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- Title
- STUDIES TOWARD THE SYNTHESIS OF (‒) AGELASTATIN A and MECHANISTIC INVESTIGATIONS OF THE UNCATALYZED CHLOROCYCLIZATION OF 4-PHENYL-4-PENTENOIC ACID
- Creator
- Dzurka, Emily R.
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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This thesis presents an investigation into efforts towards the total synthesis of agelastatin A, as well as a mechanistic study of the uncatalyzed chlorocyclization reaction of 4-phenyl-4-pentenoic acid.Chapter 1 introduces all the prior total syntheses completed to date of agelastatin A. This chapter details the benefits, and similarities between each synthesis, as well as serves as an introduction into why a different, and novel route to the molecule is beneficial. Chapter 2 presents the...
Show moreThis thesis presents an investigation into efforts towards the total synthesis of agelastatin A, as well as a mechanistic study of the uncatalyzed chlorocyclization reaction of 4-phenyl-4-pentenoic acid.Chapter 1 introduces all the prior total syntheses completed to date of agelastatin A. This chapter details the benefits, and similarities between each synthesis, as well as serves as an introduction into why a different, and novel route to the molecule is beneficial. Chapter 2 presents the current studies towards synthesizing the molecule utilizing chemistry that was developed in the Borhan lab. Within this chapter, different synthetic routes to access the molecule are described. Chapter 3 focuses on the mechanistic studies to determine the molecularities that lead to the syn- and anti-chlorolactonization. Chemical kinetics were a central part of this investigation, as well as concentration studies. This information provided key insights into the postulated transition states that lead either the syn-addition or anti-addition product.
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- Title
- TWO PARTITIONS : POSTCOLONIAL CULTURE AND NATION IN BANGLADESHI AND SOUTH ASIAN ANGLOPHONE LITERATURES
- Creator
- Iqbal, Asif
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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As a comparative and interdisciplinary study of South Asian literatures, this project traces the fracturing of the subcontinent in 1947, and the subsequent emergence of Bangladesh in 1971. I analyze Global Anglophone, diasporic and Bengali novels from 1956-2014 as a prism through which I interrogate Bangladesh’s birth through specific historic transformations: the 1947 Partition, the entity East Pakistan (1947-1970) and the 1971 War. My analysis methodologically deploys historiographical...
Show moreAs a comparative and interdisciplinary study of South Asian literatures, this project traces the fracturing of the subcontinent in 1947, and the subsequent emergence of Bangladesh in 1971. I analyze Global Anglophone, diasporic and Bengali novels from 1956-2014 as a prism through which I interrogate Bangladesh’s birth through specific historic transformations: the 1947 Partition, the entity East Pakistan (1947-1970) and the 1971 War. My analysis methodologically deploys historiographical concepts and postcolonial theory to illuminate Bangladesh in its multiplicity, including the nation’s peasant identities, religious minorities and their insecurity, gendered hypermasculinist nationalism and related diasporic perspectives. My readings at the intersections of literary works and historical documents recasts the 1947 Partition and its legacy in South Asia, pointing to interconnections between East Pakistan’s proto-national character leading up to the 1971 war and the postwar formation of Bangladesh, responsible for the country’s ongoing religious and ethnic fragmentations. In Chapter 1, “Counter-Imaginations of Partition: East Bengal and Peasant Identities in Adwaita Mallabarman’s A River Called Titash (1956) and Shaukat Osman’s Janani (1961),” I invoke the short-lived idea of a United Bengal just before the 1947 Partition to interrogate Partition-era nationalism’s adverse influence on the Hindu and Muslim peasantry in Bengal’s countryside. Chapter 2, “‘Looking-glass Border’ Novels: Reading East Pakistan’s Hindu Minority in Amitav Ghosh’s The Shadow Lines (1988) and the Unified Bengali Identity During the 1971 War in Dilruba Z. Ara’s Blame (2015),” analyzes the antagonizing of the Hindu minority during the 1965 war between India and Pakistan and the subsequent policy of Hindu extermination during the 1971 war. The third chapter, “Fracturing Pakistan, Forming Bangladesh: Class and Gender Insurgencies in the Time of ‘Passive Revolution’ in Akhteruzzaman Elias’ The Sepoy in the Attic (Chilekothar Sepai 1987) and the Many ‘Birangona’ Stories in Shaheen Akhtar’s The Search (2004),” simultaneously considers the Mass Revolution of 1969 and the 1971 war to trace the patriarchal underside of Bengali nationalism, which was an ideological force against the repressive Pakistan state. In the final chapter, “‘Us’ Beside ‘Them,’ Not ‘Us’ Versus ‘Them’: Cosmopolitan Imagination and Familial Reckoning of 1971 in Zia Haider Rahman’s In the Light of What We Know (2014) and Kamila Shamsie’s Kartography (2002),” I problematize the nationalized war narratives in present day Bangladesh and Pakistan. The chapter argues that the intricate network of South Asian kinships and diasporic belongings can create a cosmopolitan understanding of the 1971 war. Two Partitions, therefore, argues that Bangladesh’s historic emergence is intertwined with the Bengali Muslim adoption of two-nation theory during their participation in the Pakistan Movement before 1947, and their subsequent jettisoning of the idea of Pakistan in support of Bengali ethno-linguistic nationalism in postcolonial East Pakistan (1947-1970). Subsequently, the two visions continue to inform the complex postcolonial identity of the citizens of Bangladesh, this project contends.
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- Title
- Simultaneous Model Selection and Estimation of Generalized Linear Models with High Dimensional Predictors
- Creator
- Pijyan, Alex
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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In the past couple of decades the progressive use of technology made the enormous amount of data in different formats available and easily accessible. The size and volume of available data sets have grown rapidly and the technological capacity of the world to store information has almost doubled every 40 months since the 1980s. As of 2020, every day 2.5 quintillion of data are generated. Based on an International Data Group (IDG) report, the global data volume was predicted to grow...
