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Title: DO INFORMATION ACQUISITION COSTS MATTER? THE EFFECT OF SEC EDGAR ON STOCK ANOMALIES
Creator: Kim, Yong-Hyuck
Date: 2022
Collection: Electronic Theses & Dissertations
Description: I estimate the costs of information acquisition and the extent to which they explain stock anomaly returns. The SEC’s staggered implementation of EDGAR from 1993 to 1996 greatly lowered the costs of acquiring accounting information. I study how this quasi-exogenous and staggered shock affects the profitability of 126 accounting and 108 non-accounting anomalies. The EDGAR introduction lowers the average alphas for the accounting anomalies by 4.0% per year, explaining more than half of the pre...
Show moreI estimate the costs of information acquisition and the extent to which they explain stock anomaly returns. The SEC’s staggered implementation of EDGAR from 1993 to 1996 greatly lowered the costs of acquiring accounting information. I study how this quasi-exogenous and staggered shock affects the profitability of 126 accounting and 108 non-accounting anomalies. The EDGAR introduction lowers the average alphas for the accounting anomalies by 4.0% per year, explaining more than half of the pre-EDGAR alphas. The attenuation is stronger for the accounting anomaly portfolios that require more up-to-date accounting information and those consisting of EDGAR filer stocks with less information available in the pre-EDGAR period. By contrast, alphas for the non-accounting anomalies remain unaffected. These results imply that the information acquisition costs, which are usually neglected, can be as important as the transaction or short sale costs.
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Title: NUMERICAL SIMULATIONS OF PERMEABLE-WALL TURBULENCE WITH APPLICATIONS IN HYPORHEIC EXCHANGE
Creator: SHEN, GUANGCHEN
Date: 2022
Collection: Electronic Theses & Dissertations
Description: In aquatic environments such as rivers, the exchange of solutes across the interface between the sediment and the overlying water plays a signifcant role in controlling biogeochemical processes, which are important for an array of topics from nutrient transport and cycling to release of greenhouse gases such as nitrous oxide. Most previous studies on characterizing this exchange are focused on flows with sediment bedforms much larger than individual sediment grains. The physics at the pore or...
Show moreIn aquatic environments such as rivers, the exchange of solutes across the interface between the sediment and the overlying water plays a signifcant role in controlling biogeochemical processes, which are important for an array of topics from nutrient transport and cycling to release of greenhouse gases such as nitrous oxide. Most previous studies on characterizing this exchange are focused on flows with sediment bedforms much larger than individual sediment grains. The physics at the pore or grain scale were typically not resolved. The effects of grain roughness on the sedimentbed surface on the transport across the sediment-water interface (SWI), isolated from those of bed permeability and bedforms, are not well understood. In this work, direct numerical simulations (DNS) of the connected system of turbulent open-channel flow and pore-resolved sediment flow are carried out, with different arrangements of grains at the sediment surface.First, the statistics and structure of the mean flow and turbulence are characterized in flows with a friction Reynolds number of 395 and a permeability Reynolds number of 2.6 over sediments with either regular or random grain packing on a macroscopically flat bed. It is shown that, even in the absence of any bedform, the subtle details of grain roughness alone can signifcantly affect the dynamics of turbulence and the time-mean flow. Such effects translate to large differences in penetration depths, apparent permeabilities, vertical mass fluxes and subsurface flow paths. The less organized distribution of mean recirculation regions near the interface with a random packing leads to a more isotropic form-induced stress tensor, which plays a signifcant role in increasing mixing and wall-normal exchange of mass and momentum.Next, the mass exchange is characterized in detail for macroscopically flat river beds, focusing on the transit time—the time spent by a fluid particle in the sediment—which determines the role of hyporheic zones in transforming the chemical signature of stream water. Results show that bedroughness leads to interfacial pressure variations, which induces deep subsurface flow paths that yield a transit time distribution with a heavy tail. Furthermore, the addition of molecular diffusionis accounted for and is shown to increase transit times regardless of roughness texture. The results demonstrate that particle roughness on a macroscopically flat sediment bed can induce signifcant hyporheic exchange that is fundamentally similar to that induced by bedforms.Lastly, to identify possible interaction between the effect of grain roughness and that of a bedform, DNSs of open channels with a friction Reynolds number of 1580 on a porous dune with two different roughnesses are conducted. Results show that the roughness modifes the wall friction, shear penetration depth and pressure distribution along the interface. Unlike the case on a macroscopically flat bed where the random roughness induces more intense roughness-scale pressure variation than the regular roughness, over a bedform the random roughness reduces the macroscopic pressure distribution at the interface instead due to its higher hydrodynamic drag. The weaker pressure variation in turn weakens the pumping and shortens transit times. The results highlight the nonlinear interaction between the effects of bed morphological features of different scales. Pore-resolved simulations such as the ones herein can be used in the future in direct characterization of pore-scale dynamics to provide insights for pore-unresolved modeling of biogeochemical processes.
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Title: WHAT HAPPENS DURING AND AFTER MULTITASKING? CONCURRENT AND CARRY-OVER EFFECTS OF MEDIA MULTITASKING AND SELF-REGULATION ON TASK PERFORMANCE
Creator: Baek, Jong-Hwan
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Much research has suggested that multitasking impairs cognitive outcomes and task performance. Given its negative role in information processing, the vast majority of work has focused on concurrent effects during multitasking (e.g., recall, recognition). However, prior research in the multitasking literature has rarely examined short-term or lingering effects on subsequent tasks. One of the theories concerning this after-effect is ego depletion, a state of reduced self-regulatory resources.To...
Show moreMuch research has suggested that multitasking impairs cognitive outcomes and task performance. Given its negative role in information processing, the vast majority of work has focused on concurrent effects during multitasking (e.g., recall, recognition). However, prior research in the multitasking literature has rarely examined short-term or lingering effects on subsequent tasks. One of the theories concerning this after-effect is ego depletion, a state of reduced self-regulatory resources.To this end, the present study examined concurrent and carry-over effects of multitasking and self-regulation on task performance. Specifically, the current study examined whether the effects of media multitasking with different attentional demands vary by self-regulation (i.e., single-task, multitask with divided attention, multitask with selective attention, multitask with flexible attention) and how such effects occur during and after multitasking. Consistent with predictions, media multitasking decreased performance on subsequent self-control and cognitive tasks. Also, participants in the multitasking condition with flexible attention watched a subsequent movie longer, and they perceived it as more enjoyable than those in the single-task condition. Additionally, findings showed how exerting self-regulation could lead to better performance on both primary and secondary tasks. Findings and implications for research on media multitasking are further discussed.
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Title: Tunable Fluorescent Organic Salts for Imaging and Therapy
Creator: Broadwater, Deanna May
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Cancer remains a leading cause of death worldwide and many treatments still rely on non-targeted chemotherapy, which has inadequate efficacy and is plagued by toxic side effects. A promising solution is photodynamic therapy (PDT), a noninvasive clinical cancer treatment that combines a light activated photosensitizer (PS) with excitatory light to generate toxic reactive oxygen species (ROS). These photoactive agents can also produce detectable wavelengths of light upon photoactivation, which...
