The basic principles of the transient behaviour of a generator are briefly explained, and a non-linear differential equation describing the generator's performance is given. The need for a calculating aid for solving this non-linear equation is explained. An analogue of a generator is derived, and details of a simulator based on this analogue are given. Experimental results are given to how that the simulator behaves according to theory. Further development of the basic apparatus to increase its accuracy and versatility is described.

In this thesis, we firstly present a low-cost plasma display panel (PDP) data dispatcher for image enhancement. By taking advantage of the proposed ADS method with 10 subfields and data reordering, our design can reduce 20% of the PDP dispatcher cost and resolve the ¡§dynamic false contour¡¨ problem. Secondly, a bipolar-valued inner product processor for associative memory neural networks is proposed to compute the inner product of two bipolar-valued vectors. Our analysis shows that the delay of inner product is reduced significantly from O(2n) to O(n). We also propose a 3-dimensional address decoding structure associated with a corresponding data cell encoding arrangement for P+implant ROMs such that the data words are encoded and stored in the ROMs in a natural pattern. Not only is the size of the entire decoder shrunk, the access time and power dissipation is also greatly reduced, which is very suitable to be utilized in implantable devices. Finally, we introduce a multi-parameter implantable neural interface micro-stimulator system, including the external control module, the protocol, and the SOC (system-on-chip) chip. The proposed system is expected to carry out the externally given commands to stimulate the corresponding neural trunks. On the other way around, it can sense and deliver the response of the neural trunks to an external monitoring device in the future.

This thesis includes two topics. The first topic is a low power design of 8-bit ANT-based pipelining CLA. The second one is a small digital to analog converter (DAC) used in an implantable neural stimulator. An ANT-based low-power 8-bit pipelining carry-lookahead adder (CLA) using two-phase all-N-transistor (ANT) blocks which are arranged in a PLA design style with power-aware pipelining is presented. The pull-up charging and pull-down discharging of the transistor arrays of the PLA are accelerated by two feedback MOS transistors between the evaluation NMOS blocks and the outputs. Both the added power-aware clock control circuit and clock generation circuit detecting data transition take advantage of shutting down the processing stages given identical inputs in two consecutive operations by keeping high clock level. The design keeps the advantage of high speed while having the effect of low power dissipation. The implantable neural stimulator assists patients to reconstruct transmission paths of neural signals by current stimulation. The proposed small DAC not only decreases the chip area and power dissipation by reducing transistor count, but also improves the linearity with higher current output performance. All of measured performances of the proposed DAC make the chip worthy of being implemented in a field application.

<div> <div> <p>Purpose: Preclinical studies have demonstrated that cancer cells may produce innate immune signals such as type-I interferons following radiation damage, which derives from activation of the cGAS-STING pathway following detection of cytosolic dsDNA. Limited studies have explored how these mechanisms vary from the conditions of the radiation exposure. High- linear energy transfer (LET) radiation induces more DNA double-strand breaks (DSB) per dose than low-LET radiation, thus is expected to be more immunogenic. However, DNA damage in hypoxic cells is more probable to undergo chemical repair due to limitations in oxygen fixation, thus is expected to be more immunosuppressive. Our goal is to study and model the dose response characteristics of IFNβ and Trex1 in vitro following exposure of radiations with varying LET and to develop techniques for further study in vivo.<br></p><p><br></p> <p>Methods: Reference data from Vanpouille-Box (2017) on STING dose response was applied to develop empirical models of cytosolic dsDNA and Trex1 regulation as a function of dose and quantity of DNA DSB, the latter of which is dependent on particle LET and oxygenation and is calculated using Monte Carlo Damage Simulation (MCDS) software. These models were used as preliminary data to guide in vitro experiments using Merkel cell carcinoma cells. The dose response of pro-inflammatory IFNβ and exonuclease Trex1, an anti-inflammatory suppressor of cGAS-STING, was measured post-irradiation. MCDS was again used to model fast neutron relative biological effectiveness for DSB induction (RBEDSB) and compared to laboratory measurements of the RBE for IFNβ production (RBEIFNβ). RBEIFNβ models were applied to radiation transport simulations to quantify the potential secretion of IFNβ in representative clinical beams. To enable intra-tumor radiation targeting of tumor hypoxia, mice were seeded with syngeneic tumors and imaged longitudinally with PCT- spectroscopy to determine local variations hemoglobin concentration (Hb) and oxygen saturation (SaO2) over time. Hypoxia classification was based on SaO2 levels in voxels containing hemoglobin relative to a “hypoxia threshold” of SaO2 < 0.2.</p><p><br></p> <p>Results: Based on analysis of published data, our preliminary models of cytosolic DNA and Trex1 dose responses demonstrate dose enhancements from high-LET radiation, such as that at the distal edge of a Bragg peak, and suppression from cellular hypoxia. This manifests as an RBE-dependent ‘shift’ in STING response. Laboratory measurements in MCC13 cells show peak IFNβ production at 6.1 Gy following fast neutron irradiation and 14.5 Gy following x-rays (RBEIFNβ = 2.4). However, IFNβ signal amplitudes were not significantly different between these radiation types. Trex1 signal increased linearly with dose, with fourfold higher upregulation per dose for fast neutrons. Modeling of RBE in clinical beams suggests that ion sources may induce spatially localized IFNβ near their end of range, which is potentially advantageous for initiation of tumor-specific immune activity. Uncharged sources stimulate IFNβ more uniformly with depth. Longitudinal PCT-S scanning is able to localize and distinguish chronic and acute hypoxia in vivo. Changes in the hypoxic classification from tumor growth and following anti-angiogenic therapy are distinguishable.<br> </p><p> </p><div> <div> <div> <p>Conclusion: Radiation-induced immunogenicity can be induced differentially based on radiation quality and is expected to be affected by cellular oxygenation. High-LET radiation, such as fast neutrons, drives greater IFNβ innate immune response per dose than low-LET radiation, such as x-rays, which may enhance abscopal effects when used in combination with immune-stimulating agents. However, anti-inflammatory signaling is greater per dose for fast neutrons, and it remains unclear if high-LET radiations are therapeutically advantageous over low-LET radiation for pro-inflammatory tumor signaling. High resolution in vivo imaging of tumor hypoxia is feasible with photoacoustic techniques, which can potentially be leveraged to study selective immunogenicity enhancement of the hypoxic niche following radiation therapy. <br></p> </div> </div> </div> <p> </p> </div></div>

