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PROTECTING THE SACRED: AN ANALYSIS OF INDIGENOUS CHILDREN’S EXPERIENCES IN THE OKLAHOMA CHILD WELFARE SYSTEM
No full textIntroduction: Given what is known about the historical mistreatment of Indigenous children, the current study used Oklahoma data to determine if Indigenous identity was associated with specific child welfare outcomes (e.g., substantiation, removal, and service referrals) when controlling for public assistance, caregiver substance use, domestic violence, child demographics, and maltreatment allegation types. Methods: Oklahoma data from federal fiscal year 2019’s National Child Abuse and Neglect Data System’s child file was used. A simple random sample of 1000 children was used to create a calibration sample (n = 500), and validation sample (n = 500) while the remaining population level data (n = 65,200) was used as the holdout sample. Children were classified as either non-Hispanic White, Indigenous alone, Indigenous and White, Indigenous and other ethnoracial minority, or non-Indigenous ethnoracial minority for the purpose of analysis. Except for child age and number of children within the report, covariates were coded as “Yes” (1) or “No” (0). Descriptive statistics as well as hierarchical logistic and linear regressions were conducted using STATA (18) with p .05). In comparison, the validation model was statistically significant (R2 for step 1 = .0661; ΔR2 for step 2 = .0106; F(15, 458) = 2.74, p = .0005); however, none of the Indigenous ethnoracial groups were associated with service referrals. When assessing the remaining population using the holdout sample (R2 for step 1 = .0286; ΔR2 for step 2 = .2714; F(15, 52,681) = 125.25, p = .0000) – both the Indigenous and White (p = .000) and Indigenous and other ethnoracial minority (p = .000) groups were positively associated with service referrals. Despite being statistically significant the validation and holdout models accounted for low overall variance. Conclusion: By grouping multiracial Indigenous children in their own ethnoracial categories – a better picture of Indigenous child welfare experiences was obtained. This is critically important as multiracial White and Indigenous children were found to have lower odds of substantiation. Further, higher odds of removal were observed in population data for both the Indigenous and White and Indigenous and other ethnoracial minority groups. These findings further support the need to not only evaluate Indigenous children in child welfare research, but to consider different approaches to the use of multiracial identity, particularly for Indigenous children. Further research is needed to explore the percentage of multiracial Indigenous children falling outside the protections afforded to citizens of federally recognized tribes via the Indian Child Welfare Act (ICWA). Additional research is needed to determine the intersection between Indigenous identity and family/community level factors that may influence child welfare outcomes
Minutes of a Regular Meeting, The University of Oklahoma Board of Regents, Thursday and Friday, January 30–31, 2025
No full textBifunctional Multiwall Carbon Nanotubes and Their Effect on Hydration, Conductivity, and Mechanical Properties of Cement Composites
Full text linkFinancial support was provided by the University of Oklahoma Libraries' Open Access Fund.Multiwall carbon nanotubes (MWCNTs) significantly enhance hydration reactions and properties of cement composites, expanding their applicability. Interest has grown in the use of multifunctional composites with MWCNTs being a popular filler material to impart additional features. Dispersing MWCNTs in the cement matrix creates an electrical network and replaces pore areas to enhance cement performance. This work compares two novel methods by admicellar polymerization (AP) and grafting polymerization (GP) for preparing bifunctional MWCNTs. Both techniques utilized polyindole (PIn) to enhance electrical conductivity and polyvinyl acetate (PVAc) for better dispersion. Isothermal calorimetry was used to observe the hydration of the cement composites. Results showed that AP-MWCNT/cement and GP-MWCNT/cement increased exothermic heat by 8.4% and 12.1%, respectively, compared to bare MWCNT/cement with the same nanotube content (0.3 wt%). Moreover, both modified MWCNTs improved mechanical properties and electrical conductivity. When comparing AP-MWCNTs and GP-MWCNTs in cement, AP-MWCNT/cement exhibited higher electrical conductivity, while GP-MWCNTs demonstrated superior embedding within the cement matrix, which led to a reduction in pore area and the higher mechanical strength of the two modified MWCNTs.Ye
MECHANISTIC INSIGHTS INTO MULTIDRUG EFFLUX PUMP ACTIVITIES AND THEIR INHIBITION
