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- Title
- Towards Trustworthy Multiagent and Machine Learning Systems
- Creator
- Xie, Shangyu
- Date
- 2022
- Description
-
This dissertation aims to systematically research the "trustworthy" Multiagent and Machine Learning systems in the context of the Internet of...
Show moreThis dissertation aims to systematically research the "trustworthy" Multiagent and Machine Learning systems in the context of the Internet of Things (IoT) system, which mainly consists of two aspects: data privacy and robustness. Specifically, data privacy concerns about the protection of the data in one given system, i.e., the data identified to be sensitive or private cannot be disclosed directly to others; robustness refers to the ability of the system to defend/mitigate the potential attacks/threats, i.e., maintaining the stable and normal operation of one system.Starting from the smart grid, a representative multiagent system in the IoT, I demonstrate two works on improving data privacy and robustness in aspects of different applications, load balancing and energy trading, which integrates secure multiparty computation (SMC) protocols for normal computation to ensure data privacy. More significantly, the schemes can be readily extended to other applications in IoT, e.g., connected vehicles, mobile sensing systems.For the machine learning, I have studied two main areas, i.e., computer vision and natural language processing with the privacy and robustness correspondingly. I first present the comprehensive robustness evaluation study of the DNN-based video recognition systems with two novel proposed attacks in both test and training phase, i.e., adversarial and poisoning attacks. Besides, I also propose the adaptive defenses to fully evaluate such two attacks, which can thus further advance the robustness of system. I also propose the privacy evaluation for the language systems and show the practice to reveal and address the privacy risks in the language models. Finally, I demonstrate a private and efficient data computation framework with the cloud computing technology to provide more robust and private IoT systems.
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- Title
- Deep Learning Methods For Wireless Networks Optimization
- Creator
- Zhang, Shuai
- Date
- 2022
- Description
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The resurgence of deep learning techniques has brought forth fundamental changes to how hard problems could be solved. It used to be held that...
Show moreThe resurgence of deep learning techniques has brought forth fundamental changes to how hard problems could be solved. It used to be held that the solutions to complex wireless network problems require accurate mathematical modeling of the network operation, but now the success of deep learning has shown that a data-driven method could generate powerful and useful representations such that the problem could be solved efficiently with surprisingly competent performance. Network researchers have recognized this and started to capitalize on the learning methods’ prowess. But most works follow the existing black-box learning paradigms without much accommodation to the nature and essence of the underlying network problems. This thesis focuses on a particular type of classical problem: multiple commodity flow scheduling in an interference-limited environment. Though it does not permit efficient exact algorithms due to its NP-hard complexity, we use it as an entry point to demonstrate from three angles how the learning-based methods can help improve the network performance. In the first part, we leverage the graphical neural network (GNN) techniques and propose a two-stage topology-aware machine learning framework, which trains a graph embedding unit and a link usage prediction module jointly to discover links that are likely to be used in optimal scheduling. The second part of the thesis is an attempt to find a learning method that has a closer algorithmic affinity to the traditional DCG method. We make use of reinforcement learning to incrementally generate a better partial solution such that a high quality solution may be found in a more efficient manner. As the third part of the research, we revisit the MCF problem from a novel viewpoint: instead of leaning on the neural networks to directly generate the good solutions, we use them to associate the current problem instance with historical ones that are similar in structure. These matched instances’ solutions offer a highly useful starting point to allow efficient discovery of the new instance’s solution.
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- Title
- Essays on Clean Energy Finance and Cryptocurrency Market
- Creator
- Xie, Yao
- Date
- 2021
- Description
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This dissertation includes four essays with several empirical investigations in the areas of clean energy finance and cryptocurrencies.In the...
Show moreThis dissertation includes four essays with several empirical investigations in the areas of clean energy finance and cryptocurrencies.In the first essay, I investigate the heterogeneous relationship between various determinants of the clean energy market across all subsectors of the clean energy stock market. My findings reveal that VIX is the most significant predictor of all clean energy subsectors conditional volatility. During the COVID-19 stress period, economic uncertainty measures become more significant measures. The heterogeneity of clean energy market persists in the out-of-sample results. These results suggest that portfolio diversification for different clean energy subsector is necessary. In the second essay, I study the safe haven property of several volatility indexes on clean energy subsectors. I compare the current COVID-19 stress period and the time before. The results show that market volatility and commodity volatility are good safe haven assets during the COVID-19 period. But they are not safe haven assets against the clean energy subsector before the pandemic period. Among all volatility indexes, gold volatility index is the most effective safe haven assets. In the third essay, I investigate the characteristics of Bitcoin as a financial asset. A comprehensive set of information variables under five categories: macroeconomics, blockchain technology, other markets, stress level, and investor sentiment. The empirical results show that blockchain technology, stress level and investor sentiment have strong predicting power on Bitcoin returns. In the fourth essay, I aim to study how extreme sentiment measures from Google Trend and Wikipedia Pageviews affect both traditional cryptocurrency, such as Bitcoin and stablecoin, like Tether. Our results show that Tether’s return is not affected by the extreme sentiment measures during the COVID-19 stress period which suggests that stablecoin can offer price stability.
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- Title
- DEEP LEARNING AND COMPUTER VISION FOR INDUSTRIAL APPLICATIONS: CELLULAR MICROSCOPIC IMAGE ANALYSIS AND ULTRASOUND NONDESTRUCTIVE TESTING
- Creator
- Yuan, Yu
- Date
- 2022
- Description
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For decades, researchers have sought to develop artificial intelligence (AI) systems that can help human beings on decision making, data...