Show moreIn the past couple of decades the progressive use of technology made the enormous amount of data in different formats available and easily accessible. The size and volume of available data sets have grown rapidly and the technological capacity of the world to store information has almost doubled every 40 months since the 1980s. As of 2020, every day 2.5 quintillion of data are generated. Based on an International Data Group (IDG) report, the global data volume was predicted to grow exponentially and by 2025, IDG predicts there will be 163 zettabytes of data. This enormous amount of data is often characterized by its high dimensionality. Quite often, well-known statistical methods fail to manage such data due to their limitations (e.g., in high-dimensional settings they often encounter various issues such as no unique solution for the model parameters, inflated standard errors, overfitted models, multicollinearity). This resulted in resurging interest in the algorithms that are capable of handling massive quantities of data, extracting and analysing information from it, and uncovering key insights that subsequently will lead to decision making. Techniques used by these algorithms are tend to speed up and improve the quality of predictive analysis, thus, they found their application in various fields such as banking, financial market, insurance, media, education, medicine, information technology and so on. For instance, medicine becomes more and more individualized nowadays and drugs or treatments can be designed to target small groups, rather than big populations, based on characteristics such as medical history, genetic makeup etc. This kind of treatment is referred to as precision medicine. In the era of precision medicine, constructing interpretable and accurate predictive models, based on patients' demographic characteristics, clinical conditions, and molecular biomarkers, has been crucial for disease prevention, early diagnosis and targeted therapy. The models, for example, can be used to predict patients' susceptibility to disease, identify high risk groups, schedule earlier or more frequent screening, and guide behavioral changes. Therefore, predictive models play a central role in decision making. Several well-known approaches can be used to solve the problem mentioned above. Penalized regression approaches, such as least absolute shrinkage and selection operator (LASSO), have been widely used to construct predictive models and explain the impacts of the selected predictors, but the estimates are typically biased. Moreover, when data are ultrahigh-dimensional, penalized regression is usable only after applying variable screening methods to downsize variables. In this dissertation, we would like to propose a procedure for fitting generalized linear models with ultrahigh-dimensional predictors. Our procedure can provide a final model, control both false negatives and false positives, and yield consistent estimates, which are useful to gauge the actual effect size of risk factors. In addition, under a sparsity assumption of the true model, the proposed approach can discover all of the relevant predictors within a finite number of steps. The thesis work is organized as follows. Chapter 1 highlights an importance of predictive models and names several examples where these models can be implemented. The main focus of Chapter 2 is to describe all well-known and already existing in the theory methods that attempted to solve the aforementioned problems, along with their shortcomings and disadvantages. Chapter 3 proposes STEPWISE algorithm and introduces the model setup and its detailed description, followed by its theoretical properties and proof of theorems and lemmas used throughout the thesis. Additional lemmas used to construct the theory of the STEPWISE method are also stated. Later it presents results obtained from various numerical studies such as simulations and real data analysis. Simulation studies comprise seven examples and are aimed to compare STEPWISE algorithm to other competing methods, and provide numerical evidence of its superiority. Real data analysis involves studies of gene regulation in the mammalian eye, esophageal squamous cell carcinoma, and neurobehavioral impairment from total sleep deprivation, and demonstrates the utility of the proposed method in real life scenarios. Chapter 4 proposes a multi-stage hybrid machine learning ensemble method that is aimed to enhance STEPWISE's performance. It also introduces a web application that employs the method. Finally, Chapter 5 completes the thesis with final conclusion and discussions. Appendices include some tables and figures used throughout the thesis.
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- Title
- FIRM RESPONSES TO THE CONTENT AND EMOTIONS EXPRESSED IN SOCIAL-MEDIA WORD OF MOUTH
- Creator
- DEORE, AISHWARRYA
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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This study examines the influence of content and emotional feedback expressed through social-media channels on 1) firm revenues and consumer purchasing decisions, 2) firm quality outcomes, and 3) firm operational and resource allocations. Using psychology theory as a framework and textual analyses methods, I classify web scrapings of millions of social media posts for 19 US airlines for the 2007–2019 period based on their cognitive content and emotional type. I identify social media word-of...
Show moreThis study examines the influence of content and emotional feedback expressed through social-media channels on 1) firm revenues and consumer purchasing decisions, 2) firm quality outcomes, and 3) firm operational and resource allocations. Using psychology theory as a framework and textual analyses methods, I classify web scrapings of millions of social media posts for 19 US airlines for the 2007–2019 period based on their cognitive content and emotional type. I identify social media word-of-mouth (SWOM) feedback about five quality-related themes and two emotional types. The results show that negative and non-negative quality-related SWOM impact consumer and firm outcomes. Firm revenues and consumer volume decrease (increase) following negative (non-negative) quality-related SWOM. Firms improve quality outcomes (such as on-time performance) following negative quality-related SWOM. Firms also alter the level of operations (carrying capacity), change pricing strategies, and enhance quality-cost investments (quality failure and signaling costs) following quality-related emotional SWOM. In additional analyses, I find that non-quality related SWOM has little to no impact on consumer and firm choices. This research highlights the usefulness of SWOM as a source of customer feedback for firms and its decision-facilitating role. It provides evidence that firms incorporate both the content and emotional type of customer feedback in their management control design.
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- Title
- Towards Accurate Ranging and Versatile Authentication for Smart Mobile Devices
- Creator
- Li, Lingkun
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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Internet of Things (IoTs) was rapidly developed during past years. Smart devices, such as smartphones, smartwatches, and smart assistants, which are equipped with smart chips as well as sensors, provide users with many easy used functions and lead them to a more convenient life. In this dissertation, we carefully studied the birefringence of the transparent tape, the nonlinear effects of the microphone, and the phase characteristic of the reflected ultrasound, and make use of such effects to...
Show moreInternet of Things (IoTs) was rapidly developed during past years. Smart devices, such as smartphones, smartwatches, and smart assistants, which are equipped with smart chips as well as sensors, provide users with many easy used functions and lead them to a more convenient life. In this dissertation, we carefully studied the birefringence of the transparent tape, the nonlinear effects of the microphone, and the phase characteristic of the reflected ultrasound, and make use of such effects to design three systems, RainbowLight, Patronus, and BreathPass, to provide users with accurate localization, privacy protection, and authentication, respectively.RainbowLight leverages observation direction-varied spectrum generated by a polarized light passing through a birefringence material, i.e., transparent tape, to provide localization service. We characterize the relationship between observe direction, light interference and the special spectrum, and using it to calculate the direction to a chip after taking a photo containing the chip. With multiple chips, RainbowLight designs a direction intersection based method to derive the location. In this dissertation, we build the theoretical basis of using polarized light and birefringence phenomenon to perform localization. Based on the theoretical model, we design and implement the RainbowLight on the mobile device, and evaluate the performance of the system. The evaluation results show that RainbowLight achieves 1.68 cm of the median error in the X-axis, 2 cm of the median error in the Y-axis, 5.74 cm of the median error in Z-axis, and 7.04 cm of the median error with the whole dimension.It is the first system that could only use the reflected lights in the space to perform visible light positioning. Patronus prevents unauthorized speech recording by leveraging the nonlinear effects of commercial off-the-shelf microphones. The inaudible ultrasound scramble interferes recording of unauthorized devices and can be canceled on authorized devices through an adaptive filter. In this dissertation, we carefully studied the nonlinear effects of ultrasound on commercial microphones. Based on the study, we proposed an optimized configuration to generate the scramble. It would provide privacy protection againist unauthorized recordings that does not disturb normal conversations. We designed, implemented a system including hardware and software components. Experiments results show that only 19.7% of words protected by Patronus' scramble can be recognized by unauthorized devices. Furthermore, authorized recordings have 1.6x higher perceptual evaluation of speech quality (PESQ) score and, on average, 50% lower speech recognition error rates than unauthorized recordings. BreathPass uses speakers to emit ultrasound signals. The signals are reflected off the chest wall and abdomen and then back to the microphone, which records the reflected signals. The system then extracts the fingerprints from the breathing pattern, and use these fingerprints to perform authentication. In this dissertation, we characterized the challenge of conducting authentication with the breathing pattern. After addressing these challenges, we designed such a system and implemented a proof-of-concept application on Android platform.We also conducted comprehensive experiments to evaluate the performance under different scenarios. BreathPass achieves an overall accuracy of 83%, a true positive rate of 73%, and a false positive rate of 5%, according to performance evaluation results. In general, this dissertation provides an enhanced ranging and versatile authentication systems of Internet of Things.
