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Title: SIGNALING MECHANISMS OF PULMONARY ARTERIAL HYPERTENSION
Creator: Ji, Yajing
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Pulmonary arterial hypertension (PAH) is a severe and life-threatening disease that is characterized by elevated pulmonary blood pressure. A challenge in treating PAH is that while the current generation of therapeutics alleviate symptoms, they fail to target the underlying causes of the disease. Initially it was thought that PAH is caused by increased pulmonary vasoconstriction; it is now understood that PAH mainly results from remodeling of the pulmonary vasculature. Further...
Show morePulmonary arterial hypertension (PAH) is a severe and life-threatening disease that is characterized by elevated pulmonary blood pressure. A challenge in treating PAH is that while the current generation of therapeutics alleviate symptoms, they fail to target the underlying causes of the disease. Initially it was thought that PAH is caused by increased pulmonary vasoconstriction; it is now understood that PAH mainly results from remodeling of the pulmonary vasculature. Further characterization of the underlying mechanisms of PAH will identify newpharmacological targets to treat PAH. In this dissertation I seek to address this challenge from three distinct perspectives. In Chapter 2, I investigated the signaling network downstream of TGFβ and highlighted the MRTF/SRF pathway as potential therapeutical targets for PAH given its pivotal role regulating expression of contractile proteins in PASMCs. In Chapter 3, I aim to test whether TGFβ and the silencing of BMPR2, a member of the TGFβ family of receptors, contribute to the activation of lung fibroblasts in vitro. My results presented do not replicate the role of BMPR2 silencing found in other studies. This could be caused by the relatively short duration of BMPR2 silencing in our system. Finally, in Chapter 4, I perform a combined meta-analysis of several publicly available transcriptomic datasets of lung tissues from PAH patients. Using this approach, I identify PAH-associated signaling pathways, and chemical compounds which reverse a PAH-associated gene expression signature. My findings also suggest that while we bin PAH patients into various subtypes in the clinic, on a transcriptional level, PAH patients tend to group into distinct gene expression clusters without relying on their clinical subtype. These findings improve our understanding of PAH biology and also highlight several potential drug targets for PAH.
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Title: I. Determination of Absolute Configuration of Chiral 1,2-Diols. II. Progress Towards the Total Synthesis of Napyradiomycin A1.
Creator: Torabi Kohlbouni, Saeedeh
Date: 2022
Collection: Electronic Theses & Dissertations
Description: This dissertation focuses on two parts. The first part introduces an operationally simple and microscale method for the absolute stereochemical determination of 1,2-diols. In situ derivatization of 1,2-diols with dinaphthyl borinic acid generates the induced helicity of the two naphthyl groups, which leads to an observable ECCD spectrum. The observed P or M helicity follows a predictable trend for S and R chiral 1,2-diols, respectively.The Second chapter is the progress towards the asymmetric...
Show moreThis dissertation focuses on two parts. The first part introduces an operationally simple and microscale method for the absolute stereochemical determination of 1,2-diols. In situ derivatization of 1,2-diols with dinaphthyl borinic acid generates the induced helicity of the two naphthyl groups, which leads to an observable ECCD spectrum. The observed P or M helicity follows a predictable trend for S and R chiral 1,2-diols, respectively.The Second chapter is the progress towards the asymmetric catalytic synthesis of napyardiomycin A1. The chapter is divided to three sections. The first section is installation of chlorine chiral center at C3. This goal is achieved using cinchona chiral catalyst, and DCDMH as chloronium source. The second section is the synthesis of the -lapachone core of napyradiomycin A1, was accomplished using Diels-Alder/aromatization cascade reaction. The last section shows our effort toward the attachment of geranyl side chain.
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Title: Solving Computationally Expensive Problems Using Surrogate-Assisted Optimization : Methods and Applications
Creator: Blank, Julian
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Optimization is omnipresent in many research areas and has become a critical component across industries. However, while researchers often focus on a theoretical analysis or convergence proof of an optimization algorithm, practitioners face various other challenges in real-world applications. This thesis focuses on one of the biggest challenges when applying optimization in practice: computational expense, often caused by the necessity of calling a third-party software package. To address the...