Show moreFor decades, researchers have sought to develop artificial intelligence (AI) systems that can help human beings on decision making, data analysis and pattern recognition applications where analytical methods are ineffective. In recent years, Deep Learning (DL) has been proven to be an effective AI technique that can outperform other methods in applications such as computer vision, natural language processing, autonomous driving. Realizing the potential of deep learning techniques, researchers have also started to apply deep learning on other industrial applications. Today, deep learning based models are used to innovate and accelerate automation, guidance, and decision making in various industries including automotive industry, pharmaceutical industry, finance, agriculture and more. In this research, several important industrial applications (on Biomedicine and Non-Destructive Testing) utilizing deep learning algorithms will be introduced and analyzed. The first biopharmaceutical application focuses on developing a deep learning based model to automate the visual inspection process in Median Tissue Culture Infectious Dose(TCID50). TCID50 is one of the most popular methods for viral quantification. An important step of TCID50 is to visually inspect the sample and decide if it exhibits cytopathic effect(CPE) or not. Two novel models have been developed to detect CPE in microscopic images of cell culture in 96 well-plates. The first model consists of a convolutional neural network (CNN) and support vector machine(SVM). The second model is a fully convolutional network (FCN) followed by morphological post-processing steps. The models are tested on 4 cell lines and achieve very high accuracy. Another biopharmaceutical application developed for cellular microscopic images is the clonal selection. Clonal selection is one of the mandatory steps in cell line development process. It focuses on verifying the clonality of the cell culture. The researchers used to visually inspect the microscopic images to verify the clonality. In this work, a novel deep learning based model and a workflow is developed to accelerate the process. This algorithm consists of multiple steps, including image analysis after incubation to detect the cell colonies, and verify its clonality in day0 image. The results and common mis-classification cases are shown in this thesis. Image analysis method is not the only technology that has been advancing for cellular image analysis in biopharmaceutical industry. A new class of instruments are currently used in biopharmaceutical industry which enable more opportunities for image analysis. To make the most of these new instruments, a convolutional neural network based architecture is used to perform accurate cell counting and cell morphology based segmentation. This analysis can provide more insight of the cells at very early stage in characterization process of cell line development. The architecture and the testing results are presented in this work. The proposed algorithm has achieved very high accuracy on both applications, and the cell morphology based segmentation enables a brand new feature for scientists to predict the potential productivity of the cells. Next part of this dissertation is focused on hardware implementation of Ultrasonic Non-Destructive Testing (NDT) methods based on deep learning, which can be highly useful in flaw detection and classification applications. With the help of a smart and mobile Non-Destructive Testing device, engineers can accurately detect and locate the flaws inside the materials without reliance on high performance computation resources. The first NDT application presents a hardware implementation of a deep learning algorithm on Field-programmable gate array(FPGA) for Ultrasound flaw detection. The Ultrasound flaw detection algorithm consists of a wavelet transform followed by a LeNet inspired convolutional neural network called Ultra-LeNet. This work is focused on implementing the computationally difficult part of this algorithm: Ultra-LeNet, so that it can be used in the field where high performance computation resources (e.g., AWS) are not accessible. The implementation uses resource partitioning to design two dedicated pipelined accelerators for convolutional layers and fully connected layers respectively. Both accelerators utilize loop unrolling, loop pipelining and batch processing techniques to maximize the throughput. The comparison to other work has shown that the implementation has achieved higher hardware utilization efficiency. The second NDT application is also focused on implementing a deep learning based algorithm for Ultrasound flaw detection on a FPGA. Instead of implementing the Ultra-LeNet, the deep learning model used in this application is Meta-learning based Siamese Network, which is capable for multi-class classification and it can also classify a new class even if it does not appear in the training dataset with the help of automated learning features. The hardware implementation is significantly different than the previous algorithm. In order to improve the inference operation efficiency, the model is compressed with both pruning and quantization, and the FPGA implementation is specifically designed to accelerate the compressed CNN with high efficiency. The CNN model compression method and hardware design are novel methods introduced in this work. Comparison against other compressed CNN accelerators is also presented.
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- Title
- MARKETABLE LIMIT ORDERS AND NON-MARKETABLE LIMIT ORDERS ON NASDAQ
- Creator
- ZHANG, DAN
- Date
- 2022
- Description
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My research includes two parts. In the first part of my research, I classify marketable limit orders into three different types: large...
Show moreMy research includes two parts. In the first part of my research, I classify marketable limit orders into three different types: large marketable order to buy, large marketable order to sell, and small marketable order. I use dummy variance method to research the effect of the three marketable orders on standardized variance, and find that LMOB and LMOS play significant role in variance increase. The second part of my research is about modelling of time to execution and time to cancellation of Non-marketable limit orders. I construct variables and model time to execution for NLO to buy and time to cancellation for NLO to buy and NLO to sell based on exponential distribution with accelerated failure time specification. My research shows that the longer the distance of limit price to buy away from the best bid price, the longer time to execution is. The longer the distance of limit price to buy away from the best bid price or limit price to sell away from the best ask price, the longer the time to cancellation is.
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- Title
- Stochastic dynamical systems with non-Gaussian and singular noises
- Creator
- Zhang, Qi
- Date
- 2022
- Description
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In order to describe stochastic fluctuations or random potentials arising from science and engineering, non-Gaussian or singular noises are...
