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SYNTHESIS AND CHARACTERIZATION OF NEXT-GENERATION MULTIPHASE SILICON NITRIDE-BASED STRUCTURAL CERAMICS
No full textThis study demonstrated that Si2ON2/Si3N4/SiO2/BN ceramics can be produced using novel near-atmospheric processing techniques as compared to traditional high-pressure methods. Nitridation mixtures of Si, SiO2, and BN powders in a tube or graphite furnace with N2 gas flow yielded ceramics with α-Si3N4, β-Si3N4, and Si2ON2 while maintaining BN in the matrix. XRD, SEM with EDS, TEM, and STEM were used for phase and microstructural analysis. These observations elucidated the formation mechanisms of Si2ON2, α-Si3N4, β-Si3N4, and SiC phases. Changes in nitridation parameters, such as sample geometry and getter efficiency, were optimized based on phase and microstructural analysis. Powder nitridation increased the diffusion pathways, leading to Si3N4 production, but not Si2ON2, which was only achieved using pellet samples. Pellet geometry trapped O2 and SiO gas, creating localized high-pressure regions that encouraged the reaction between Si3N4 and O2 gas to form Si2ON2. Getter efficiency was explored via nitridation with and without tantalum getters of various geometries. Decreasing the getter led to the formation of an amorphous SiO2 shell on the surface of the pellets, which cracked due to the production of SiO. The cracks served as additional diffusion pathways for gases to react with bulk material, leading to increased reactions and the formation of Si3N4 and Si2ON2 phases. Whisker morphology was analyzed via SEM and TEM, confirming them to be α-Si3N4. Pellet samples nitrided in N2+4%H2 and NH3 gases produced Si3N4, Si2ON2, and SiC. Graphite was hypothesized to react with both gaseous environments to form methane, which was predicted to react with SiO2 to form the SiC. Calcination of the nitrided product in a pressureless environment did not lead to the formation of Si2ON2; however, Si2ON2 was observed to form on pressure-calcined samples, highlighting the role of localized high-pressure regions of oxygen in the production of Si2ON2. Novel processing considerations regarding formation mechanisms gleaned from this work will pave the way for advanced ceramic composite phase tailoring, enabling a more precise selection of properties for this family of ceramics based on stringent application requirements
THE HIDDEN RISKS: EXAMINING OBESITY, HIGH BLOOD PRESSURE, AND FACTORS ASSOCIATED WITH IT AMONG AFRICAN AMERICAN SEXUAL MINORITY MEN IN TWO U.S. SOUTHEASTERN CITIES
No full textIntroduction: Current, public health research has shown that African American men are disproportionately impacted by obesity and high blood pressure when compared to their Non-Hispanic White and Hispanic men counterparts. Additionally, several interpersonal, psychological, and environmental factors have been shown to increase prevalence among this population. However, African American men that identify as gay, bisexual, and other sexual minorities are not included in the data collection of federal health surveys. Therefore, it is unclear whether obesity or high blood pressure impacts African American sexual minority men or whether the interpersonal, psychological, and environmental factors associated are seen among AASMM also. Methods: A quantitative analysis was conducted using data from the Ecological Study of Sexual Behaviors and HIV/STI among African American Men Who Have Sex with Men in the Southeastern United States. A secondary analysis was conducted using modified Poisson regressions as well as sensitivity analysis for certain continuous exposure variables. Results: The analysis found that certain interpersonal factors such as major life events were associated with obesity prevalence, and higher experiences of discrimination decreases high blood pressure prevalence. Depressive symptomology was associated with both outcomes, with increased risk in obesity and decreased risk in high blood pressure. High social cohesion decreases prevalence for both obesity and high blood pressure, whereas higher neighborhood problems were associated with an increase in obesity prevalence. Conclusion: This novel research adds to the growing literature in the field by examining both obesity and high blood pressure as well as the impact of selected factors among a new specific population. Additionally, this work and future work aims to normalize and prioritize the need for including individuals of diverse sexual orientations in federal health surveys across a variety of health outcomes
The Changing Dynamics of Asymmetric Warfare: Why Great Powers Struggle Against Weaker Opponents
