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African Sleeping Sickness: From Basic Biology to Future Directions
Get PDFAfrican Sleeping Sickness is a Neglected Tropical Disease (NTD) which poses a significant health risk to impoverished populations in 36 Sub-Saharan African countries. It is a devastating disease caused by the protozoan parasite Trypanosoma brucei, which is transmitted to mammals via the bite of infected tsetse flies. The disease manifests in two stages: the hemolymphatic stage and the meningoencephalitic stage. In the latter stage, it invades the Central Nervous System (CNS) and can be fatal if left untreated. It is caused by morphologically indistinguishable species of Trypanosoma brucei in both humans and animals, where in humans it is known as Human African Trypanosomiasis (HAT) and in animals as nagana. Despite ongoing control efforts, there is no vaccine, and the current treatments are toxic, expensive, and difficult to administer. Vaccine development is continually hindered due to the parasite’s ability to rapidly change its Variant Glycoprotein Surface (VSG) coat, which helps it evade the host’s immune responses. However, with the introduction of new drugs like fexinidazole and acoziborole, treatment is becoming more accessible. Understanding the genetics of the disease can be substantial in the identification of host and parasite genes, as well as parasite-derived molecules that influence disease pathogenesis. These factors can then be targeted for therapeutic intervention. Further research is essential to develop effective long-term solutions. Genetic studies offer valuable insights into host-parasite interactions and may help identify new targets for therapy. Molecules such as TbKHC1 (Kinesin Heavy Chain 1) and TbAdc (Adenylate Cyclase) from the parasite, along with host immune factors like TNFɑ, HLA-G, and Daxx, play important roles in disease progression and immune response modulation. Investigating these genetic and molecular factors could aid in overcoming vaccine challenges and reducing the socioeconomic burden of the disease. Improving diagnosis, treatment, and surveillance while ensuring proper distribution of funds for research is necessary to achieve the 2030 elimination goal set by the WHO. While it is possible to eliminate it, consistent efforts are the only way to achieve it, as the disease has the tendency to reemerge
Fully Bio-Based, Flexible, Non-isocyanate Polyurethane Foams With High Lignin Content for Protective Packaging Applications
Get PDFPolyurethane foam is a valuable material with applications across the automotive, packaging, construction, appliance, and furniture industries. However, traditional polyurethane foams are made from petroleum-based precursors including harmful isocyanates. Isocyanates are the leading cause of workplace asthma and are made from toxic phosgene gas, representing a challenge to green chemistry principles such reducing risk and environmental footprint. To address these concerns, non-isocyanate polyurethane (NIPU) foams have been the focus of research for the past decade, but they still face significant challenges in achieving commercial viability. NIPUs replace the traditional polyurethane reaction with a safer, non-isocyanate process most often employing cyclic carbonates and diamines. Current approaches to NIPU foams struggle to meet the low-density and flexibility of commercial foams and also employ many petroleum-derived and toxic agents. This work demonstrates the use of kraft lignin, a crosslinked aromatic polymer produced by the dominant chemical pulping process today, as an effective raw material for flexible NIPU foams, reaching densities below 70 kg/m3 while displaying flexibility. A biobased, aliphatic agent was added in various amounts to introduce flexibility to the polymer structure while modifying the viscosity of the reaction mixture to enable increased rise height for products containing over 30% lignin. The thermal, mechanical, cushion testing, and burn testing results of a series of NIPU foams are compared to a conventional PU reference foam and the structure-property relationships of the novel materials are explored based on the lignin-to-aliphatic content. The results show a fully biobased, flexible, NIPU foam from lignin that can approach commercial properties, helping to demonstrate the relevance of NIPU foams for many applications focusing on protective packaging applications
Blockchain-Integrated Version Control for Secure and Transparent Software Supply Chains
No full textThe software supply chain encompasses all stages of software development and delivery from initial coding and version control to integration and deployment. As development environments become increasingly distributed and reliant on external dependencies, ensuring the integrity, auditability, and consistency of code changes has become a pressing challenge. Traditional version control systems like Git, while effective for collaboration and tracking revisions, do not inherently provide tamper-evident commit histories. Features such as history rewriting (e.g., git rebase, git push --force) can be exploited to manipulate commit logs without detection, posing risks in security-sensitive domains. This thesis proposes a blockchain-integrated version control framework that addresses these limitations by recording Git commit metadata on a per- missioned distributed ledger. The system is implemented using Hyperledger Fabric and employs smart contracts to log commit events immutably, creating a verifiable chain of custody for software updates. The research evaluates the system’s feasibility through experimental deployment across simulated distributed developer nodes, measuring synchronization time, resource consumption (CPU, memory, disk), and consistency of commit state. Experimental results show that the system achieves low synchronization latency, stable memory and disk usage, and cross-node consistency, with CPU utilization identified as the primary factor influencing performance under load. These findings demonstrate that blockchain integration can improve transparency and traceability in software version control without introducing significant overhead. By contributing a secure and auditable mechanism for commit tracking, this work advances the field of software supply chain security and provides a foundation for future research into scalable, verifiable development workflows in high-assurance environments