Show moreOptimization is omnipresent in many research areas and has become a critical component across industries. However, while researchers often focus on a theoretical analysis or convergence proof of an optimization algorithm, practitioners face various other challenges in real-world applications. This thesis focuses on one of the biggest challenges when applying optimization in practice: computational expense, often caused by the necessity of calling a third-party software package. To address the time-consuming evaluation, we propose a generalizable probabilistic surrogate-assisted framework that dynamically incorporates predictions of approximation models. Besides the framework's capability of handling multiple objectives and constraints simultaneously, the novelty is its applicability to all kinds of metaheuristics. Moreover, often multiple disciplines are involved in optimization, resulting in different types of software packages utilized for performance assessment. Therefore, the resulting optimization problem typically consists of multiple independently evaluable objectives and constraints with varying computational expenses. Besides providing a taxonomy describing different ways of independent evaluation calls, this thesis also proposes a methodology to handle inexpensive constraints with expensive objective functions and a more generic concept for any type of heterogeneously expensive optimization problem. Furthermore, two case studies of real-world optimization problems from the automobile industry are discussed, a blueprint for solving optimization problems in practice is provided, and a widely-used optimization framework focusing on multi-objective optimization (founded and maintained by the author of this thesis) is presented. Altogether, this thesis shall pave the way to solve (computationally expensive) real-world optimization more efficiently and bridge the gap between theory and practice.
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Title: FIBER-OPTIC SILICON FABRY-PEROT INTERFEROMETERS FOR HIGH-SPEED ANEMOMETER AND HIGH-SENSITIVITY BOLOMETER APPLICATIONS
Creator: Uddin, Nezam
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Fiber-optic silicon Fabry-Perot interferometric temperature sensor offers the advantage of high-speed and high-resolution to characterize the ocean turbulence in oceanographic research. Compared to silica, the material that makes the optical fiber, silicon has a thermo-optic coefficient ten times higher and a thermal conductivity sixty time higher. Silicon is highly transparent in the infrared wavelength range and can be easily processed with the mature microfabrication technology. All of...
Show moreFiber-optic silicon Fabry-Perot interferometric temperature sensor offers the advantage of high-speed and high-resolution to characterize the ocean turbulence in oceanographic research. Compared to silica, the material that makes the optical fiber, silicon has a thermo-optic coefficient ten times higher and a thermal conductivity sixty time higher. Silicon is highly transparent in the infrared wavelength range and can be easily processed with the mature microfabrication technology. All of these make silicon a very attractive material for high-speed and high-resolution turbulence measurement. We attached a small silicon pillar to the end of an optical fiber to make fiber-optic Fabry-Perot interferometric sensor demodulated by a white light system for fast turbulence measurement. We studied the two modes of fiber-optic hot wire anemometer operation for turbulence measurement theoretically and experimentally. The constant temperature operation of the fiber-optic hot wire anemometer was introduced for the first time to reduce the time constant significantly. The anemometer used for demonstration is based on a silicon low-finesse Fabry-Perot interferometer (FPI) attached to the tip of a single mode fiber. Turbulent flow measurement method based on constant temperature operation offers high measuring speed, because the wire temperature is kept constant, the effect of thermal inertia of the wire is suppressed. We also investigated a new sensor structure experimentally and theoretically for the measurement of water flow with reduced directivity. This sensor consists of a laser heated silicon FPI embedded in a metal microsphere. Herein, the spherical shape of the outside metal shell gives a symmetric response to water flow direction; thus, the directivity is reduced greatly. Moreover, the water flow measurement by the hot wire fiber-optic water flow sensor based on laser heated silicon FPI need to compensate the effect of water temperature variation. We reported a technique to compensate the effect of water temperature change in the flow measurement by using another sensor which will track the temperature of the water. By using the information of the water temperature change, baseline can be defined which will provide unique wavelength change for the flow. Finally, the wavelength change corresponding to the flow speed were calibrated using the sensor pair after compensating the effect of water temperature variation. We expanded the use of silicon Fabry-Perot interferometric sensor in the measurement of plasma radiation by modifying the structure with gold coated silicon and multimode graded index fiber between the