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No description available.

Voltage clamp fluorometry (VCF) was first developed in the mid 1990s by Isacoff and his colleagues. In this approach fluorophores are attached to substituted cysteine residues that are engineered by site-directed mutagenesis. Changes in the dielectric environment of the fluorophore report local transitions that are associated with electrically-related and electrically-silent transitions. VCF provides a powerful technique to observe real time reports of ion channel gating conformations. It has proven to be a useful technique because it adds insight that is not available using other techniques. X-ray crystallography studies give a predominantly static picture of the channel, while patch clamping of channels gives information only about residues that effect ionic current flow. Similarly, gating current provides insight only about residues that are charged and move across the membrane electric field. In this thesis we examined the structural rearrangements of the Shaker channel and the effect of 4-AP on channel gating. We also examined for the first time the structural rearrangements of the Kv1.5 gating and the how the channel responds to depolarization pulses. This work is instrumental in the examination of the potassium channel gating.

This research was undertaken in order to investigate the robustness of the Anzai respiratory gating system. Tests were performed to verify the transfer of image data, to identify the method of gating and the accuracy of phase identification. It was found to have sizeable limitations which could result in either incorrectly gated images or serious artefacts. For these reasons it is recommended it be used under the guidance of a suitably qualified physicist.

Voltage clamp fluorometry (VCF) was first developed in the mid 1990s by Isacoff and his colleagues. In this approach fluorophores are attached to substituted cysteine residues that are engineered by site-directed mutagenesis. Changes in the dielectric environment of the fluorophore report local transitions that are associated with electrically-related and electrically-silent transitions. VCF provides a powerful technique to observe real time reports of ion channel gating conformations. It has proven to be a useful technique because it adds insight that is not available using other techniques. X-ray crystallography studies give a predominantly static picture of the channel, while patch clamping of channels gives information only about residues that effect ionic current flow. Similarly, gating current provides insight only about residues that are charged and move across the membrane electric field. In this thesis we examined the structural rearrangements of the Shaker channel and the effect of 4-AP on channel gating. We also examined for the first time the structural rearrangements of the Kv1.5 gating and the how the channel responds to depolarization pulses. This work is instrumental in the examination of the potassium channel gating.

Thesis (M.S.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record.

Voltage clamp fluorometry (VCF) was first developed in the mid 1990s by Isacoff and his colleagues. In this approach fluorophores are attached to substituted cysteine residues that are engineered by site-directed mutagenesis. Changes in the dielectric environment of the fluorophore report local transitions that are associated with electrically-related and electrically-silent transitions. VCF provides a powerful technique to observe real time reports of ion channel gating conformations. It has proven to be a useful technique because it adds insight that is not available using other techniques. X-ray crystallography studies give a predominantly static picture of the channel, while patch clamping of channels gives information only about residues that effect ionic current flow. Similarly, gating current provides insight only about residues that are charged and move across the membrane electric field. In this thesis we examined the structural rearrangements of the Shaker channel and the effect of 4-AP on channel gating. We also examined for the first time the structural rearrangements of the Kv1.5 gating and the how the channel responds to depolarization pulses. This work is instrumental in the examination of the potassium channel gating. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Respiratory gating limits the radiation to a specific part of the breathing cycle and reduces the size of the Planning Target Volume (PTV). This thesis describes a novel quality assurance method for amplitude gating of Stereotactic ABlative Ra- diotherapy (SABR) treatments of liver delivered using Volumetric Modulated Arc Therapy (VMAT) using a 10 MV beam in Flattening Filter Free (FFF) mode. This method takes advantage of the high dose gradient region of SABR treatments to detect any inaccuracies in the performance of the Varian Real-time Position Manage- ment (RPM) gating system. This study involves the design and construction of an interface that connects the translation stage of the Quasar respiratory motion phan- tom to an ion chamber insert. This insert can hold and drive a pinpoint ion chamber inside the ArcCheck diode array based on the breathing pattern imported into the Quasar phantom. The pinpoint ion chamber dose measurements were acquired at the isocentre and along the penumbra using synthetic breathing traces. Our results show that the changes in PTV size and exhale duration do not influence the dose measured by iii the pinpoint ion chamber. Changes in gate width and baseline drift, however, affect the detector residual motion, which results in variation in the level of dose-blurring and interplay effects. A new parameter, Average Residual Detector Displacement (ARDD), is introduced in this thesis and is used to take into account the effect of dose-blurring. For gate widths smaller than 8 mm and baseline drift levels smaller than 4 mm, if the effect of dose-blurring is taken into account, the pinpoint ion chamber dose measurements are mostly within 2σ positional uncertainty from the Eclipse dose profile. As the gate width and baseline drift increases, accounting for the dose-blurring effect is no longer sufficient to explain the discrepancy between measured and calculated doses. This thesis also includes dose measurements for radiation deliveries that are gated using six real breathing traces with gate widths of 2 mm, 2.8 mm, and 4 mm. Once the parameter ARDD is used to account for dose-blurring, the dose measurements are mostly within 2σ positional uncertainty from Eclipse calculated doses. These results demonstrate the reliability and accuracy of the RPM gating system at British Columbia Cancer Agency - Vancouver Island Cancer Centre (BCCA - VICC). Lastly, the overall dose distribution was monitored using the ArcCheck diode array measure- ments under various gating schemes and was compared to the Eclipse calculated dose map using a 2D Gamma analysis. The Gamma pass rates for 2mm/2% criteria show that the beam interruptions during the treatment do not degrade the fidelity of the radiation delivery in a gated treatment. / Graduate