Show moreIn order to describe stochastic fluctuations or random potentials arising from science and engineering, non-Gaussian or singular noises are introduced in stochastic dynamical systems. In this thesis we investigate stochastic differential equations with non-Gaussian Lévy noise, and the singular two-dimensional Anderson model equation with spatial white noise potential. This thesis consists of the following three main parts. In the first part, we establish a linear response theory for stochastic differential equations driven by an α-stable Lévy noise (1<α<2). We first prove the ergodic property of the stochastic differential equation and the regularity of the corresponding stationary Fokker-Planck equation. Then we establish the linear response theory. This result is a general fluctuation-dissipation relation between the response of the system to the external perturbations and the Lévy type fluctuations at a steady state.In the second part, we study the global well-posedness of the singular nonlinear parabolic Anderson model equation on a two-dimensional torus. This equation can be viewed as the nonlinear heat equation with a random potential. The method is based on paracontrolled distribution and renormalization. After splitting the original nonlinear parabolic Anderson model equation into two simpler equations, we prove the global existence by some a priori estimates and smooth approximations. Furthermore, we prove the uniqueness of the solution by classical energy estimates. This work improves the local well-posedness results in earlier works.In the third part, we investigate the variation problem associated with the elliptic Anderson model equation in a two-dimensional torus in the paracontrolled distribution framework. The energy functional in this variation problem is arising from the Anderson localization. We obtain the existence of minimizers by a direct method in the calculus of variations, and show that the Euler-Lagrange equation of the energy functional is an elliptic singular stochastic partial differential equation with the Anderson Hamiltonian. We further establish the L2 estimates and Schauder estimates for the minimizer as weak solution of the elliptic singular stochastic partial differential equation. Therefore, we uncover the natural connection between the variation problem and the singular stochastic partial differential equation in the paracontrolled distribution framework.Finally, we summarize our results and outline some research topics for future investigation.
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- Title
- Expanding the Magic Circle and the Self: Integrating Discursive Topics into Games
- Creator
- da Rosa Faller, Roberto
- Date
- 2020
- Description
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This study focuses on games for self-development and how they communicate ideas, challenge established assumptions, cause reflection, and...
Show moreThis study focuses on games for self-development and how they communicate ideas, challenge established assumptions, cause reflection, and provoke change. It explores the integration of discursive topics – specifically those perceived as difficult, political, philosophical, taboo, or controversial – into games, and how to manage player exposure to these topics through design while avoiding player disengagement to achieve self-development goals. Using a Research Through Design approach, this study was conducted in two phases. The first exploratory phase resulted in an analytical framework with four distinct lenses: engaging play experience; player’s emotional investment; the friction points of discursive topics; and, controlled exposure to the topic. During the second phase, this framework was used to analyze eight case studies and three prototypes. The resultant insights from analysis revealed five categories – topic depiction, emotional climate, emotional anchors, topic delivery, and exposure timing – that form the Discursive Topic Integration Framework for self-development. This framework offers a new theoretical perspective for design scholars and practicing designers about how to manipulate the “magic circle” (a safe temporary space for the act of play), by intentionally designing for discursive topics and their friction points. It contributes strategies about when, how, how frequently, and with what intensity discursive topics may be introduced and abstracted in games. It frames the discursive topic, creates the emotional climate, and anchors the player inside the magic circle of the game so that they feel engaged, motivated, and curious without becoming overwhelmed. This study also generated two additional frameworks, including: the Self-Development Opportunity Matrix that can be used to generate or evaluate self-development goals; and, the Five Categories of Transitional and Traumatic Experiences that can assist in the design of games and other experiences that build a person’s capacity, self-determination, and commitment to positive change.
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- Title
- Development of a novel ultra-nanocrystalline diamond (UNCD) based photocathode and exploration of its emission mechanisms
- Creator
- Chen, Gongxiaohui
- Date
- 2020
- Description
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High quality electron sources are one of the most commonly used probing tools used for the study of materials. Photoemission cathodes, capable...
Show moreHigh quality electron sources are one of the most commonly used probing tools used for the study of materials. Photoemission cathodes, capable of producing ultra-short and ultra-high intensity beams, are a key component of accelerator based light sources and some microscopy tools. High quantum efficiency (QE), low intrinsic emittance, and long lifetime (or good vacuum tolerance) are three of the most critical features for a photocathode; however, these are difficult to achieve simultaneously and trade-offs need to be made for different applications. In this work, a novel semi-metallic material of nitrogen-incorporated ultrananocrystalline diamond ((N)UNCD) has been studied as a photocathode. (N)UNCD has many of the unique diamond properties, such as low intrinsic as-grown surface roughness (at the order of 10~nm) due to its nanometer scale crystalline size, relatively long lifetime in air, high electrical conductivity with nitrogen doping, and potentially high QE performance due to the high grain boundary densities where most of electron emission occurs. High contrast interference of incident and reflected radiation within (N)UNCD thin films was observed, and this feature allows fast thickness determination based on an analytical optics methodology. This method has been extended to study and calculate the etching rates of two commonly used O$_2$ and H$_2$ plasmas for use with future (N)UNCD microfabrication processes. The mean transverse energy (MTE) of (N)UNCD was determined over a wide UV range in a DC photogun. Unique MTE behavior was observed; it did not scale with photon energy unlike most metals. This behavior is associated with emission from spatially-confined states in the graphite regions (with low electron effective mass) between the diamond grains. Such behavior suggests that beam brightness many be increased by the simple mechanism of increasing the photon energy so that the QE increases, while the MTE remains constant.Two individual (N)UNCD photocathodes synthesized two years apart have been characterized in a realistic RF photogun. Both the QE and intrinsic emittance were characterized. It was found that the QE of $\sim4.0\times 10^{-4}$, is more than an order of magnitude higher than that of most commonly used metal cathodes (such as Cu and Nb). The intrinsic emittance (0.997~$\mu$m/mm) is comparable to that of photocathodes now deployed in research accelerators. The most impressive feature is the excellent robustness of (N)UNCD material; there was no evidence of performance degradation, even after years-long atmospheric exposure. The results of this work demonstrate that a cathode made of (N)UNCD material is able to achieve balanced performance of three of the primary critical photocathode figures-of-merit.