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- Title
- STRUCTURAL AND AGENTIC CONTRIBUTORS TO JUSTICE- AND SUBSTANCE-INVOLVED WOMEN’S EMPLOYMENT : A FEMINIST ANALYSIS
- Creator
- Roddy, Ariel L.
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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Using interviews with 60 women leaving substance use treatment after spending time in jail, this dissertation examines the structural and agentic contributors to the employment of justice- and substance-involved women. Qualitative and quantitative findings illuminate the relevancy of spatial mismatch and social capital to women’s employment, the barriers women face looking for work and their strategies to overcome them, and the effects of the COVID-19 pandemic on finding and maintaining a job...
Show moreUsing interviews with 60 women leaving substance use treatment after spending time in jail, this dissertation examines the structural and agentic contributors to the employment of justice- and substance-involved women. Qualitative and quantitative findings illuminate the relevancy of spatial mismatch and social capital to women’s employment, the barriers women face looking for work and their strategies to overcome them, and the effects of the COVID-19 pandemic on finding and maintaining a job. Policy and practice recommendations include 1) improved access to mixed-income housing in areas of high economic opportunity for justice-involved women of color, 2) mentorship programing with a focus on career development, 3) occupational licensing reform, 4) expansion of gender-responsive reentry programs and training for criminal justice practitioners, 5) increased access to state and federal support for justice-involved populations, and 6) a moratorium on employment requirements for supervision during crises of exceptional magnitude.
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- Title
- THE GREAT CHINESE CULTURAL DEBATE : REVOLUTION AND RENAISSANCE ACROSS THE TAIWAN STRAIT, 1973-1976
- Creator
- Buck, Patrick David
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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This dissertation is an intellectual history of the Criticize Lin Biao Criticize Confucius Campaign in the People’s Republic of China and the Chinese Cultural Renaissance Campaign in the Republic of China (Taiwan), from 1973 to 1976. Utilizing archival sources from mainland China, Hong Kong, and Taiwan, this dissertation is a cross-straits history of the last major campaign of the Great Proletarian Cultural Revolution and of the Mao Zedong era, while also incorporating the broader Sinophone...
Show moreThis dissertation is an intellectual history of the Criticize Lin Biao Criticize Confucius Campaign in the People’s Republic of China and the Chinese Cultural Renaissance Campaign in the Republic of China (Taiwan), from 1973 to 1976. Utilizing archival sources from mainland China, Hong Kong, and Taiwan, this dissertation is a cross-straits history of the last major campaign of the Great Proletarian Cultural Revolution and of the Mao Zedong era, while also incorporating the broader Sinophone world by introducing the Chinese Cultural Renaissance Campaign at the end of the Chiang Kai-shek era of Taiwan’s history. The chapters of this dissertation move from the grassroots upwards, starting in factories, moving up into government office and universities, to secret internal government reports and leading intellectuals. It incorporates declassified high-level governmental reports, local-level government documents, propaganda, popular media, and academic scholarship. Chapter 1 focuses on the political theory small study groups of Shanghai as sites of local knowledge production. Chapter 2 discusses and disentangles complex and seemingly contradictory rhetoric of the effort to criticize Confucianism in 1970s China. Chapter 3 introduces the first English-language history of the Chinese Cultural Renaissance Campaign, as well as how the nationalist Chinese regime in Taiwan discussed and viewed the Cultural Revolution happening in the mainland at that time. Chapter 4 examines the ideas and writings of a leading intellectual figure behind the Cultural Renaissance, Ch’en Li-fu. My dissertation advances understandings in PRC History, Postwar Taiwanese History, the Cultural Revolution, Maoism, Chinese Nationalism, the history of communism, and the role of Confucianism in modern China. By introducing the Taiwanese and Nationalist Chinese reaction, my dissertation further expands on our understandings of the Cultural Revolution as a global phenomenon and major event of the twentieth century through the inclusion of the broader Sinophone world. This dissertation also shows that the two sides of the Taiwan Strait cannot be wholly separated in the history of Cold War-era China, as people on both sides believed themselves to be partaking in the same debate and spoke at each other in the same language.
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- Title
- CARBON-MEDIATED ECOLOGICAL AND PHYSIOLOGICAL CONTROLS ON NITROGEN CYCLING ACROSS AGRICULTURAL LANDSCAPES
- Creator
- Curtright, Andrew James
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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The sustainable intensification of agriculture relies on the efficient use of ecosystem services, particularly those provided by the microbial community. Managing for these ecosystem services can improve plant yields and reduce off-site impacts. For instance, increasing plant diversity is linked to positive effects on yield, and these beneficial effects are often mediated by the microbial community and the nutrient transformations it carries out. My dissertation has aimed to elucidate the...
Show moreThe sustainable intensification of agriculture relies on the efficient use of ecosystem services, particularly those provided by the microbial community. Managing for these ecosystem services can improve plant yields and reduce off-site impacts. For instance, increasing plant diversity is linked to positive effects on yield, and these beneficial effects are often mediated by the microbial community and the nutrient transformations it carries out. My dissertation has aimed to elucidate the mechanisms by which plant diversity improves agricultural production. In particular, I have focused on how changes to the amount and diversity of carbon (C) inputs affects soil microorganisms involved in the nitrogen (N) cycle. My work spans multiple scales of observation: from a global meta-analysis to mechanistic studies utilizing denitrification as a model system.In a global meta-analysis, I found that increasing plant diversity through intercropping yields a net increase in extracellular enzyme activity. This effect varied by plant species and soil type suggesting that increases in the quality of nutrient inputs mediates these positive effects on microbial activity. Then, I looked at how intercropping cover crops into corn affects soil nutrient pools and microbial activities in a field experiment. No effect of interseeding cover crops into corn was found on soil nutrient pools or microbial activities. However, by analyzing differences in relationships between nutrient pools and microbial activities at two locations throughout Michigan, I was able to describe how the availability of dissolved organic C (DOC) drives differences in microbial N-cycling processes. I then investigated how C availability drives activity in microbial hotspots within the soil by comparing differences in denitrification potential in bulk soil versus the rhizospheres of corn and interseeded cover crops. Here, I found that denitrification rates were increased in the rhizospheres of all plant types, and this effect varied depending on the species of plant. I was able to further differentiate the impact of DOC and microbial biomass C on the rhizosphere effect and found that C availability was the primary driver of differences in denitrification rates between rhizospheres. Since plants provide many different forms of C to soil microbes, it is important to understand how the chemistry of C inputs affects microbial activity. I used a series of C-substrate additions to determine how C chemistry affects denitrifiers. I found that amino acids and organic acids tended to stimulate the most nitrous oxide (N2O) production and reduction. Although management and site affected overall rates of denitrification, C-utilization patterns of microbes were mostly similar between locations. To identify the mechanisms responsible for these effects, I performed a final experiment to track how denitrifiers utilized different C compounds. The C substrates that stimulated the most complete reduce of N2O also were utilized with the lowest C-use efficiency (CUE). This suggests possible trade-offs between N2O reduction and CUE, with important implications for how to manage microbial communities. Overall, my work demonstrates that land management can impact microbial community activity by influencing the identity of soil C inputs. While the importance of increasing soil C inputs has been known, this dissertation supports the notion that the chemical identity of C inputs can exert significant controls on microbial activity. Moreover, by comparing microbial traits I highlight the importance of trade-offs in how microbially mediated C- and N cycling are coupled.