single mode fiber (SMF) and silicon. We reported the design, fabrication, and characterization of a fiber-optic bolometer (FOB) with improved noise equivalent power density (NEPD) performance and increased absorption to high energy photons by engineering the absorber of the FOB. We also have developed a multichannel fiberoptic bolometry system with five bolometers connected to each channel of the coarse wavelength division multiplexer (CWDM), a single light source of super luminescent LED (SLED) and a single I-MON 512 OEM spectrometer. Easy sensor fabrication, significantly enhanced measurement range compared to the previous high-finesse FPI bolometer system for measuring radiation are some of the advantages. Moreover, utilization of the FOB in the vacuum for radiation measurement with reduced time constant was also studied which is practically required in the fusion devices. This was done by adding a heat sink with the current FOB structure and using the deconvolution method to get better temporal resolution. Finally, the FOB with the heat sink was tested in the vacuum condition to measure the radiation using the deconvolution method. Experimental results are presented to support the idea of heat sink and deconvolution method for plasma radiation measurement.
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Title: KNOWLEDGE SPILLOVERS AND SAFE DRINKING WATER ACT COMPLIANCE
Creator: Redican, Kyle James
Date: 2022
Collection: Electronic Theses & Dissertations
Description: In the wake of the 2014 Flint Water Crisis, researchers, regulators, and utility professionals have given increased attention to understanding drivers of (CWS) Safe Drinking Water Act (SDWA) compliance by community water systems (CWSs). Most of this research has only explored system traits while ignoring the vital role of human capital, especially the operator. The status of CWS operators can vary widely between different systems. More critically, scholars have not investigated how effective...
Show moreIn the wake of the 2014 Flint Water Crisis, researchers, regulators, and utility professionals have given increased attention to understanding drivers of (CWS) Safe Drinking Water Act (SDWA) compliance by community water systems (CWSs). Most of this research has only explored system traits while ignoring the vital role of human capital, especially the operator. The status of CWS operators can vary widely between different systems. More critically, scholars have not investigated how effective external linkages between CWS operators have impacted SDWA compliance. Drawing from the theories of Organizational Learning’s inter-organizational learning, Innovation Systems’ knowledge transfers, and Agglomeration Economics’ knowledge spillovers, I hypothesized that increased interactions between CWS operators, facilitated in part by geographic proximity, would lead to more information sharing, increased CWS performance, and fewer SDWA violations. Remarkably little is known about the drivers of inter-operator interactions or whether such interactions improve SDWA compliance, and this research helped fill the data gap through a large-sample survey of CWS operators in Michigan to capture the frequency of interactions along with a range of operator and system characteristics which may explain why some operators participate in more inter-operator interactions than others. With this novel dataset, along with publicly available system and community data, this research first investigated what endogenous operator characteristics were associated with more reported inter-operator interactions. Through multiple methods on reported operator interactions, the Utility and Contract operators and operators with memberships in professional organizations appear more likely to report more interactions than Non-Affiliated operators and all operators who were not members of professional organizations. Second, based on Tobler’s first law of geography, there should be some spatial autocorrelation in the number of reported interactions, and this was tested using variogram modeling. Observed spatial autocorrelation indicated location-based differences in the number of reported interactions. Third, we used multiple methods to explore the primary research question to identify endogenous and spatial drivers of reported inter-operator interactions. Multiple models found that rural districts had a higher probability of fewer SDWA violations with increased interactions, while the urban districts had the inverse relationship. Fourth, the research incorporated CWS-specific and operator-specific variables, as the operator-specific data were not independent of the CWS observations (since some operators run multiple CWSs). I used a Generalized Linear Mixed-Model to estimate these relationships accounted for the multiple levels and found that more interactions increased the probability of SDWA compliance for certain types of operators. The broader implications of this research encourage stakeholders to pursue more inter-operator interactions as a low-cost mechanism to increase SDWA compliance. Seven avenues to increase interactions are outlined, ranging from open operator contact lists to operator focus groups to identify common problems and solutions to creating a state-level operator mentorship program to support new operators.