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- Title
- H1 LUBRICANT TRANSFER FROM A HYDRAULIC PISTON FILLER INTO A SEMI-SOLID FOOD SYSTEM
- Creator
- Chao, Pin-Chun
- Date
- 2020
- Description
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The machinery used to prepare, and process food products need grease and oil for the lubrication of machine parts. H1 (food-grade) lubricants...
Show moreThe machinery used to prepare, and process food products need grease and oil for the lubrication of machine parts. H1 (food-grade) lubricants commonly used in the food industry are regulated as indirect additives by the FDA because they may become components of food through transfer due to incidental contact between lubricants and foods. The maximum level of H1 lubricants currently permitted in foods is 10 ppm, which was derived from FDA data gathered over 50 years ago. Although modern equipment has been designed to minimize the transfer of lubricants during processing and packaging, incidental food contact can still occur resulting from leaks in lubrication systems or over-lubrication. However, there is a lack of data for the FDA to evaluate and determine whether safety issues in the aspect of chemical contamination should be addressed concerning the use of food-grade lubricants in the production of foods. This research was conducted to determine the transfer of an H1 lubricant (Petrol-Gel) into a semi-solid model food from a hydraulic piston filler during conventional operating conditions at 25°C and 50°C. Xanthan gum solutions with concentrations of 2.3% at 25°C and 1.9% at 50°C were used to simulate the viscosity of ketchup at 50°C (970 cP). Petrol-Gel H1 lubricant with a viscosity grade of 70 cSt at 40°C was selected and the aluminum (Al) in the lubricant was targeted as a tracer metal. Analytical methods to quantify Al in both Petrol-Gel and xanthan gum solutions were successfully developed and validated by using inductively coupled plasma – mass spectrometry (ICP-MS) combined with microwave-assisted acid digestion technique. The concentration of Al in the Petrol-Gel was determined to be 3103 ± 26 μg/g. A total of 1.35 g of Petrol-Gel was applied to four ring gaskets in the filler, and 50 g samples of xanthan gum solution were collected into a 100-mL polypropylene tube (DigiTube) with low leachable metals during 500 filling cycles (the full capacity of the piston filler hopper).Results showed that the concentrations of Petrol-Gel transferred into 2.3% xanthan gum solution at 25°C ranged from 1.6 to 63.5 μg/g. A total of 64.47 mg of the applied Petrol-Gel (1.35 g) was transferred into 25 liters of the solution. The average concentration of Petrol-Gel in 2.3% xanthan gum solution was calculated to be 2.84 μg/g, which was lower than the current regulatory limit of 10 ppm. In general, the transfer of Petrol-Gel during the first 100 filling cycles was higher at 50°C than at 25°C. The concentration of Petrol-Gel transferred into 1.9% xanthan gum solution at 50°C for the first 100 filling cycles ranged from 1.6 to 35.06 μg/g and was 6.37 μg/g on average. This research will help FDA to calculate more realistic limits of the H1 lubricants permissible in foods at modern food processing conditions as well as estimate consumer dietary exposure to these indirect food additives.
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- Title
- WASTEWATER COLLECTION SYSTEM MODELING: TOWARDS AN INTEGRATED URBAN WATER AND ENERGY NETWORK
- Creator
- Wang, Xiaolong
- Date
- 2020
- Description
-
Wastewater collection systems, among the oldest features of urban infrastructure, are typically dedicated to collect and transport wastewater...
Show moreWastewater collection systems, among the oldest features of urban infrastructure, are typically dedicated to collect and transport wastewater from users to water resource recovery facilities (WRRFs). Since the 1970s, wastewater engineers and scientists have come to understand that wastewater collection systems can bring benefits for urban water and energy networks, including thermal energy recovery and converting pipelines to bioreactors. However, there is little knowledge about the temporal and spatial changes of collection systems parameters that are important for these applications. Furthermore, the vast majority of existing studies of these applications have focused on laboratory or extremely small-scale systems; there have been few studies about beneficial applications associated with large-scale systems. The purpose of this study is to increase our understanding of how urban wastewater collection systems can bring potential benefits to urban water and energy systems. Models describing wastewater hydraulics, temperature, and water quality can provide valuable information to help evaluate thermal energy recovery and wastewater pretreatment feasibility. These kinds of models, and supporting data from a case study, were used in this study; sizes of the theoretical wastewater collection systems range from 2.6 L/s to 52 L/s, and the sample locations of the case study had flows ranging from 2.3 L/s to 24.5 L/s. A cost-benefit analysis of wastewater source heat pumps was used to evaluate the thermal energy recovery feasibility for different sizes of wastewater collection systems. Results show that the large collection system can support a large capacity heat pump system with a relatively low unit initial cost. Small collection systems have a slightly lower unit operating cost due to the relatively high wastewater temperature. When the heat pump system capacity design was based on the average available energy from the collection system, larger systems have lower payback times; the lowest payback time is about 3.5 years. The wastewater quality model was used to describe the dissolved oxygen (DO) and organic matter concentrations changes in the collection system. The model provides a framework for predicting pretreatment capability. Model results show that DO concentration is the limiting parameter for organic matter removal. Larger collection systems can provide more organic matter removal because they provide relatively longer retention times, and they offer the potential for greater DO reaeration. The model can also be used to identify environmental conditions in sewer pipelines, providing information for potential issues predication.