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- Title
- ELO GROWTH LARGE AREA SINGLE CRYSTAL CVD DIAMOND USING POCKET HOLDERS
- Creator
- Bai, Shengyuan
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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Single crystal diamond is a promising ultra-wide band-gap material. Epitaxial lateral outgrowth using microwave plasma assisted chemical vapor deposition has shown promise towards synthesizing large size high quality single crystal diamond, but growth of this material is a continued challenge. This work explores the growth dynamics of single crystal diamond in a constrained system, namely a pocket holder, used to suppress the formation of polycrystalline diamond. Results demonstrate...
Show moreSingle crystal diamond is a promising ultra-wide band-gap material. Epitaxial lateral outgrowth using microwave plasma assisted chemical vapor deposition has shown promise towards synthesizing large size high quality single crystal diamond, but growth of this material is a continued challenge. This work explores the growth dynamics of single crystal diamond in a constrained system, namely a pocket holder, used to suppress the formation of polycrystalline diamond. Results demonstrate significant and reproducible effects of the pocket design on growth behavior and growth morphologies, with strong positive correlations observed between pocket dimensions and epitaxial outgrowth fronts. Enhanced growth rates at the leading edge of epitaxial lateral outgrowth are also observed. Internal structure of grown samples mapped by scanning x-ray rocking curve measurement reveal outgrown regions are consistently lower quality despite the smooth morphology. This result is compared with the growth rates of the top surface and edges which shows a strong correlation between growth rate and crystal quality. Traditional pocket holders are shown to constrain ELO in a 1st order exponential decay fashion in previous work and the lateral size of as grown diamond has an upper limit subject to its holder configurations. As an upgraded research project, this research will include the SCD grown by MPACVD in a series of angled holders designed to achieve better ELO and to maintain a good lateral growth rate. The growth using angled holders from wider pocket to narrower pocket, respectively results in larger size ELO with PCD growth, appropriate smooth ELO growth at constant lateral growth rate, and inward lateral growth. Constant lateral growth is reproduced by iterative growth using regrowth angled holder. Larger area SCD are thus grown by MPACVD with constant vertical rate about 25 um/hr, 100 lateral rate about 18 um/hr, and 110 lateral rate about 12 um/hr. All as grown samples are measured with x-ray rocking curve (XRC) mapping technique to reveal the crystallographic structural properties, and compared to the original substrates. Diamond 400 crystal plane curvature/flatness and morphology, XRC FWHM of 400/113/111 diamond peaks are plotted using self-made analytical software to compare the quality revolution before and after the growth. Quantitative birefringence (QB) maps and cross polar birefringence (CPB) photos are also taken to present the internal crystal structural defect within the CVD diamond. XRC mapping results show that growth using wider angled pocket, though with PCD rims, has better flatness (small curvature) and higher average structural quality (small FWHM); growth with intermediate pocket, with pure SCD growth, also has a good lateral growth behavior, with intermediate crystal morphology and intermediate structural quality; growth using smaller pocket results area shrink, but with larger crystal plane curvature, indicating the SCD is compressed due to the smaller size of the pocket. Thus, an intermediate choice would be the best way for iterative SCD growth to maintain the lateral growth rate and the crystal quality at the same time. In summary, the technique of growing CVD single crystal diamond using a pocket holder provides the possibility for the diamond to keep growing at a constant lateral growth rate in both 100 and 110 directions along with a constant vertical growth rate. The iterative growth strategies also illustrate this unlimited growth mode and crystal structural quality of such as grown CVD diamonds are characterized by novel established measurement techniques. Under such way, larger area and high quality single crystal CVD diamond can be grown by using Microwave Plasma Assisted Chemical Vapor Deposition.
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- Title
- DETERMINANTS OF SINGLEHOOD SATISFACTION
- Creator
- Oh, Jeewon
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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lthough everyone experiences singlehood, people’s experiences and satisfaction with singlehood have not been as thoroughly examined as people’s experiences with romantic relationships. However, single people make up a heterogeneous group and the proportion of single people is rising in many places (Jones & Gubhaju, 2009; Lee & Payne, 2010; U. S. Census Bureau, 2020), making it particularly timely to identify predictors of a satisfying single life. Across a series of studies, this dissertation...
Show morelthough everyone experiences singlehood, people’s experiences and satisfaction with singlehood have not been as thoroughly examined as people’s experiences with romantic relationships. However, single people make up a heterogeneous group and the proportion of single people is rising in many places (Jones & Gubhaju, 2009; Lee & Payne, 2010; U. S. Census Bureau, 2020), making it particularly timely to identify predictors of a satisfying single life. Across a series of studies, this dissertation aimed to examine psychological factors underlying a satisfying single life. First, I examined how attitudes about romantic relationships changed and their links to well-being (Study 1). Expectations toward relationships at the societal level and individual level changed over time. Fewer people perceived marriage as a necessity in recent years. However, even among single people, those who perceived marriage as a necessity tended to report higher life satisfaction. Within individuals, people expected fewer benefits and fewer negatives from being in a relationship over time, and expectations had differential links with life satisfaction and singlehood satisfaction. Even though expectations and resulting singlehood satisfaction might be assumed to change because of major life events (e.g., job loss), trajectories of singlehood satisfaction were not moderated by most major life events except experiencing declines in self-rated health was associated with lower levels of singlehood satisfaction (Study 2). Asking long-term single people, I identified events that single people perceived to be influential for their singlehood (Study 3; e.g., experiences that highlighted their independence). Regardless of the actual event, perceiving the event to be positive predicted higher life satisfaction and singlehood satisfaction. I integrated findings across studies and discuss implications, limitations, and future directions.
