Analysis of interfraction setup errors, performed with US, CBCT, planar kV images, and electromagnetic transponders, from a large dataset revealed intermodality shifts were comparable (within 3-4 mm). Interfraction planning margins, relative to setup based on skin marks, were generally within the 10 mm prostate-to-planning target volume margin used in our clinic. With image guidance, interfraction residual planning margins were reduced to approximately less than 4 mm. These findings are potentially important for dose escalation studies using smaller margins to better protect normal tissues.
Prostate deformation over a course of fractionated prostate radiotherapy may not be insignificant and may need to be accounted for in the planning margin design. A consequence of these results is that use of highly reduced planning margins must be viewed with caution.
We report on an improved method to interpret single molecule dissociation measurements using atomic force microscopy. We describe an easy to use methodology to reject nonspecific binding events, as well as estimating the number of multiple binding events. The method takes nonlinearities in the force profiles into account that result from the deformation of the used polymeric linkers. This new method is applied to a relevant enzyme-inhibitor system, latent matrix metalloprotease 9 (ProMMP-9, a gelatinase), and its inhibitor, tissue inhibitor of metalloproteases 1 (TIMP 1), which are important players in cancer metastasis. Our method provides a measured kinetic off-rate of 0.010 ± 0.003 s(-1) for the dissociation of ProMMP9 and TIMP1, which is consistent with values measured by ensemble methods.
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