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- Title
- COMPREHENSIVE ANALYSIS OF EXON SKIPPING EDITS WITHIN DYSTROPHIN D20:24 REGIONS
- Creator
- Niu, Xin
- Date
- 2020
- Description
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Exon skipping is a disease modifying therapy that operates at the RNA level. In this strategy, oligonucleotide analog drugs are used to...
Show moreExon skipping is a disease modifying therapy that operates at the RNA level. In this strategy, oligonucleotide analog drugs are used to specifically mask specific exons and prevent them from being included in the mature mRNA. Exon skipping can also be used to restore protein expression in cases where a genetic frameshift mutation has occurred, and this how it is applied to Duchenne muscular dystrophy, DMD. DMD most commonly arises as a result of large exonic deletions that juxtapose flanking exons of incompatible reading frame, which abolishes dystrophin protein expression. This loss leads to the pathology of the disease, which is severe, causing death generally in the second or third decade of life. Here, the primary aim of exon skipping is to restore the reading frame by skipping an exon adjacent to the patient’s original. While restoring some protein expression is good, how removing some region from the middle of protein affects its structure and function is unclear. Complicating this in this case is that the dystrophin gene is very large, containing 79 exons. Many different underlying deletions are knowns, and exon skipping can be applied in many ways. It has previously been shown that many exon-skip edits result in structural perturbations of varying degrees. Very few studies are focused on the protein biophysical study and it is still basically unclear whether and how such editing can be done to minimize such perturbations. In order to provide the solid evidences which prove the significant variation among those cases (especially for the clinically relevant cases) and better understanding the general principles of “what makes a good edit”, we examine a systematic and comprehensive panel of possible exon edits in a region of the dystrophin protein. The domain D20:24 of dystrophin rod region are selected for its entirety which is separated by hinge region (mostly random coiled structure) and addition of other STRs will not disrupt the structure stability. Also D20:24 regions lie in the Hot Spot region II (HS2) which holds the most number of DMD patients. During the comprehensive scan, we identify for the first time, exon edits that appear to maintain structural stability similar to wild-type protein and those clinically relevant edits. Then we figure out the factors that appear to be correlated with the degree of structural perturbation, such as the number of cooperative protein domains, as well as how the edited exon structure interacts with the protein domain structure. Our study is the first systematic and comprehensive scan for an entire multiple STRs domain. This would help us understand the protein nature of various exon skipping edits and provide useful target for clinical treatment. Also the knowledge we learned may be applied to produce more sophisticated CRISPR edits in the future work.
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- Title
- DEVELOPMENT OF FULLY BIOCOMPATIBLE HYDROGEL NANOPARTICLE FORMULATIONS FOR CONTROLLED-RELEASE DELIVERY OF A WIDE VARIETY OF BIOMOLECULES
- Creator
- Borges, Fernando Tancredo Pereira
- Date
- 2020
- Description
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In recent years, our group has focused on the production of PEGDA-based hydrogel scaffolds and nanoparticles for drug delivery of small...
Show moreIn recent years, our group has focused on the production of PEGDA-based hydrogel scaffolds and nanoparticles for drug delivery of small molecules. However, with recent advances in modern therapeutic treatments, such as protein and genetic engineering, there is an increasing need for the development of drug delivery devices that would be able encapsulate larger molecules. Therefore, the goal of this thesis work was to develop a systematic way to produce fully biocompatible PEGDA-based hydrogel nanoparticle formulations that would be able to encapsulate any size molecule, ranging from small ionic molecules, to peptides and proteins, all the way to large nucleic acids, and deliver it in a controlled manner.The first of part of this work consisted of developing a stable and reproducible process for the production of hydrogel PPi-NPs. Initial studies were done in order to assess the influence of phosphate salts in the polymerization system and it was found that both monophosphate and polyphosphate salts significantly damper the NVP homo-polymerization kinetics, but do not affect the co-polymerization of NVP and PEGDA. Then, emulsion stability studies were done to determine whether phosphate salts affected the stability of the minimeulsion system used in the production of the nanoparticles. Cloud point measurements and droplet size screening measurements showed that by transitioning from a Pi-loaded emulsion system to a PPi-loaded emulsion system, the required HLB of the emulsion shifts by 1.5 points. Upon correction for that shift, a reproducible process for production of PPi-loaded nanoparticles was obtained. A parametric study was then performed to see how the different process parameters affected the different properties of the produced particles. The second part of the work consisted in developing a platform for encapsulation of large to very-large molecules within these hydrogel systems. A new set of equations was developed for better estimation of the interstitial space, available for encapsulation of molecules, of crosslinked polymers that used very high molecular weight crosslinkers and/or high amounts of crosslinker. Upon development of this new set of equations, hydrogel discs were made via photopolymerization in order to validate the equations. By introducing a third monomer, EGA, and varying the molecular weight and concentration of the crosslinker, hydrogels with a wide range of mesh dimensions from 25 to 700 were achieved. These gels were then used to encapsulate 4 different sample molecules of varying molecular weights and size. A new heuristic was developed for encapsulation of non-spherical molecules, where the aspect ratios of the molecule and of the polymer network are considered. By varying the size of the ratios of the dimensions of the hydrogel network to the dimensions of the molecule, significantly different release profiles of small molecules, peptides and oligonucleotides were obtained. Finally, in order to explore different administration routes, the process was transitioning into being fully biocompatible. The organic solvent previously used in the emulsion system was replaced by soybean oil and the surfactants were replaced by a food-grade surfactant, PGPR, to form Bio-Compatible Nanoparticle Emulsions (BCNEs). Qualitative release from the BCNEs was shown. A new method for quantitative measuring of release from BCNE was developed. Release from QK-BCNE was observed up to 46 days, which is unprecedented for sustained-release and revolutionary for the field. A BCNE spreadable ointment formulation was also developed.