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- Title
- Investigating the Role of Sensor Based Technologies to Support Domestic Activities in Sub-Saharan Africa
- Creator
- Chidziwisano, George Hope
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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In sub-Saharan Africa (SSA), homes face various challenges including insecurity, unreliable power supply, and extreme weather conditions. While the use of sensor-based technologies is increasing in industrialized countries, it is unclear how they can be used to support domestic activities in SSA. The availability of low-cost sensors and the widespread adoption of mobile phones presents an opportunity to collect real-time data and utilize proactive methods to monitor these challenges. This...
Show moreIn sub-Saharan Africa (SSA), homes face various challenges including insecurity, unreliable power supply, and extreme weather conditions. While the use of sensor-based technologies is increasing in industrialized countries, it is unclear how they can be used to support domestic activities in SSA. The availability of low-cost sensors and the widespread adoption of mobile phones presents an opportunity to collect real-time data and utilize proactive methods to monitor these challenges. This dissertation presents three studies that build upon each other to explore the role of sensor-based technologies in SSA. I used a technology probes method to develop three sensor-based systems that support domestic security (M-Kulinda), power blackout monitoring (GridAlert) and poultry farming (NkhukuApp). I deployed M-Kulinda in 20 Kenyan homes, GridAlert in 18 Kenyan homes, and NkhukuProbe in 15 Malawian home-based chicken coops for one month. I used interview, observation, diary, and data logging methods to understand participants’ experiences using the probes. Findings from these studies suggest that people in Kenya and Malawi want to incorporate sensor-based technologies into their everyday activities, and they quickly find unexpected ways to use them. Participants’ interactions with the probes prompted detailed reflections about how they would integrate sensor-based technologies in their homes (e.g., monitoring non-digital tools). These reflections are useful for motivating new design concepts in HCI. I use these findings to motivate a discussion about unexplored areas that could benefit from sensor-based technologies. Further, I discuss recommendations for designing sensor-based technologies that support activities in some Kenyan and Malawian homes. This research contributes to HCI by providing design implications for sensor-based applications in Kenyan and Malawian homes, employing a technology probes method in a non-traditional context, and developing prototypes of three novel systems.
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- Title
- INVESTIGATION OF THE PERFORMANCE OF LABYRINTH SEALS FOR CENTRIFUGAL COMPRESSOR APPLICATIONS
- Creator
- Palanca, Casey
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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ABSTRACTINVESTIGATION OF THE PERFORMANCE OF LABYRINTH SEALS FOR CENTRIFUGAL COMPRESSOR APPLICATIONS By Casey Palanca Labyrinth seals were one of the first seal configurations used in modern turbomachinery and, due to their robust qualities and relatively low-cost productions, remain one of the most widely used seal configurations today. Their primary purpose is to control internal leakage between the rotating and stationary components of rotating machinery, including the centrifugal...
Show moreABSTRACTINVESTIGATION OF THE PERFORMANCE OF LABYRINTH SEALS FOR CENTRIFUGAL COMPRESSOR APPLICATIONS By Casey Palanca Labyrinth seals were one of the first seal configurations used in modern turbomachinery and, due to their robust qualities and relatively low-cost productions, remain one of the most widely used seal configurations today. Their primary purpose is to control internal leakage between the rotating and stationary components of rotating machinery, including the centrifugal compressor. A reduction in secondary leakage flow will always be accompanied by an increase in efficiency. However, while fulfilling the objective of restricting secondary fluid flow, labyrinth seals have been known to cause adverse stability effects on the rotor. Driving forces inside the cavities from the circumferential flow path have been known to be a potential source of destabilizing vibrations. Therefore, accurately predicting these forces is a primary interest in compressor design. These forces are characterized by stiffness and damping coefficients. The present study utilizes the growing advances in CFD to understand, model, and predict the aerodynamic and rotordynamic performance of labyrinth seals. The scope of this work progresses from a well-established steady state CFD method to a more novel transient CFD approach. The benefits and disadvantages of each method are evaluated and discussed by comparing accuracy, reliability, and computational efficiency. Each method is validated with experimental data. Additionally, the proposed transient CFD method can be used to perform a reasonably accurate prediction of the frequency-dependent rotordynamic coefficients by using a Fast Fourier Transform analysis on the monitored force response and displacement data. Lastly, the transient CFD approach is expanded upon by investigating the flow characteristics of long 18 tooth on rotor balance piston labyrinth seal modeled with abradable grooves on the stator. It was discovered that the creation of abradable grooves on the stator can cause the vortex between the labyrinth teeth to change directions (clockwise to counterclockwise). This observation is used to determine the relationship between the flow pattern and rotordynamic performance. A parametric study shows the effect of abradable groove geometries and operating flow conditions on the labyrinth seal rotordynamic coefficients.
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- Title
- GENETIC INFLUENCES ON SOCIAL COGNITION, EXECUTIVE FUNCTION, AND ASSOCIATED NEURAL NETWORKS
- Creator
- Blanchett, Reid
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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Fundamental cognitive domains include executive function and social cognition. Both social cognition and executive functioning can be studied using neuroimaging techniques that allow direct observations to be made about brain structure and function. These techniques can also be applied to the study of brain development, revealing how circuits involved in executive function and social cognition change during important developmental periods such as infancy. Along with providing a window into...
Show moreFundamental cognitive domains include executive function and social cognition. Both social cognition and executive functioning can be studied using neuroimaging techniques that allow direct observations to be made about brain structure and function. These techniques can also be applied to the study of brain development, revealing how circuits involved in executive function and social cognition change during important developmental periods such as infancy. Along with providing a window into brain maturation, neuroimaging can be used to study cases where cognitive domains are disrupted and make comparisons to learn about typical brain development and function. For my dissertation, I have explored these cognitive domains and associated neural circuits both in typically developing individuals and in individuals with Turner syndrome, a condition caused by the full or partial absence of the second sex chromosome. First, I used a classic twin design and demonstrated relatively low narrow-sense heritability estimates for neonatal resting-state functional connectivity phenotypes. I studied both between- and within- network connectivity in neonates and demonstrated that only 6 out of 36 phenotypes had heritability estimates greater than 0.10; no estimates were statistically significant. These within- and between-network phenotypes included networks heavily recruited for social cognition and executive functioning. I also showed statistically significant associations between neonate resting-state functional connectivity phenotypes and specific demographic and medical history variables. Second, I compared structural and functional connectivity between typically developing male and female infants and infants with Turner syndrome. I saw no differences between the three groups in integrity of the superior longitudinal fasciculus or reduced connectivity between the right precentral gyrus and brain regions in the occipital and parietal regions involved with social cognition, visuospatial reasoning, and executive function. Fronto-parietal connectivity and integrity of the superior longitudinal fasciculus are disrupted in older individuals with Turner syndrome and these results suggested that these changes emerge after the first year of life. I conducted a further exploratory analysis of 54 fiber tracts and showed significant group differences that primarily reflected masculinization of white matter microstructure in TS. Other differences may have arisen due to hemizygosity of the pseudoautosomal region. Finally, I developed a browser-based online testing platform targeting domains such as executive functioning and social cognition, which are often disrupted in Turner syndrome. I then validated the battery via administration to neurotypical males and females and to adult women with Turner syndrome, who performed more poorly on tests of executive function and visuospatial reasoning. Taken together, the results presented in this dissertation contribute greatly to our understanding of the role of genetics in social cognition, executive function, and their related neural networks. These results can be further utilized in longitudinal studies of brain development and in future cognitive testing research.
