University of Illinois at Chicago
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Using Community Engagement to Address Injustices: A Case Study of San Francisco Tobacco-Free Coalition
No full textThis case study research examined the San Francisco Tobacco-Free Coalition (SFTFC)’s fight to remove menthol and flavored tobacco products from the marketplace. The SFTFC relies on grassroots infrastructure to guide and shape tobacco control efforts in African American communities. SFTFC operates at the intersection of social injustice and public health policy. The uniqueness of SFTFC is its work with health jurisdictions, elected officials, community-based organizations, activities, and faith-based communities. SFTFC also strives to ban menthol and flavored tobacco products using community engagement methods to address anti-tobacco initiatives. This case emphasized the possibility of replicability across the United States (U.S.).Tobacco use remains the leading cause of preventable illnesses and early death both in the U.S. and around the world. Tobacco use plays a major role in health conditions that disproportionately affect African Americans, including heart disease, cancer, and stroke. Ongoing tobacco use within racial and ethnic minority communities in the U. S. remains a serious public health issue. Community engagement can impact changes to elevate the regulation of the sale of menthol and flavored tobacco products and contribute appropriately to policy changes. Currently, there is a need for continued evidence on how community engagement works for such tobacco-related changes in the African American community. This study explored how this is done and includes recommendations for the future. </p
Phasic Dopamine Signaling During Ingestion: Modulation Across the Need-to-Satiety Arc
No full textMaintaining body homeostasis is essential for survival, and deviations from physiological balance trigger goal-directed behaviors aimed at consuming the needed stimulus. The mesolimbic dopamine system plays a key role in driving and reinforcing such behaviors. While it is well established that physiological need states potentiate dopamine responses to relevant stimuli, less is known about how ongoing ingestion and the transition to satiety influence the mesolimbic dopamine system. To address this gap, I investigated how dopamine signaling is modulated as rats transition from need to satiety across three distinct conditions: sodium appetite, thirst, and hunger. Using in vivo fiber photometry, I measured dopamine release in the nucleus accumbens lateral shell during intraoral delivery of sodium chloride, water, or sucrose. Behavioral reactivity was tracked using deep learning-based pose estimation. Sodium and water evoked greater dopamine release in sodium deplete and water deprived rats, respectively, compared to ad lib controls. Dopamine release declined across trials, suggesting that negative feedback from ongoing ingestion dynamically modulates mesolimbic signaling. This feedback was further supported in sodium deplete rats, where a lower concentration of sodium resulted in a shallower decline in dopamine. In contrast, food restriction only moderately increased dopamine responses to sucrose, which remained relatively stable throughout ingestion despite a main effect of physiological state. Moreover, I applied different manipulations to evaluate their influence on slope of decline during ingestion. Systemic administration of nociceptin receptor antagonist, shown to influence the breakpoint in reward behavior, didn’t affect dopamine responses to water. In contrast, systemic treatment with GLP-1 receptors agonists, known to promote satiety, differentially modulated dopamine responses to sucrose. Exendin-4, but not Semaglutide, significantly suppressed dopamine release without influencing slope of decline, indicating a reduction in overall dopamine activity. This difference may be due to pharmacokinetics properties, as Exendin-4 crosses the blood-brain barrier, whereas Semaglutide does not. Together, these findings suggest that the mesolimbic dopamine system acts as a dynamic integrator of physiological signals, modulating motivational drive as ingestion progresses. These results provide insights into neural mechanisms underlying the transition from need to satiety and have implications for understanding and treating disorders of overconsumption, such as obesity
Computer Simulations of Rare Earth Erbium Ion-Extractant Binding at Liquid-Liquid Interfaces
No full textThis thesis focuses on understanding the molecular mechanisms underlying the solvent extraction of trivalent lanthanide ions in bulk water and at the aqueous-organic interface. Solvent extraction is a critical process in the separation of rare earth elements, which are essential for technologies like the nuclear fuel cycle, electronics, and renewable energy. The process involves the binding of extractants to metal ions in aqueous solution and transfers to the organic phase. We focus on the interaction of erbium (Er³⁺) with the organophosphorus extractant bis(2-ethylhexyl) phosphoric acid (HDEHP).
