Relative biological effectiveness (RBE) of 210 Po alpha-particles versus X-rays on lethality in bovine endothelial cells

Purpose : Alpha-radiation from polonium-210 (210 Po) can elevate background radiation dose by an order of magnitude in people consuming large quantities of meat and seafood, particularly caribou and reindeer. Because up to 50% of the ingested 210 Po body burden is initially found in the blood, a primary target for the short range alpha-particles is the endothelial cells lining the blood vessels. This study examined the relative biological effectiveness (RBE) of 210 Po alpha-particles versus 250 kVp X-rays in producing injury to cultured bovine aortic endothelial cells. Materials and methods : Radiation effects on cells were measured in four different ways: the percentage viable cells by trypan blue dye exclusion, the number of live cells, the lactate dehydrogenase (LDH) release to medium and the ability to form colonies (clonogenic survival). Results : Comparison of dose-response curves yielded RBE values of 13.1 ±2.5 (SEM) for cell viability, 10.3 ±1.0 for live cell number and 11.1 ±3.0 for LDH activity. The RBE values for clonogenic survival were 14.0 ±1.0 based on the ratio of the initial slopes of the dose-response curves and 13.1, 9.9 and 7.7 for 50, 10 and 1% survival rate, respectively. At X-ray doses <0.25 Gy, a pronounced stimulatory effect on proliferation was noted. Conclusions : Exposure to 210 Po alpha-particles was seven to 14 times more effective than X-ray exposure in causing endothelial cell damage.     

Sampling Patients within Physician Practices and Health Plans: Multistage Cluster Samples in Health Services Research

Objective. To better inform study design decisions when sampling patients within health plans and physician practices with multiple analysis goals.
Study Setting. Chronic eye care patients within six health plans across the United States.
Study Design. We developed a simulation-based approach for designing multistage samples. We created a range of candidate designs, evaluated them with respect to multiple sampling goals, investigated their tradeoffs, and identified the design that is the best compromise among all goals. This approach recognizes that most data collection efforts have multiple competing goals.
Data Collection. We constructed a sample frame from all diabetic patients in six health plans with evidence of chronic eye disease (glaucoma and retinopathy).
Principal Findings. Simulations of different study designs can uncover efficiency gains as well as inform potential tradeoffs among study goals. Simulations enable us to quantify these efficiency gains and to draw tradeoff curves.
Conclusions. When designing a complex multistage sample it is desirable to explore the tradeoffs between competing sampling goals via simulation. Simulations enable us to investigate a larger number of candidate designs and are therefore likely to identify more efficient designs.     

Molecular rulers for measuring RNA structure: sites of crosslinking in chlorambucilyl-phenylalanyl-tRNAPhe (yeast) and chlorambucilyl-pentadecaprolyl-phenylalanyl-tRNAPhe (yeast) intramolecularly crosslinked in aqueous solution.

Intramolecular crosslinking of yeast phenylalanine tRNA in aqueous solution with rigid, variable-length crosslinking reagents, which we call "molecular rulers," has given results in reasonable agreement with the crystal structure. Chlorambucilyl-[3H]phenylalanyl-tRNAPhe crosslinked intramolecularly at G-71 and A-73, whereas chlorambucilyl-pentadecaprolyl-[3H]phenylalanyl-tRNAPhe crosslinked at G-20 and Y-37. The pentadecaprolyl reagent was predicted to be 62 A long, including chlorambucil and phenylalanine; the sites that it reached are 60 A distant from the 3' OH (in the case of G-20) or 80 A distant (in the case of Y-37) in the crystal structure of tRNAPhe. The close agreement between the length of the reagent and the distance of G-20 from the 3' OH in the crystal structure illustrates the rigidity of the tRNAPhe molecule in the dihydrouridine loop region at the corner of the molecule. The apparent ability of the 62-A-long reagent to crosslink to a site, Y-37, that is 80 A distant from the 3' OH in the crystal structure appears to illustrate the flexibility of both the 3' A-C-C-A terminus and the anticodon stem and loop, with respect to the tRNA molecule. These observations demonstrate the utility of oligoproline-based crosslinking reagents as rigid, variable-length molecular rulers for biological macromolecules in solution.