No full textThe rise of multidrug-resistant (MDR) Gram-negative pathogens poses a critical threat to global public health. The Resistance-Nodulation-Division (RND) family efflux pumps are central to this resistance, which actively expel a broad range of antibiotics, detergents, and host-derived compounds from bacterial cells. Despite their clinical importance, the detailed molecular mechanisms by which RND pumps coordinate substrate recognition, energy transduction, and channel gating remain incomplete, particularly regarding how environmental cues and inhibitors dynamically regulate these processes. This dissertation dissects the molecular mechanisms and functional regulation of two archetypal RND systems: the AcrAB—TolC efflux pump of Escherichia coli and the MexEF—OprN pump of Pseudomonas aeruginosa. Through a multidisciplinary approach integrating site-directed mutagenesis, in vivo efflux assays, disulfide trapping, inhibitor studies, and collaborative hydrogen-deuterium exchange mass spectrometry (HDX-MS) conducted by Eamonn Reading’s group at King’s College London, molecular docking carried out by Dr. Paolo Ruggerone's group at the University of Cagliari, and molecular dynamics (MD) simulations performed by James C. Gumbart’s group at Georgia Institute of Technology, we provide new insights into how conformational dynamics, environmental conditions, and small-molecule inhibitors converge to control efflux pump activity and antibiotic resistance. Chapter 3 elucidates the role of the membrane fusion protein (MFP), AcrA, in the AcrAB—TolC efflux system. Consistent with prior structural studies, our mutagenesis and covalent locking studies reveal that interdomain flexibility within AcrA is essential for coupling substrate-induced conformational changes in AcrB to TolC opening. Targeted cysteine substitutions at eight hinge residues demonstrated that AcrA tolerates single-point mutations without losing efflux function. However, thiol-reactive locking of key hinge sites, L50, T205, and N232, abolished efflux activity, pinpointing the importance of these regions. Environmental modulation experiments further demonstrated that AcrAB—TolC is functional at a wide range of pH (from pH 5.0 to pH 8.0) but its activity is pH-sensitive, with optimal efflux between pH 6.0 and 7.0, and sharply reduced activity at extreme acidic or alkaline pH. Through mutational analysis, H285 of AcrA emerged as a protonation-sensitive protein residue: substitution to alanine abolished efflux under acidic conditions but preserved activity at neutral pH, suggesting that protonation of H285 destabilizes the interaction network essential for pump activation. Collaborative HDX-MS conducted by Eamonn Reading’s group at King’s College London and MD simulations performed by James C. Gumbart’s group at Georgia Institute of Technology provided complementary insights, revealing that protonation of H285 and the absence of Mg2+ increased AcrA flexibility, particularly in the membrane-proximal and αβ barrel domains. Collectively, these findings support a model in which AcrA acts as a pH-and cation-sensitive MFP, whose interdomain flexibility is finely tuned to efflux competency in response to environmental cues. Chapter 4 builds on these findings to investigate how the coupling between AcrA and TolC governs the opening of the channel, TolC. Through systematic cysteine mutagenesis and in vivo disulfide trapping, we mapped the interface between the α-helical hairpin of AcrA and the periplasmic coiled coil of the TolC domain. Single cysteine substitutions at key tip residues, AcrA Q136, Y137, L132 and TolC Q139, Q142, R143, preserved efflux activity under tested conditions, suggesting that the interface tolerates some static contacts. However, enforced covalent trapping of the AcrAQ136C—TolCQ142C pair abolished efflux activity, indicating that structural flexibility at this interface is essential for function. Inhibitor studies demonstrated that the small molecule NSC-60339 selectively disrupted disulfide bond formation at specific AcrA–TolC sites, suggesting that it affects efflux by modulating conformational dynamics rather than physically occluding the interface. In vitro reconstitution experiments with disulfide-stabilized AcrA—AcrB complexes further support that productive TolC engagement requires pre-alignment and is not driven by spontaneous oxidation alone. These results refine the mechanistic model of efflux activation, proposing that the AcrA—TolC interface is modulated by flexible domain alignment. In conclusion, we propose that NSC-60339 stabilizes AcrA in a conformation incompatible with the TolC opening, thus turning off the efflux function of the tripartite assembly. Chapter 5 shifts our focus to MexEF—OprN efflux pump of P. aeruginosa, an RND system whose substrate specificity remains poorly understood despite the important role of MexEF—OprN in the resistance of fluoroquinolones, trimethoprim, and chloramphenicol. Through targeted mutagenesis of four nonconserved MexF residues, D132, P136, G626, and S729, we mapped the structural determinants of substrate recognition and transport. Mutations in P136 and S729 enhanced or impaired the efflux of multiple substrates, while mutations at D132 and G626 produced substrate-specific effects. Efflux accumulation assays and MIC profiling revealed that substrate-specific phenotypes are distributed throughout the MexF structure, with fluoroquinolones and trimethoprim sharing overlapping but distinct efflux pathways. Competitive inhibition studies using Hoechst 33342 further demonstrated that chemically distinct substrates compete for shared binding determinants. These findings align with collaborative ensemble docking and cluster analysis carried out by Dr. Paolo Ruggerone's group at the University of Cagliari, which showed that certain mutations reshape ligand trajectories and alter contact frequencies within the translocation pathway. Together, we propose that MexF substrate specificity arises from an integrated network of adaptable