Indiana University-Purdue University Indianapolis (IUPUI) / Glaucoma is a multi-factorial ocular disease associated with death of retinal ganglion cells and irreversible vision loss. Many risk factors contribute to glaucomatous damage, including elevated intraocular pressure (IOP), age, genetics, and other diseases such as diabetes and systemic hypertension. Interestingly, alterations in retinal hemodynamics have also been associated with glaucoma. A better understanding of the factors that contribute to these hemodynamic alterations could lead to improved and more appropriate clinical approaches to manage and hopefully treat glaucoma patients. In this thesis, we develop several mathematical models aimed at describing ocular hemodynamics and oxygenation in health and disease. Precisely we describe: (i) a time-dependent mathematical model for the retinal circulation that includes macrocirculation, microcirculation, phenomenological vascular regulation, and the mechanical effect of IOP on the retinal vasculature; (ii) a steady-state mathematical model for the retinal circulation that includes macrocirculation, microcirculation, mechanistic vascular regulation, the effect of IOP on the central retinal artery and central retinal vein, and the transport of oxygen in the retinal tissue using a Krogh cylinder type model; (iii) a steady-state mathematical model for the transport of oxygen in the retinal microcirculation and tissue based on a realistic retinal anatomy; and (iv) a steady-state mathematical model for the production and drainage of aqueous humor (AH). The main objective of this work is to study the relationship between IOP, systemic blood pressure, and the functionality of vascular autoregulation; the transport and exchange of oxygen in the retinal vasculature and tissue; and the production and drainage of AH, that contributes to the level of IOP. The models developed in this thesis predict that (i) the autoregulation plateau occurs for different values of IOP in hypertensive and normotensive patients. Thus, the level of blood pressure and functionality of autoregulation affect the changes in retinal hemodynamics caused by IOP and might explain the inconsistent outcomes of clinical studies; (ii) the metabolic and carbon dioxide mechanisms play a major role in the vascular regulation of the retina. Thus, the impairment of either of these mechanisms could cause ischemic damage to the retinal tissue; (iii) the multi-layer description of transport of oxygen in the retinal tissue accounts for the effect of the inner and outer retina, thereby improving the predictive ability of the model; (iv) a greater reduction in IOP is obtained if topical medications target AH production rather that AH drainage and if IOP-lowering medications are administrated to patients that exhibit a high initial level of IOP. Thus, the effectiveness of IOP-lowering medications depend on a patient’s value of IOP. In conclusion, the results of this thesis demonstrate that the insight provided by mathematical modeling alongside clinical studies can improve the understanding of diseases and potentially contribute to the clinical development of new treatments.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第19996号 / 工博第4240号 / 新制||工||1656(附属図書館) / 33092 / 京都大学大学院工学研究科電気工学専攻 / (主査)教授 土居 伸二, 教授 小林 哲生, 准教授 蛯原 義雄 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

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A complex bio-mechanism, referred to as calcium homeostasis, regulates plasma ionized calcium (Ca++) concentration in the human body to within a narrow physiologic range which is crucial for maintaining normal physiology and metabolism. Various metabolic disorders and pathologic conditions originate from acute and/or chronic disturbances/disorders in calcium homeostatic system. This system relies on numerous sub-systems which operate in different time-scales ranging from minutes to weeks. In this thesis we focus on a particular sub-system that operates on the time-scale of minutes; the dynamics involves the response of the parathyroid glands to acute changes in plasma Ca++ concentration. We develop a two-pool, linear time-varying model describing the dynamics of the sub-system. We show that this model can predict dynamics observed in clinical tests of induced hypo- and hyper-calcemia in normal humans. In addition, we develop a new protocol for the construction of a Ca-PTH reverse sigmoid curve based on the mathematical model. This protocol removes deficiencies in current protocols in that the resulting curve is invariant with respect to the subject's axis dynamics and calcium clamp test dynamics.

