This paper describes the development and initial evaluation of a human cell assay to identify potentially efficacious agents for preventing melanoma. Four human cell lines were used: normal melanocytes, a radial growth-phase-like melanoma cell line (WM3211), a vertical growth-phase-like melanoma cell line (Lu1205), and 83-2c, a cell strain cloned from metastatic melanoma. Four endpoints were evaluated in ultraviolet B-treated cells: annexin V, human leukocyte antigen-DR; E-cadherin, and N-cadherin. Annexin V was induced by nimesulide, 4-hydroxyphenylretinamide, and difluoromethylornithine in ultraviolet-B-treated radial growth-phase-like melanoma cells. None of the agents inhibited human leukocyte antigen-DR expression in ultraviolet-B-treated radial growth-phase-like melanoma cells, the only cells that strongly expressed human leukocyte antigen-DR. E-cadherin was overexpressed only in radial growth-phase-like melanoma cells relative to melanocytes, and ultraviolet B exposure dramatically reduced this expression. E-cadherin was only induced by difluoromethylornithine in ultraviolet-B-treated radial growth-phase-like melanoma cells. N-cadherin was over- expressed in all melanoma cell lines relative to melanocytes. In this study, all candidate preventive agents inhibited N-cadherin in ultraviolet B-treated radial growth-phase-like melanoma cells. Four agents inhibited N-cadherin in ultraviolet B-treated vertical growth-phase-like melanoma cells. The mean ratios of N-cadherin to E-cadherin levels and specific endpoint responses for both the radial growth-phase-like melanoma and vertical growth-phase-like melanoma cells were used to rank the agents. Agents were evaluated at clinically relevant concentrations. The rankings were difluoromethylornithine>4-hydroxyphenylretinamide>nimesulide>9-cis-retinoic acid>polyphenon E. Diphenylhydramine, D-mannitol, and nordihydroguaiaretic acid were inactive. The results of these initial studies suggest that ultraviolet-B-treated radial growth-phase-like melanoma cells are the most responsive to chemopreventive agents, and may be the cell line of choice for screening melanoma prevention agents.

The second and final version of ColdADC, called ColdADC_P2, is presented. ColdADC_P2 is a 16-channel, 12-bit, 2 MS/s digitizer application-specific integrated circuit (ASIC) intended for use inside the DUNE Far Detector. ColdADC_P2 contains two 16 MS/s pipelined analog-to-digital converters (ADCs) that each digitizes the output of eight sample-and-hold amplifiers (SHAs). Because the application requires immersion in liquid argon (LAr), ColdADC_P2 was developed using specialized design techniques for long-term reliability in cryogenic environments and a customized cryogenic standard cell library. ColdADC_P2, with a die area of approximately 52.4 mm2 and fabricated in 65-nm CMOS technology, achieves 130- μ V rms noise performance and 11.8-bit effective-number-of-bits (ENOB) at a temperature of 77 K, with channel-to-channel crosstalk of < 0.06% while dissipating 338 mW (21 mW per channel). Residual nonlinearity that is consistent with dielectric absorption in the capacitors internal to the ADC is corrected using a lookup table.