Show moreCancer remains a leading cause of death worldwide and many treatments still rely on non-targeted chemotherapy, which has inadequate efficacy and is plagued by toxic side effects. A promising solution is photodynamic therapy (PDT), a noninvasive clinical cancer treatment that combines a light activated photosensitizer (PS) with excitatory light to generate toxic reactive oxygen species (ROS). These photoactive agents can also produce detectable wavelengths of light upon photoactivation, which has been used clinically to image tumors in cancer diagnostics and image-guided surgery. Having uses as both diagnostic and therapeutic agents, these molecules are known as theranostics. However, current light-activated theranostics are limited by low brightness, poor tissue penetration, and nonspecific cytotoxicity independent of light excitation. Due to these obstacles, PDT is currently limited to precancerous lesions, superficial neoplastic tissue, or palliative care. Therefore, improved theranostic agents are needed. Prevailing efforts to improve existing photoactive agents focus on chemical modifications that cannot independently control electronic properties (which dictate toxicity) from optical properties. To overcome these limitations, work in this dissertation develops a novel counterion pairing platform to modulate the toxicity of organic salts composed of a photoactive cationic heptamethine cyanine (Cy+) and a non-photoactive anion. These counterion-tuned fluorescent organic salts can be designed to be either nontoxic for imaging, or phototoxic for PDT. Organic salts self-organize into nanoparticles with shifted frontier molecular orbital levels dependent on the counterion while the bandgap remains the same. This allows for tuning of electronic properties without affecting optical properties. Improvements in these areas could expand light-activated theranostics into a wider range of cancers and improve patient outcomes. This dissertation will begin with a review of current photoactive agents used in cancer therapy and ongoing challenges to the adoption of PDT as a frontline therapy. Modern PDT regimens and potential combinatorial therapies will be appraised, and recent advances in rational PS design will be highlighted. Initial in vitro studies investigated the optoelectronic tuning capabilities of counterion pairing in human lung carcinoma (A549) and melanoma (WM1158) cell lines. Viability assays establish that pairings with weakly coordinating bulky anions could generate organic salts that are non-cytotoxic and selectively phototoxic, while pairing with standard hard anions yield cytotoxic organic salts. These studies demonstrate that anion pairing can be exploited to shift energy levels and influence ROS generation to either enhance photokilling of cancer cells or improve cell imaging. Organic salts were further investigated in a metastatic breast cancer mouse model to characterize biodistribution, antitumor efficacy within a complex tumor microenvironment, and off-site toxicity. In vivo experiments confirm that counterion tuning can generate a selectively phototoxic antitumor PS which abolishes tumor growth and reduces metastasis without systemic toxicity in a breast cancer mouse model. Overall, this work demonstrates the utility of using counterion tuning to control phototoxicity, and further demonstrates the untapped potential of photoactive theranostic agents for clinical cancer therapy.
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Title: ENHANCING CORPORATE CRIME ENFORCEMENT WITH MACHINE LEARNING—A MULTIDISCIPLINARY RISK FACTOR APPROACH
Creator: Chan, Fiona
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Despite its severe and lasting social and financial ramifications, corporate financial crime remains one of the most understudied crime types, as it is often hindered by two challenges. First, its multidisciplinary nature requires both financial and criminological expertise among others to conduct proper investigations. Second, corporate crime data is fraught with constraints such as high dimensionality, complex interactions, and nonlinear functional forms that are ill-suited for classical...
Show moreDespite its severe and lasting social and financial ramifications, corporate financial crime remains one of the most understudied crime types, as it is often hindered by two challenges. First, its multidisciplinary nature requires both financial and criminological expertise among others to conduct proper investigations. Second, corporate crime data is fraught with constraints such as high dimensionality, complex interactions, and nonlinear functional forms that are ill-suited for classical statistical modeling. The lack of research coupled with the limited resources in corporate crime enforcement represent a great impediment to the advancement of fraud interventions. This dissertation seeks to overcome these specific challenges by unifying cross-disciplinary financial fraud research under a risk factor framework, and by leveraging recent advancements in artificial intelligence. The goal is to examine whether two machine learning algorithms—random forest and neural network—can be used to enhance corporate fraud risk detection/prediction beyond more commonly employed analytical techniques. Findings from the analysis showed that the random forest algorithm outperformed logistic regression and a naïve classifier in a 1:1 matched sample. The neural network performed better than a naïve classifier but slightly worse than logistic regression. Feature selection improved the algorithms’ predictive accuracy and ability to distinguish between classes even further. Despite promising results from the 1:1 matched sample, both machine learning algorithms struggled with a heavily imbalanced 1: many dataset, which represents a more realistic setting. With the implementation of an oversampling strategy and feature selection, the algorithms improved substantially in identifying the rare fraud cases, and showed promise of improvement with further research on imbalanced classification. Feature importance from the random forest classifier identified risk factors that are consistent with findings from prior studies. Measures of financial distress ranked lower in importance than measures of financial health, suggesting future research can build on prior findings on corporate strain to examine specific mechanisms. The analysis also identified auditor independence as a key concept of guardianship and opportunity structure that warrants further study. Findings from this research also have important methodological implications for corporate crime studies—namely, the need to improve measurements of organizational-level fraud risk factors.
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Title: Topological Approaches for Quantifying the Shape of Time Series Data
Creator: Tymochko, Sarah
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Topological data analysis (TDA) is field that started only two decades ago and has already shown promise both in theory and in applications. The goal of TDA is to quantify the shape of data in a manner that is concise and robust using concepts from algebraic topology. Persistent homology, arguably the most popular tool from TDA, studies the shape of a filtered space by watching how its homology changes. The output of persistent homology is a persistence diagram, which encodes information...
Show moreTopological data analysis (TDA) is field that started only two decades ago and has already shown promise both in theory and in applications. The goal of TDA is to quantify the shape of data in a manner that is concise and robust using concepts from algebraic topology. Persistent homology, arguably the most popular tool from TDA, studies the shape of a filtered space by watching how its homology changes. The output of persistent homology is a persistence diagram, which encodes information about the changing homology.Persistent homology has shown success in various application areas; one ever growing area of study in this field is time series analysis. Nonlinear time series analysis is a research field in and of itself that aims to capture structure in time series data, however, it lacks theoretically justified tools to analyze the resulting structure. Persistent homology comes with a solid theoretical framework, is robust to noise, and quantifies the same type of structure as appears in time series data. Thus combining tools from time series analysis and TDA provides a new approach to analyze and quantify behavior in time series data.One field where time series are prevalent is dynamical systems, since a time series arises from a projection of a solution to a system. Specifically, given a time series, Takens' theorem can be leveraged to embed the time series as a point cloud in a higher dimensional space, where this point cloud is a sampling of the full state space. Then for each time series, persistent homology can be computed on the embedding. The result is a persistence diagram for each time series. The question then becomes how do we analyze this collection of persistence diagrams to learn something about the original time series data? Many people have developed methods to answer this question, through methods such as machine learning or statistics. This dissertation provides several new methods leveraging tools from both TDA and nonlinear time series analysis to study time varying data.