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In recent years, customers' life stylish and behaviour have been changed and their tendencies become more diverse than before. As well as, market researches show a growing trend of special demands in their inclination. Accordingly, the companies compete to meet market demands for the reason of satisfying and maintaining the loyalty of their customers. This has led researchers to seek flexible methods and optimum solutions in production processes. In this regard, the manufacturing flow is one of the places in which flexibility and optimization can cause improvement is the assembly line. So, to meet the increasing diversity of market demand, assembly line processes must have the flexibility and ability to dynamically change product specifications and features while minimizing the operating and production processes' costs. For this reason, companies use solutions for designing assembly lines based on designing a flexible manufacturing system (FMS) for fast and better managing material feeding and handling. The FMS is a manufacturing method that is developed to easily can compatible with changes in production in the type and quantity of the product that has been manufactured. The performance of an FMS depends on the precise and efficient scheduling of material handling equipment. In this regard, the use of automated guided vehicles (AGV) instead of conveyors in an assembly line provid effectiveness and transformative.The aim of this research is to obtain the optimal numbers of AGVs required for the purpose of material handling at assembly lines. To solve the problem, a mathematical model has been developed. The objective function of the model is the number of AGVs. Accordingly, a set of variables and constraints have been determined have been considered to solve the linear optimization equation. In addition, the influence of workstations’ buffer capacity on material handling activities and the number of AGVs are studied by using this developed mathematical model.In order to evaluate experiments and analysis of the problem, Python programming software and its libraries have been used to calculate rapidly and accurately equations of the model. Preliminary results show that according to the layout of the production line and demand/production planning, as well as determining the size of input and output buffers of workstations, the proposed mathematical model calculates the minimum number of required vehicles and by changing the size of buffers we achieve different results. The aforementioned IT artefact is implemented in the direction of industrial digitalization and can be developed as application software in the eventuality. And further, this master project is desirable to take performance to continue sustainable development principles. / <p>Examensarbetet är på 16,5 hp:</p><p>Master Degree Project in Virtual Product RealizationOne year Level 16.5 ECTSSpring term 2022</p>

Current state-of-the-art thermoregulatory models do not predict body temperatures with the accuracies that are required for the development of automatic cooling control in liquid cooling garment (LCG) systems. Automatic cooling control would be beneficial in a variety of space, aviation, military, and industrial environments for optimizing cooling efficiency, for making LCGs as portable and practical as possible, for alleviating the individual from manual cooling control, and for improving thermal comfort and cognitive performance. In this study, we adopt the Fiala thermoregulatory model, which has previously demonstrated state-of-the-art predictive abilities in air environments, for use in LCG environments. We validate the numerical formulation with analytical solutions to the bioheat equation, and find our model to be accurate and stable with a variety of different grid configurations. We then compare the thermoregulatory model s tissue temperature predictions with experimental data where individuals, equipped with an LCG, exercise according to a 700 W rectangular type activity schedule. The root mean square (RMS) deviation between the model response and the mean experimental group response is 0.16°C for the rectal temperature and 0.70°C for the mean skin temperature, which is within state-of-the-art variations. However, with a mean absolute body heat storage error (e_BHS_mean) of 9.7 W·h, the model fails to satisfy the ±6.5 W·h accuracy that is required for the automatic LCG cooling control development. In order to improve model predictions, we modify the blood flow dynamics of the thermoregulatory model. Instead of using step responses to changing requirements, we introduce exponential responses to the muscle blood flow and the vasoconstriction command. We find that such modifications have an insignificant effect on temperature predictions. However, a new vasoconstriction dependency, i.e. the rate of change of hypothalamus temperature weighted by the hypothalamus error signal (DThy·dThy/dt), proves to be an important signal that governs the thermoregulatory response during conditions of simultaneously increasing core and decreasing skin temperatures, which is a common scenario in LCG environments. With the new DThy·dThy/dt dependency in the vasoconstriction command, the e_BHS_mean for the exercise period is reduced by 59% (from 12.9 W·h to 5.2 W·h). Even though the new e_BHS_mean of 5.8 W·h for the total activity schedule is within the target accuracy of ±6.5 W·h, e_BHS fails to stay within the target accuracy during the entire activity schedule. With additional improvements to the central blood pool formulation, the LCG boundary condition, and the agreement between model set-points and actual experimental initial conditions, it seems possible to achieve the strict accuracy that is needed for automatic cooling control development.