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Title: BUILDING STATE WILDLIFE AGENCY CAPACITY FOR EFFECTIVE PARTNERSHIPS
Creator: Cross, Megan M
Date: 2022
Collection: Electronic Theses & Dissertations
Description: State wildlife agencies (SWAs) partner with organizations of various types, on projects of various types, at what is anticipated to be an increasing rate. Inclusion of multiple and diverse stakeholders and partners is postulated to improve effectiveness of wildlife management (Anderson & Loomis, 2007; Jacobson et al., 2010). Through partnerships, actors from private, civil, and public sectors work together to reduce negative impacts from wildlife and improve access to and benefits of wildlife...
Show moreState wildlife agencies (SWAs) partner with organizations of various types, on projects of various types, at what is anticipated to be an increasing rate. Inclusion of multiple and diverse stakeholders and partners is postulated to improve effectiveness of wildlife management (Anderson & Loomis, 2007; Jacobson et al., 2010). Through partnerships, actors from private, civil, and public sectors work together to reduce negative impacts from wildlife and improve access to and benefits of wildlife resources. Although partnerships can improve the ability of SWAs to address these issues, little is known about how the perspectives of internal employees and external partners and stakeholders differ regarding factors affecting perceived success of partnerships in wildlife conservation.This dissertation addresses SWA partnerships through an examination of one prototypical SWA’s partnership arrangements. I propose a typology for categorization of SWA partnerships and apply a theory of collaborative capacity to the assessment of them. I surveyed all employees of the Michigan SWA and asked them to identify the three partners they consider most key to their work and found gaps in the frequencies of partners considered key to the work of SWA employees based on their locations in the defined typology. Additionally, the model of collaborative capacity tested varied in performance when applied to SWA employees and SWA partners. This research has implications for transparency regarding how state power is shared and considers how the disparate prevalence of various partnership arrangements may affect wildlife governance. Furthermore, my research findings may be used to improve SWA partnership arrangements and improve their alignment with governance and management-relate goals, as well as increase awareness of differences in views regarding partnership success as defined by SWA employees and partners.
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Title: Life Cycle Monitoring of Reversible Adhesive Bonded Joints using Guided Waves
Creator: Palanisamy, Rajendra Prasath
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Recent advancements in automotive, aerospace, civil and wind-energy industries have resulted in an ever-increasing demand for lightweight, cost-effective, rapidly manufactured and recyclable/reusable of structural components. Adopting composite materials is a popular solution to achieve light-weighting, however it requires complex joining methods compared to traditional mechanical fasteners. Electromagnetic targeted heating of nano-Fe3O4 reinforced thermoplastic adhesives (Reversible-Adhesive...