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Title: Robust Maxwell Solvers for Large Scale Particle-in-Cell Simulations
Creator: Crawford, Zane Daniel
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The design of modern devices is impacted heavily by the use and availability of robust, accurate, and efficient computational tools. This includes modeling devices that exploit plasma physics like particle accelerators, klystrons, ion thrusters, and micro-plasma generators among many other applications. While there are a number of current and emerging applications, the common thread between all is the need to accurately and efficiently capture all the relevant physics in geometrically...
Show moreThe design of modern devices is impacted heavily by the use and availability of robust, accurate, and efficient computational tools. This includes modeling devices that exploit plasma physics like particle accelerators, klystrons, ion thrusters, and micro-plasma generators among many other applications. While there are a number of current and emerging applications, the common thread between all is the need to accurately and efficiently capture all the relevant physics in geometrically intricate structures. The holy grail is to enable topology optimization to explore the design space. But all this requires rigorous translation from the continuous to the discrete world, while capturing all the underlying physics and not adding spurious artifacts due to discretization.A common computational model to perform this analysis is the particle-in-cell (PIC) method. It provides a straightforward paradigm to self-consistently solve for the distribution of the plasma as a collection of particles. The prevailing approach to solve for the fields in PIC is the finite difference time domain method (FDTD), or EM-FDTDPIC. But this effort leaves much to be desired, given the leaps that have been made in the finite element method; indeed, the latter is the method of choice for most commercial tools that that have become the de-facto workhorse in RF design industry. As a result, in the past decade, considerable effort has been expended in developing finite element (FEM) based PIC schemes, EM-FEMPIC. But we are still not there. One major concern of utilizing EM-FEMPIC over EM-FDTDPIC is the computational cost of FEM, which is greater than FDTD, despite the advantages of field and geometry accuracy FEM affords.This dissertation seeks to develop (i) a theoretically rigorous means to translate from the continuous to the discrete world while ensuring that there are no spurious artifacts, (ii) develops a higher order accurate method in both space and time, and (iii) overcomes cost complexity by introducing a linear scaling domain decomposition scheme. In all of these, the methods developed ensure that the necessary conservation properties are satisfied to machine precision. Numerous examples developed demonstrate these claims.
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Title: Machine Learning on Drug Discovery : Algorithms and Applications
Creator: Sun, Mengying
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Drug development is an expensive and time-consuming process where thousands of chemical compounds are being tested and experiments being conducted in order to find out drugs that are safe and effective. Modern drug development aims to speed up the intermediate steps and reduce cost by leveraging machine learning techniques, typically at drug discovery and preclinical research stages. Better identification of promising candidates can significantly reduce the load of later processes, e.g.,...
Show moreDrug development is an expensive and time-consuming process where thousands of chemical compounds are being tested and experiments being conducted in order to find out drugs that are safe and effective. Modern drug development aims to speed up the intermediate steps and reduce cost by leveraging machine learning techniques, typically at drug discovery and preclinical research stages. Better identification of promising candidates can significantly reduce the load of later processes, e.g., clinical trials, saving tons of resources as well as time.In this dissertation, we explored and proposed novel machine learning algorithms for drug discovery from the aspects of robustness, knowledge transfer, molecular generation and optimization. First of all, labels from high-throughput experiments (e.g., biological profiling and chemical screening) often contain inevitable noise due to technical and biological variations. We proposed a method that leverages both disagreement and agreement among deep neural networks to mitigate the negative effect brought by noisy labels and better predict drug responses. Secondly, graph neural networks (GNNs) has become popular for modeling graph-structured data (e.g., molecules). Graph contrastive learning, by maximizing the mutual information between paired graph augmentations, has been shown to be an effective strategy for pretraining GNNs. However, the existing graph contrastive learning methods have intrinsic limitations when adopted for molecular tasks. Therefore, we proposed a method that utilizes domain knowledge at both local- and global-level to assist representation learning. The local-level domain knowledge guides the augmentation process such that variation is introduced without changing graph semantics. The global-level knowledge encodes the similarity information between graphs in the entire dataset and helps to learn representations with richer semantics. Last but not least, we proposed a search-based approach for multi-objective molecular generation and optimization. We show that given proper design and sufficient information, search-based methods can achieve performance comparable or even better than deep learning methods while being computationally efficient. Specifically, the proposed method starts with existing molecules and uses a two-stage search strategy to gradually modify them into new ones, based on transformation rules derived from large compound libraries. We demonstrate all the proposed methods with extensive experiments.
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Title: Toward a Virulent Community Literacy : Constellating the Science, Technology, and Medicine of Queer Sexual Health
Creator: Flores, Wilfredo Antonio
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Toward a Virulent Community Literacy: Constellating the Science, Technology, and Medicine of Queer Sexual Health is a qualitative study (informed by Indigenous and decolonial methodologies) of how queer and trans people of color generate and share knowledge about their sexual health on Twitter with regards to HIV/AIDS. With a Twitter archive of 15,000 discrete tweets built with the keywords “Truvada,” PrEP,” and “HIV,” three datasets were derived comprising general utterances from queer users...
Show moreToward a Virulent Community Literacy: Constellating the Science, Technology, and Medicine of Queer Sexual Health is a qualitative study (informed by Indigenous and decolonial methodologies) of how queer and trans people of color generate and share knowledge about their sexual health on Twitter with regards to HIV/AIDS. With a Twitter archive of 15,000 discrete tweets built with the keywords “Truvada,” PrEP,” and “HIV,” three datasets were derived comprising general utterances from queer users of color, public health officials using social media for outreach, and organizations sharing research findings. Focusing on the data subset comprising 300 discrete users of color and relevant media (i.e., news articles, public health advertisements, other emergent artifacts from the data), this dissertation recounts three case studies focusing on: the rollout of HIV prevention advertisements within queer-centered media; the patent breaking of Truvada, a once-daily medication for preventing HIV; and the use of social media to take to task bad actors and misinformed healthcare providers. The data are used as part of an argument that the manner by which medicine and public health interface with queer and trans people of color hinges on ongoing colonization via the medical and outreach practices derived from colonial practices. Moreover, using a theoretical argument derived from Black and Native technology studies (as well as Black Feminist Thought, Anishinaabe cosmology, settler colonial studies, and digital rhetorical theory), the data was reviewed through a protocol for understanding identity construction amid technology use. The results revealed three rhetorical strategies: 1) continuing community-born public health practices created during the HIV/AIDS crisis of the 1980s and 90s by deploying descriptive hashtags to challenge stigma; 2) creating emergent whisper networks for sharing information about dealing with healthcare providers, navigating insurance networks, and communicating the symptoms of taking the medication; and 3) recognizing and countering the complex systems of late capitalist biomedicalization that prioritize profit over life. To contribute to ongoing commitments within writing and rhetoric studies to create equitable healthcare experiences, an HIV/AIDS health literacy framework follows the data results, which allows for outreach in non-clinical settings through relational design, or a participatory communication design process that incorporates community voices via an attunement to social media such as Twitter. This dissertation contributes to ongoing incursions within technical and professional communication, as well as the rhetoric of health and medicine, to upcycle disciplinary savvy into building better public health and clinical experiences for queer and trans people of color.
