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A GENETIC PROGRAMMING TECHNIQUE FOR PROTEIN OPTIMIZATION DEMONSTRATED IN MRI REPORTER GENES
No full textReporter genes are important tools for researchers studying molecular and cellular biology as they give location and measurable values to the expression level of a given gene, by linking the activation of a gene to a detectable phenomenon. Reporter genes for MRI, allow these functions to be done noninvasively at arbitrary tissue depth. Chemical Exchange Saturation Transfer (CEST) based reporter genes have shown promise in acting as reliable reporters in MRI, but the relatively low sensitivity of the method has limited its utility in research situations. Initial attempts to optimize existing CEST reporter genes proved difficult due to a series of technical challenges. This led to the development of a new machine learning tool for protein engineering, the Protein Optimization Engineering Tool (POET). Using POET and experimentation to develop improved CEST reporter genes resulted in new peptides that produce nearly a fourfold increase in contrast over prior art. Additionally POET is used to generate a reporter gene that produces significant contrast at a farther downfield frequency than prior CEST reporter genes.Thesis (Ph.D.)--Michigan State University. Biomedical Engineering - Doctor of Philosophy, 2024Includes bibliographical reference
DISCOVERY AND DESIGN OF NOVEL 20S PROTEASOME ACTIVATORS FOR TARGETED PROTEIN DEGRADATION AND THEIR EVALUATION IN NEURODEGENERATION MODELS
No full textThesis (Ph.D.)--Michigan State University. Chemistry - Doctor of Philosophy, 2024In cells, proteostasis is a constant and highly choreographed process that maintains a balance between the synthesis and degradation of proteins. The ubiquitin-proteasome system is a critical player in this orchestration through both ubiquitin-dependent and ubiquitin-independent pathways. The former pathway is mainly responsible for the degradation of folded proteins, or proteins with a stable 3D conformation, by using ubiquitin tags to flag proteins for degradation. Conversely, the ubiquitin-independent pathway targets proteins that lack stable 3D conformations, including intrinsically disordered proteins (IDPs). Proteostasis can become perturbed when the synthesis of proteins outpaces their degradation, leading to the accumulation of proteins within a cell. IDP accumulation is linked to various disorders, including neurodegenerative diseases. The small molecule enhancement of the ubiquitin-independent pathway represents a promising therapeutic target to modify protein degradation pathways for treating human diseases. The chemical space of small molecule proteasome enhancers is small, with only a few promising candidates. A significant reason for this lack of progress is the need for cellular systems that easily evaluate levels of IDPs and efficiently screen candidate compounds on a large scale. Two of the projects described in this dissertation directly address these problems. My first project focused on the development of a cell-based high throughput assay and its utilization to screen 30,000 compounds to identify novel small molecule proteasome enhancers. The second project focused on designing and synthesizing a library of 32 small molecules that enhance the ubiquitin-independent proteasomal pathway. Herein, the utilization of in silico molecular docking studies to refine structure-activity relationships is discussed. This approach led to the identification and synthesis of a new small molecule class that includes some of the most potent enhancers of the ubiquitin-independent pathway. In parallel, cellular disease models were developed that allowed for scoring the small molecules' therapeutic potential in treating waste protein accumulation in neurogenerative diseases.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
\u201cStriving To Do Things Differently\u201d : A Mixed-Methods Pilot Investigation of Tuning in to Kids for Black Parents of Preschoolers
No full textThesis (Ph.D.)--Michigan State University. School Psychology - Doctor of Philosophy, 2024A growing body of literature is emerging to examine the utility of emotion-focused parenting programs, as behaviorally-based programs currently dominate the parenting literature. Few of those studies examine differences in how Black parents benefit from emotion-focused parenting programs when they are often situated in the literature as unsupportive, which ignores cultural differences in parenting values and practices (Bocknek et al., 2009; Leerkes et al., 2015). However, evidence indicates that these practices are adaptive in Black families (e.g., McLoyd et al., 2019). This mixed-method randomized pilot study sought to examine preliminary fidelity, efficacy, and acceptability of a virtually-delivered Tuning in to Kids (TIK; Havighurst & Harley, 2007), an emotion-focused parenting program targeting parenting practices and children\u2019s emotion regulation through a strengths-based approach using emotion coaching strategies. Quantitative and qualitative methods were used to examine the impact of TIK for Black parents (N = 21; 9 Intervention; 12 Waitlist Control) of preschoolers based in the United States. Parents in both groups completed pre-, post-test, and one-month follow-up assessments. While there were no statistically significant main effects for the treatment group, based on this small sample, these preliminary quantitative results indicate greater positive trends for parents in the TIK condition compared to parents in a waitlist control group. The qualitative interviews provide essential information to support further examinations of TIK within a sample of Black parents. These promising preliminary outcomes coupled with interview data suggest that TIK is a promising parenting program to improve Black parents\u2019 emotion coaching beliefs and positive parenting practices, which indicates the need for future research to investigate the effectiveness of TIK and other emotion-focused parenting programs with Black parents and assess the necessity of future cultural adaptations.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
