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BMC Molecular Biology (1)
Physics in medicine and biology (1)
Hansen, Steven (2)
Abedi, Majid (1)
Caponigro, Giordano (1)
Chell, Erik (1)
Gertner, Michael (1)
Kamb, Alexander (1)
Newhauser, Wayne D (1)
Sandrock, Tanya (1)
Shen, Jiaxiang (1)
Taddei, Phillip J (1)
Year of Publication
Assessment of targeting accuracy of a low-energy stereotactic radiosurgery treatment for age-related macular degeneration
Taddei, Phillip J
Newhauser, Wayne D
Physics in medicine and biology
Age-related macular degeneration (AMD), a leading cause of blindness in the United States, is a neovascular disease that may be controlled with radiation therapy. Early patient outcomes of external beam radiotherapy, however, have been mixed. Recently, a novel multimodality treatment was developed, comprising external beam radiotherapy and concomitant treatment with a vascular endothelial growth factor inhibitor. The radiotherapy arm is performed by stereotactic radiosurgery, delivering a 16 Gy dose in the macula (clinical target volume, CTV) using three external low-energy x-ray fields while adequately sparing normal tissues. The purpose of our study was to test the sensitivity of the delivery of the prescribed dose in the CTV using this technique and of the adequate sparing of normal tissues to all plausible variations in the position and gaze angle of the eye. Using Monte Carlo simulations of a 16 Gy treatment, we varied the gaze angle by ±5° in the polar and azimuthal directions, the linear displacement of the eye ±1 mm in all orthogonal directions, and observed the union of the three fields on the posterior wall of spheres concentric with the eye that had diameters between 20 and 28 mm. In all cases, the dose in the CTV fluctuated <6%, the maximum dose in the sclera was <20 Gy, the dose in the optic disc, optic nerve, lens and cornea were <0.7 Gy and the three-field junction was adequately preserved. The results of this study provide strong evidence that for plausible variations in the position of the eye during treatment, either by the setup error or intrafraction motion, the prescribed dose will be delivered to the CTV and the dose in structures at risk will be kept far below tolerance doses.
Transcriptional transactivation by selected short random peptides attached to lexA-GFP fusion proteins
BMC Molecular Biology
Transcriptional transactivation is a process with remarkable tolerance for sequence diversity and structural geometry. In studies of the features that constitute transactivating functions, acidity has remained one of the most common characteristics observed among native activation domains and activator peptides.
We performed a deliberate search of random peptide libraries for peptides capable of conferring transcriptional transactivation on the lexA DNA binding domain. Two libraries, one composed of C-terminal fusions, the other of peptide insertions within the green fluorescent protein structure, were used. We show that (i) peptide sequences other than C-terminal fusions can confer transactivation; (ii) though acidic activator peptides are more common, charge neutral and basic peptides can function as activators; and (iii) peptides as short as 11 amino acids behave in a modular fashion.
These results support the recruitment model of transcriptional activation and, combined with other studies, suggest the possibility of using activator peptides in a variety of applications, including drug development work.
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