checkpoints distributed along the access and deep pockets, modulating efflux in a substrate-selective manner. Chapter 6 builds upon this mechanistic understanding to explore pharmacological targeting of MexF. By screening a small-molecule library, Dr. Zgurskaya's lab identified SLU-1642, a 2-aminobenzothiazole derivative, as a selective inhibitor of MexF-mediated efflux, and our study provides direct mechanistic details to establish SLU-1642 as a selective inhibitor of MexF. Hoechst 33342 accumulation assays demonstrated that SLU-1642 selectively inhibited MexF without affecting MexB or efflux-deficient strains, distinguishing it from broad-spectrum efflux inhibitors. SLU-1642 potentiated the activity of trimethoprim and doxycycline in MexF-overproducing strains, but had limited impact on other antibiotics, suggesting substrate-selective inhibition. Structure-activity relationship (SAR) analysis of SLU-1642 analogs revealed that modifications to the core scaffold or side-chain flexibility dramatically altered MexF inhibition, underscoring the narrow chemical window required for activity. Mechanistically, single-point mutations at MexF residues, especially S729, variably impaired SLU-1642 function. The S729W mutation abolished SLU-1642 activity across all substrates, confirming that S729 is a critical residue for substrate translocation and inhibitor engagement. The four chapters of this dissertation build a unified mechanistic framework to understand how RND efflux pumps integrate environmental cues, conformational flexibility, and pharmacological inhibition to maintain their functions. In the AcrAB—TolC system, AcrA acts as a dynamic bridge between AcrB and TolC, whose flexibility is modulated by pH, Mg2+, and small-molecule inhibitors, NSC-60339, to control efflux function. In MexEF—OprN, substrate specificity and inhibition arise from a distributed network of adaptable checkpoints within MexF, with key residues such as S729 coordinating substrate binding and transport. Across both systems, conformational trapping by selective inhibitors—NSC-60339 for AcrA and SLU-1642 for MexF—demonstrates that efflux inhibition can be achieved by stabilizing nonproductive conformations that prevent channel opening and substrate extrusion. These findings have broad implications for the development of antimicrobial drugs. They suggest that targeting the dynamics of efflux pumps may provide a new avenue for their inhibition and future overcoming multidrug resistance. By stabilizing specific conformational states of key efflux components, it may be possible to selectively disable efflux without broadly inhibiting homologous transporters, reducing the likelihood of toxicity and resistance development. In addition, our work highlights the critical role of environmental modulation in efflux pump regulation, suggesting that therapeutic efficacy may vary between infection niches with different pH and ion concentrations. In conclusion, this dissertation advances the mechanistic understanding of multidrug efflux systems in Gram-negative bacteria, demonstrating that flexibility of certain regions, environmental sensing, and conformational inhibition converge to regulate efflux competency. By integrating the experimental dissection of AcrAB-TolC and MexEF-OprN with collaborative structural and computational studies, this work establishes a basis for rational design of next-generation efflux pump inhibitors (EPIs) that target bacterial resistance mechanisms
Ecological disturbance in the anthropocene: legacy effects of orphaned oil wells on metabolic phenotype of free-living rodents and vegetative community
No full textWhile catastrophic large marine oil spills often receive considerable media attention, highly localized and smaller-scale inland spills occur from defunct oil and natural gas wells. Oklahoma has over 15,965 documented orphaned, unplugged oil wells (UOWs) and the environmental impacts of these are not fully understood. As piping from UOWs corrode over time, petroleum escapes via open well bores, fractures in well casings, valves, connectors, and cracks in old wellheads. These escaping compounds contaminate soil and groundwater, presenting direct hazards to plant and animal species. Polycyclic aromatic hydrocarbons (PAHs) are a class of hazardous compounds found in crude oil and can persist in the environment for decades. Specifically, 16 PAHs are listed by the United States Environment Protection Agency (US EPA) as priority contaminants of concern. Currently, the effects of UOWs on plant and animal communities are not well understood. Using two study locations in Cushing, Oklahoma, we assessed the effects of UOWs on (1) site-specific habitat quality and (2) resident deer mice (genus Peromyscus) physiology. To assess habitat quality, we conducted site-specific vii vegetative surveys and Floristic Quality Assessment (FQA) was used to measure site disturbance. At the same sites, we measured free-living deer mice resting metabolic rates and hematological indices. In accordance with substantial data showing PAH exposure causes mammalian hematological damage, altered immune function, and metabolic rate shifts, we hypothesized legacy PAH contamination will lead to physiological differences in free-living Peromyscus individuals collected near UOWs. Results from this study showed decreased metabolic rates and hematological changes in deer mice collected