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HIV-1 viral particle assembly occurs specifically at the plasma membrane and is driven primarily by the viral polyprotein Gag. Selective association of Gag with the plasma membrane is a key step in the viral assembly pathway, which is traditionally attributed to the MA domain. MA regulates specific plasma membrane binding through two primary mechanisms including: (1) specific interaction of the MA highly basic region (HBR) with the plasma membrane phospholipid phosphatidylinositol (4,5) bisphosphate [PI(4,5)P2], and (2) tRNA binding to the MA HBR, which prevents Gag association with non-PI(4,5)P2 containing membranes. Gag multimerization, driven by both CA–CA inter-protein interactions and NC-RNA binding, also plays an essential role in viral particle assembly, mediating the establishment and growth of the immature Gag lattice on the plasma membrane. In addition to these functions, the multimerization of HIV-1 Gag has also been demonstrated to enhance its membrane binding activity through the MA domain. This review provides an overview of the mechanisms regulating Gag membrane binding through the MA domain and multimerization through the CA and NC domains, and examines how these two functions are intertwined, allowing for multimerization mediated enhancement of Gag membrane binding.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to persist, demonstrating the risks posed by emerging infectious diseases to national security, public health, and the economy. Development of new vaccines and antibodies for emerging viral threats requires substantial resources and time, and traditional development platforms for vaccines and antibodies are often too slow to combat continuously evolving immunological escape variants, reducing their efficacy over time. Previously, we designed a next-generation synthetic humanized nanobody (Nb) phage display library and demonstrated that this library could be used to rapidly identify highly specific and potent neutralizing heavy chain-only antibodies (HCAbs) with prophylactic and therapeutic efficacy in vivo against the original SARS-CoV-2. In this study, we used a combination of high throughput screening and machine learning (ML) models to identify HCAbs with potent efficacy against SARS-CoV-2 viral variants of interest (VOIs) and concern (VOCs). To start, we screened our highly diverse Nb phage display library against several pre-Omicron VOI and VOC receptor binding domains (RBDs) to identify panels of cross-reactive HCAbs. Using HCAb affinity for SARS-CoV-2 VOI and VOCs (pre-Omicron variants) and model features from other published data, we were able to develop a ML model that successfully identified HCAbs with efficacy against Omicron variants, independent of our experimental biopanning workflow. This biopanning informed ML approach reduced the experimental screening burden by 78% to 90% for the Omicron BA.5 and Omicron BA.1 variants, respectively. The combined approach can be applied to other emerging viruses with pandemic potential to rapidly identify effective therapeutic antibodies against emerging variants.

Uropathogenic Escherichia coli (UPEC) is the primary cause of uncomplicated urinary tract infections (UTIs). Whereas most infections are isolated cases, 1 in 40 women experience recurrent UTIs. The rise in antibiotic resistance has complicated the management of chronic UTIs and necessitates new preventative strategies. Currently, no UTI vaccines are approved for use in the United States, and the development of a highly effective vaccine remains elusive. Here, we have pursued a strategy for eliciting protective immunity by vaccinating with small molecules required for pathogenesis, rather than proteins or peptides. Small iron-chelating molecules called siderophores were selected as antigens to vaccinate against UTI for this vaccine strategy. These pathogen-associated stealth siderophores evade host immune defenses and enhance bacterial virulence. Previous animal studies revealed that vaccination with siderophore receptor proteins protects against UTI. The poor solubility of these integral outer-membrane proteins in aqueous solutions limits their practical utility. Because their cognate siderophores are water soluble, we hypothesized that these bacterial-derived small molecules are prime vaccine candidates. To test this hypothesis, we immunized mice with siderophores conjugated to an immunogenic carrier protein. The siderophore–protein conjugates elicited an adaptive immune response that targeted bacterial stealth siderophores and protected against UTI. Our study has identified additional antigens suitable for a multicomponent UTI vaccine and highlights the potential use of bacterial-derived small molecules as antigens in vaccine therapies.

The field of parking and transportation is essential to the operations, development, and success of nearly every major discipline in our global society. There is a heavy global dependence on parking and transportation technology by businesses, schools, hospitals, manufacturing, agriculture, and tourism, which all utilize parking and transportation infrastructure to transport goods, services, and consumers. Any major disruption to the parking and transportation field caused by natural disasters, terrorism, or other threats will also disrupt the many related fields which rely on parking and transportation infrastructure, potentially causing a complete socioeconomic collapse. It is therefore paramount for the field of emergency management and homeland security to protect and secure parking and transportation infrastructure. As modern technology continues to innovate, so will parking and transportation technologies and infrastructure develop. New technologies and concepts are constantly entering the parking and transportation market, resulting in a dynamic field of study, yet emergency management’s treatment of the parking and transportation field remains stagnant. The purpose of this thesis is to introduce new technologies and concepts that are emerging in the parking and transportation field and purpose how these new technologies can be utilized to help aid emergency management efforts. This thesis will discuss four newly developing technologies: bollard developments, emergency notification systems, license plate reading cameras, and GPS technologies. These four technologies have seen significant developments in recent years and can be applied to support parking and transportation efforts and be utilized by emergency management in the event of an emergency or crisis.