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Title: ECOPHYSIOLOGY OF (PERI)ORAL BACTERIA AND IMPACT OF OTIC COLONIZATION
Creator: Jacob, Kristin Marie
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The middle ear is typically assumed to be sterile in health due to its secluded location, closed off from external forces by the tympanic membrane (ear drum) and from the naso/oropharynx by a collapsed Eustachian tube. However, the periodic opening of the Eustachian tube to the naso/oropharyngeal space, which releases pressure across the eardrum and drains otic fluids, could introduce bacteria. Previous studies have tested for the presence of bacteria in the uninfected otic cavity using...
Show moreThe middle ear is typically assumed to be sterile in health due to its secluded location, closed off from external forces by the tympanic membrane (ear drum) and from the naso/oropharynx by a collapsed Eustachian tube. However, the periodic opening of the Eustachian tube to the naso/oropharyngeal space, which releases pressure across the eardrum and drains otic fluids, could introduce bacteria. Previous studies have tested for the presence of bacteria in the uninfected otic cavity using samples collected via invasive surgeries (through or around the eardrum). Findings from these studies are controversial due to contradictory results between studies, lack of critical experimental controls, and sampling of participants with underlying ailments (i.e., cochlear implant surgery) that could impact the microbiology of the otic mucosa. The studies reported herein bypass these limitations by using samples of otic secretions collectively non-invasively (through the mouth) in a cohort of healthy young adults. This dissertation describes cultivation-dependent methods to investigate the microbiology of the middle ear in health. The study used an IRB-approved protocol (#17-502) to collect otic secretions in order to 1) sequence their microbiome (contribution by Dr. Joo-Young Lee) and 2) recover in pure culture otic bacteria for further characterization (my contribution). As controls, we also collected buccal (top palate and inside of cheeks) and oropharyngeal swabs from each participant. Of the collected secretions, samples from 19 individuals were used for culture independent studies, while samples from the remaining 3 participants were subjected to culture dependent studies. 16S rRNA-V4 sequencing detected a diverse and distinct microbiome in otic secretions comprised primarily of strictly anaerobic bacteria belonging to the phyla Bacteroidetes, Firmicutes and Fusobacteria, and to a lesser extent facultative anaerobes (Streptococcus). I recovered from the otic, oropharyngeal, and buccal secretions 39 isolates of predominantly facultative anaerobes belonging to Firmicutes (Streptococcus and Staphylococcus), Actinobacteria (Micrococcus and Corynebacterium), and Proteobacteria (Neisseria) phyla, and used partial 16S rRNA amplicon sequences to demonstrate the distinct phylogenetic placement of otic streptococci compared to the oral ancestors (Chapter 2). This finding is consistent with the ecological diversification of oral streptococci once in the middle ear microenvironment. The recovery of streptococci and transient migrants (Staphylococcus, Neisseria, Micrococcus and Corynebacterium) from otic secretions prompted us to study the adaptive responses that give the streptococcal migrants a competitive advantage during the colonization of the middle ear (Chapter 3). For these studies, I sequenced and partially assembled the genomes of the otic isolates and used the full length 16S rRNA sequences for taxonomic demarcation at the species levels. Phylogenetic analyses demonstrated the oral ancestry of the otic streptococci, which retained from the otic adaptive traits critical for growth and reproduction in the middle ear mucosa (biofilm formation, mucolytic and proteolytic activity, robust growth under redox fluctuations, and fermentative production of lactate, a key metabolic intermediate in the otic trophic webs). These adaptive traits give oral streptococci a colonization advantage over competing (peri)oral migrants such as Staphylococcus. Furthermore, the otic streptococci inhibited the growth of otopathogens, including Staphylococcus aureus. These antagonistic interactions give streptococci a competitive advantage during the colonization of the middle ear and suggest a role for these commensals in promoting mucosal health. The ability of staphylococcal migrants to breach the middle ear mucosal barrier and cause infections prompted us to study the environmental factors that facilitate the spreading of staphylococci from the nasal to the middle ear mucosa. Allergies, respiratory maladies (cold, flu), or (peri)oral bacterial infections (sinus, adenoids, tonsils, etc.) lead to inflammation of the Eustachian tube and changes in the rheological properties of the otic mucus that increase the risk of infections. Thus, we examined the spreading of staphylococci on mucus-like viscous surfaces (semisolid agar plates). In Chapter 4, I show that mucins, the mucosal glycoproteins that control the viscosity and wettability of the mucus layer, induce the rapid spreading and dendritic expansion of clinical isolates closely related to S. aureus and Staphylococcus epidermidis but not of Staphylococcus hominis. Mucin glycosylation controlled the hydration of the mucoid surface and the ability of the cells to spread rapidly, in a process that was dependent on the secretion of surfactant-active, phenol-soluble modulins via the agr-quorum sensing two-component system. These results provide a plausible explanation for the rapid spreading of staphylococcal otopathogens from the nasopharynx to the middle ear through a swollen, and mucin-rich Eustachian tube. The work described in this dissertation provides much needed understanding of the adaptive responses that allow (peri)oral bacteria to colonize the middle ear. The studies add to the accumulating evidence that the middle ear mucosa is not sterile but rather harbors a commensal microbiota in health. These commensal community shares many metabolic similarities with ancestors in oral biofilms and retain adaptive traits critical for growth in the otic mucosa and inhibition of otopathogens. Additionally, this work identifies environmental factors that could contribute to staphylococcal virulence, broadening the understanding of newly identified motility phenotypes in the genus that could provide novel pharmaceutical targets.
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Title: Assessing Safety Performance of Roadway Characteristics in Rural and Urban Contexts
Creator: Chakraborty, Meghna
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Evaluating the safety performance of roadway segments and intersections typically involves associating traffic crashes, injuries, and fatalities to various roadway and traffic characteristics, which typically vary broadly between rural and urban contexts. In rural areas, roadway geometric characteristics often play a critical role in the safety performance of a given roadway, while myriad other factors, including driveways and intersections, tend to have a greater influence on urban roadway...