It is a known problem that a Spinal Cord Stimulator (SCS) can interact with an Implantable Cardioverter Defibrillator (ICD) when both devices are implanted in the same patient. Interactions between the SCS and ICD can cause inappropriate therapy which can be harmful to the patient. While ICD devices have a distinct narrowband sensing bandwidth, the pulse configurations that current SCS devices deliver were not designed with this frequency region in mind. In this thesis, I recommend a new pulse configuration for SCS devices that will minimize the interaction between the two devices. I produce a theoretical equation for each pulse configuration in the frequency domain using the Laplace transform and present the results in Matlab. I also design my own SCS device to deliver multiple pulse configurations and use it to gather empirical data. The theoretical and empirical results are used to show the extent of the improvement between the new pulse and existing pulse configurations. The results prove that the new pulse configuration will significantly reduce crosstalk within the desired ICD bandwidth. A reduction in crosstalk will decrease the probability that an SCS will interact with a ICD device.

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京都大学 / 新制・課程博士 / 博士(医学) / 甲第23804号 / 医博第4850号 / 新制||医||1058(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 井上 治久, 教授 林 康紀, 教授 竹内 理 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

The problem of this study concerns the reduction of spasticity in physically handicapped persons with CP. The hypotheses tested were: that there would be no significant difference between the mechanical efficiency (ME) of persons with spastic CP following application of the TENS Unit and following application of the placebo unit; that there would be no significant difference between the ME of males with spastic CP, following application of the TENS Unit or the placebo unit, and the ME of females with spastic CP, following application of the TENS Unit or the placebo unit; and that there would be no significant interaction between the treatment factor and the gender category.

The objective of the proposed research is to advance the power efficiency of wireless neural stimulating systems in inductively powered implantable medical devices (IMD). Several innovative system- and circuit-level techniques are proposed towards the development of power-management circuits and wireless neural stimulating systems with inductive power transmission to improve the overall stimulation power efficiency. Neural stimulating IMDs have been proven as effective therapies to alleviate neurological diseases, while requiring high power and performance for more efficacious treatments. Therefore, power-management circuits and neural stimulators in IMDs should have high power efficiencies to operate with smaller received power from a larger distance. Neural stimulating systems are also required to have high stimulation efficacy for activating the target tissue with a minimum amount of energy, while ensuring charge-balanced stimulation. These features provide several advantages such as a long battery life in an external power transmitter, extended-range inductive power transfer, efficacious and safe stimulation, and less tissue damage from overheating. The proposed research presents several approaches to design and implement the power-efficient wireless neural stimulating IMDs: 1) optimized power-management circuits for inductively powered biomedical microsystems, 2) a power-efficient neural stimulating system with adaptive supply control, and 3) a wireless switched-capacitor stimulation (SCS) system, which is a combination structure of the power-management circuits and neural stimulator, to maximize both stimulator efficiency (before electrodes) and stimulus efficacy (after electrodes).