By providing effective shading correction, our approach has the potential to improve the accuracy of more advanced CBCT-based clinical applications for IGRT, such as tumor delineation and dose calculation.

No abstract

We report the results of a selection for single-stranded DNA oligonucleotide ligands to the serine protease thrombin using recently developed methods. This selection yielded a family of DNA sequences that conform to a consensus structure comprised of a unimolecular quadruplex motif and complementary flanking sequences capable of forming an additional Watson-Crick duplex motif. This novel quadruplex/duplex structure was not reported in a previous selection for DNA molecules which bind to thrombin [Bock et al. (1992) Nature 355, 564-566]. All quadruplex/duplex molecules tested bound to thrombin with higher affinity than quadruplex structures lacking the duplex structure. However, binding affinities did not always correlate with inhibitory potency since some molecules with high affinity were not potent inhibitors in vitro. 1H NMR spectroscopy studies demonstrated that the complementarity of bases in the duplex portion of a selected sequence allows it to form multimolecular structures. Constraining these molecules to the unimolecular quadruplex/duplex structure by bridging the 5' and 3' ends of the duplex motif with either triethylene glycol or disulfide bonds improved their thrombin inhibitory activity. All bridged quadruplex/duplex molecules were more potent inhibitors than molecules with only a quadruplex motif. Bridging the ends of these structures not only increased thrombin inhibition but also improved resistance to nucleases in serum more than 40-fold over the unbridged quadruplex. In addition, we have found that both the length and sequence of the duplex motif are important for inhibition.

Nitrogen NMR of specifically labeled molecules has the potential to provide unique information about structure and interactions.1•2 The chemical shift of an sp2 nitrogen, for example, is strongly affected by protonation. In the case of the adenine Nl, protonation is known to cause an upfield shift of ~70 ppm.2

On the three phantom studies, good scatter correction performance of the proposed method has been demonstrated using both image comparisons and quantitative analysis. The theory and experiments demonstrate that a strong primary modulation that possesses a low transmission factor and a high modulation frequency is preferred for high scatter correction accuracy.