Show moreEvaluating the safety performance of roadway segments and intersections typically involves associating traffic crashes, injuries, and fatalities to various roadway and traffic characteristics, which typically vary broadly between rural and urban contexts. In rural areas, roadway geometric characteristics often play a critical role in the safety performance of a given roadway, while myriad other factors, including driveways and intersections, tend to have a greater influence on urban roadway safety. However, certain geometric aspects, such as the characteristics of the horizontal curvature and the impact of driveway land-use type have not been well-explored in prior roadway safety research. There has also been limited research on the safety performance for roadways of lower functional classifications, such as minor arterial and collector roadways, which comprise a substantial portion of the nationwide roadway network but are often designed to lower standards and possess driver and trip characteristics that typically differ from those of principal arterials. Therefore, assumptions made on the general effect of the predictor variables from typical safety performance functions may not apply to lower roadway classes. This research sought to explore those gaps in the roadway safety research domain. To accomplish this objective, roadway characteristics were collected along with traffic volume and crash data for greater than 13,000 miles of two-lane roadways in rural, urban, and suburban areas from across the state of Michigan for the period of 2011 through 2018. A series of safety performance functions were developed using a mixed-effects negative binomial modeling structure, which included fixed-effects and random-effects to account for the unobserved heterogeneity associated with varying design standards and site characteristics. The results indicated that driveway density significantly influences crash occurrence across all land-use categories for paved highways, although no impact was observed on unpaved roads. Commercial driveways possessed a stronger effect on crash occurrence than residential driveways or industrial driveways. In urban areas, posted speed limit had a significant positive association with crash frequency, and this effect increased when the speed limit exceeded 40 mph. The effect of speed limit was stronger on urban minor arterial segments (compared to collectors) and for fatal and injury crashes (compared to property damage only). This research also assessed the safety impacts associated with horizontal curve characteristics on rural highway segments, including curve type, curve direction, curve-approaching, curve-following, and inner-curve tangent distances, and curve design speed on rural two-lane undivided highways. Similar to prior research, curves with design speeds lower than the posted speed limit showed elevated crash occurrence. Most notably, compound and reverse curves were associated with greater crash occurrence compared to simple curves, with the greatest impact by the reverse curves. The increased approaching tangent distance for the simple curve or the first of a series of compound or reverse curves increased crash likelihood, perhaps due to the decreased driver expectancy for curvature with increasing tangent distance. However, increased inner-curve tangent distance was found to be associated with decreased crash occurrence. Lastly, the left-turning curves were found to be associated with greater crash occurrence than that on the right-turning curves.
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Title: COBALT REDOX MEDIATORS FOR DYE-SENSITIZED SOLAR CELLS
Creator: Raithel, Austin L.
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Dye-sensitized solar cells have become an affordable alternative to conventional photovoltaics.Their efficiencies have become competitive by continued optimization of the semiconductor, dye, redox shuttle, and counter electrode. This thesis will evaluate low-spin Co(II) redox shuttles’ ability to minimize photovoltage losses due to dye regeneration and recombination to semiconductor electrons. Their synthesis and properties will be described along with a comparison to typical high-spin Co(II)...
Show moreDye-sensitized solar cells have become an affordable alternative to conventional photovoltaics.Their efficiencies have become competitive by continued optimization of the semiconductor, dye, redox shuttle, and counter electrode. This thesis will evaluate low-spin Co(II) redox shuttles’ ability to minimize photovoltage losses due to dye regeneration and recombination to semiconductor electrons. Their synthesis and properties will be described along with a comparison to typical high-spin Co(II) redox shuttles. The kinetic properties will be evaluated in terms of Marcus Theory with a particular focus being made on reorganization energy and free energy of electron transfer events. Chapter 1 will describe the motivation for dye-sensitized solar cells along with a description of their development and operation. Chapter 2 and 3 will describe the two extremes of redox potential of the redox shuttle. Chapter 4 demonstrates a system with a tunable potential inbetween. Chapter 5 will report other redox shuttle candidates and future directions to surpass 15% power conversion efficiency with low-spin Co(II) redox shuttles.
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Title: CONTRIBUTIONS TO EPIDEMIOLOGICAL RESEARCH ON THE SELLING OF INTERNATIONALLY REGULATED DRUGS
Creator: Yuan, Sha
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The existing research on drug selling among teenagers is limited. A few research teams have studied aspects of adolescent drug dealing. The scope of research includes economic factors relaed to youths involved in drug gangs (Levitt & Venkatesh, 2000) as well as psychosocial factors that might prompt teenagers to sell drugs (Fagan J, 1990; Little & Steinberg, 2006). Few have thought about adolescent drug selling from an epidemiological perspective, with a conceptualization based on agent-host...
Show moreThe existing research on drug selling among teenagers is limited. A few research teams have studied aspects of adolescent drug dealing. The scope of research includes economic factors relaed to youths involved in drug gangs (Levitt & Venkatesh, 2000) as well as psychosocial factors that might prompt teenagers to sell drugs (Fagan J, 1990; Little & Steinberg, 2006). Few have thought about adolescent drug selling from an epidemiological perspective, with a conceptualization based on agent-host-environment triad models, and with attention to potential public health control methods required for effective interventions.An early contributor, Isidore Chein and his research team (1964) launched important psychosocial research on youthful drug selling. According to that research, adolescents involved in heroin use often conducted drug dealing. However, the samples were limited to male adolescents in New York City, and the data collection period was from 1949 to 1955. This doctoral dissertation research project builds upon progress made by Chein and his colleagues. It summarizes a set of studies of youthful drug selling that merit attention. The project then aims to contribute new epidemiological findings on adolescents selling internationally regulated drugs (IRD) such as cannabis and cocaine. From an epidemiologist’s point of view, a drug seller can be considered a vector in the person-to-person spread of drug involvement. For this reason, a comprehensive view of the epidemiology of drug involvement should not neglect drug selling. For this dissertation research project, I conducted four investigations with focus on the drug onset and drug selling experiences of 12-to-17-year-old adolescents in the United States community populations. The first investigation aims to estimate the age-specific prevalence of recent drug selling behaviors for the age period of 12 to 17 years, with attention to the following subgroups that Salas-Wright and colleagues (2017) recently identified as having a higher prevalence of drug selling in the non-institutionalized U.S. population: (a) males and (b) older adolescents. The second study aims to produce estimates concerning birth cohort variations in drug selling prevalence. The third study divides youths into three groups: “never used any IRD” group, “cannabis only at first IRD use” group, and “used a non-cannabis IRD with or without concurrent cannabis use at first IRD use” group. The investigation then turns to an estimation of the likelihood of being a seller of drugs in the past 12 months for each of these three groups, with attention to the duration of IRD use, The fourth study aims to compare non-users and users whose first drug is cannabis with respect to their odds of selling drugs in the second year after first drug use. The population under study was sampled for annual United States National Surveys of Drug Use and Health (NSDUH). The NSDUH sampled, recruited, and assessed non-institutionalized US civilian residents aged 12 and above each year. After Institutional Review Board-approved consent procedures, all participants were assessed using confidential audio computer-assisted self-interviews. There are cannabis and youth experience modules and modules on other drugs and health topics in the self-interview sessions. The findings of all the four studies in this dissertation are from statistical analyses of NSDUH public-use data files based on the survey questions in the aforementioned modules. The main findings and implications, summarized across the four research projects, are as follows: • Study 1: The estimated prevalence of drug selling increases with age during the adolescent years under study. The estimated prevalence for boys is larger than the corresponding estimates for girls. • Study 2: Estimated age-specific prevalence patterns do not vary appreciably across recent birth cohorts. The general pattern is one of cohort-specific increases in the odds of drug-selling from age 12 to age 17; estimates of 17-year olds are larger. • Study 3: Starting to use cannabis and no other IRD is associated with greater odds of drug selling in the subsequent adolescent years. The study estimates suggest that as time passes since first IRD use, the odds of drug selling increase (up to a point). If the first IRD use is not cannabis, then the estimated odds of drug selling may be larger than if cannabis is the only IRD that has been used. • Study 4: Adolescents who start to use cannabis but none of the other internationally regulated drugs are observed to be more likely to sell drugs in the second year after the first use, compared to adolescents who have never used any drug. Subject to limitations described in this dissertation report, these findings merit further investigation and attention in public health initiatives to prevent the person-to-person spread of drug use during adolescence. The dissertation research report also describes some future research directions that can build upon this project’s findings, which include future longitudinal and prospective investigations.