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- Title
- I WON’T DO WHAT YOU TELL ME : AN EXPLORATION OF ORGANIZATIONAL EMOTIONAL DISPLAY RULE SOURCES
- Creator
- Awasty, Nikhil
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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Emotional display rules, guidelines for which emotion is appropriate for a given situation, have largely stayed in the background of research on emotional labor with most of the prior work focusing instead on the emotion regulation strategies of surface and deep acting. This dissertation brings emotional display rules to the foreground by focusing on where these display rules come from. Specifically, research has assumed that emotion regulation and emotional labor are a response to...
Show moreEmotional display rules, guidelines for which emotion is appropriate for a given situation, have largely stayed in the background of research on emotional labor with most of the prior work focusing instead on the emotion regulation strategies of surface and deep acting. This dissertation brings emotional display rules to the foreground by focusing on where these display rules come from. Specifically, research has assumed that emotion regulation and emotional labor are a response to organizationally prescribed emotional display rules (such as displaying positive emotions to customers). I challenge this assumption (as well as other problematic assumptions made by the extant literature on emotional labor) by integrating situations where employees create their own display rules in response to the specific context they are in (for instance they might decide to show frustration towards a customer). Further, this dissertation asserts that the aforementioned narrow conceptualization of emotional display rules has had the unintended consequence of focusing only on a small portion of employees (i.e., those that attempt to follow the display rules prescribed to them by their organization). Across 3 studies, I developed two new measures capturing the situation-person interaction of emotional display rule sources and conduct both variable- and person-centered analyses that allow me to integrate previously unidentified subpopulations of employees into the larger emotional labor literature.
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- Title
- IMPACT OF AGRICULTURAL MANAGEMENT AND MICROBIAL INOCULATION ON SOYBEAN (GLYCINE MAX) AND ITS ASSOCIATED MICROBIOME
- Creator
- Longley, Reid
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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Soybean (Glycine max) is a globally important crop with uses as food, cooking oil livestock feed, and biodiesel. Soybean can be considered holobionts because they host diverse microbiomes which extend plant genotypes and phenotypes through various microbial functions such as nitrogen fixation and increased disease resistance. My research focused on assessing the impact of three agricultural management strategies on the soybean holobiont. Soybean cropping systems can be managed using various...
Show moreSoybean (Glycine max) is a globally important crop with uses as food, cooking oil livestock feed, and biodiesel. Soybean can be considered holobionts because they host diverse microbiomes which extend plant genotypes and phenotypes through various microbial functions such as nitrogen fixation and increased disease resistance. My research focused on assessing the impact of three agricultural management strategies on the soybean holobiont. Soybean cropping systems can be managed using various strategies, including conventional tillage, no-till, and organic management regimes. These management systems have been shown to impact the microbiomes of soybean-associated soils, however, their impacts on plant-associated microbiomes are still not well understood. In this study, I assessed the impact of conventional, no-till, and organic management treatments on soybean microbiomes at Michigan State’s Kellogg Biological Station Long-Term Ecological Research site (KBS LTER). I found that management impacted microbiome composition and diversity in soil, roots, stems, and leaves and that this impact persisted throughout the season. Additionally, when comparing the same soybean genotype grown in conventional and no-till management systems, tillage regime impacted the microbiome throughout the plant and the growing season. This effect impacted microbial taxa which are likely to be plant beneficial, including nitrogen fixing Bradyrhizobium. Another important management tool that is expected to impact plant-associated microbial communities is the application of foliar fungicides. While fungicides are known to protect plants from particular fungal pathogens, non-target impacts of fungicides on crop microbiomes, and the impact of management on microbiome recovery are not well understood. To address this knowledge gap, I assessed the impact of foliar fungicide application on the maize (Headline® fungicide, 2017) and soybean (Delaro® fungicide, 2018) microbiomes in conventional and no-till plots at the KBS LTER. I found that fungicide applications have a non-target impact on Tremellomycete yeasts in the phyllosphere and this impact was greater in soybean than maize. Co-occurrence network analysis and random forest modelling indicated that changes in fungal communities may lead to indirect impacts on prokaryotic communities in the phyllosphere. Importantly, this work demonstrated that phyllosphere communities of soybeans under no-till management had greater recovery from fungicide disturbance. This novel finding exemplifies how tillage regime can impact phyllosphere microbiomes and their responses to disturbance. Microbial inoculants in agriculture have long been used for biocontrol of pathogens, but there is also interest in their use to dampen the impacts of abiotic stress including drought. In this study, I tested whether inoculating soybeans with hub taxa identified through network analysis from no-till soybean root microbiome data from the KBS LTER could provide protection against water limitation. Soybean seedlings were enriched in consortia of hub bacteria and fungi and were grown in no-till field soil. Seedlings were then exposed to low-moisture stress, and plant phenotypes, plant gene expression, and amplicon sequencing of microbial DNA and cDNA were assessed throughout the stress period. Inoculation increased plant growth, nodule numbers, and led to increased expression of nodulation-associated genes. 16S sequencing of cDNA revealed higher levels Bradyrhizobium in inoculated samples. These results indicate that inoculation with hub microbes can benefit soybean plants, possibly through interaction with other microbes, interaction with the plant, or both. In summary, fungicide, tillage, and inoculation all impact the soybean microbiome, indicating that management choices impact the entire holobiont.
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- Title
- Probing Spin-Isospin Excitations in Proton-Rich Nuclei via the 11C(p,n)11N Reaction
- Creator
- Schmitt, Jaclyn Marie
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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Understanding nuclear structure and predicting nuclear properties from first principles are major goals of nuclear physics research. Many nuclear models have been created for these purposes, and benchmarking them with new data is critical for their continued development. Exotic nuclei provide fertile testing grounds for nuclear models because nuclear properties evolve and new phenomena emerge as one moves away from stability towards the driplines. In the present work, the 11C(p,n)11N reaction...