Get PDFThis research investigates why great powers struggle to adapt in asymmetric conflicts, despite their superior resources and military capabilities. Through case studies of the Iraq War (2003–2011), the Russian war in Ukraine (2022–present), and others, it identifies four barriers to adaptation: cognitive biases, institutional inertia, legitimacy constraints, and adversarial innovations. These factors interact to create feedback loops that delay strategic recalibration, allowing weaker adversaries to exploit vulnerabilities and prolong conflicts. By integrating perspectives from international relations, military strategy, and organizational theory, the study develops a framework for understanding these challenges and recurring patterns. It argues that while institutional reform and proactive learning can improve adaptability, the interplay of cost-imposition and cost-mitigation strategies ensures these barriers remain significant. The findings offer critical insights for policymakers and military planners navigating the complexities of modern asymmetric warfare
Mixed Reality for Precision in Joint Replacement Surgeries: Bridging the Gap from Planning to Execution
No full textThe precision of surgical interventions, particularly in orthopedic surgeries, faces notable challenges due to the discrepancy between detailed pre-operative plans and their execution during surgery. This gap stems from the inability of traditional methods to provide direct guidance intra-operatively and adapt to real-time variations and anatomical shifts. These methods, which rely heavily on the surgeon's experience and manual alignment of tools with anatomical landmarks, often result in inconsistent outcomes. The difference in performance between novice and experienced surgeons highlights this issue, emphasizing the need for techniques that can bridge this gap effectively. In this context, mixed reality (MR) technologies, especially optical see-through head-mounted displays (OST-HMDs), have been identified as a potential solution to bridge this gap by overlaying digital information directly onto the surgical field. Nonetheless, the effective integration of MR into surgical workflows encounters several impediments.
This dissertation endeavors to address a subset of these challenges through a comprehensive research approach designed to enhance MR-guided joint replacement surgeries. To start with, we assess the capability of depth sensing technologies, including Time-of-Flight (ToF) cameras and stereo RGB cameras, to facilitate marker-less registration. This is a pivotal step for achieving an accurate alignment of virtual and physical spaces. Although these technologies hold potential, their application is restrained by factors like sensor accuracy under varying lighting conditions and occlusion issues. To overcome these limitations, we introduced novel methodologies aimed at enhancing the precision of the registration processes, including the development of a continuous drift correction mechanism and the implementation of near-infrared fluorescent markers for robust tracking of anatomical features.
Through comprehensive evaluations, including comparative analyses with traditional methods and FDA-cleared non-MR guiding solutions, our research demonstrates the viability and improved accuracy of the proposed solutions in MR-guided orthopedic surgeries. This research suggests that MR technologies could enhance surgical precision, potentially reduce operation times, and ultimately improve patient outcomes. While these benefits are promising, ongoing development and clinical validations are necessary to fully realize the potential of MR in diverse surgical applications
Understanding the Evolution of Diet Quality in U.S. Infants and Toddlers from Households with Low-Income Utilizing Diet Quality Indices
No full textBackground
Diet in early life sets the stage for later eating habits. The 2020-2025 Dietary Guidelines for Americans included infants and toddlers for the first time, making it possible to measure early life diet quality compared to recommendations.
Objectives
To improve our understanding of how diet quality initiates in infancy and tracks into early toddlerhood in children from households with low-income.
Methods
Using 24-hour diet recall and questionnaire data from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) Infant and Toddlers Feeding Practices Study-2, we characterized diet quality in infants (year 1) using the Infant Diet Quality Index (IDQI) score and the Diet Quality Index Score (DQIS), and in toddlers (year 2) using the Healthy Eating Index-Toddlers-2020 (HEI-Toddlers-2020). Linear mixed effects models evaluated change in HEI-Toddlers-2020 score over time and the association between infant and toddler diet quality. Subgroups of diet quality trajectory from 12-24 months were investigated with a parallel process growth mixture model of refined grains, sodium, saturated fat, and added sugars. Early life factor association with class membership was investigated.