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- Title
- Development of Human Brain Atlas Resources
- Creator
- Qi, Xiaoxiao
- Date
- 2020
- Description
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Digital human brain atlases play an increasingly critical role and are widely used in neuroimaging studies such as developing biomarkers,...
Show moreDigital human brain atlases play an increasingly critical role and are widely used in neuroimaging studies such as developing biomarkers, training data for machine learning algorithms, functional connectivity analysis and so on. A brain atlas typically consists of brain templates of different imaging modalities that are representative of individual brains under study in a standard atlas space and semantic labels that delineate brain regions according to the characteristics of the underlying tissue.The IIT Human Brain Atlas project has developed the state-of-the-art diffusion tensor imaging (DTI) template, high angular resolution diffusion imaging (HARDI) template, and anatomical templates for the young adult brain in a standardized space. The probabilistic maps of gray matter (GM) labels and tissue segmentations were also constructed based on the anatomical information of the atlas. This thesis introduced an enhanced T1-weighted template that were developed by combining information from both diffusion and anatomical data. The GM labels and tissue segmentation maps in the standardized space were also improved. Existing white matter (WM) atlases typically lack specificity in terms of brain connectivity. A new approach named regionconnect was developed in this work based on precalculated average healthy adult brain connectivity information stored in standard space in a fashion that allows fast retrieval and integration. This thesis first generated and evaluated the white matter connectome of the IIT Human Brain Atlas v.5.0. Next, the new white matter connectome was used to develop multi-layer, connectivity-based labels for each white matter voxel of the atlas, consistent with the fact that each voxel may contain axons from multiple connections. The regionconnect algorithm was then developed to rapidly integrate information contained in the multi-layer labels across voxels of a white matter region and to generate a list of the most probable connections traversing that region. The regionconnect algorithm as well as the white matter tractogram and connectome, multi-layer, connectivity-based labels, and associated resources developed for the IIT Human Brain Atlas v.5.0 in this work are available at www.nitrc.org/projects/iit. Furthermore, it was well established that use of a young adult atlas in studies of older adults is inappropriate due to the age-related characteristic changes of the brain, resulting in an increasing demand of digital brain atlases for the older adults. To fulfill this demand, a function of fiber orientation distribution (fODF) template that is representative of older adults was developed in a standardized atlas space for studies of white matter of older adult human brains, which built a solid foundation for the development of the white matter resources for the older adults human brain atlas.
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- Title
- AMPLIFICATION AND PURIFICATION OF RECOMBINANT PRO-DEATH BAXΔ2 PROTEINS FOR STRUCTURE ANALYSIS
- Creator
- Zhou, Yi
- Date
- 2020
- Description
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BaxΔ2 is an isoform of the pro-apoptotic Bax family of proteins, which is an important anti-cancer protein. BaxΔ2 behaves differently from...
Show moreBaxΔ2 is an isoform of the pro-apoptotic Bax family of proteins, which is an important anti-cancer protein. BaxΔ2 behaves differently from Baxα to induce apoptosis. The current computationally predicted model of BaxΔ2 is based on known Baxα structure, which is considered biased. Therefore, the elucidation of the BaxΔ2 crystal structure is critical. The goal of this project was to obtain a sufficient amount of purified recombinant Bax∆2 protein for crystallization. We cloned full-length BaxΔ2 fused with a poly-histidine tag on either N-terminus (His-Bax∆2) or C-terminus (Bax∆2-His) into an inducible bacterial expression vector. We found that His-Bax∆2 proteins were expressed better than Bax∆2-His, which totally inhibit host growth. However, the protein concentration of His-Bax∆2 was still too low to be detected by Coomassie blue staining. To increase His-Bax∆2 expression and avoid cytotoxicity, we further tested different bacterial host cells and applied the chaperone system. However, all attempts could not overcome Bax∆2 cytotoxicity and the protein expression levels were not high enough to be feasible for further large-scale purification. The mechanism underlying how Bax∆2 inhibits bacterial growth is still a mystery because Bax∆2 eukaryotic targets (mitochondria and caspases) do not exist in bacteria. Further experiments are required to explore the mechanism of Bax∆2 cytotoxicity in bacteria, so as to finally optimize and elevate the BaxΔ2 protein yields.
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- Title
- Development of Microfluidic Platform to Study Insulin Resistance
- Creator
- Tanataweethum, Nida
- Date
- 2020
- Description
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Insulin resistance, a precursor for the development of type 2 diabetes (T2D), propagates among heterologous tissues through dysregulated lipid...