Gene Editing Combined With APAP Diet-Mediated Selection in a Ldlr-/- Mouse Model of Familial Hypercholesterolemia
No full textCell-based gene therapy has garnered significant interest in treating familial hypercholesterolemia (FH), an autosomal co-dominant disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels. However, achieving a therapeutic threshold level of engraftment of gene-modified cells is a significant hurdle. In FH, as in most liver diseases, the transplantation of healthy gene-modified hepatocytes does not result in a selective advantage for the healthy hepatocytes over native hepatocytes for clonal expansion in the liver. In FH, as in most liver diseases, the transplantation of healthy gene-modified hepatocytes does not provide a selective advantage for the healthy hepatocytes over native hepatocytes regarding clonal expansion in the liver. Therefore, a robust selective strategy is essential for repopulating the liver with genetically modified hepatocytes in vivo to treat FH using a cell therapy approach.
Cypor (NADPH-cytochrome P450 reductase) is a cofactor required by Cyp enzymes to metabolize acetaminophen (APAP), an over-the-counter drug, and convert it into N-acetyl-p-benzoquinone imine (NAPQI), a hepatotoxic byproduct. Hence, knocking down Cypor provides the hepatocytes resistance against APAP-induced hepatotoxicity. A recent study demonstrated that a novel therapeutic strategy involving the disruption of Cypor and the temporary addition of acetaminophen (APAP) to the chow diet resulted in a strong selective pressure for healthy gene-modified hepatocytes to repopulate the liver and phenotypically correct a mouse model of phenylketonuria. Here, we explore a new therapeutic approach for treating FH that involves electroporation to introduce Cypor-aiming CRISPR-Cas9 ribonucleoproteins into LDLR+/+ hepatocytes, combined with transplantation and transient APAP administration through the diet to repopulate the liver in an FH mouse model (Ldlr-/-)
Investigating Psychological Moderators of the Effect of a Slow-Paced Breathing Intervention on Decision-Making Performance
Get PDFDecision-making is a ubiquitous cognitive process that individuals engage in constantly—some decisions are inconsequential while others can have drastic implications. Identifying ways to improve decision-making, therefore, has potential to have lasting positive effects. One potential approach is slow-paced breathing interventions. While such interventions have shown promise for improving certain aspects of cognition, such as working memory, few studies have examined the effect of slow-paced breathing on decision-making performance. The current study sought to examine the effect of a brief slow-paced breathing intervention on performance on the Iowa Gambling Task (IGT), a reward-based decision-making task. Potential moderating variables such as stress, worry, anxiety, and depressive symptoms were also explored. Participants (n=216) were undergraduates recruited through fliers and an online subject pool. Participants were randomized into either an experimental slow-paced breathing intervention group or a mind wandering control group. Participants completed a preliminary demographics and trait measures survey, completed the assigned manipulation, and then performed the IGT. A hierarchical linear regression was employed to compare IGT decision-making performance between the slow-paced breathing and mind wandering control conditions and assess potential moderating effects of stress, worry, anxiety, and depressive symptoms. The primary study results revealed an interaction between study condition and perceived stress such that those with greater perceived stress exhibited poorer decision-making performance in the control group but better decision-making in the slow-paced breathing intervention group. No overall group differences between the intervention and control condition on decision-making performance were observed, and no other moderators significantly influenced IGT performance. This study shows that an accessible, easy-to-implement intervention can significantly improve decision making, but only among those with high perceived stress
Chromosome Evolution Model Reveals Hidden Variation in Karyotype-Driven Speciation in Ferns
Get PDFBecause karyotype change commonly generates reproductive isolation between diverging species, rapid karyotype evolution, like that seen in plants, may increase the total rate of diversification. However, few studies have investigated this predicted relationship. Tests of this prediction have identified a positive correlation between the rate of karyotype change (specifically whole genome duplications) and diversification, but tests have been restricted to relatively small and young clades. Fortunately, novel macroevolutionary models have recently become available to investigate patterns of karyotype evolution in large phylogenies, providing new opportunity to investigate variation in karyotype driven diversification. Ferns are one of the most karyotype rich lineages of land plants, but it is not well understood how karyotype changes contribute to diversification across the fern phylogeny. To investigate variation in the contribution of karyotype