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Title: Quantum coherent transport phenomena in epitaxial halide perovskite thin films
Creator: Zhang, Liangji
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The subject of this dissertation is the experimental study of quantum coherent transport phenomena in epitaxial single-crystal halide perovskite thin films. The experiments consist of low-temperature (down to 10 mK) magnetotransport measurements at high magnetic field (up to 14 T).The recent advent of epitaxial thin film growth of inorganic halide perovskites has made it possible to investigate the quantum behavior of charge carriers in these materials in low-dimensional form. We present...
Show moreThe subject of this dissertation is the experimental study of quantum coherent transport phenomena in epitaxial single-crystal halide perovskite thin films. The experiments consist of low-temperature (down to 10 mK) magnetotransport measurements at high magnetic field (up to 14 T).The recent advent of epitaxial thin film growth of inorganic halide perovskites has made it possible to investigate the quantum behavior of charge carriers in these materials in low-dimensional form. We present results on epitaxial single-domain cesium tin iodide (CsSnI3) thin films that clearly demonstrate quantum transport in this material for the first time. The observed low-field magnetoresistance shows signatures of weak anti-localization (WAL) that reveals coherent quantum interference effects and spin-orbit coupling. A micron-scale (≈5 um) low-temperature phase coherence length for charge carriers in the system is extracted from these WAL measurements.Additionally, we present low-temperature quantum magnetotransport measurements on thin film devices made of epitaxial single-crystal CsSnBr3, which exhibit two-dimensional Mott variable range hopping (VRH) and a large negative magnetoresistance. These findings are described by the Nguyen-Spivak-Shkovskii (NSS) model for quantum interference between different directed hopping paths, and we extract the temperature-dependent hopping length of charge carriers, their localization length, and a lower bound for their phase coherence length of ~100 nm at low temperatures. These results from CsSnI3 and CsSnBr3 devices demonstrate that epitaxial halide perovskite devices are emerging as a material class for low-dimensional quantum coherent transport devices.In addition to the works that are described above, I have also been involved in several additional projects, such as experiments on low-dimensional electron systems and superconducting qubit experiments, which will not be described in this dissertation.
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Title: PLANNING FOR AUTONOMY AND ELECTRIFICATION IN FUTURE TRANSPORTATION SYSTEMS
Creator: Singh, Harprinderjot
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Autonomous vehicles (AVs) and electric vehicles (EVs) will improve safety, mobility, roadway capacity and provide efficient driving, efficient use of travel time, and reduced emissions. However, these technologies affect vehicle miles traveled (VMT), travel time, ownership cost, and electric grid network. Shared mobility systems can ameliorate the high price of these technologies. However, the shared mobility system poses additional problems such as users’ waiting time, inconvenience, and...
Show moreAutonomous vehicles (AVs) and electric vehicles (EVs) will improve safety, mobility, roadway capacity and provide efficient driving, efficient use of travel time, and reduced emissions. However, these technologies affect vehicle miles traveled (VMT), travel time, ownership cost, and electric grid network. Shared mobility systems can ameliorate the high price of these technologies. However, the shared mobility system poses additional problems such as users’ waiting time, inconvenience, and increased VMT. Further, the impact of these emerging technologies varies on different groups of users (different values of travel time (VOTT). Another hurdle to the adoption of EVs is the limited range and scarcity of charging infrastructure. A well-established network of charging infrastructure, especially the direct current fast chargers (DCFC), can alleviate this challenge. However, the widespread adoption of EVs and the growing network of DCFC stations will increase the electric energy demand affecting the electric grid stability, demand-supply imbalance, overloading, and degradation of the electric grid components. Distributed energy resources (DER) such as solar panels and energy storage systems (ESS) can support the EV demand and reduce the load on the electric grid. This study develops modeling frameworks for the optimal adoption of AVs and EVs, considering their effect on transportation systems, the environment, and the electric grid network. Further, it suggests different scenarios that would promote the adoption of these technologies and provide a sustainable and resilient system.This study proposes a multi-objective mathematical model to estimate the optimal fleet configuration in a system of private manual-driven vehicles (PMVs), private AVs (PAVs), and shared AVs (SAVs) while minimizing the purchase and operating costs, time (travel and waiting time), and emission production. SAVs can be the optimal solution with the efficient use of travel time or the purchase price below a certain relative threshold. PAVs can be the optimal solution only if the onboard amenities are improved, lifetime mileage is increased, AV technology is installed in luxurious cars, and adopted by people with high VOTT. The framework is extended to consider different combinations of EVs, AVs, and conventional human-driven vehicles in a private and shared mobility system. The metaheuristics based on genetic and simulated annealing algorithms are developed to solve the large-scale NP-hard nonlinear optimization problem. The model is implemented for the network of Ann Arbor, Michigan. The results suggest that EVs are optimal for the system due to low operating costs and zero tailpipe emissions. Shared autonomous electric vehicles (SAEVs) are the best option for users with low VOTT. Private autonomous electric vehicles (PAEVs) would favor the system if the travel time savings are at least 20% or the price of AV technology is less than one-third of the vehicle price. The study then investigates the optimum investment technology to support the rising energy demand at the DCFC stations and reduce the load on the electric grid network. The different investments include purchasing and installing various ESS (new batteries (NB), second-life batteries (SLB), flywheels), solar panels, electric grid upgrades, and the cost of buying/selling electricity from/to the electric grid. The model is implemented for the DCFC stations supporting the future needs of EV charging demand for urban trips in the major cities of Michigan in 2030. The combination of SLBs and solar panels provides maximum benefits. The total annual and electricity savings are $25,000-$165,000 and $40,000-$300,000 per city.