Show moreInsulin resistance, a precursor for the development of type 2 diabetes (T2D), propagates among heterologous tissues through dysregulated lipid flux, as well as dysregulated glucose production, and secretion of cytokines, adipokines and hepatokines. Although T2D is characterized by systemic insulin resistance, disruption of insulin signaling in the liver and adipose tissue recapitulates many aspects of T2D, including enhance endogenous glucose production as well as defects of insulin action. Mechanistic studies often aim to provide fundamental understanding of the observations from human and animal studies. Due to the complexity of animal models and the multifactorial character of T2D, there is a strong need to develop advanced experimental systems such as in vitro models that can enable the recapitulation of the complex physiology of the in vivo system and enable investigation of the pathological pathways as well as identify novel treatment options. The overall goal of this study was to develop insulin resistant models of adipose tissue and liver to study the metabolic function of each organ as well as to the organ-organ crosstalk. To accomplish this goal, four specific aims were pursued: (1) Establish adipose tissue on-a-chip to study the metabolic function of the adipocytes in flow culture; (2) Develop towards an insulin resistant adipose on-a-chip to study the metabolic function of adipocytes in setting of insulin resistance; (3) Develop insulin resistant liver on-a-chip to investigate the metabolic function of hepatocytes in setting of insulin resistance; (4) Develop adipose-liver on-a-chip in setting of insulin resistance to identify the metabolic interaction between organs.
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- Title
- Exploiting contextual information for deep learning based object detection
- Creator
- Zhang, Chen
- Date
- 2020
- Description
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Object detection has long been an important research topic in computer vision area. It forms the basis of many applications. Despite the great...
Show moreObject detection has long been an important research topic in computer vision area. It forms the basis of many applications. Despite the great progress made in recent years, object detection is still a challenging task. One of the keys to improving the performance of object detection is to utilize the contextual information from the image itself or from a video sequence. Contextual information is defined as the interrelated condition in which something exists or occurs. In object detection, such interrelated condition can be related background/surroundings, support from image segmentation task, and the existence of the object in the temporal domain for video-based object detection. In this thesis, we propose multiple methods to exploit contextual information to improve the performance of object detection from images and videos.First, we focus on exploiting spatial contextual information in still-image based object detection, where each image is treated independently. Our research focuses on extracting contextual information using different approaches, which includes recurrent convolutional layer with feature concatenation (RCL-FC), 3-D recurrent neural networks (3-D RNN), and location-aware deformable convolution. Second, we focus on exploiting pixel-level contextual information from a related computer vision task, namely image segmentation. Our research focuses on applying a weakly-supervised auxiliary multi-label segmentation network to improve the performance of object detection without increasing the inference time. Finally, we focus on video object detection, where the temporal contextual information between video frames are exploited. Our first research involves modeling short-term temporal contextual information using optical flow and modeling long-term temporal contextual information using convLSTM. Another research focuses on creating a two-path convLSTM pyramid to handle multi-scale temporal contextual information for dealing with the change in object's scale. Our last work is the event-aware convLSTM that forces convLSTM to learn about the event that causes the performance to drop in a video sequence.
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- Title
- IMAGE-ANALYSIS WITH FIJI PROGRAM ON PERIPHERAL BLOOD MONOCULAR CELLS AFTER CONSUMPTION OF HIGH-FAT, HIGH CARBOHYDRATE MEAL WITH OR WITHOUT ADDITION OF SPICES – A SINGLE-CENTER RANDOMIZED, BLINDED, PLACEBO-CONTROLLED, 4-ARM, 24HR ACUTE CROSSOVER STUDY
- Creator
- Tsai, Meng Fu
- Date
- 2020
- Description
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Chronic low-grade inflammation plays a significant role in developing various chronic diseases, such as cardiovascular disease and type II...
Show moreChronic low-grade inflammation plays a significant role in developing various chronic diseases, such as cardiovascular disease and type II diabetes. Western-type diets characterized by high-fat (saturated fat) and high-carbohydrate (HFHC) calories induce oxidative stress leading to inflammation. Polyphenol rich foods, such as berries, tea, and herbs and spices, have antioxidant properties. Spices have been shown to have anti-inflammatory effects in cell and animal studies; however, data are limited in humans. In the present study, we hypothesized that bioactive polyphenolic compounds in herbs and species would reduce diet-induced inflammation in overweight and obese (OW/OB) individuals. In a randomized, single-blinded 4-arm, 24-h, crossover clinical trial, sixteen OW/OB adults consumed an HFHC meal with and without three herbs and spices combinations, including Italian herbs (rosemary, basil, thyme, oregano, and parsley), cinnamon and pumpkin pie spice (cinnamon, ginger, nutmeg, and allspice) on four separate occasions at least three days apart. Markers of inflammation were assessed before and at 2, 4, 5.5, and 7 hours after meal consumption by tracking nuclear translocation of nuclear factor kappa B (NF-κB), a transcription factor in inflammatory signaling, in human peripheral blood monocular cells (PBMCs) and by measuring plasma interleukin-6 (IL-6), a pro-inflammatory cytokine. Nuclear translocation of NF-κB and the proportion of PBMCs activated were estimated through a new method leveraging machine-learning immunofluorescence image analysis. Metabolic markers were also investigated by RX Daytona automated clinical chemistry analyzer. Statistical analysis was conducted using a statistical package for the social sciences (SPSS) (α<0.05, significance). Preliminary results suggested the pumpkin pie spice mixture may improve inflammatory status. Compared to the control meal, the meal with pumpkin spice reduced nuclear translocation of NF-κB and proportion of PBMCs activation, p=0.007, and p=0.005, respectively. The addition of herbs/spices in HFHC meal had no apparent effect on postprandial glucose, insulin, or IL-6 concentrations compared to the control meal. Increased triglyceride concentrations were suggested after consuming the meal with Italian herbs compared to control (p=0.004). Overall, the results of this research suggested the potential of pumpkin pie spice as having anti-inflammatory effects in the context of a typical western-style eating pattern. A major component of this research was to develop a new method for assessing real-time inflammation in the human body. While the method and data are encouraging, upgrading image resolution and programming will be the subject of future research.