High pressure processing (HPP) and gamma irradiation were applied to inactivate <i>Vibrio vulnificus</i> (MO624) and <i>Vibrio parahaemolyticus</i> (O3:K6 TX2103) in pure culture and in inoculated live oysters. <i>Vibrio</i> pure culture and inoculated oysters were exposed to pressures of 207 MPa (30 kpsi) to 552 MPa (80 kpsi) for 0 min to maximum of 20 min. More than 5.4 log reductions of <i>V. vulnificus</i> occurred at 345 MPa for 0 min in oysters; 345 MPa for 2 min can achieve 4 log reductions on <i>V. parahaemolyticus</i>. Dosage of 1 kGy gamma-irradiation was proved to be effective in producing <i>Vibrio</i> free oysters with comparable organoleptic quality to raw oysters. Thermal conductivity of shucked oysters was measured to be 0.58 to 0.68 W/m°C, as temperature increased from 0 to 50 °C, using a line heat source probe. The specific heat was measured by differential scanning calorimeter methods. It increased from 3.80 to 4.05 kJ/kg °C, when temperature rose from 10 to 50 °C. The thermal diffusivity was calculated employing the data of thermal conductivity, specific heat and density of shucked oysters. The results showed that, under the tested temperature range, thermal properties did not change significantly with temperature. The dielectric constant and loss factor of oysters were determined by an open-ended coaxial line probe connected to a network analyzer at frequency of 30 MHz to 3000 MHz from 1 to 55 °C. The penetration depth of dielectric heating was calculated to be 1.1 cm with the dielectric constant of 55 and loss factor of 14. A two-dimensional mathematical model was established to simulate the heat transfer of microwave heating using a fish gel. Finite difference method was utilized to solve partial differential heat transfer equations. The model was able to predict the temperature distribution in heated fish gel with an accuracy of ± 8°C. Applying the developed mathematical model, the lethality of <i>Vibrio</i> spp., artificially inoculated in live oysters, was estimated collectively by integrating the individual localized lethality of designated heating units. The predicted lethality was compared with microwave enumeration data on Vibrios in oysters. The observed maximum log reductions by microbial enumeration were 4.4 and 3.4 for <i>V. vulnificus</i> and <i>V. parahaemolyticus</i>, respectively. The lethality calculated by integrating temperature profiles was acceptable. The discrepancy between the estimated lethality and microbial test was attributed to the simplified model construction. The quality of processed oysters, including color, aroma and texture properties, was evaluated instrumentally by a digital image system, an electronic nose and universal testing machine. The performance of two electronic nose systems on their abilities to detect oyster aroma and classify the aroma data into distinct groups was evaluated using a trained sensory panel and microbial tests. Cyranose 320 system has demonstrated potential as a quality assessment tool due to its sound correlation with microbial quality data and sensory evaluation scores. According to the quality measurement results, high pressure processing conditions were recommended to be at 345 MPa for less than 3 min and 379 MPa for less than 1.5 min. Deterioration of the quality was distinct for oyster meats exposed to 60 °C or above by thermal processing. The critical thermal processing condition was identified to be 55 °C for 2 min. With careful control, microwave processing could be considered as a candidate for seafood processing to reduce potential bacterial hazard but still retain the quality of the product. / Ph. D.