Despite its industrial importance, it is not well understood how extractants bind to lanthanide ions at the molecular level. This includes the removal of water molecules upon ion binding and the geometry and dynamics of binding. Our work addresses this knowledge gap by employing classical molecular dynamics (MD) simulations to investigate the binding mechanism of HDEHP to Er³⁺ in two separate environments: bulk water and the aqueous-organic interface.
In our first study, we investigated the binding of a single DEHP⁻ (deprotonated HDEHP) extractant to fully hydrated Er³⁺ in bulk water. Using MD simulations, we discovered that the binding process is remarkably fast, despite the strong hydration energy of Er³⁺. As the DEHP⁻ headgroup approaches Er³⁺, water molecules in the first hydration shell undergo collective rotational motions, creating space for the incoming extractant. This concerted motion leads to the ejection of a water molecule located 180° opposite to the incoming DEHP⁻ oxygen. When the headgroup binds, it positions its oxygen atom closer to Er³⁺ than the water molecules in the ion's first hydration shell. This study provided the first detailed molecular-level understanding of how DEHP⁻ binds to Er³⁺ in bulk water, highlighting the importance of collective water dynamics and geometric specificity in the binding process.
Building upon the first study, we extended our research to investigate the binding of multiple DEHP⁻ extractants to Er³⁺, both in bulk water and at the aqueous-organic interface. This second work aimed to understand how sequential binding events occur and how the presence of multiple extractants affects the binding kinetics and hydration shell structure. The binding probability decreases as more DEHP⁻ molecules bind to Er³⁺, with an especially significant decrease at the interface, likely due to steric constraints. The highly charged ion Er3+ is surrounded by a well-ordered hydration shell of water molecules. When a DEHP- ligand binds to Er3+, it can partially or fully displace water molecules from this strong hydration shell. Bound DEHP- occupies space that can make it more difficult for additional DEHP- molecules to approach and bind to Er3+. At the interface, this steric constraint becomes more relevant because DEHP- tails are preferentially solvated by the organic phase. This further reduces the available space for additional DEHP- to approach and bind. When we investigate the ejection of water molecules by the incoming DEHP-, we find that water can be ejected before or after the DEHP- is fully bound to the Er3+ ion. However, in the case of binding of the third DEHP⁻, water ejection occurs mostly after the binding event, which may be related to the significant drop in binding probability for the third DEHP-. These simulations reveal how the multi-step binding and hydration shell dynamics are influenced by the number of bound extractants and the different environments of bulk water and water-dodecane interface
Shp2 Regulates Vascular Endothelial Matrix Degradation in Phosphatase-Independent Manner
No full textShp2 is a protein tyrosine phosphatase that is implicated in many diseases such as developmental disorders and cancers. One of its suggested physiological functions is regulation of angiogenesis, which is often impacted in Shp2 pathologies. However, its role in angiogenesis is still poorly understood. In our work, we show that Shp2 plays a critical role in the initiation of the first step of angiogenesis: matrix degradation. Intriguingly, Shp2’s phosphatase activity and substrate binding are not needed for its regulation of this process. Our studies suggest that scaffolding by Shp2’s properly structured phosphatase domain mediates matrix degradation. This mechanism is supported by our analysis of Shp2 mutants causing Noonans Syndrome with Multiple Lentigines. These findings propose a novel mechanism by which Shp2 regulates angiogenic matrix degradation and presents Shp2’s phosphatase domain scaffolding as an attractive anti-angiogenic therapeutic target
Validity Evidence for Construct-Aligned Entrustment Assessments in Vascular Surgery
No full textOBJECTIVE
Workplace-based assessments of surgical trainees historically demonstrate poor alignment between faculty and learner perception of competence and autonomy in a given clinical encounter. Furthermore, demographic differences in assessment of trainees have been demonstrated across specialties. Given that trainee perception of receiving low autonomy is associated with higher rates of burnout, depression, and attrition, it is important to better align faculty and trainee perceptions of clinical experiences. We sought to evaluate validity evidence data of vascular surgery Entrustable Professional Activities assessments (EPAs) using national pilot implementation data.
