With the introduction of four dimensional-computed tomography (4DCT), treatment centers are now better able to account for respiration-induced uncertainty in radiation therapy treatment planning for lung cancer. We examined two practices in which 4DCT is used in radiotherapy. Our first study investigated the dosimetric uncertainty in four-dimensional (4D) dose calculation using three temporal probability distributions: 1) uniform distribution, 2) sinusoidal distribution, and 3) patient-specific distribution derived from the respiratory trace. Four-dimensional dose was evaluated in nine lung cancer patients. First, dose was computed for each of 10 binned CTs using 4DCT and deformable image registration. Next, the 10 deformed doses were summed together using one of three temporal probability distributions. To compare the two approximated 4D dose calculations to the 4D calculation derived using the patient's respiratory trace, 3D gamma analysis was performed using a tolerance criteria of 3% dose difference and 3mm distance to agreement. Additionally, mean lung dose (MLD), mean tumor dose (MTD), and lung V20 were used to assess clinical impact. For all patients, both uniform and sinusoidal dose distributions were found to have an average gamma passing rate >99% for both the lung and PTV volumes. Compared with 4D dose calculated using the patient respiratory trace, uniform distribution and sinusoidal distribution showed a percentage difference on average of -0.1±0.6% and -0.2±0.4% in MTD, -0.2±2.0% and -0.2±1.3% in MLD, 0.9±2.8% and -0.7±1.8% in lung V20, respectively. We concluded that 4D dose computed using either a uniform or sinusoidal temporal probability distribution is able to approximate 4D dose computed using the patient-specific respiratory trace. Our second study evaluated the dosimetric and temporal effects of respiratory gated radiation therapy using four different gating windows (20EX-20IN, 40EX-40IN, 60EX-60IN, and 80EX-80IN) and estimated the corresponding treatment delivery times for normal (500MU/min) and high (1500MU/min) dose rates. Five patients (3 non-gated, 2 gated 80EX-80IN) were retrospectively evaluated. For each patient, four individual treatment plans corresponding to the four different gating windows were created, and treatment delivery time for each plan was estimated using a MATLAB (MathWorks, Natick, MA) algorithm. Results showed that smaller gating windows reduced PTV volume, mean lung dose, and lung V20, while maintaining mean tumor dose and PTV coverage. Treatment times for gated plans were longer when dose rate was unchanged, however, increased dose rates were shown to achieve treatment times comparable to or faster than non-gated delivery times. We concluded that gated radiation therapy in lung cancer patients could potentially reduce lung toxicity, while as effectively treating the target volume. Furthermore, increased dose rates with gated radiation therapy are able to provide treatment times comparable to non-gated treatment.

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In the mammalian visual system, the lateral geniculate nucleus is commonly thought to act merely as a relay for the transmission of visual information from the retina to the visual cortex, a relay without significant elaboration in receptive field properties or signal strength. However, many morphological and electrophysiological observations are at odds with this view. In this paper, we will review the different anatomical pathways and biophysical mechanisms possibly implementing a selective gating of visual information flow from the retina to the visual cortex. We will argue that the lateral geniculate nucleus in mammals is one of the earliest sites where selective, visual attention operates and where general changes in neuronal excitability as a function of the behavioral states of the animal, for instance, sleep, paradoxical sleep, arousal, etc., occur.

Voltage-gated ion channels play fundamental roles in neural excitability, they are for instance responsible for every single heart beat in our bodies, and dysfunctional channels cause disease that can be even lethal. Understanding how the voltage sensor of these channels function is critical for drug design of compounds targeting neuronal excitability. The opening and closing of the pore in voltage-gated potassium (Kv) channels is caused by the arginine-rich S4 helix of the voltage sensor domain (VSD) moving in response to an external potential. In fact, VSDs are remarkably efficient at turning membrane potential into conformational changes, which likely makes them the smallest existing biological engines. Exactly how this is accomplished is not yet fully known and an area of hot debate, especially due to the lack of structures of the resting and intermediate states along the activation pathway. In this thesis I study how the VSD activation works and show how toxic compounds modulate channel gating through direct interaction with these quite unexplored drug targets. First, I show that a secondary structure transition from alpha- to 3(10)-helix in the S4 helix is an important part of the gating as this helix type is significantly more favorable compared to the -helix in terms of a lower free energy barrier. Second, I present new models for intermediate states along the whole voltage sensor cycle from closed to open and suggest a new gating model for S4, where it moves as a sliding 3(10)-helix. Interestingly, this 3(10)-helix is formed in the region of the single most conserved residue in Kv channels, the phenylalanine F233. Located in the hydrophobic core, it directly faces S4 and creates a structural barrier for the gating charges. Substituting this residue alters the deactivation free energy barrier and can either facilitate the relaxation of the voltage sensor or increase the free energy barrier, depending on the size of the mutant. These results are confirmed by new experimental data that supports that a rigid ring at the phenylalanine position is the rate-limiting factor for the deactivation gating process, while the activation is unaffected. Finally, we study how the activation can be modulated for pharmaceutical reasons. Neurotoxins such as hanatoxin and stromatoxin push S3b towards S4 helix limiting S4's flexibility. This makes it harder for the VSD to activate and might explain the stronger binding affinities in resting state. All these results are highly important both for the general topic of biological macromolecules undergoing functionally critical conformational transitions, as well as the particular case of voltage-gated ion channels where understanding of the gating process is probably the key step to explain the effects of mutations or drug interactions. / <p>QC 20121115</p>