There are thousands of species of mosquitoes, but only a handful of these species carry pathogens that cause human diseases. Here, we study two species, Aedes albopictus and Aedes aegypti, which transmit infections such as dengue, Zika, Mayaro virus, and La Crosse virus. Curtailing these diseases is a good reason to consider control of mosquito populations. However, mosquitoes are quite hardy and spraying of pesticides is typically a short-term solution. Thus, more long-term solutions require careful thought about mosquito populations, including early juvenile aquatic stages: egg, larva, and pupa. In this dissertation, we examine the factors that affect the dynamics of aquatic stages by creating mathematical models. The goal is to assess what key biological features most impact the total population. Both Aedes albopictus and Aedes aegypti lay eggs in small containers, producing limitations on space and food. We investigate how restricting resources changes development time, survival to adulthood, and body mass at emergence. The interactions between these changes are complicated, so to disentangle their effects we create three different mathematical models. The first model is discrete in time and focuses on the best way to incorporate the influence of larval density. We compare the impact of larval density by inputting seven different functional forms altering survival and development time. Larval density used in the model is determined from the average of the population size over the past one to thirty-six days. The second model is also discrete in time but focuses on the interaction between survival, development time, and mass. This model considers three levels of mass. Here, we use the density-dependent function determined from our first model and fit the maximum value for development time from experimental data. Survival values are fit using constants and a density-dependent function. Finally, growth is built in as a function of food. Food decreases at each time point as a function of the total larvae in the environment. We compare between model formulations with Akaike information criterion. The third model examines the ramifications of constricting resources on growth verses death. We employ a partial differential equation that has three independent variables: time, age, and mass. We find that density dependence is highly influential in the maturation of mosquitoes, and it is more essential to include its impacts on development time than on survival. These findings can be incorporated into a larger framework of disease dynamics, and give insight into better control of mosquitoes and disease spread. / Doctor of Philosophy / There are thousands of species of mosquitoes, but only a handful of these species spread human diseases. We specifically study mosquitoes that transmit diseases such as dengue and Zika, which plague large portions of the world. One way to reduce disease spread by mosquitoes is to eliminate the mosquito population, but mosquitoes are becoming resistant to commonly used insecticides. Thus, additional ways to combat mosquitoes are needed. To do so requires a better understanding of how mosquito populations change. This necessitates incorporating information from all life stages of the mosquito, including the juvenile stages that live in the water. In this dissertation, we examine various factors that affect the population size and characteristics of young mosquitoes by creating mathematical models. The goal is to assess what key biological features most impact the population. As young mosquitoes live in aquatic environments, there are limitations on space and food. We investigate how restricting resources changes the time it takes for mosquitoes to develop into adults, how many survive to adulthood, and what their body mass is as new adults. These outcomes interact in complicated way. To disentangle this, we create three different mathematical models. The first model focuses on the best way to incorporate the influence of limiting space or density on population size. The second model focuses on the interaction between mosquito body mass, survival, and time spent as a juvenile. The third model examines how resources alter growth and death and the ensuing mass of mosquitoes. Models are fit to experimental data and validated based on how accurately they describe known patterns. We find that population density is highly influential in the maturation of juvenile mosquitoes and its most important effect is on time spent as a juvenile mosquito. By correlating growth of juvenile mosquitoes to density and resources, our second model is better able to reproduce data. These findings provide important understanding on mosquito populations, which provides insight into how to better control mosquitoes and the diseases they spread.

No / Antenna array technology has attracted the attention of the research community as a means to increase system capacity and improve the signal reception. Space division multiple access (SDMA) is a multi-access scheme based on the use of antenna arrays to separate users by exploiting their positions in space. Several works have been carried out to examine the improvement in the system capacity provided by SDMA. A theoretical model to determine the blocking probability for SDMA is derived. A closed-form linear system of equations is obtained whose numerical solution gives the blocking probability. The formulation is employed to assess the capacity gain improvement of a single-cell system under specific conditions. It is found from the results that SDMA is not efficient for low traffic loads, whereas it is so for high traffic.