Results
Mean total HEI-Toddlers-2020 scores ranged from 56.3 to 58.1 across year 2. Scores were lower with age comparing 18- and 24-month scores to 13-month scores ( = -1.83, 95% CI: -2.88, -0.78; and = -1.54, 95% CI: -2.65, -0.45, respectively). Total Vegetables, Refined Grains, Sodium, and Added Sugars decreased. Almost two-thirds of 13-month toddlers consumed no Greens/Beans or Seafood/Plant Protein. There were positive associations between the IDQI ( = 1.74, 95% CI 1.48-1.99) and the DQIS ( = 0.43, 95% CI 0.33-0.52) and the HEI-Toddlers-2020 score. Three subgroups of moderation component trajectory were identified. Class membership was significantly associated with caregiver age, but not duration of human milk or solids introduction. Sugar-sweetened beverages may displace milk for some children.
Conclusions
Diet quality in infancy is positively associated with toddler diet quality but begins to decline by year 2. Declines were driven by increased refined grains, sodium, and added sugars. These findings provide evidence that interventions targeting reduction in moderation foods may have the biggest impact on overall child diet quality
HIGH-THROUGHPUT APPROACHES TO PROTEIN ENGINEERING APPLIED TO THE CAS9 AND AAV2 REP GENES
No full textWhen attempting to imbue a protein with new or improved functions, protein engineers are faced with the challenge of having to search the staggeringly large pool of possible variants to find what they seek. Consequently, the ability to access a sufficiently large subset of this pool and to efficiently sort desirable from undesirable variants stands as the foundation of many protein engineering experiments. Broadly, a focus on these approaches serves as the throughline to the efforts discussed in this work. Part of this work addresses bacterial dCas9, a programmable protein which can bind to DNA sequences with high specificity and act as a nuclease, transcription factor, base editor, and more depending on how it is deployed. We sought to generate a dCas9 switch protein that binds to its target DNA in an inducer-dependent manner. First, we generated a novel system for enriching active or inactive dCas9 variants based on targeted repression of two bacterial antibiotic resistance genes. In principle, this system can efficiently identify switchable dCas9 variants by first eliminating inactive variants in the absence of inducer, then eliminating active variants in the presence of inducer. We then deployed this system to screen a library of random insertions of the E. coli glycine betaine binding protein gene into the dCas9 gene for variants that responded to glycine betaine or changes in temperature. However, we were unable to isolate a switchable dCas9 variant due to constraints on the size of the library. The second part of this work focusses on the Adeno-Associated Virus (AAV), which is a promising delivery vector for gene therapies. We sought to improve AAV production in an industrial context by addressing the AAV rep gene, which encodes a set of proteins responsible for efficiently replicating and packaging viral DNA. To do this we generated a library of single codon substitutions within the gene and performed a high-throughput replication competition assay to determine the efficacy of each variant relative to the wild type gene. We were able to generate a fitness landscape mapping the changes in function for variants from three segments of the gene and identified multiple variants with improved viral titers over the wild type. Further characterization of these variants revealed host cell line-dependent differences in the effects of mutations
METHODOLOGIC APPROACHES TO UNDERSTANDING THE EPIDEMIOLOGY AND PATHOGENESIS OF VANCOMYCIN-INDUCED IMMEDIATE HYPERSENSITIVITY REACTIONS
Get PDFStatement of the Problem: Immediate drug-induced reactions (IDRs) are a significant health concern, with over 221,600 cases reported annually in the U.S., 6% of which result in anaphylaxis. While IgE-mediated IDRs are the most severe, most IDRs are non-IgE-mediated and may only require administration adjustments rather than complete drug avoidance. The lack of validated diagnostic tools complicates distinguishing between these IDRs, often leading to unnecessary drug restrictions. This research focuses on the recently discovered mas-related G-protein coupled receptor X2 (MRGPRX2) as a critical mechanism of non-IgE-mediated IDRs, particularly in IDRs to vancomycin.