ESSAYS ON TRANSFORMING AGRIFOOD VALUE CHAINS IN SUB-SAHARAN AFRICA : IMPACTS, DYNAMICS, AND POLICY PERSPECTIVES
No full textThesis (Ph.D.)--Michigan State University. Agricultural, Food and Resource Economics - Doctor of Philosophy, 2024This dissertation explores the intricate dynamics of agrifood value chains in Sub-Saharan Africa (SSA), examining the interplay between policy interventions, market responses, and the challenges encountered by value chain participants. The first essay examines the unintended impacts of agricultural input subsidy programs (ISPs) on smallholder farm households\u2019 dietary diversity. Despite ISPs\u2019 resurgence in SSA as popular policy tools for intensifying agricultural production and ultimately improving food security, questions persist regarding their effects on households\u2019 access to diverse food. Using nationally representative household panel data from Zambia, I investigate the potential underlying mechanisms through which Zambia\u2019s Farmer Input Support Programme (FISP) may influence smallholders\u2019 household dietary diversity scores (HDDS) employing a fixed effects instrumental variables approach. Contrary to prior findings, the analysis uncovers a negative association between FISP fertilizer subsidies and HDDS. The program\u2019s pronounced emphasis on maize fertilizer appears to have incentivized beneficiary households to allocate more resources to maize cultivation, to the detriment of both crop production diversity and crop income, thereby negatively affecting HDDS. In the second essay, I investigate the impacts of various risks stemming from climate change, violent conflicts, and spoilage on the often-overlooked middle segment within agrifood value chains. Using data from a survey of maize wholesale traders in Nigeria\u2019s major maize-producing and consuming states, I explore traders\u2019 maize storage behaviors in response to prevailing weather risks and past experience of weather, conflict, and spoilage shocks, based on their primary market channel. Given potential disparities in contract design and quality standards between the modern market channel (e.g., industrial food and feed mills) and traditional market channel (e.g., retailers, other wholesalers, and consumers), traders may adapt their storage behaviors accordingly. I use a triple-hurdle model to incorporate the initial stage of traders\u2019 selection of their primary market channel. Subsequently, I examine how these diverse risks are associated with traders\u2019 decision to store maize and then specific damage control practices (i.e., applying chemicals or using non-chemical methods) among those opting for storage. I find that traders selling to the traditional channel opt to promptly sell maize amid high rainfall and temperature variability and use chemicals on stored maize when previously confronted with adverse shocks. In contrast, traders selling to the modern channel tend to store maize even under unfavorable weather conditions to compensate for potential losses from risks and to consistently fulfill contractual obligations. Concerned with preserving maize quality with minimal chemical residues, these traders do not appear to apply chemicals unless they were previously exposed to spoilage shocks. In the third essay, I investigate the preferences of Nigerian maize wholesale traders regarding policies to address conflict and weather shocks. With growing concerns about the multifaceted challenges faced by agrifood value chains in SSA, understanding the perspectives of value chain participants becomes vital for designing effective policies to address the challenges. I use the best-worst scaling (BWS) method to evaluate maize traders\u2019 preferences across various policy options. This includes nine alternative policy options for addressing violent conflicts and eight aimed at mitigating extreme weather events; these are also categorized as hard and soft infrastructure policy measures. The BWS experiment reveals that traders make trade-offs between soft and hard infrastructure policy options depending on the type of shocks encountered. Additionally, traders\u2019 demographic and business characteristics significantly influence their policy preferences, highlighting the need for tailored policy responses aligned with the specific nature of shocks and trader characteristics.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
PLANTING PRACTICES FOR IMPROVED STAND ESTABLISHMENT AND YIELD POTENTIAL IN WINTER WHEAT