change to fern diversification, we extend the Chromosome Number Hidden State-dependent Speciation and Extinction model (ChromoHiSSE) to include polyploidy and demi-polyploidy. We use our extended RevBayes implementation of ChromoHiSSE to investigate the evolution of karyotype across 962 leptosporangiate ferns. We recover two distinct modes of chromosome number evolution in ferns. Our Diversification mode is characterized by low rates of karyotype change and net positive diversification, while the Karyotype-change mode is characterized by rapid cladogenetic and anagenetic state changes but net negative diversification. Our investigation is the first to simultaneously model anagenetic and cladogenetic chromosome change in ferns and provides the most complete reconstruction of fern chromosome number evolution. We reinforce the conclusion that modern fern diversity is shaped substantially by polyploid speciation but challenge the assertion that diversification rates are enhanced by karyotype-driven cladogenesis. In ferns, we find that lineages with high chromosome number lability are less likely to persist in the long-term
Understanding and Modeling Pooled Rideshare Acceptance: Influential Factors, Preferred User Experiences, and Implications
Get PDFThis dissertation explores factors influencing pooled rideshare (PR) adoption to provide actionable insights for transportation network companies (TNCs) and policymakers. PR allows travelers to share rides with unknown passengers, offering benefits such as cost reduction and congestion relief. However, adoption remains limited due to safety concerns, privacy issues, and trust in rideshare platforms. A national U.S. survey with 5,385 respondents examined transportation preferences and barriers to PR adoption. Exploratory and confirmatory factor analyses identified five key factors influencing PR consideration—safety, service experience, privacy, traffic/environment, and time/cost. Second factor analyses examined ways to optimize PR experiences, revealing four factors—comfort/ease of use, convenience, vehicle technology/accessibility, and passenger safety. Privacy concerns, for instance, using regression analysis, were found to reduce the likelihood of PR adoption by 77%, and convenience had the potential to increase it by 156%. The Pooled Rideshare Acceptance Model (PRAM), based on the Technology Acceptance Model, assessed the impact of these factors using the Structural Equation Model (SEM). Privacy, safety, trust, and convenience had a large effect (Cohen\u27s f2 \u3e 0.35) on PR acceptance, while multigroup analyses (PRAMMA) explored 16 demographic variables such as gender, generation, and income, emphasizing the need for tailored strategies. Based on all the statistical analysis and workshops using descriptive statistics, 95 actionable recommendations were made from the riders\u27 perspective. Findings highlight the importance of customized services, user experience improvements, and policy interventions to enhance PR adoption. This dissertation provides a roadmap for future research and policy development, ensuring evidence-based, practical strategies to improve PR services in the U.S. and beyond
Maximizing Crop Production and Profitability through Double Cropping Corn and Soybean Systems in South Carolina
Get PDFProfitability is critical for farm sustainability, efficiency, and longevity. Over the last decade, corn and soybean commodity prices have fluctuated considerably, and more recently, extreme increases in input prices have narrowed profit margins. Non-traditional cropping systems that can boost profit are becoming of interest to farmers in South Carolina, specifically double cropping soybean behind corn. In this scenario, corn is harvested at high moisture contents and followed by ultra-late planted soybean. However, prior research related to the agronomic production practices of double cropping corn and soybean is minimal. To develop best management practices for growers interested in double cropping corn and soybean, research trials were initiated from 2022 through 2024 to evaluate corn and soybean agronomic production practices, the use of nematicides and nematode resistant varieties on plant parasitic nematodes (PPN) in this system, and the use of an early application of nitrogen fertilizer on ultra-late planted soybean. Results from these studies over three years suggest that growers who are interested in double cropping corn and soybean should plant corn in March, consider utilizing an at-plant granular nematicide, and harvest their corn at high moisture contents. Furthermore, growers should utilize indeterminate MG V soybean varieties planted during the window of July through early August to maximize grain yield and PH. The impact this research could have on farm profitability in South Carolina suggest total gross profit may increase by 28 to 74% per acre compared to growing corn or soybean in a monocrop system, respectively
The Effect of Storyline Units on the Self-Efficacy and Science Identity of High School Multilingual Learners
Get PDFScience can be a complex subject for multilingual learners (MLLs) because it requires investigating science concepts through modeling and analysis in addition to reading and writing skills. This complexity often leaves teachers unsure of how to support the MLLs, leading to MLLs missing out on grade-appropriate content and science experiences. Storyline instruction uses 3D instruction to teach science content necessary to explain a real-world anchoring phenomenon. Storyline instruction grounds learning in real-world contexts through anchoring phenomena and provides coherence for students throughout the lessons. This mixed methods study aimed to discover the impact of storyline units on the self-efficacy (SE) and science identity (SI) of MLLs in high school biology classes.