METHODS
A multi-institutional pilot implementation of 15 vascular surgery EPAs was open to Accreditation of Graduate Medical Education (ACGME) vascular surgery residencies and fellowships from April-June of 2024. Participating programs collected faculty, resident, and fellow assessments on entrustment for clinical encounters. Descriptive statistics were conducted on matched encounter assessments. A linear mixed-effects model was conducted to examine factors associated with the alignment. Intraclass correlation was calculated between trainee and faculty assessments. A random effects model was applied to all assessments to demonstrate sources of variance in entrustment ratings. Linear mixed effects models clustering by trainee, faculty, program, and EPA were applied to examine differences in faculty assessed and trainee self-assessed entrustment scores by faculty gender, trainee gender, race, and ethnicity, post-graduate year, phase of care, and faculty-trainee gender concordance.
RESULTS
Twenty-nine programs contributed 1,620 matched assessments (n=79 trainees, n=87 faculty). There were no differences in absolute alignment scores by trainee gender, race, ethnicity, faculty gender, faculty-trainee gender concordance, or EPA phase of care. ICC ranged from moderate to excellent across all EPA types (ICC=0.51-0.89), and excellent for all EPAs combined (ICC=0.76). Variance in faculty entrustment ratings was attributed primarily to the interaction between EPA and trainee (31%). Faculty entrustment ratings were not different when considering trainee gender, race, ethnicity, faculty gender, or faculty-trainee gender concordance.
CONCLUSION
In this retrospective analysis of national EPA pilot implementation data, response process, internal construct, and consequence validity evidence were demonstrated. Shortcomings of other workplace-based assessments used in surgical training were not evident with the use of behaviorally-anchored EPA assessments
Charge Density Waves and Superconductivity in Rare Earth Compounds from First Principles
No full textHigh-temperature superconductivity at ambient pressures has been a major goal in condensed matter physics for decades. For conventional superconductors, strong electron-phonon coupling and high frequency phonons are the key ingredients to realizing this. However, strong electron-phonon coupling also leads to charge density waves and structural distortions which compete with superconductivity. To better understand this competition, I use first-principles simulations to study rare-earth tritellurides (RTe3) and doped rare-earth trihydrides (RH3), which host superconducting states when their charge-density-waves/structural transitions are suppressed. I develop useful computational tools for this purpose and find that the effects of strong correlation (captured with DFT+U simulations) has a nontrivial effect on the susceptibility of these materials to structural distortions. In doped rare earth trihydrides, nuclear quantum effects are found to stabilize the system against structural distortions and allow superconducting temperatures to reach above 120 K. We benchmark Tc estimation methods and use them for larger supercells which indicate Tc's up to 220 K may be possible in the doped RH3 system
Application and Performance of High Entropy Metal Nanoparticles in the Field of Antibacterial
No full textAntibacterial agents are increasingly applied and demanded in numerous industries such as the pharmaceutical industry, food industry, and medical implantation. In some industries, antibacterial agents not only need to have good antibacterial properties but also need to meet other characteristics. This study explores the potential of various different metal particles in antibacterial aspects and reviews a new method for synthesizing high-entropy alloy oxide nanoparticles (HEO NPs), which is expected to possess the advantages of multiple metals while retaining the antibacterial properties of metals themselves. We tested the antibacterial properties of different phase alloy nanoparticles and discussed the influence of different metals on the antibacterial properties of metal oxide nanoparticles
Investigating the Biomechanical and Electrophysiological Responses of Astrocytes to Mechanical Trauma
No full textTraumatic brain injury (TBI) is a known risk factor for neurodegeneration, including Alzheimer’s disease (AD). Astrocytes, the brain’s primary homeostatic glial cells, respond dynamically to injury, and alterations in their calcium signaling have been implicated in both TBI and AD pathology. Human induced pluripotent stem cell (hiPSC)-derived astrocytes cultured in 2D monolayers can be mechanically stretched to mimic strain experienced during TBI, providing a controlled in vitro model to study injury response. However, analyzing astrocytic structural and functional responses in this system presents technical challenges due to complex cell morphology and functional dynamics. To address this, the goal of this work was to develop a set of image analysis tools capable of quantifying injury-induced changes in astrocyte structure and function across a range of experimental conditions.