No full textThesis (M.S.)--Michigan State University. Crop and Soil Sciences - Master of Science, 2024While planting time is an important factor in determining yield potential in winter wheat (Triticum aestivum L.), adverse weather conditions in the US Midwest often pose a challenge for achieving timely planting. In recent years, broadcast incorporation of seed has gained some traction as a faster, cheaper alternative to the traditional grain drill or air seeder, but there are concerns with imprecise seed placement. Precision planting, which results in more precise seed placement but does not have the speed or cost benefits of broadcast incorporation, is also being considered as an alternative planting method. Multiple field trials were conducted across Michigan to examine the influence of planting time, seeding rate, planting method, and seeding depth on stand establishment and yield in winter wheat. A significant reduction in yield was observed when planting occurred after mid-October, with >20% yield decline in all three years. Precision planting exhibited an 8\u201333% yield increase over drill or air seeder at 4 out of 11 site-years. Broadcast incorporation showed a 63\u2013103% increase in depth variability relative to drill or air seeder but did not consistently result in yield difference. This may have been due to a 50\u2013169% increase in the number of effective tillers plant-1. Yield showed no relation to seeding depth, except in 2022, where shallow seeding depth of 1.3 cm resulted in higher yield, likely due to favorable fall weather allowing for more fall tiller formation. Overall, while precision planting in winter wheat may result in a yield increase compared to a grain drill, broadcast incorporation may be a better choice in situations where its increased speed of operation allows for earlier planting.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
LASER FUSION BASED 3D-PRINTING OF NITINOL SHAPE MEMORY ALLOY FOR BIOMEDICAL APPLICATIONS
No full textThesis (Ph.D.)--Michigan State University. Mechanical Engineering - Doctor of Philosophy, 2024Nitinol is highly attractive for biomedical applications because of its unique shape memory and superelastic properties as well as acceptable biocompatibility. Additive manufacturing (AM) is getting significant attention in making complex and patient customizable nitinol devices. However, due to its high microstructural and compositional sensitivities, it is still challenging to fabricate functional NiTi devices via AM. It has been widely reported that evaporation of Ni, oxidation of Ti and formation of precipitation phases during fabrication significantly diverts the expected functional properties. To this date, laser powder bed fusion (LPBF) was the choice among many AM techniques to fabricate NiTi devices but successfully fabricated only on a NiTi substrate because of its poor bonding to other substrates (i.e., steel and Ti). In this work, a multi-step printing approach was systematically developed, which enabled printing NiTi on a Ti substrate using a very low laser energy density of 35 J/mm3 without any visible defect such as delamination and crack. This printing method reduced the high warping issue due to the process induced residual stress, avoided the Ni evaporation issue as well as formation of undesirable precipitation phase during printing. It was also found that a higher oxygen level in the printing chamber reduced the austenite finish (Af) temperature and negatively affected the printability. These results showed the feasibility of LPBF in printing NiTi on a substrate other than nitinol, providing a possible route to reduce the cost of NiTi fabrication via AM. The as-printed NiTi sample exhibited distinct one-step phase transformation with the Af temperature of 2.1\ub0C. To increase the Af temperature to 30.2\ub0C (within the recommended range of Af temperature for biomedical applications), a heat treatment protocol was developed, which includes a solution cycle (at 900 \ub0C for 1 hour) followed by an aging cycle (at 450\ub0C for 30 minutes). The heat treatment protocol enabled to attain the homogenized microstructure while creating ultrafine metastable Ni-rich precipitate, Ni4Ti3, which facilitated the desirable phase transformation behavior with the increased Af temperature. The heat-treated sample showed narrower and sharper two-step martensitic phase transformation with the formation of intermediate R-phase. The presence of both Ni4Ti3 and the R-phase was confirmed by the transmission electron microscopic (TEM) analysis. In the superelasticity test at the body temperature, these samples, starting from the 2nd cycle, demonstrated a recovery ratio of more than 90% and a recoverable strain of more than 6.5%. After 10th cycles, the stable recoverable strain was 6.52% with a recovery ratio of 96%, which is the highest superelasticity reported for the LPBF processed NiTi to the best of our knowledge. After the initial deformation process, we expect these samples to attain near full superelasticity during service. The micro-hardness study showed that the hardness of the heat-treated samples is less affected by the cyclic loading. Nitinol stent is attractive since they are self-expandable and behave superelastically when deployed inside the body. In contrast to the multi-step conventional manufacturing route, AM is attractive in making nitinol stent since it provides one-step processing as well as wide option for customizable design. However, the individual strut of a stent is less than 150 \u3bcm which is very challenging to fabricate by LPBF with structural accuracy, mechanical integrity and maintaining proper superelasticity. In this work, the LPBF processing parameter, as well as the post heat treatment and surface finish has been systematically developed to minimize the porosity, avoid structural failure during deformation and maximize the superelastic property at body temperature. Finally, the processed thin strut showed the Af temperature of 33 \ub0C (which is less than the body temperature) and demonstrated complete superelasticity with 100% strain recovery ratio with 4.5% recoverable strain at body temperature, which is first time to report complete susperelasticity in AM processed NiTi thin sample that is suitable for the stent application. The work presents an important roadmap in making NiTi devices by AM while maintaining excellent functional properties of NiTi for biomedical applications.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
