Modeling, Simulation, and Experiments of Coating Growth on Nanofibers

This work is a comparison of modeling and simulation results with experiments for an integrated experimental/modeling investigation of a procedure to coat nanofibers and core-clad nanostructures with thin film materials using plasma enhanced physical vapor deposition. In the experimental effort, electrospun polymer nanofibers are coated with metallic materials under different operating conditions to observe changes in the coating morphology. The modeling effort focuses on linking simple models at the reactor level, nanofiber level and atomic level to form a comprehensive model. The comprehensive model leads to the definition of an evolution equation for the coating free surface around an isolated nanofiber. This evolution equation was previously derived and solved under conditions of a nearly circular coating, with a concentration field that was only radially dependent and that was independent of the location of the coating free surface. These assumptions permitted the development of analytical expressions for the concentration field. The present work does not impose the above-mentioned conditions and considers numerical simulations of the concentration field that couple with level set simulations of the evolution equation for the coating free surface. Further, the cases of coating an isolated fiber as well as a multiple fiber mat are considered. Simulation results are compared with experimental results as the reactor pressure and power, as well as the nanofiber mat porosity, are varied. (C) 2008 American Institute of Physics

HdmX overexpression inhibits oncogene induced cellular senescence

Cellular senescence is an irreversible state of terminal growth arrest that requires functional p53. Acting to block tumor formation, induction of senescence has also been demonstrated to contribute to tumor clearance via the immune system following p53 reactivation.1,2 the Hdm2-antagonist, Nutlin-3a, has been shown to reactivate p53 and induce a quiescent state in various cancer cell lines,3,4 similar to the G1 arrest observed upon RNAi targeting of Hdm2 in MCF7 breast cancer.5 In the present study we show that HdmX, a negative regulator of p53, impacts the senescence pathway. Specifically, overexpression of HdmX blocks Ras mediated senescence in primary human fibroblasts. the interaction of HdmX with p53 and the re-localization of HdmX to the nucleus through Hdm2 association appear to be required for this activity. Furthermore, inhibiting HdmX in prostate adenocarcinoma cells expressing wild-type p53, mutant Ras and high levels of HdmX-induced cellular senescence as measured by an increase in irreversible β-galactosidase staining. Together these results suggest that HdmX overexpression may contribute to tumor formation by blocking senescence and that targeting HdmX may represent an attractive anti-cancer therapeutic approach

Cisplatin and siRNA interference with structure and function of Wnt-5a mRNA: design and in vitro evaluation of targeting AU-rich elements in the 3' UTR.

Wnt-5a is a secreted glycoprotein which has been shown to be involved in the regulation of cell adhesion and motility, processes which are of importance in metastasis formation by cancer cells. We here present an initial study aiming at evaluating whether small interfering RNA (siRNA) in combination with cisplatin can be used to modulate protein expression levels under in vitro conditions. For this purpose, an AU-rich region corresponding to the initial 260 bases of the Wnt-5a 3' untranslated region was chosen as the target. The effect of four different siRNAs was evaluated by analysis of protein suppression levels in rabbit reticulocyte lysate (RRL) and an immortalized noncancerous mammary epithelial (HB2) cell line by monitoring the activity of transiently expressed luciferase. The specificity and kinetics for hybridization of the siRNA with the messenger RNA target were followed by digestion techniques and analysis by polyacrylamide gel electrophoresis. Specific and temperature-dependent hybridization was observed, with a half-life of approximately 0.5 h at 4 degrees C. Significant downregulation of luciferase activity was obtained in the micromolar and nanomolar range, for RRL and HB2, respectively. In addition, the downregulation of protein production caused by addition of cisplatin could be further potentiated by addition of siRNA in a selective manner. The latter observation suggests that combined use of cisplatin and siRNA could be a method to decrease therapeutically used cisplatin concentrations. Thus, toxic side effects could be minimized while key proteins are targeted in a highly specific manner