near UOWs. We found differences in FQA values between sites, indicating disturbance in vegetative communities near UOWs. This study expands understanding of the environmental impacts of UOWs. These FQAs provide landowners and Oklahoma Energy Resource Board (OERB) with information regarding the area following remediation for some UOW sites and prior to remediation of others. In addition to this research, further FQAs conducted across the state, as well as a comprehensive species list for Oklahoma, will springboard what is known about vegetative disturbance associated with UOWs. Additionally, Peromyscus health data from this study can be used for biomonitoring and across-site comparisons. Finally, future studies can monitor deer mice population trends at the sites for the present study to characterize temporal shifts associated with UOW remediation. All this information can be used to assess the success of UOW habitat remediation and restoration projects
ASPECT RATIO AND SURFACE CHEMISTRY EFFECTS ON POLYMER-NANOTUBE COMPOSITES
Full text linkWhile carbon nanotubes have demonstrated efficacy as additives in polymer composites due to their superior properties, economic imitations associated with nanotube synthesis have hindered any large-scale applications. Recent advancements in carbon nanotube synthesis on multilayered catalyst supports have greatly surpassed yields of nanotubes grown on traditionally spherical catalysts, potentially removing the need for extra purification processes and thus reducing total cost of production. While most commercially available carbon nanotubes possess aspect ratios (length to diameter ratios) near 100, nanotubes grown on multilayered supports can reach aspect ratios well over 1,000. Hence, this research aimed to enhance the understanding of carbon nanotube aspect ratio on polymer-nanotube composites with additional emphasis on the effects of nanotube surface chemistry. Planetary ball milling, a simple and industrially relevant process, was employed to modify nanotube aspect ratio and surface chemistry. It was found that the kinetic length reduction behavior of carbon nanotubes subject to ball milling could be predicted by a simple exponential expression regardless of nanotube wall morphology, bulk morphology, or initial average length. Additionally, ball milling carbon nanotubes in the presence of species like ammonium carbonate, melamine, and sulfur was found to result in a variety of covalently and noncovalently bonded oxygen, nitrogen, and sulfur containing groups, respectively. Polycarbonate composites containing pristine, ultrahigh aspect ratio carbon nanotubes were found to exhibit high melt viscosities during compounding, leading to notable polymer degradation. Additionally, nanotube dispersion was found to be less than ideal due to the existing interleaved bundle morphology, resulting in higher-than-expected percolation thresholds. Upon ball milling for nanotube length reduction, the processability of composites was found to improve substantially; however, dispersion worsened due to the formation of small, tightly packed agglomerates. Mechanochemically oxygen-functionalized nanotubes exhibited improved dispersion and lower percolation thresholds than plain ball milled nanotubes of similar lengths due to enhanced interactions with the polymer via hydrogen bonding interactions. Tire tread rubber compounds filled with carbon nanotubes and carbon black/nanotube hybrid filler systems displayed increasing degrees of mechanical reinforcement with increasing filler aspect ratio. Mechanochemically sulfur-doped nanotubes resulted in further improved mechanical reinforcement and reduced rolling resistance, suggesting there may be merit to further study in reducing tire filler content toward improving automobile fuel economy. The implications of this research demonstrate potential for using ball milling as a scalable procedure for controlling carbon nanotube length and surface chemistry for targeted polymer composite properties
Unified modeling language code generation from diagram images using multimodal large language models
Full text linkFinancial support was provided by the University of Oklahoma Libraries' Open Access Fund.The Unified Modeling Language is a standardized visual language widely used for modeling and documenting the design of software systems. Although many tools are available that generate UML diagrams from UML code, generating executable UML code from image-based UML diagrams remains challenging. This paper proposes a new approach to generate UML code using a large multimodal language model automatically. Synthetic UML activity and sequence diagram datasets were created to train and test the model. We compared the standard fine-tuning with LoRA techniques to optimize base models. The experiments measured the code generation accuracy across different model sizes and training strategies. These results demonstrated that domain-adapted MM-LLMs perform for UML code generation automation, whereby, at the best model, it achieved BLEU and SSIM of 0.779 and 0.942 on sequence diagrams. This will enable the modernization of legacy systems and decrease the manual effort put into software development workflows.Ye
Toward an Understanding of Linear Scaling Relations through Energy Decomposition Analysis