A novel calcium activity metric, the Asynchronous Activity Index (AAI), was developed using a CellProfiler-based pipeline. The AAI quantifies fluctuations in total fluorescence over time to assess population-wide calcium activity, providing an alternative when reliable cell-specific segmentation was not feasible. For all other assays, nuclei served as the primary segmentation masks. Analytical pipelines were customized based on the biological interpretation of each signal, with measurements extracted from nuclear regions or defined spatial domains surrounding them. For cell-specific calcium analysis, a custom MATLAB script was used to exclude dim nuclei that had shifted outside the cytoplasmic boundary during the Calbryte time series, due to the motile nature of astrocytes. The nuclear image was captured as a single static frame, while the Calbryte signal was recorded as a time-lapse sequence, leading to spatial drift. The script filtered traces across paired video segments for temporal consistency.
These analysis tools successfully identified statistically significant differences in markers across injury conditions. Results mirrored qualitative visual trends and helped reveal whether strain- and time-dependent changes in astrocyte behavior were present and experimentally repeatable. The biologically informed pipelines developed in this work provide a framework for quantifying astrocyte injury responses that will support future studies of astrocyte mechanobiology and calcium signaling in the context of TBI
Regularity of Solution Maps of the Generalized Surface Quasi-Geostrophic Equations
No full textIn Chapter 1, we present some preliminaries. In Chapter 2 we drive generalized SQG equations as Euler-Arnold equations. Chapter 3, we establish analyticity of the exponential map associated to the generalized SQG equations. In Chapter 4, we establish that the Eulerian data-to-solution map for the generalized SQG equations fails to be uniformly continuous in Sobolev spaces
Investigating Epigenetics as a Mechanism to Regulate Bacterial Heterologous Expression
No full textEpigenetic DNA methylation in bacteria is involved in phage defense, and it can also affect gene transcription. Epigenetic methylation as part of restriction-modification systems is frequently considered a barrier in synthetic biology since it can prevent the introduction of heterologous genes to new host organisms. Due to this, many studies that construct bacterial hosts for use in synthetic biology often remove these restriction-modification systems. There are no studies however that have attempted to optimize restriction-modification systems and orphan DNA methyltransferases to boost heterologous gene product yields.
For this study, our ultimate goal was to investigate whether epigenetic DNA methylation can be used as a tool to increase heterologous expression yields in bacteria. We carried this study out by obtaining and comparing DNA methyltransferase deletion mutants in a variety of bacterial species that have been widely used as heterologous hosts, namely gram-positive Bacillus subtilis, and gram-negative Escherichia coli and Pseudomonas putida.
For the gram-negative strains, we confirmed the expected epigenetic methylation in the wildtype strains. Additionally for Pseudomonas putida, we generated four double-crossover deletion mutants and two single-crossover mutants.
For B. subtilis we obtained deletion mutants from the Bacillus Genetic Stock Center. For each of two B. subtilis DNA methyltransferase deletion mutants, we compared it to the wildtype strain, B. subtilis 168, for differences in cell growth, motility, methylome, and metabolome. We found that epigenetic methylation in B. subtilis regulates the metabolome and serves as rationale for continuing the investigation on whether epigenetic methylation can be used to optimize heterologous gene expression
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