HIGH RECALL DEEP LEARNING METHODS FOR PEDIATRIC RIB FRACTURE DETECTION
No full textThesis (Ph.D.)--Michigan State University. Computational Mathematics, Science and Engineering - Doctor of Philosophy, 2024Numerous data-driven, machine-learned models have been developed to localize pathologies in medical images. The work in this dissertation focuses on model development for the application of rib fracture detection in pediatric radiographs. Child abuse leading to physical harm is a severe problem, with over 100,000 confirmed instances in the United States during 2020, and children under 3 having higher susceptibility for fatal outcomes. Rib fractures are the most prevalent fracture site observed in young children with a near 100% positive predictive value for abuse if discovered. However, the detection of rib fractures in pediatric radiographic scans proves an arduous challenge, with even specialized radiologists failing to identify up to two-thirds of present fractures upon initial reviews. There are various reasons for this difficulty: fractures can be obliquely oriented to the imaging detector, obfuscated by other structures, incomplete, subtle, and/or non-displaced. In this dissertation, we curate a custom dataset of 1,109 pediatric chest radiographs that were labeled by seven board-certified pediatric radiologists, yielding 624 fracture-present images. We analyze fracture prevalence patterns within the dataset, stratifying by age groups and examining factors such as fracture sidedness and rib locations. We investigate several methods for improving the sensitivity performance of two one-stage deep convolutional neural network (CNN) object-detection architectures, RetinaNet and YOLOv5. These include testing different input image filtering techniques, model ensembling approaches that combine predictions from multiple models, and a novel avalanche decision scheme we developed that dynamically adjusts the acceptance threshold during inference based on the number of fractures already detected.We examine the performance of these networks using several metrics, including F2 score which summarizes precision and recall weighted toward high-sensitivity tasks. Fine-tuning of prior state-of-the-art one-stage models, RetinaNet and YOLOv5, achieves F2 scores of 0.48 +/- 0.01 and 0.48 +/- 0.04 respectively. Our best performing model used three ensembled YOLOv5 models with multiple image filters and an avalanche decision scheme, achieving an F2 score of 0.73 +/- 0.01. When we conducted an expert inter-reader performance evaluation on the same test set of images, it resulted in an F2 score of 0.732. We then take inspiration from our fracture prevalence analysis to create a domain-specific two-stage detection scheme, reliant on a prevalence-weighted region proposal method. The results demonstrated throughout this dissertation assert that a combination of sensitivity-driving methods yields object detector performance that approaches capabilities of expert radiologists, suggesting these methods may provide a viable approach to help identify these difficult-to-find rib fractures.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
Development of a Thermo-Chemical Moving Bed Reduction Reactor for Charging a Pelletized Material Capable of Short- and Long-Term Energy Storage
No full textThesis (Ph.D.)--Michigan State University. Mechanical Engineering - Doctor of Philosophy, 2024Large-scale storage of renewable energy is necessary to increase reliability of this intermittently, but abundantly available resource. Of special concern is the storage of energy and its subsequent use in industrial processes requiring high temperature heat. A promising emerging technology is based on using redox reactions of metal oxides at high temperatures. The shelf-stable redox material MgMnO was identified as a potential candidate due to its high energy density, cyclic stability, high reaction temperature and good scalability. This work describes the conception, design, manufacturing, testing and improvement of a solid fuel reduction reactor used to charge the energy storage material MgMnO. The reactor enables continuous charging of the pelletized material via a packed bed moving through a 1500\ub0C furnace. A counter-currently flowing sweep gas is used to separate the released oxygen from the charged material to prevent re-oxidation. It also acts as a heat recuperation carrier that cools charged particles and pre-heats particles before entering the reaction zone. This approach enables high thermal efficiency as the sensible heat is almost entirely recovered. A lab-scale reactor was built and tested successfully. Challenges such as particle flowability at high temperatures, fluidization of the bed, and low extent of reaction were encountered and solved by managing the counter-flowing gas and increasing the residence time of the particles in the reactor. The reactor output reached a maximum of 2500 W of charged chemical potential. Several models were developed and used to design experiments and validate the performance of the system. High energetic cost for separation of oxygen and sweep gas nitrogen was identified as a roadblock to improved efficiencies and potential scale-up of the system. This led to mathematical and experimental investigation of using water vapor as alternative sweep gas. Results show that water vapor is superior to nitrogen as a reducing agent and has a lower energetic cost of production. The proposed reactor can be scaled up and results of this study indicates that using the pelletized MgMnO pelletized material offers thermo-chemical energy storage at low-cost. The extraction of this energy at high temperature offers a path toward the decarbonization of a variety of industrial processes that are currently relying on the combustion of hydrocarbon fuels for high-grade heat.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