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Title: Teaching Presence in a Fully Online Asynchronous Undergraduate Mathematics Course and its Impact on Social and Cognitive Presence
Creator: Elmore, Robert Andrew
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The number of fully online asynchronous undergraduate mathematics courses is growing rapidly, making it imperative that the instructional choices that are chosen by instructors and their effects on students’ opportunities to learn in the online learning environment be further explored. Therefore, this research aims to understand instructors' choices when teaching an online undergraduate mathematics course, and how these decisions impact students' communication opportunities. This research...
Show moreThe number of fully online asynchronous undergraduate mathematics courses is growing rapidly, making it imperative that the instructional choices that are chosen by instructors and their effects on students’ opportunities to learn in the online learning environment be further explored. Therefore, this research aims to understand instructors' choices when teaching an online undergraduate mathematics course, and how these decisions impact students' communication opportunities. This research organized the instructors' decisions and their impacts on students using the community of inquiry framework. The three categories of the community of inquiry framework, teaching presence, social presence, and cognitive presence, were analyzed through course artifacts, an instructor interview, student interviews, student surveys, and course usage data. The primary analysis was performed using the interviews with the other data sources providing further detail and explanation. Four claims were generated while analyzing these data sources. Claim one posits that students tend to have singular preferences of the course’s direct instructional elements. Claim 2 proffers that students who chose to work with others report having positive experiences, and those who decided not to work with others report not needing help, with one exception. Claim 3 states that meaningful contact points can be created between the instructor and student using surveys and personalized mass emails; however, most describe learning mathematics in Math 101 as not making them feel a part of a learning community. And claim 4 posits that elements of the teaching presence were more likely to foster participation if they were associated with a grade. The results of this study have implications for both the research and practice communities. The current study’s results imply that—even though sizes of online mathematics classes may still grow—there are ways instructors can facilitate high levels of social processes using mass email, surveys, cooperative learning groups, and other online tools. These specific tools should be studied and evaluated for their effects on social presence and cognitive presence on the mass scale. The present study suggests four specific things that instructors should familiarize themselves with that are available today, (a) prescribe opportunities for students to communicate with each other such as having assignments that are completed in cooperative learning groups, (b) communicate with your students through personalized means (e.g., emails, surveys, and Zoom sessions), (c) use feedback from surveys to inform your future teaching practice, and (d) ensure that students observe your communication and direct instruction by tying them to elements associated with grades. Keywords: teaching presence, social presence, cognitive presence, online mathematics learning.
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Title: DO INTERFACES MATTER? A REEXAMINATION OF XBRL USING FINANCIAL STATEMENT ACQUISITION AND MARKET ACTIVITY
Creator: Anderson, James J.
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Starting in 2009 the eXtensible Business Reporting Language (XBRL) standard was mandated for financial statements by the SEC. The XBRL standard was intended to encourage less-sophisticated trader disclosure processing; however, previous literature has conjectured that the standard primarily aided more-sophisticated traders’ disclosure processing. I reexamine the effect of XBRL on more- and less-sophisticated trader disclosure processing by testing whether XBRL influenced their information...
Show moreStarting in 2009 the eXtensible Business Reporting Language (XBRL) standard was mandated for financial statements by the SEC. The XBRL standard was intended to encourage less-sophisticated trader disclosure processing; however, previous literature has conjectured that the standard primarily aided more-sophisticated traders’ disclosure processing. I reexamine the effect of XBRL on more- and less-sophisticated trader disclosure processing by testing whether XBRL influenced their information acquisition and testing whether the proportional relationship between information acquisition and market activity is different for more- and less-sophisticated traders. I find the staggered implementation of XBRL is associated with a 49% (26%) increase in less (more) sophisticated trader information acquisition. Next, I find the proportional relationship between information acquisition and market activity is greater for less-sophisticated traders when compared to more-sophisticated traders. Specifically, I find information acquisition for less-sophisticated traders has a greater proportional relationship with abnormal price movement, abnormal trading volume, and abnormal bid-ask spreads. Together these findings suggest that XBRL did not provide a disproportionate information advantage to more-sophisticated traders, but rather benefited less-sophisticated traders by decreasing their information acquisition costs.
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Title: QUALITY OF LIFE IN CONTEMPORARY NEIGHBORHOOD DESIGN INITIATIVES : AN EMPIRICAL STUDY TO ASSESS QUALITY OF LIFE THROUGH SPATIAL DIMENSION IN NEW URBANIST AND LEED-ND CERTIFIED NEIGHBORHOODS
Creator: Shaaban, Amal Hamdy
Date: 2022
Collection: Electronic Theses & Dissertations
Description: The overarching purpose of this study is to analyze qualitatively and quantitatively the spatial characteristics of two types of neighborhoods, namely New Urbanist (NU) neighborhoods and Leadership in Energy and Environmental Design (LEED) certified neighborhoods. LEED certified neighborhoods are commonly referred to as LEED for Neighborhood Development (LEED-ND). In this research study, the spatial quality of these two types of neighborhoods was examined through assessing the quality of five...
Show moreThe overarching purpose of this study is to analyze qualitatively and quantitatively the spatial characteristics of two types of neighborhoods, namely New Urbanist (NU) neighborhoods and Leadership in Energy and Environmental Design (LEED) certified neighborhoods. LEED certified neighborhoods are commonly referred to as LEED for Neighborhood Development (LEED-ND). In this research study, the spatial quality of these two types of neighborhoods was examined through assessing the quality of five dimensions of a neighborhood’s urban form, which are: safety, comfort, connectivity, place making and aesthetic quality. Three types of neighborhoods were selected and examined using two main analytical tools: neighborhood scorecard, and residents’ survey. Two neighborhoods were selected to examine NU neighborhoods in Michigan in the United States, which are Cherry Hill Village (CHV) a greenfield residential development, and Mason Run (MR) a brownfield residential development. The third neighborhood was selected to examine LEED-ND certified neighborhoods, which is Saint Luke (SL) neighborhood in Ohio in the United States. The neighborhood scorecard included a total of 150 design guidelines that yield better Quality of Life (QoL) in residential developments through urban form. The residents’ survey included a set of questions that examined the residents’ perceptions regarding the five physical characteristics necessary to yield better QoL. A total of 154 surveys were collected for data analysis that used one-way ANOVA tests, Tukey’s post-hoc tests, and multiple regression models. The major findings from the neighborhood scorecard are that CHV neighborhood provides was safer than the brownfield NU residential development and the LEED-ND certified neighborhood. Both NU neighborhoods provided more comfortable environments of their residents to live in more than the LEED-ND certified neighborhood. The greenfield NU neighborhood earned more points than the other two neighborhoods in terms of the internal and external connectivity degree of the neighborhood. In terms of fulfilling the recommended design guidelines for place making and aesthetic quality, again the Greenfield NU neighborhood had earned higher points than the other two neighborhoods. The major findings from the survey are: Survey participants living in both NU neighborhoods were more satisfied with their QoL more than the participants living in the LEED-ND certified neighborhood. Also, respondents living in NU neighborhoods perceived their neighborhoods as safer places to live in more than participants living in the LEED-ND certified neighborhood. On the other hand, respondents living in the NU brownfield development perceived their neighborhood as the least comfortable neighborhood. In terms of the internal connectivity of the neighborhood, respondents living in NU greenfield development identified the internal connectivity of their neighborhood as the highest compared to the other two neighborhoods. On the other hand, the perception of the internal connectivity perception was the lowest amongst respondents living in the LEED-ND certified neighborhood. Respondents living in the LEED-ND certified neighborhood had the highest mean in terms of their perceptions of sense of belonging. On the other hand, respondents living in the NU brownfield development had the lowest mean in terms of their perception of sense of belonging. The perception of the aesthetic quality of the neighborhood was the highest among respondents living in the NU greenfield development. On the other hand, the perception of aesthetic quality of the neighborhood was the least among respondents living in NU brownfield development.This research study concludes by suggesting recommendations to improve the principles and design guidelines of NU and LEED-ND certified neighborhoods to achieve better QoL. The recommendations suggest emphasizing certain spatial characteristics that yield better QoL in Greenfield, and brownfield residential developments.