Show moreUnderstanding nuclear structure and predicting nuclear properties from first principles are major goals of nuclear physics research. Many nuclear models have been created for these purposes, and benchmarking them with new data is critical for their continued development. Exotic nuclei provide fertile testing grounds for nuclear models because nuclear properties evolve and new phenomena emerge as one moves away from stability towards the driplines. In the present work, the 11C(p,n)11N reaction was measured in inverse kinematics at 95 MeV/u at the National Superconducting Cyclotron Laboratory to both provide a benchmark for current models and to lay the groundwork for future experiments. The Gamow-Teller transition strength, B(GT), was extracted from the measured cross section using a well-established proportionality relationship between the charge-exchange cross section and B(GT). The results were B(GT) = 0.18(1)stat(3)sys to the first 1/2- state and B(GT) = 0.18(1)stat(4)sys to the first 3/2- state in 11N. These results are consistent with shell-model calculations after introducing a phenomenological quenching factor and with ab-initio Variational Monte Carlo calculations without any scaling. These results are also consistent with B(GT) values extracted from mirror 11B(n,p) and 11B(t,3He) reactions, assuming isospin symmetry. Additionally, this experiment demonstrates the feasibility of using the (p,n) probe in inverse kinematics to extract B(GT) from transitions to proton-rich unbound nuclei, although improved background suppression will be critical in future experiments.
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- Title
- Using Neurotypical Siblings as Intervention Agents in Family-Implemented Motor and Physical Activity Interventions for Children with Autism Spectrum Disorder
- Creator
- Lu, Yuemei
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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There is a consensus that individuals with Autism Spectrum Disorder (ASD) fall short of the recommended 60-minute daily moderate-to-vigorous physical activity (MVPA), and some experience motor delays and abnormalities. Yet ASD interventions focusing on addressing these challenges are insufficient in the existing literature. Research evidence supports the effectiveness of neurotypical (NT) sibling involvement in ASD intervention, therefore, using NT siblings as intervention agents to promote...
Show moreThere is a consensus that individuals with Autism Spectrum Disorder (ASD) fall short of the recommended 60-minute daily moderate-to-vigorous physical activity (MVPA), and some experience motor delays and abnormalities. Yet ASD interventions focusing on addressing these challenges are insufficient in the existing literature. Research evidence supports the effectiveness of neurotypical (NT) sibling involvement in ASD intervention, therefore, using NT siblings as intervention agents to promote PA and motor skills in their sister/brother with ASD may be a viable option. The three studies within this dissertation were conducted during the COVID-19 pandemic when free and unstructured physical activity (PA) was suggested to be achieved by playing with siblings. This dissertation’s first investigation was a qualitative study investigating the perceptions of NT siblings and caregivers on prospective sibling-guided motor intervention in children with ASD. The principal investigator also gathered information that ball games, in-person format, once or twice per week frequency, weekend days, and 30-minute session duration were most preferred. Prior to designing and implementing the PA intervention, a cross-sectional study was conducted with 18 parent-ASD-NT triads (54 participants) to understand PA, parental perceived motor competence, and PA-related family dynamics in children with ASD during COVID-19. The findings from the PA questionnaire revealed that children with ASD spent a significantly greater amount of time in sedentary behaviors (mean = 2379.06 mins; SD = 1480.10) during an entire week than in leisure time activities (mean = 316.88 mins; SD = 301.48) and sports activities (mean = 183.00 mins; SD = 153.94). Also, parents perceived their children’s competence on most skills listed in the parental proxy of the Pictorial Scale of Perceived Movement Skill Competence (PMSC-parent) as not too good or sort of good. In addition, it was indicated that NT siblings’ self-efficacy in supporting children with ASD was lower than that of parents. By incorporating the findings from the first two studies, the third study within this dissertation provided an online family-implemented PA intervention for children with ASD to promote the variables that were measured in the cross-sectional study. The intervention used a randomized control trial with three intervention conditions: (a) Group A: PA intervention carried out by both a parent and a NT sibling, (b) Group B: PA intervention delivered by a parent only, and (c) Group C: control condition with only sedentary activities provided, rather than PA intervention. Among families who completed more than 60% of the intervention, significant differences were found in scores of object control skills [F (1,6) = 17.163, p = 0.006, ηp2 = 0.741], fundamental motor skills [F (1,6) = 7.385, p = 0.035, ηp2 = 0.552], and PMSC-parent total scores [F (1,6) = 6.914, p = 0.039, ηp2 = 0.535] over time across the three groups [F (2,6) = 6.838, p = 0.028, ηp2= 0.695], [F (2,6) = 13.507, p = 0.006, ηp2 = 0.818], and [F (2,6) = 6.844, p = 0.028, ηp2 = 0.695], with Group A showed more significant improvements. In addition, a significant within-group difference was found in parent-ASD interaction across time [F (1,6) = 6.964, p = 0.039, ηp2 = 0.537]. Lastly, a process evaluation was conducted to examine the reach, dose, fidelity, and participant enjoyment. Results from this dissertation inform the design of future sibling-guided motor and PA interventions for children with ASD and encourage researchers to provide quality and enjoyable motor, PA intervention, and play-based services in an online format at the family level.
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- Title
- High-Speed Millimeter-Wave Active Incoherent Fourier Domain Imaging
- Creator
- Vakalis, Stavros
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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Millimeter-wave imaging is used in applications such as security screening, remote sensing, medical imaging, and non-destructive testing due to the good penetration characteristics of millimeter-wave radiation which can provide "see-through" capabilities. Electromagnetic signals in the frequency range of 30 - 300 GHz can penetrate easily through materials like clothing, fog, and smoke, and at the same time provide image reconstruction with fine spatial resolution. Millimeter-wave imaging is...
Show moreMillimeter-wave imaging is used in applications such as security screening, remote sensing, medical imaging, and non-destructive testing due to the good penetration characteristics of millimeter-wave radiation which can provide "see-through" capabilities. Electromagnetic signals in the frequency range of 30 - 300 GHz can penetrate easily through materials like clothing, fog, and smoke, and at the same time provide image reconstruction with fine spatial resolution. Millimeter-wave imaging is typically implemented by means of mechanical or electrical scanning which requires long data acquisition times or a large number of active components. Computational imaging can reduce both the data acquisition time and the number of active components, but this comes at the cost of heavy computational loads, which makes real-time operation challenging. Passive millimeter-wave imaging systems that capture thermal signals and operate similarly to optical cameras, are very costly because they need to employ highly sensitive receivers due to thermal radiation being extremely low power at millimeter-wave frequencies. A paradigm shift is needed in order to advance the current imaging modalities in millimeter-wave frequencies.In this dissertation, I present a newly developed millimeter-wave imaging technique called active incoherent millimeter-wave (AIM) imaging which combines the benefits of active and passive millimeter-wave imaging. This approach combines the high signal-to-noise ratio capabilities of active millimeter-wave imaging systems with the fast image formation potential of passive millimeter-wave imaging systems. The combination is achieved by illuminating the scene with multiple spatially distributed noise transmitters that mimic the randomness of thermal radiation. Because the concept of incoherent noise illumination has not been investigated thoroughly in the literature of millimeter-wave imaging, I discuss design considerations for creating a space-time incoherent transmitter and novel measurements for characterizing space-time incoherence. Starting from my earlier work in microwave frequencies, I present the system design and calibration approach, along with an experimental demonstration of a millimeter-wave active incoherent digital array. The array is capable of generating millimeter-wave video at very high frame rates, and millimeter-wave imaging results of 652 frames per second of a sphere moving in a pendulum motion are included. The scenario of using the stray reflections from a small set of communications transmitters is also examined and I present results using WiFi and fifth-generation (5G) communications signals. I also expand interferometric imaging to three dimensions using a novel pulse modulation as an envelope on the noise signals to provide differentiation along the range dimension. Prior to this work, three-dimensional interferometric millimeter-wave imaging had only been implemented in the near-field region or using three-dimensional volumetric arrays, which pose significant size and volume concerns. A new algorithm for three-dimensional interferometric image formation is presented along with simulated results and experimental measurements.
