization is shown to be rapid but transient, and to act without altering nuclear transcription or cytoplasmic translation rates. These data support the view that calcium release likely stabilizes short-lived mRNAs by altering trans-acting decay factors that promote AU-rich mRNA turnover