The promise of new architectures and more cost-effective miniaturization has prompted interest in molecular and biomolecular electronics. Bioelectronics offers valuable near-term potential, because evolution and natural selection have optimized many biological molecules to perform tasks that are required for device applications. The light-transducing protein bacteriorhodopsin provides not only an efficient photonic material, but also a versatile template for device creation and optimization via both chemical modification and genetic engineering. We examine here the use of this protein as the active component in holographic associative memories as well as branched-photocycle three-dimensional optical memories. The associative memory is based on a Fourier transform optical loop and utilizes the real-time holographic properties of the protein thin films. The three-dimensional memory utilizes an unusual branching reaction that creates a long-lived photoproduct. By using a sequential multiphoton process, parallel write, read, and erase processes can be carried out without disturbing data outside of the doubly irradiated volume elements. The methods and procedures of prototyping these bioelectronic devices are discussed. We also examine current efforts to optimize the protein memory medium by using chemical and genetic methods.
A novel small animal conformal radiation therapy system has been designed and prototyped: MicroRT. The microRT system integrates multimodality imaging, radiation treatment planning, and conformal radiation therapy that utilizes a clinical 192Ir isotope high dose rate source as the radiation source (teletherapy). A multiparameter dose calculation algorithm based on Monte Carlo dose distribution simulations is used to efficiently and accurately calculate doses for treatment planning purposes. A series of precisely machined tungsten collimators mounted onto a cylindrical collimator assembly is used to provide the radiation beam portals. The current design allows a source-to-target distance range of 1-8 cm at four beam angles: 0 degrees (beam oriented down), 90 degrees, 180 degrees, and 270 degrees. The animal is anesthetized and placed in an immobilization device with built-in fiducial markers and scanned using a computed tomography, magnetic resonance, or positron emission tomography scanner prior to irradiation. Treatment plans using up to four beam orientations are created utilizing a custom treatment planning system-microRTP. A three-axis computer-controlled stage that supports and accurately positions the animals is programmed to place the animal relative to the radiation beams according to the microRTP plan. The microRT system positioning accuracy was found to be submillimeter. The radiation source is guided through one of four catheter channels and placed in line with the tungsten collimators to deliver the conformal radiation treatment. The microRT hardware specifications, the accuracy of the treatment planning and positioning systems, and some typical procedures for radiobiological experiments that can be performed with the microRT device are presented.
The sponsor initially approved the study concept and the original protocol, required regular updates regarding protocol accrual and data safety monitoring and provided funds to each participating center for each protocol accrual. The sponsor had no role in the collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Purpose: To develop and validate methods for small-animal CNS radiotherapy using the microRT system. Materials and Methods: A custom head immobilizer was designed and built to integrate with a pre-existing microRT animal couch. The Delrin ® couch-immobilizer assembly, compatible with multiple imaging modalities ͑CT, microCT, microMR, microPET, microSPECT, optical͒, was first imaged via CT in order to verify the safety and reproducibility of the immobilization method. Once verified, the subject animals were CT-scanned while positioned within the couch-immobilizer assembly for treatment planning purposes. The resultant images were then imported into CERR, an in-house-developed research treatment planning system, and registered to the microRTP treatment planning space using rigid registration. The targeted brain was then contoured and conformal radiotherapy plans were constructed for two separate studies: ͑1͒ a whole-brain irradiation comprised of two lateral beams at the 90°and 270°microRT treatment positions and ͑2͒ a hemispheric ͑left-brain͒ irradiation comprised of a single A-P vertex beam at the 0°microRT treatment position. During treatment, subject animals ͑n =48͒ were positioned to the CERR-generated treatment coordinates using the three-axis microRT motor positioning system and were irradiated using a clinical Ir-192 high-dose-rate remote after-loading system. The radiation treatment course consisted of 5 Gy fractions, 3 days per week. 90% of the subjects received a total dose of 30 Gy and 10% received a dose of 60 Gy. Results: Image analysis verified the safety and reproducibility of the immobilizer. CT scans generated from repeated reloading and repositioning of the same subject animal in the couch-immobilizer assembly were fused to a baseline CT. The resultant analysis revealed a 0.09 mm average, center-of-mass translocation and negligible volumetric error in the contoured, murine brain. The experimental use of the head immobilizer added Ϯ0.1 mm to microRT spatial uncertainty along each axis. Overall, the total spatial uncertainty for the prescribed treatments was Ϯ0.3 mm in all three axes, a 0.2 mm functional improvement over the original version of microRT. Subject tolerance was good, with minimal observed side effects and a low procedure-induced mortality rate. Throughput was high, with average treatment times of 7.72 and 3.13 min/animal for the whole-brain and hemispheric plans, respectively ͑dependent on source strength͒. Conclusions: The method described exhibits conformality more in line with the size differential between human and animal patients than provided by previous prevalent approaches. Using pretreatment imaging and microRT-specific treatment planning, our method can deliver an accurate, conformal dose distribution to the targeted murine brain ͑or a subregion of the brain͒ while minimizing excess dose to the surrounding tissue. Thus, preclinical animal studies assessing the radiotherapeutic response of both normal and malignant CNS tissue to complex dose distributions, which closer resem...
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