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- Title
- THE EPIGENETIC MECHANISMS OF POLYCOMB AND TRITHORAX PROTEINS IN STEM CELL MAINTENANCE AND LEUKEMOGENESIS
- Creator
- Aljazi, Mohammad
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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Functionally, Polycomb repressive complex 2 (PRC2) mediates transcriptional repression of differentiation genes critical for mouse embryonic stem cell (mESC) maintenance. Culturing mESCs in 2i serum-free medium inhibits FGF/ERK signaling and activates the Wnt/β-catenin pathway, which induces a naive cell state characterized by a reduced expression of lineage-specific genes. Interestingly, in naive mESCs, both PRC2 chromatin occupancy and the repressive histone3 lysine 27 trimethylation ...
Show moreFunctionally, Polycomb repressive complex 2 (PRC2) mediates transcriptional repression of differentiation genes critical for mouse embryonic stem cell (mESC) maintenance. Culturing mESCs in 2i serum-free medium inhibits FGF/ERK signaling and activates the Wnt/β-catenin pathway, which induces a naive cell state characterized by a reduced expression of lineage-specific genes. Interestingly, in naive mESCs, both PRC2 chromatin occupancy and the repressive histone3 lysine 27 trimethylation (H3K27me3) modification they mediate are largely depleted. To explore the molecular mechanism attributing to the transcriptional changes in naive cells, we performed RNA-sequencing for mESCs cultured in serum versus 2i medium. Gene expression analysis revealed reduced Jarid2 levels in naive mESCs. Reactivation of FGF/ERK signaling caused elevated Jarid2 expression, whereas ERK1/2 deletion decreased its expression levels. Ectopic expression of ERK depleted cells restored Jarid2 expression, showing that Jarid2 expression dependent on ERK signaling. Using ChIP-seq analysis, we observed reduced occupancy for Jarid2 and PRC2 and decreased H3K27me3 levels in both naive and Erk1/2 depleted mESCs. Expression of Jarid2 in Erk1/2 depleted cells reestablished PRC2 occupancy and H3K27me3 modifications. Taken together, these results reveal the molecular mechanism associated with FGF/ERK signaling and PRC2 recruitment in mESCs.The TrxG (Trithorax) group member ASH1L serves as a regulator of cell development. However, its functional role in MLL-rearranged leukemia initiation and maintenance is not well understood. Using an Ash1L conditional knockout mouse model, we demonstrated that ASH1L in hematopoietic progenitor cells (HPCs) impaired initiation of MLL-AF9-induced leukemic transformation in vitro. Ablation of ASH1L in the MLL-AF9-transformed leukemia cells impeded maintenance in vitro and leukemia progression in vivo. Furthermore, Ash1L depleted cells expressing wild-type ASH1L rescued MLL-AF9-induced leukemia transformation, while the transformation of cells expressing enzymatically inactive ASH1L inhibited their maintenance. Implementation of RNA-sequencing analysis revealed that ASH1L controls the expression of MLL-AF9 target genes by occupying their promoters and depositing H3K36me2 marks at these sites. Altogether, these results demonstrate that the enzymatic activity of ASH1L is crucial for MLL-AF9-induced leukemic transformation and maintenance. In addition, our study identifies a potential therapeutic target in MLL-AF9-induced leukemias. Histone post-translational modifications are vital for epigenetic mediated gene regulation. While past studies have characterized the functional role of many histone H3 lysine residues modifications, the post-translational modification of histone H3 lysine 37 and the factors contributing to these modifications remain undefined in mammals. Using in vitro methyltransferase assays, we found that SMYD family member 5 (SMYD5) catalyzes mono-methylation of H3 lysine 36 and 37 (H3K36/K37me1). Mutation of the conserved histidine within the catalytic SET domain abolished SMYD5 methyltransferase activity in vitro. Additionally, loss of Smyd5 in mESCs reduces the global histone H3K37me1 level in cells. Thus, our data functionally identifies SMYD5 as an H3 specific methyltransferase that mediates H3K36me/H3K37me1 in vitro. It also reveals that SMYD5 serves as one of the histone methyltransferases catalyzing histone H3K37me1 in vivo.
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- Title
- Algorithms for noisy quantum computers and techniques for error mitigation
- Creator
- LaRose, Ryan
- Date
- 2022
- Collection
- Electronic Theses & Dissertations
- Description
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Quantum computation will likely provide significant advantages relative to classical architectures for certain computational problems in number theory and physics, and potentially in other areas such as optimization and machine learning. While some key theoretical and engineering problems remain to be solved, experimental advances in recent years have demonstrated the first beyond-classical quantum computation as well as the first experiments in error-corrected quantum computation. In this...
Show moreQuantum computation will likely provide significant advantages relative to classical architectures for certain computational problems in number theory and physics, and potentially in other areas such as optimization and machine learning. While some key theoretical and engineering problems remain to be solved, experimental advances in recent years have demonstrated the first beyond-classical quantum computation as well as the first experiments in error-corrected quantum computation. In this thesis, we focus on quantum computers with around one hundred qubits that can implement around one thousand operations, the so-called noisy-intermediate scale quantum (NISQ) regime or kilo-scale quantum (KSQ) regime, and develop algorithms tailored to these devices as well as techniques for error mitigation that require significantly less overhead than fault-tolerant quantum computation. In the first part, we develop quantum algorithms for diagonalizing quantum states (density matrices) and compiling quantum circuits. These algorithms use a quantum computer to evaluate a cost function which is classically hard to compute and a classical computer to adjust parameters of an ansatz circuit, similar to the variational principle in quantum mechanics and other variational quantum algorithms for chemistry and optimization. In the second part, we extend an error mitigation technique known as zero-noise extrapolation and introduce a new framework for error mitigation which we call logical shadow tomography. In particular, we adapt zero-noise extrapolation (ZNE) to the gate model and introduce new methods for noise scaling and (adaptive) extrapolation. Further, we analyze ZNE in the presence of time-correlated noise and experimentally show ZNE increases the effective quantum volume of various quantum computers. Finally, we develop a simple framework for error mitigation that enables (the composition of) several error mitigation techniques with significantly fewer resources than prior methods, and numerically show the advantages of our framework.
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