This thesis contains two components of research: studies of supercontinuum pulses generated in the novel microstructure fiber, and research on spatio-temporal coupling in ultrafast laser beams. One of the most exciting developments in optics in recent years has been the invention of the microstructure optical fiber. By controlling the structural parameters of these novel fibers in design and manufacturing, their dispersion profile can be freely tailored, opening up a huge application base. One particularly interesting effect in the microstructure fiber is the generation of ultrabroadband supercontinuum with only nJ-level Ti:sapphire oscillator pulse pump. This supercontinuum is arguably the most complicated ultrafast pulse ever generated, with its huge time-bandwidth product (> 1000 from a 16-cm-long fiber). Although many applications have been demonstrated or envisioned with this continuum, its generation is a very complicated process that is poorly understood, and the characteristics of the continuum pulses are not clearly known. In this work, we make a full-intensity-and-phase measurement of the continuum pulses using cross-correlation frequency-resolved optical gating (XFROG). The results reveal surprising unstable fine spectral structure in the continuum pulses, which is confirmed by single-shot measurements. Our study on the coherence of the continuum, on the other hand, shows that the spectral phase of the supercontinuum is fairly stable. Numerical simulations are carried out whose results are in good agreement with experiments. The second component of this thesis is the study of spatio-temporal coupling in ultrafast beams. We propose two definitions of spatial chirp, point out their respective physical meanings, and derive their relationship. On the common perception of the equivalence between pulse-front tilt and angular dispersion, we show that the equivalence only holds for plane waves. We establish a generalized theory of ultrafast laser beams with first-order spatio-temporal couplings, and discover a new pulse-front tilt effect associated with the combination of spatial chirp and temporal chirp. For the measurement of spatio-temporal distortions, the effects of such distortions in the input beam to a GRENOUILLE trace are carefully studied. An algorithm is proposed and tested to retrieve information about the distortions from the GRENOUILLE trace.

Based on the acquisition trajectory, PROPELLER MRI repeatedly sampled the center k-space in every blade, which was used to provide most of the energy of an image. The purpose of view sharing PROPELLER is to improve the spatio-temporal resolution of dynamic imaging by reducing the acquisition time of single frame to that of single blade. With the center k-space provided by only one blade, which is called the target blade, the high spatial-frequency components were appropriately contributed by a set of neighboring blades with different rotation angles, leading to the high spatial resolution after reconstruction. In this study, a flow phantom experiment with the injection of T1-shortening Gd-DTPA solution was performed to exam the feasibility and accuracy of view-sharing PROPELLER. Furthermore, cardiac imaging of healthy volunteer obtained by the proposed technique was also done with ECG gating to test the image quality without any injection of contrast agent. The in-vivo experiment was done with and without breath holding. In addition to slight aliasing artifact due to insufficient FOV, no other artifact was observed.

Memory unit is one of the fundamental hardware components in system-on-chip (SoC) design, and takes a significant portion of total area cost. Although commercial memory compilers exist, they usually contains memory unit with single-port or dual ports. However, many SoC designs require memory units that support simultaneous multiple reads and writes. They cannot be efficiently generated using the existing memory compilers in the standard cell library. In this thesis, we develop a memory generator that can automatically produce the circuits of multi-port SRAM and all the necessary models required in the standard cell-based design flow. Compared to the design based on dual-port SRAM from memory compilers which usually consists of duplicated copies of SRAM units for supporting multiple write at the same, the proposed design has smaller area cost. Furthermore, we employ various low-power design concepts, including power-gating and adaptive body-bias, to reduce the dynamic and static power of the generated SRAM circuits. Experimental results show that the proposed multi-port SRAM generator can be used to synthesize low-power and low-area register file circuits that support multiple reads and writes at the same time.

A multi-precision function interpolator, which is fitted in with the IEEE-754 single precision floating point standard, is proposed in this paper. It provides logarithms, exponentials, reciprocal and square root reciprocal operations. Each operation is able to dynamically select four different precision modes in demand. The hardware architecture is designed with fully pipeline in order to comply with hardware architectures of general digital signal processors (DSPs) and graphics processors (GPUs). When considering the usefulness of each precision mode, it is designed to minimize the error among various modes as far as possible in the beginning. According to the precision from high to low, function interpolator can provide 23, 18, 13 and 8-bit accuracy respectively in spite of the rounding effect. This function interpolator is designed based on the look-up table method. It can get the approximation value of target function through the calculation of quadratic polynomial. The coefficient of quadratic polynomial is obtained by piecewise minimax approximation. Before implementing the hardware, we use the Maple algebra software to generate the quadratic polynomial coefficients of aforementioned four operations, and estimate whether these coefficients can meet IEEE-754 single precision floating point standard. In addition, we take the exhaustive search to check the results generated by our implementation to make sure that it can meet the requirements for various operations and precision modes. When performing one of the above four operations, only the tables of the operation are used to obtain the quadratic polynomial coefficient. Therefore, we can take the advantage of the tri-state buffer as a switch to reduce dynamic power consumption of tables for the other three operations. In addition, when performing lower precision modes, we can turn off a part of hardwares, which are used to calculate the quadratic polynomial, to save the power consumption more effectively. By providing multi-precision hardware, we hope users or developers, those who use the battery device, can choose a lower precision mode within the permissible error range to extend the battery life.

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 108-119).

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 68-82).