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Silver, A.

Publications and source records attributed to Silver, A..

Elevated breast cancer risk in irradiated BALB/c mice associates with unique functional polymorphism of the Prkdc (DNA-dependent protein kinase catalytic subunit) gene

Female BALB/c mice are unusually radiosensitive and more susceptible than C57BL/6 and other tested inbred mice to ionizing radiation (IR)-induced mammary tumors. This breast cancer susceptibility is correlated with elevated susceptibility for mammary cell transformation and genomic instability following irradiation. In this study, we report the identification of two BALB/c strain-specific polymorphisms in the coding region of Prkdc, the gene encoding the DNA-dependent protein kinase catalytic subunit, which is known to be involved in DNA double-stranded break repair and post-IR signal transduction. First, we identified an A --> G transition at base 11530 resulting in a Met --> Val conversion at codon 3844 (M3844V) in the phosphatidylinositol 3-kinase domain upstream of the scid mutation (Y4046X). Second, we identified a C --> T transition at base 6418 resulting in an Arg --> Cys conversion at codon 2140 (R2140C) downstream of the putative leucine zipper domain. This unique PrkdcBALB variant gene is shown to be associated with decreased DNA-dependent protein kinase catalytic subunit activity and with increased susceptibility to IR-induced genomic instability in primary mammary epithelial cells. The data provide the first evidence that naturally arising allelic variation in a mouse DNA damage response gene may associate with IR response and breast cancer risk.

Non-NASA Center

A deficiency in DNA repair and DNA-PKcs expression in the radiosensitive BALB/c mouse

We have studied the efficiency of DNA double strand break (DSB) rejoining in primary cells from mouse strains that show large differences in in vivo radiosensitivity and tumor susceptibility. Cells from radiosensitive, cancer-prone BALB/c mice showed inefficient end joining of gamma ray-induced DSBs as compared with cells from all of the other commonly used strains and F1 hybrids of C57BL/6 and BALB/c mice. The BALB/c repair phenotype was accompanied by a significantly reduced expression level of DNA-PKcs protein as well as a lowered DNA-PK activity level as compared with the other strains. In conjunction with published reports, these data suggest that natural genetic variation in nonhomologous end joining processes may have a significant impact on the in vivo radiation response of mice.

Non-NASA Center

Report of the sensor readout electronics panel

The findings of the Sensor Readout Electronics Panel are summarized in regard to technology assessment and recommended development plans. In addition to two specific readout issues, cryogenic readouts and sub-electron noise, the panel considered three advanced technology areas that impact the ability to achieve large format sensor arrays. These are mega-pixel focal plane packaging issues, focal plane to data processing module interfaces, and event driven readout architectures. Development in each of these five areas was judged to have significant impact in enabling the sensor performance desired for the Astrotech 21 mission set. Other readout issues, such as focal plane signal processing or other high volume data acquisition applications important for Eos-type mapping, were determined not to be relevant for astrophysics science goals.

Fossum, Eric R.

Photoionization of lithium

The photoionization of lithium from threshold to 50 eV above threshold is calculated using the method of polarized orbitals. The method is applied in as orthodox a manner as possible; this means that total wave functions are constructed as by Temkin and Lamkin (1961) using only the static dipole part of the perturbation of core electrons by the outer part of the external electron. According to other previously given prescriptions, both initial (bound) and final (continuum) wave functions are so polarized, only the length form of the matrix is calculated, and bilinear terms from the polarization contributions are retained (although their effect in this calculation is small). The results themselves are essentially identical to those of a recent diagrammatic calculation of Chang and Poe (1975) (in the region below 5 eV where thay have calculated), and as such they differ in certain significant components from exchange-adiabatic and extended-polarization results of Matese and LaBahn (1969) (although their overall result is similar). The s- and p-wave e-Li(+) phase shifts, which are derived as by-products of this calculation, are also presented and compared with other phase-shift calculations.

Bhatia, A. K.