Participants engaged in four storyline units. Prior to the units, they took a pre-survey to measure their initial SE and SI. They completed a self-reflection at the end of each unit. Each participant was observed twice during the units. At the end of all four units, they took the post-survey and completed an interview. The survey scores were analyzed for descriptive statistics. The self-reflections and interviews were analyzed using provisional coding for sources of SE and SI. The qualitative and quantitative data were integrated to look for convergence and divergence in the data.
The findings of this study indicated that all four sources of SE (mastery experience, vicarious experience, social impact, affective state) increased after participating in storyline units. Three sources (competence/performance, Funds of Knowledge, interest) of SI increased with divergence in the recognition source of SI. Three components of storyline units positively impacted MLLs: anchoring phenomena, three-dimensional learning, and navigation. Culturally and linguistically responsive pedagogy practices (interactional scaffolding and translanguaging) that were embedded in the storyline units were particularly impactful for Newcomers. Implications for educators and researchers are discussed
Development of Small-Molecule Inhibitors for Bacteroides, Naegleria, and Toxoplasma Microorganisms and Synthesis of N-Heterocycles From Thiolated ENE-YNES and Azodicarboxylates
Get PDFHumans and microorganisms are intricately interconnected, with microbes constituting an essential component of human biology and ecology. This interdependence necessitates a delicate balance between leveraging beneficial microbes and mitigating the impact of harmful ones. The human gut microbiome, home to trillions of microorganisms, predominantly comprises commensal species that support health. However, dysbiosis within this ecosystem has been linked to serious diseases. For instance, an overrepresentation of Bacteroides species is associated with Type I diabetes mellitus (T1D) and various chronic gut disorders, including ulcerative colitis, inflammatory bowel disease, celiac disease, and colorectal cancer. Similarly, Naegleria fowleri, a free-living amoeba, causes the highly fatal primary amebic meningoencephalitis, while Toxoplasma gondii, a pervasive parasite, infects approximately one-third of the global population.
This dissertation presents efforts to develop targeted therapeutic strategies against Bacteroides spp., Naegleria fowleri, and Toxoplasma gondii. Chapter one describes our group’s continual effort towards a non-microbicidal approach to gut microbiota modulation. This strategy leverages molecular modeling in the design of small molecules targeting the Bacteroides starch utilization system (Sus), offering a novel strategy for selective microbial control. Chapter two introduces a structure-based drug design strategy to inhibit Naegleria fowleri enolase (NfENO), an enzyme critical for glucose metabolism in the trophozoite life-cycle stage, thus impeding infection establishment. Chapter three highlights the development of potent antiparasitic compounds targeting protoporphyrinogen oxidase (PPO), a key enzyme in Toxoplasma gondii heme biosynthesis.
In addition to microbial therapeutics, the dissertation explores innovative organic synthesis methodologies. Chapter four presents a regio- and stereoselective debenzylative cycloetherification reaction for synthesizing stereochemically rich tetrahydrofuran compounds under mild conditions. Chapter five details a cascade cyclization approach for generating richly functionalized tetrahydroindoles and fused pyrroles, compounds with significant potential in medicinal chemistry. Collectively, this work advances both therapeutic interventions for pathogenic microorganisms and synthetic strategies for bioactive molecule development