INSIGHTS OF CONTEMPORARY DIFFUSION WEIGHTED IMAGING SIGNAL MODELING TECHNIQUES ON WHITE MATTER MICROSTRUCTURAL CHANGES FOLLOWING MILD TRAUMATIC BRAIN INJURY
No full textThesis (Ph.D.)--Michigan State University. Neuroscience - Doctor of Philosophy, 2024Mild traumatic brain injury, which accounts for up to 90% of traumatic brain injuries, is currently diagnosed and monitored with a thorough history and physical exam. There is growing consensus in the literature that pathophysiologic changes in white matter extend past symptomatic recovery, and that these biological changes should be the target of diagnosis and monitoring. This would replace the current clinical consensus that symptom resolution and a level of functioning that allows return to work/play indicates recovery. Diffusion magnetic resonance imaging has been a critical tool for studying white matter change, and the diffusion tensor model developed in the 1990s has been the cornerstone of studying white matter in human subjects with mild traumatic brain injury. This model has several limitations, however, which in part may contribute to inconsistencies observed in the localization and direction of changes in diffusion tensor metrics such as fractional anisotropy. The past decade has brought forth scanner advancements, including stronger gradients, high angular-resolution imaging, and modeling strategies specific to these imaging data. Here, we review these contemporary techniques and apply them in a secondary analysis of data collected during the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study. Constrained spherical deconvolution and fixed-based analysis were applied to diffusion magnetic resonance imaging data collected during the study, revealing significant differences in tract-specific and global fiber-density and fiber-density cross-section measures between patient and control groups. However, results remained relatively stable over time, indicating that in this population-based sample of patients, not much change occurred in the white matter from 2 weeks to 6-months post-injury. This would seem to suggest there is a drastically different timeline for white matter recovery than was previously thought, even in injuries categorized as mild in the general population. Additionally, this reinforces the notion that multimodal tools for diagnosis and monitoring need further evaluation to create gold-standard objective classifiers of injury severity. In the short-term, future work should focus on the development of an imaging technique that when collected in the acute period following injury can predict prolonged recovery in individual patients with reasonable accuracy. Finally, characteristics which convey resiliency to poor outcomes should be investigated to facilitate development of interventions that hasten biological recovery.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
"Think People. Not [Just] Scale" : Technical Communication Approaches to Accessible Cybersecurity Workforce Frameworks
No full textThesis (Ph.D.)--Michigan State University. Rhetoric and Writing - Doctor of Philosophy, 2024Engaging recent points of discussion within academia and practitioner research focused on access/ibility in the cybersecurity workplace, this dissertation examines the impacts of National Initiative for Cybersecurity Education (NICE) cybersecurity workforce frameworks on people and communities within the field of cybersecurity. The emerging era in workforce formation provides a timely opportunity to attend to the conversation around workforce development, pipelines and pathways, and what it means to create greater access to the technical field of cybersecurity for diverse, underrepresented, and/or disabled prospective employees. These developments emerge at a time when the social justice turn in technical communication has become a major focal point in the discipline. Taking up Walton, Moore, and Jones\u2019 foundational work, Technical Communication after the Social Justice Turn (2019) and numerous scholars writing about the need to examine possibilities for justice work within user experience (Swartz, 2019), engaging with issues of linguistic justice and translation in technical communication (Gonzales, 2024; Mendoza, Haywood, Pouncil, and Kang, 2024), arguing for reciprocity in communication (Gonzales and del Hierro, 2017; Haywood, 2019; Powell and Takayoshi, 2003), and attending to questions of ethics in digital research (Haywood, 2022), this dissertation discusses a mixed-methods research study consisting of critical constructivist grounded theory analysis of the 2023 National Initiative for Cybersecurity Education Conference, whose theme titled "Resetting Expectations: Creating Accessible Cybersecurity Career Pathways," focused broadly on reimagining cybersecurity workforce pathways. The dissertation research discusses open ended, reflexive interviews with members of the cybersecurity workforce. Research discussion is followed by recommendations regarding career pathways and workforce development. A closer look into the ways technical communication has historically discussed accessibility and inclusion in digital workspaces, combined with extending the conversation using intersectional frameworks and embodied (third-space) remote work realities post-COVID, may provide new pathways into TCP research.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references