PAX2 Regulates ADAM10 Expression and Mediates Anchorage-Independent Cell Growth of Melanoma Cells

PAX transcription factors play an important role during development and carcinogenesis. In this study, we investigated PAX2 protein levels in melanocytes and melanoma cells by Western Blot and immunofluorescence analysis and characterized the role of PAX2 in the pathogenesis of melanoma. In vitro we found weak PAX2 protein expression in keratinocytes and melanocytes. Compared to melanocytes increased PAX2 protein levels were detectable in melanoma cell lines. Interestingly, in tissue sections of melanoma patients nuclear PAX2 expression strongly correlated with nuclear atypia and the degree of prominent nucleoli, indicating an association of PAX2 with a more atypical cellular phenotype. In addition, with chromatin immunoprecipitation assay, PAX2 overexpression and PAX2 siRNA we present compelling evidence that PAX2 can regulate ADAM10 expression, a metalloproteinase known to play important roles in melanoma metastasis. In human tissue samples we found co-expression of PAX2 and ADAM10 in melanocytes of benign nevi and in melanoma cells of patients with malignant melanoma. Importantly, the downregulation of PAX2 by specific siRNA inhibited the anchorage independent cell growth and decreased the migratory and invasive capacity of melanoma cells. Furthermore, the downregulation of PAX2 abrogated the chemoresistance of melanoma cells against cisplatin, indicating that PAX2 expression mediates cell survival and plays important roles during melanoma progression

Long-term safety issues associated with mixer pump operation

In this report, we examine several long-term issues: the effect of pump operation on future gas release events (GREs), uncontrolled chemical reactions, chronic toxic gas releases, foaming, and erosion and corrosion. Heat load in excess of the design limit, uncontrolled chemical reactions, chronic toxic gas releases, foaming, and erosion and corrosion have been shown not to be safety concerns. The effect of pump operation on future GREs could not be quantified. The problem with evaluating the long-term effects of pump operation on GREs is a lack of knowledge and uncertainty. In particular, the phenomena governing gas retention, particle size distribution, and settling are not well understood, nor are the interactions among these factors understood. There is a possibility that changes in these factors could increase the size of future GREs. Bounding estimates of the potential increase in size of GREs are not possible because of a lack of engineering data. Proper management of the hazards can reduce, but not eliminate, the possibility of undesirable changes. Maintaining temperature within the historical limits can reduce the possibility of undesirable changes. A monitoring program to detect changes in the gas composition and crust thickness will help detect slowly occurring changes. Because pump operation has be shown to eliminate GREs, continued pump operation can eliminate the hazards associated with future GREs

Data reconcilation study of Tank 241-AN-105 at the Hanford Site

The Project Hanford Management Contractor gave the Los Alamos National Laboratory Nuclear Systems Design and Analysis Group (TSA-10) the task of performing data reconciliation studies on flammable-gas watchlist tanks at the Hanford Site. This task is being performed in support of the flammable-gas programs at the Hanford Site and for closure of the flammable-gas unreviewed safety question. In our data reconciliation studies, we examine all available data from a global point of view. Our goal is to find an explanation, or conceptual model, of the tank behavior that is consistent with all available data. Our primary tool in this study of Tank 241-AN-105 is the maximum likelihood method of data reconciliation, which we have applied successfully to other tanks in the past. This method helps us (1) determine whether a model is consistent with the data, and (2) obtain quantitative estimates that are consistent with the data. A release of a flammable quantity of hydrogen in Tank 241-AN-105 is possible but unlikely at the current time. Any changes to the waste that could cause large releases would be accompanied by a measurable increase in the surface level of the waste. We also theorize that a significant increase in the waste temperature may signal a qualitative change in the behavior of the waste and an increase in the flammability hazard