Black carbon (BC) is an environmental pollutant of particular concern to many international organizations for both its health effects and environmental effects. Fluorescent carbon dots (FCDs) were chosen to be used as a surrogate to evaluate BC individually. Characterization of the FCDs occurred with the use of dynamic light scattering (DLS), lowresolution transmission electron microscopy (LR-TEM), high-resolution transmission electron microscopy (HR-TEM), infrared spectroscopy (IR), X-ray photoelectron spectroscopy (XPS), and electron-paramagnetic spectroscopy (EPR). Evaluation of the optical properties were studied using fluorescence spectroscopy. The photostability, chemical stability, and physical stability was tested as well. The FCDs produced in this research ranged in size from 10-50 nm, exhibiting a graphene oxide structure with suggestions of hydroxide functional groups on the surface and semiquinonetype radicals. Fluorescence quenching was also tested. Metal ions were tested for their ability to quench the fluorescence of the FCDs, followed by a testing of fluorescence recovery by a reducing agent. Ferric ions were the optimal quencher, quenching 100% of the fluorescence. Only limited fluorescence recovery was possible. Characterization of the FCDs before and after fluorescence quenching allowed for proposal of a quenching mechanism. The proposed mechanism, involving the stabilization of a semiquinone radical by the ferric ions is the first of its kind reported in literature to this point. Cellular studies regarding the health effects of the FCDs, and therefore BC, was performed on lung epithelial cells (BEAS-2B). Uptake was evaluated by confocal fluorescence imaging and LR-TEM. Cytotoxicity was evaluated by trypan blue assay, MTT assay, and MTS assay and revealed cytotoxic effects when FCDs are exposed to cells for long time periods (8 hours) and high concentrations (8 mg/mL). The metal ion quencher increases the overall toxicity of the FCDs. Through an evaluation of the GSH:GSSG ratio, no cellular oxidative stress was witnessed at short time periods, though further study is warranted. The cell studies of FCDs in this dissertation are more comprehensive regarding time period and FCD concentration than any found in literature.

The spectra of predicted particles from elementary quark models (CQMs) are expansive, accurate for the low-lying spectra, but incomplete. The GlueX experiment at Jefferson Lab is a vehicle to study medium energy photoproduction of hadronic states. The primary goal of the GlueX collaboration is to study Quantum Chromodynamics (QCD, also known as the strong nuclear force) and the nature of quark confinement. The GlueX collaboration uses a polarized photon beam incident on a liquid hydrogen target (LH2) to investigate the aftermath of photon-proton interactions.The cascade baryons, denoted by Ξ, are defined by having two, second-generation, strange quarks with an additional first-generation light quark (u or d). Experimentally, few cascades have been discovered, which is the antithesis of what most models expect. The cascades have some favorable attributes but are difficult to detect because the production cross sections are small and direct production is unlikely. Fortunately, in the 12 GeV era of the GlueX experiment, there is sufficient energy, beam time and data analysis tools for the detection of excited cascade states and their properties.From the reaction γp→K^+ K^+ Ξ^- π^0, the invariant mass spectra of Ξ^- π^0 system was surveyed for new possible resonances. The invariant mass spectrum has a strong Ξ(1530) signal with other smaller resonances throughout the spectrum. Preliminary cross sections for the Ξ(1530) that was photoproduced from the proton are presented at energies never before explored. While the Ξ(1530) couples almost exclusively to the Ξπ channel, there is an easily identifiable Ξ(1690) signal decaying Ξπ. Through the use of a simultaneous fitting routing of the Ξ*- mass spectra, I was able to observe the Ξ(1690) decaying to the KΛ, as well as to the Ξ-π0 branch. With additional statistics, a measurement of the branching ratio should be possible. Lastly, a partial wave analysis (PWA) was completed to verify that the total angular momentum of Ξ(1530) is J = 3/2 and consistent with having positive parity. Additionally, there is evidence of a potentially interesting feature slightly above the mass of the Ξ(1530) that should be more fully explored as new GlueX data becomes available.