Show moreRecent advancements in automotive, aerospace, civil and wind-energy industries have resulted in an ever-increasing demand for lightweight, cost-effective, rapidly manufactured and recyclable/reusable of structural components. Adopting composite materials is a popular solution to achieve light-weighting, however it requires complex joining methods compared to traditional mechanical fasteners. Electromagnetic targeted heating of nano-Fe3O4 reinforced thermoplastic adhesives (Reversible-Adhesive) is an emerging technique for rapid assembly, dis-assembly, and re-assembly of bonded composite parts. Alternate magnetic field applied to the dispersed ferromagnetic nanoparticles (FMNP) within a thermoplastic adhesive results in these particles acting as nano-heaters and rapidly heating the surrounding material resulting in melting and flow of the adhesive, which upon cooling forms a structural bond. This process can be repeated and hence termed reversible adhesive. Reversible-adhesive bonded composite structures (RBCS) offer a greater advantage over thermosets or mechanical joints such as rapid processing, easy repair, quick disassembly, and possible re-usability of components. However, it is essential to accurately measure the temperature of the adhesive during processing and repair, since overheating may cause chemical degradation and underheating may introduce improper bonds. Adhesively bonded composite structures provide a more uniform stress distribution in the bond-line than riveted joints resulting in higher fatigue life. However, modeling the physics behind crack initiation and propagation inside bonded regions is challenging especially under fatigue loading. As a result, real-time in-service bond monitoring is required to ensure structural safety. In addition to monitoring the damage state, prediction of damage area and remaining useful life of the component is imperative. Thus, this research work focusses on developing a life cycle monitoring solution for RBCS using the guided wave (GW) technique. Ultrasonic guided waves were made to propagate across the bond-line of the joint by exciting and sensing them using miniature piezoelectric wafers. Analysis of dispersion relations and dynamic wave propagation were performed using finite element modeling (FEM). Fundamental longitudinal mode L_0 at 35 kHz was found optimal for bond process monitoring. Mapping between the FE-simulated transmission coefficient of L_0 and actual temperature of the thermoplastic adhesive was established using the DMA test data. Real-time guided wave measurements were used as feedback in the discrete control of the induction heater so as to provide optimal bonding and prevent adhesive degradation. The developed ultrasonic technique was successfully validated by fiber-optic temperature sensing. Results indicate that the bondlines processed with GW control offer better ultimate strength compared to uncontrolled processing.Guided wave modal and frequency sensitivity analysis for fatigue damage was performed. Based on the analysis, symmetric mode at 85 kHz was found optimal for fatigue damage detection. Further, a damage propagation model based on Paris law was developed to estimate remaining useful life in terms of the GW signal features. Finally, the remaining useful life of the lap-joint was predicted and validated experimentally. One of the major advantages of reversible adhesive is its ability to repair/heal the damage. The controlled processing technique developed earlier was used for controlled healing of fatigue damaged joints. Experimental investigation proves the healed-bond line have returned to its original strength. A holistic approach of a complete lifecycle monitoring of bonded joints was aimed at increasing the confidence in the use of bonded joints relative to mechanical fasteners, and can be easily extended to other structural applications.
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Title: High-precision and Personalized Wearable Sensing Systems for Healthcare Applications
Creator: Tu, Linlin
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The cyber-physical system (CPS) has been discussed and studied extensively since 2010. It provides various solutions for monitoring the user's physical and psychological health states, enhancing the user's experience, and improving the lifestyle. A variety of mobile internet devices with built-in sensors, such as accelerators, cameras, PPG sensors, pressure sensors, and the microphone, can be leveraged to build mobile cyber-physical applications that collected sensing data from the real world...
Show moreThe cyber-physical system (CPS) has been discussed and studied extensively since 2010. It provides various solutions for monitoring the user's physical and psychological health states, enhancing the user's experience, and improving the lifestyle. A variety of mobile internet devices with built-in sensors, such as accelerators, cameras, PPG sensors, pressure sensors, and the microphone, can be leveraged to build mobile cyber-physical applications that collected sensing data from the real world, had data processed, communicated to the internet services and transformed into behavioral and physiological models. The detected results can be used as feedback to help the user understand his/her behavior, improve the lifestyle, or avoid danger. They can also be delivered to therapists to facilitate their diagnose. Designing CPS for health monitoring is challenging due to multiple factors. First of all, high estimation accuracy is necessary for health monitoring. However, some systems suffer irregular noise. For example, PPG sensors for cardiac health state monitoring are extremely vulnerable to motion noise. Second, to include human in the loop, health monitoring systems are required to be user-friendly. However, some systems involve cumbersome equipment for a long time of data collection, which is not feasible for daily monitoring. Most importantly, large-scale high-level health-related monitoring systems, such as the systems for human activity recognition, require high accuracy and communication efficiency. However, with users' raw data uploading to the server, centralized learning fails to protect users' private information and is communication-inefficient. The research introduced in this dissertation addressed the above three significant challenges in developing health-related monitoring systems. We build a lightweight system for accurate heart rate measurement during exercise, design a smart in-home breathing training system with bio-Feedback via virtual reality (VR) game, and propose federated learning via dynamic layer sharing for human activity recognition.
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