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Title: SYNTHETIC BIOLOGY APPROACHES ESTABLISH THE FOUNDATION FOR SUSTAINABLE PRODUCTION OF HIGH VALUE TERPENOIDS
Creator: Bibik, Jacob David
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Plants have become a promising platform for sustainable bioproduction of an array of natural products and specialty chemicals. Of particular interest are terpenes and the functionalized terpenoids, which represent the largest and most diverse class of natural products. These natural products are commonly used commercially as major constituents of flavorings and fragrances, oils, pigments, and pharmaceuticals, while having many other applications. Given the diversity and structural complexity...
Show morePlants have become a promising platform for sustainable bioproduction of an array of natural products and specialty chemicals. Of particular interest are terpenes and the functionalized terpenoids, which represent the largest and most diverse class of natural products. These natural products are commonly used commercially as major constituents of flavorings and fragrances, oils, pigments, and pharmaceuticals, while having many other applications. Given the diversity and structural complexity of many terpenoids, they are often expensive and difficult, if not impossible, to chemically synthesize. Engineering these biosynthetic pathways in plant hosts may provide a sustainable platform to access terpenoids for industrial production. While plants offer a sustainable production platform, metabolic engineering for chemical production has largely focused on microbial hosts, and further development of strategies and tools for plant engineering is needed. In my dissertation, I have taken multi-pronged approaches to further develop sustainable bioproduction of terpenoids in plants. First, I developed strategies to optimize, re-target, and compartmentalize production of squalene, a C30 triterpene, within plant cells to improve yields in plants. Re-targeting the final steps in squalene production, farnesyl diphosphate synthase (FDPS) and squalene synthase (SQS), from the cytosol to plastids enabled compartmentalization of biosynthesis away from competing cytosolic enzymes. I then anchored an optimized FDPS and SQS pair to the surface of cytosolic lipid droplets through fusions to the Nannochloropsis oceanica Lipid Droplet Surface Protein (NoLDSP), where squalene can be sequestered and stored. Scaffolding the pathway to the surface of lipid droplets increased yields to more than twice that of plastidial targeting. Re-targeting this lipid droplet scaffolding to plastids, produced similar squalene yields as the soluble, plastid targeted pathway, and ameliorated some of the negative effects on photosynthesis. Second, I worked to engineer poplar, a bioenergy crop which emits large amounts of the hemiterpene isoprene, with these pathways as a platform for bioproduction and adding value to a bioenergy pipeline. Transformants were successfully created for plastid targeted squalene production, producing up to 0.63mg/gFW of squalene. The lipid droplet scaffolding strategies appeared toxic during tissue regeneration, suggesting a need for tissue specific engineering of these pathways in future iterations. Third, I developed a pipeline to identify, characterize, and engineer bidirectional promoters (BDPs), which enable divergent expression of two genes and improve gene stacking in plant constructs. As seen above with poplar, plant engineering is often limited by construct size, diverse promoter availability, and expression regulation, and a BDP library enables a range of expression in more compact constructs. I identified 34 BDPs from Populus trichocarpa and Arabidopsis thaliana, characterized their activity via Nicotiana benthamiana transient expression, and engineered select BDPs to further alter activities. Combining these BDPs with previously developed terminator sequences provided further regulation of expression. These genetic tools provide an array of expression activities and enable greater gene stacking options while offering the potential for more fine tuning of expression for multiple genes in a metabolic pathway. The work performed in this dissertation provide strategies to improve production of terpenoids in plants, establish production hosts, and engineer larger, complex pathways.
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Title: UNDERSTANDING DRIVERS OF PLANT MICROBIOME IN MICHIGAN AGRICULTURE : STUDIES OF THE APPLE ROOT ZONE AND COMMON BEAN SEEDS
Creator: Bintarti, Ari Fina
Date: 2022
Collection: Electronic Theses & Dissertations
Description: Plant-associated microbial communities are crucial for plant health and fitness, and may enhance plant tolerance to various environmental stresses. As global climate change threatens crop production and increases demands on sustainable agriculture, harnessing the plant microbiome has become one potential strategy to address these issues. Thus, it is fundamental to understand the relative contributions of both the host plant as well as the environment in shaping the plant microbiome. Moreover,...
Show morePlant-associated microbial communities are crucial for plant health and fitness, and may enhance plant tolerance to various environmental stresses. As global climate change threatens crop production and increases demands on sustainable agriculture, harnessing the plant microbiome has become one potential strategy to address these issues. Thus, it is fundamental to understand the relative contributions of both the host plant as well as the environment in shaping the plant microbiome. Moreover, the response of plant microbiomes to stress and any consequences of microbiome stress responses for the host plants are poorly understood, though this information is critical to achieve a basis of knowledge for plant microbiome engineering. My research aimed to contribute to this knowledge by investigating the factors that structure root- and seed-associated microbial communities of two valuable crops for Michigan’s agricultural economy: apple and common bean. The first chapter of my dissertation aimed to assess the biogeography of bacterial, archaeal, fungal, and nematode communities in the root zone of apple trees, and to determine their relationships with each other and their changes over natural abiotic gradients across orchards. I also assessed the influence of plant cultivar on microbiome structure in the root zone. I found that root zone microbiome community structure was strongly affected by geographic location and edaphic properties of soil. The next chapter of my dissertation investigated the variability of seed endophyte community of common bean (Phaseolus vulgaris L.). My results showed that plant-to-plant variability under controlled growth conditions exceeded within-plant variability among seeds from different pods. My study developed protocols and added insights to the growing toolkit of approaches to understand the plant-microbiome engagements that support the health of agricultural and environmental ecosystems. The last chapter assessed the responses of common bean seed endophytes to drought stress in the field across two growing locations and four genotypes of common bean. To summarize, this work advances foundational knowledge of the seed microbiome as a critical component of the plant microbiome, and in the context of two key crops for Michigan agriculture.
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