Efficient and selective excitation of lattice vibrations is central to controlling energy flow at the nanoscale, yet remains challenging under conventional optical excitation. Here, we introduce a mid-infrared-assisted phonon amplification approach, termed MIRAPA, that enables efficient energy injection directly into vibrational bonds. Using surface-enhanced resonant Raman scattering in few-layer \\(MoS_2\\), we exploit strong exciton--phonon coupling to monitor phonon populations. When mid-infrared (MIR) light is introduced, it couples directly to out-of-plane lattice vibrations, leading to room-temperature phonon amplification exceeding \\(80\\%\\). Crucially, MIRAPA bypasses electronic excitation pathways, allowing the MIR power density to be nearly \\(300\\) lower than that required for visible excitation to achieve comparable enhancement. The resulting phonon modulation is robust, persisting over more than \\(2800\\) on/off cycles and exceeding \\(15\\) hours of continuous-wave laser illumination without degradation. Quantitative analysis yields an effective noise-equivalent power of approximately \\(0.3\\,nW/Hz\\) for MIR detection, highlighting the sensitivity of the approach. By combining vibrational selectivity, low-power operation, and long-term stability, MIRAPA provides a robust platform for probing and amplifying phonons in two-dimensional semiconductors. These results open new opportunities for nanoscale vibrational sensing, mid-infrared detection, and phonon-based coherent devices, including routes toward phonon lasing.

F\"orster energy transfer underpins modern photonics, yet establishing an analogous vibrational pathway in the mid-infrared (MIR) remains highly challenging, as sub-picosecond intramolecular vibrational redistribution (IVR) suppresses intermolecular coupling. Here we demonstrate vibrational donor--acceptor transfer in the MIR and subsequent upconversion to visible luminescence enabled by sub-2 nm plasmonic nanogaps. The extreme lateral field confinement in metal--molecule--metal ring cavities defined by self-assembled molecular spacers couples efficiently to in-plane molecular dipoles. Continuous-wave MIR excitation selectively populates \\(-C\\) vibrational donors, and plasmon-enhanced near-field coupling transfers this energy to nearby electronic acceptors, generating anti-Stokes visible emission under low power densities. Upconversion efficiencies exceeding \\(0.3\\%\\) are observed, limited by competition between the plasmon-mediated transfer rate and IVR. These results show that extreme plasmonic confinement can redirect molecular vibrational relaxation pathways, opening a route toward vibrational nanophotonics, intermolecular interactions for bioimaging, and room-temperature MIR detection based on molecular degrees of freedom.

Engineered monoclonal antibodies (mAbs) have proven to be highly effective therapeutics in recent viral outbreaks due to their specificity and ability to provide immediate protection, regardless of immune status. However, despite technical advancements in the field, an ability to rapidly adapt or increase antibody affinity and by extension, therapeutic efficacy, has yet to be fully realized. We endeavored to stand-up such a pipeline using molecular modeling combined with experimental library screening to increase the affinity of a given antibody, F5, to recombinant E1E2 antigen from Venezuelan Equine Encephalitis Virus (VEEV) subtype IAB (TC-83). F5 is a monoclonal antibody with potent neutralizing activity against VEEV that was isolated from human bone marrow donors. F5 is known to bind to spikes on the surface of VEEV made up of a trimer of heterodimers of the glycoproteins E1 and E2. In this work we modeled the interaction of F5 with the E1E2 trimer of VEEV (TC-83) and generated predictions for mutations to improve binding using a Rosetta-based approach and dTERMen, an informatics approach. Modeling the structure of the complex was complicated by the fact that a high-resolution structure of F5 is not available and the H3 loop of F5 exceeds the length for which current modeling approaches can determine a unique structure. To overcome these challenges nine F5 structures with varying H3 loop conformations were generated using RosettaAntibody, PIGS (Prediction of ImmunoGlobulin Structure), and SWISS-Model and these base antibody structures were evaluated in docking trials to recombinant VEEV E1E2 based on relative binding affinity for several subtypes. The structure that gave the best agreement with the experimental trend in relative binding affinity was used for mutation analysis. A subset of the predicted mutations from both methods were incorporated into a phage display library of scFvs (single-chain variable fragments) and screened for binding affinity to the recombinant E1E2 antigen. Results from this screen were used to identify favorable mutations which were then incorporated into twelve human-IgG1 variants. All twelve variants showed increased binding relative to the parental F5 human-IgG1. The best case showed > 60x increased binding to recombinant E1E2 relative to the parental antibody, notably showing a drastic improvement of the Kd or “off rate” compared to the parental F5 IgG. These results demonstrate the ability of our methods to rapidly increase affinity and could be leveraged for increasing Ab binding breadth to additional viral variants.