Procedure or Methods: This dissertation consists of five studies. The first paper reviews the literature on non-IgE-mediated IDRs, highlighting current knowledge, clinical recommendations, and future research. The second and third studies analyze vancomycin IDRs epidemiology using electronic health records (EHRs) from two large U.S. healthcare systems. In the fourth study, a novel skin testing protocol was developed in vancomycin-naïve individuals. The fifth study explores diagnostic tools, including skin testing and basophil activation test (BAT), to aid in characterizing and differentiating VIR from vancomycin-tolerant subjects. The final study examines the immunogenicity frequency of vancomycin in exposed individuals.
Summary of Results: The literature review highlighted the challenges distinguishing between IgE- and non-IgE-mediated IDRs due to overlapping clinical presentations. Epidemiological analysis revealed an increase in vancomycin ADRs and documented disparities, advocating for replacing the outdated term "Red Man Syndrome" (RMS) with "Vancomycin Infusion Reaction" (VIR) to reflect the underlying pathophysiology of non-IgE-mediated IDRs better. The novel skin testing protocol demonstrated a broad range of dose sensitivities to vancomycin, underscoring the variability in non-IgE-mediated responses. The protocol revealed a 3.5-fold lower skin test dose-response EC50 in VIR subjects than in vancomycin-tolerant individuals, indicating heightened sensitivity. The BAT was insufficient for detecting VIR, and there was a weak immunogenic response to vancomycin in vancomycin-exposed individuals.
Conclusion: This research underscores the need for improved diagnostic tools to distinguish between IgE- and non-IgE-mediated IDRs, particularly for IDRs like VIR and its emerging link to MRGPRX2. Understanding these mechanisms can prevent unnecessary drug avoidance and enhance patient care. The work provides a framework for future research into non-IgE-mediated reactions
Further Design and Development of Pendant Photochromic Molecules and Polymers
No full textDiarylethenes (DAEs) are an attractive class of compounds which undergo reversible photochromism, often called molecular switches. Photochromism is the reversible change between two colored states, stimulated by a light source. The switches are of particular interest for photoresponsive materials. To develop such materials, others and our group have tried incorporating these switches into polymers.
Chapter 1 is a literature review of DAE photoswitches and the work done in the Tovar lab. Several different graduate students have investigated pendant photochromic switches, where the DAE is part of fused ring system with a polymerizable “head” and a photoswitching “tail”. Photochromism for many of these systems was mixed, but not fully investigated. This chapter uses computational tools to determine whether other switching motifs on these systems would exhibit photochromism.
Chapter 2 summarizes an outstanding question from our group’s investigation into a thieno[3-4b]thiophene (TT) photoswitch. Previous researchers found that photochromism can be deactivated, due to other available absorption pathways. We envisioned a series of TT-based photochromes with various sterically demanding aromatic caps. Guided by computations, these compounds were synthesized. These model systems provide a better understanding of the behavior of photochromic units within extended oligomeric and polymeric π-conjugated materials.
Chapter 3 describes efforts to incorporate TT switches into responsive materials. First TT switches were functionalized and electropolymerized at various monomer compositions. Preliminary results suggest there is an electrochromic response, though it has yet to be determined whether this deactivates the photochromism of the polymer. In a similar vein the TT switches were functionalized to form metal organic frameworks (MOFs). Since the switching motif is segregated from the polymer head in the pendant TT switch, the photochromism will not perturb the MOF geometry. With the Thoi group at JHU, several MOFs were formed, though photochromism was not observed.
Chapter 4 is an investigation into a different DAE photoswitch, benzo[b]furan (BF). Due to the “L” shaped geometry the BF switch, the DAE switching motif and polymer backbone in closer proximity, allowing for further probing of those interactions. Several switches were envisioned, computed, and were indicative of photochromism. These BF switches and phenyl capped BF switches were then synthesized and were all photochromic. The phenyl capped BF switches serve as models for BF-polymers, indicating that aromatic caps do not deactivate photochromism in these switches, making it a promising switch architecture.