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- Title
- Three Essays on the Internet Economy
- Creator
- Sun, Yidan
- Date
- 2024
- Description
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In an era of digital platforms, the integrity and visibility of consumer reviews, the dynamics of digital advertising markets, and the role of...
Show moreIn an era of digital platforms, the integrity and visibility of consumer reviews, the dynamics of digital advertising markets, and the role of software development kits (SDKs) emerge as pivotal elements shaping user experiences and platform economics. My research spans three distinct but interconnected domains: the impact of safety reviews on Airbnb, the effects of privacy protections on digital advertising markets, and the significance of SDK releases in the evolution of Apple's iOS app market. We find that critical reviews concerning the safety of an Airbnb listing's vicinity influence guest bookings negatively and, therefore, could boost platform revenues if such reviews were obscured, highlighting a misalignment between consumer interests and platform revenue objectives. This effect is more pronounced in low-income and minority neighborhoods, suggesting a nuanced impact on different community segments. In the digital advertising sector, we identify that data frictions disproportionately harm small publishers, especially when associated with smaller ad intermediaries, underscoring the vulnerability of niche players to market and regulatory changes. Lastly, our analysis of the iOS app market reveals the instrumental role of SDK releases in fostering the app ecosystem's growth, independent of the expanding iPhone user base. Together, these findings underscore the complex interplay between consumer feedback, technological advancements, and market dynamics in digital environments, urging a balanced approach that safeguards consumer interests while fostering innovation and equitable market practices.
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- Title
- Gender Stereotype Biases Within Law Enforcement Clinical Psychological Evaluation
- Creator
- Porter, Maxwell G.
- Date
- 2023
- Description
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Female representation in law enforcement, despite significant improvements in past decades, remains markedly low at approximately 12%. One...
Show moreFemale representation in law enforcement, despite significant improvements in past decades, remains markedly low at approximately 12%. One possible barrier is the clinical psychological evaluation (CPE), a type of individualized assessment used to evaluate the mental or emotional fitness for duty of applicants. The present study examines the presence of potential gender bias in CPE for law enforcement positions by examining self-report personality assessment scores as well as narrative CPE recommendation reports generated by evaluating psychologists. Archival CPE data collected between 2014 through 2019 was obtained from a personnel selection consulting firm for entry-level law enforcement candidates (n = 390). Data included candidate scores on self-report psychological assessments (16PF, IPI-2), candidate background information, and psychologist-generated evaluation reports. A computer-aided text analysis using LIWC-22 was used to measure gender related inferences in the narrative report. Results indicated that (a) women received significantly lower assessor recommendation ratings than men, (b) significant differences in self-report personality scores were observed, however these were limited to a narrow subsection of traits, (c) gender was no longer a significant predictor of CPE outcome after controlling for applicant personality trait scores, and (d) meaningful differences in agency-related inferences in the narrative reports were observed, but it is unclear whether gender stereotypes influenced the reports. Practical implications, study limitations, and directions for future research are discussed.
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- Title
- Prediction and Control of In-Cylinder Processes in Heavy-Duty Engines Using Alternative Fuels
- Creator
- Pulpeiro Gonzalez, Jorge
- Date
- 2024
- Description
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This Ph.D. thesis focuses on advancing diagnostic techniques and control-oriented models to enhance the efficiency and performance of internal...
Show moreThis Ph.D. thesis focuses on advancing diagnostic techniques and control-oriented models to enhance the efficiency and performance of internal combustion (IC) engines, particularly heavy-duty engines utilizing alternative fuels. The research endeavors to contribute to the field of model-based control of engines through the development and implementation of innovative methodologies. The primary emphasis is on the development of diagnostic methods, control-oriented models and advanced control strategies for compression ignition engines using alternative fuels. The first key topic explores the determination of the Most Representative Cycle for Combustion Phasing Estimation based on cylinder pressure measurements. The method developed extracts crucial information from experimental data obtained from four distinct engines: the heavy-duty single-cylinder GCI engine, the light-duty multi-cylinder diesel engine, a CFR engine, and a single-cylinder light-duty Spark Ignition (SI) engine. This work lays the foundation for precise combustion phasing estimation, a critical parameter for engine control. The second major contribution involves the development of control-oriented models for Variable Geometry Turbochargers (VGT) and inter-coolers. Two models are established: a data-driven turbocharger model and an empirical inter-cooler model. These models are meticulously calibrated and validated using experimental data from a multi-cylinder light-duty diesel engine, providing valuable insights into the behavior of these components under varying conditions. The outcomes contribute to facilitate predictive control of engine air systems. The third core aspect of the thesis revolves around Model Predictive Control of Combustion Phasing in heavy-duty compression-ignition engines utilizing alternative fuels. A combustion phasing and engine load model is derived from experimental data and incorporated into an MPC framework. The MPC strategy is subsequently tested in the heavy-duty GCI test cell and compared against a conventional Proportional-Integral-Derivative (PID) control strategy. The results showcase the effectiveness of the MPC approach in achieving precise control of combustion phasing, demonstrating its potential for optimizing engine performance. In summary, this Ph.D. thesis contributes significantly to the field of engine controls by advancing diagnostic techniques, control-oriented models, and implementing a cutting-edge MPC-based control strategy for compression ignition engines using alternative fuels. The research findings not only enhance the understanding of in-cylinder processes but also pave the way for more efficient and sustainable heavy-duty engines using alternative fuels.
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