Full text linkFinancial support was provided by the University of Oklahoma Libraries' Open Access Fund.The discovery of linear scaling relations has fundamentally changed the field of heterogeneous catalysis. The scaling relations have been rationalized based on the d-band theory, specifically a separation of sp and d electron contributions to adsorption energies. Within the framework of energy decomposition analysis, a full understanding of such a separation would require one to further break down the adsorption energy into distinct energy components such as electrostatics, polarization, charge transfer, and van der Waals interactions, and to examine the sp and d contributions to each of them. As a step in this direction, we analyzed the interaction energy between CHx (x = 1–4) adsorbates and fcc(100) transition metal surfaces (M = Cu, Ag, Au, Rh, and Pt), with the surfaces represented both as slabs in plane-wave density functional theory (pw-DFT) calculations and as atomic clusters in atomic-orbital basis density functional theory (ao-DFT) calculations. Through an absolutely localized molecular orbital (ALMO) based energy decomposition analysis of the ao-DFT adsorption energy, each of the interaction energy components (electrostatics, polarization, van der Waals, and charge transfer) was found to follow its own scaling relations, with an intricate interplay among these energy components yielding the overall scaling relations for the total adsorption energies. Using the recently introduced ALMO-based polarization and charge-transfer analysis schemes, we further dissected polarization into metal surface and adsorbate contributions, and charge transfer into metal → adsorbate and adsorbate → metal contributions. The contributions from the sp and d electrons of the metal to these terms were further quantified, and the dominant role of the metal d electrons was reaffirmed. These results shed light on how CHx adsorbates interact with metal surfaces and further reveal the physical origin of the scaling relations.Ye
ARTIFICIAL INTELLIGENCE FOR EVALUATING GAIT IN CANCER PATIENTS UNDERGOING CHEMOTHERAPY USING IMU SENSOR DATA
Full text linkGait analysis plays a crucial role in understanding motor impairments, an example of that is cancer patients undergoing chemotherapy who can be at risk of chemotherapy-induced peripheral neuropathy (CIPN). Inertial measurement units (IMUs) offer an objective and accessible means of tracking movement [1], enabling the extraction of gait features that may indicate early functional deterioration. By integrating signal processing techniques with machine learning (ML), this thesis aims to utilize IMU gait data to identify and segment gait events, assess its potential in biometric identification of different people under two walking conditions with the use of signal processing and machine learning techniques, and quantify gait changes over multiple visits for normal walking speed, all in cancer patients undergoing chemotherapy, providing a data-driven approach to assessing their mobility impairments.The first stage of this work focuses on preprocessing IMU data collected from 34 individuals under two different walking speeds, using signals obtained from foot-mounted IMUs, demonstrating that each person has their own unique walking pattern from features extracted from singular value decomposition (SVD) and discrete wavelet transform (DWT) used to train a support vector machine (SVM) classifier. This classification framework establishes the foundation for understanding individualized gait patterns and their variability. Building upon this, the later chapter shifts toward analyzing how gait evolves over time for each study subject undergoing treatment. The previously extracted (DWT) gait features are further examined using machine learning techniques for the purpose of identifying meaningful changes across multiple visits. These methods aim to track longitudinal changes and determine whether observed differences reflect inherent individual fluctuations or potential early indicators of functional decline. By integrating step-level analysis and feature-based modeling, this work seeks to provide a more comprehensive understanding of gait deterioration before it becomes clinically apparent, to enable earlier intervention, potentially improving the patient’s quality of life by addressing mobility issues before they impact a person’s daily activities
Boson Josephson Junctions based on Exciton-Polariton Condensates
Full text linkThis dissertation is a theoretical treatise on the Josephson effect in dilute quantum gases of excitons and exciton-polaritons. An exciton is a kind of elementary excitation in semiconductors, which, through strong coupling with photons, can form a light-matter hybrid particle called an exciton-polariton. Similar to superconducting systems, excitons and exciton-polaritons show superfluidity and phase coherence in their Bose-Einstein condensates, which allows us to explore macroscopic quantum phenomena such as the Josephson effect. This dissertation surveys the existing experiments of polariton Josephson junctions, focusing on optical control, and proposes an alternative method focusing on electrical control. A theoretical model unifying the two approaches is developed based on the microscopic mechanisms of exciton-polaritons. The unique dynamics of the proposed device, including the switching between oscillation modes, the externally driven and intrinsic chaotic behaviors, are discussed in detail