Finally, Chapter 5 summarizes future directions for the photochromic switch project. It highlights previously investigated switches that are worth revisiting and proposes several improved syntheses. Several applications of pendant DAEs are summarized. Particularly the idea of using TT switches as a responsive dye for colorimetric assays. Other novel switches and their syntheses are proposed in this chapter. Finally, this chapter summarizes possible analytical tools which can be used to determine kinetics of photochromism for all the proposed switches
MEASLES VIRUS INFECTION OF THE RESPIRATORY TRACT
Get PDFMeasles virus (MeV) is one of the most infectious viruses known to man. MeV is a respiratory virus which spreads primarily through droplets and aerosols; therefore, it is important to understand virus transmission and the immune response to MeV infection within the respiratory tract. We used primary differentiated tracheal epithelial cell cultures (rhTECs) derived from rhesus macaques (Macaca mulatta) as well as samples from macaques infected with wild-type (WT MeV) or live-attenuated MeV (LAMV) to study the biology of MeV infection and host response within the respiratory tract. In this dissertation, we first investigate mechanisms driving the extrusion of MeV-infected respiratory epithelial cells through the apical surface of the respiratory epithelium. We show that both WT MeV and LAMV infection induce cell shedding through sphingosine-1-phophate signaling. We then explore the innate response of respiratory epithelial cells to WT MeV infection in rhTECs, as well as the cytokines and chemokines present in the lungs of WT MeV and LAMV infected macaques. We find that WT MeV and LAMV infection within the respiratory tract induces production of the chemokine CXCL10, but no evidence of interferon or inflammasome-related pathways. We also show that peripheral intramuscular (IM) vaccination with LAMV produces MeV-specific IgG in the respiratory tract, and that LAMV is often found within the lungs of immunocompetent macaques after IM vaccination, with occasional evidence of local replication. Our preliminary results suggest that the local lung immune response may be important for protection against WT MeV challenge. In summary, this dissertation explores the important role of the respiratory tract in MeV infection and immunity
INVESTIGATIONS OF ALL-DIELECTRIC AND TOPOLOGICAL INSULATOR METAMATERIALS VIA LINEAR AND NONLINEAR TERAHERTZ SPECTROSCOPY
No full textThis thesis investigates the terahertz (THz) optical responses of metamaterials (MMs) integrated with topological insulators (TIs) and all-dielectric insulators. MMs have gained attention in the past two decades for their innovative manipulation of electromagnetic waves. These engineered composites control electromagnetic properties through designed resonances influenced by component geometry at subwavelength scales. As a result, MMs are often used to probe coupling regimes between electromagnetic fields and localized quasiparticles. They facilitate enhanced light-matter interactions across various materials, including insulators, semiconductors, metals, and superconductors. Recently, this approach has been extended to TIs, materials with protected metallic surface states that allow exploration of their electronic band structures.
Progress has been made in using MMs to modulate electron-phonon interactions in TIs through their surface states. We examine light-matter interactions in topological insulator metamaterials via terahertz time-domain spectroscopy (TDTS). Our experiments show coupling between the phonon mode in bismuth antimony (BixSb1−x)2Te3 (BST) thin films and the LC resonance of a split ring resonator (SRR) metasurface. Numerical simulations refined the SRR design to modify the coupling strength, leading to the fabrication of multiple metasurfaces through photolithography. Results indicate significant repulsion and hybridization, characteristic of Rabi splitting, demonstrating the modulation of TIs’ mechanical properties at THz frequencies.
We also explored the nonlinear THz response of coupled TIs and all-dielectric metamaterials through THz two-dimensional coherent spectroscopy (2DCS). The search for effective nonlinear materials led us to study nonlinear metamaterials and TIs. Nonlinear metamaterials, mainly through SRRs, enhance local electric fields in capacitive gaps, achieving global nonlinearities even at low intensities. In contrast, TIs exhibit strong nonlinear optical behavior in the THz regime due to quasi-free carriers, though their interactions limit overall conversion efficiency. Integrating SRRs with TIs can amplify local fields and enhance nonlinear responses. Using 2DCS, we investigated the nonlinear optical response in sapphire (Al2O3-SRR) and BST-SRR. For Al2O3-SRR, we aligned the SRR’s LC resonance with lithium niobate’s fundamental frequency (0.63 THz) to enhance the nonlinear response. For BST-SRR, we focused on coupling to the phonon resonance to facilitate high-order harmonic generation, achieving significant signal enhancement through SRRs, indicating the potential for tunable THz nonlinear optical devices based on these materials