Chemicals and Drugs Commons^™

Normative Variability In Retinal Nerve Fiber Layer Thickness: Does It Matter Where The Peaks Are?, Sowjanya Gowrisankaran, Ashkan Abbasi, Xubo Song, Joel Schuman, Gadi Wollstein, Bhavna Antony, Hiroshi Ishikawa

Wills Eye Hospital Papers

PURPOSE: Retinal nerve fiber layer thickness (RNFLT), a glaucoma biomarker, has a wide normative range affecting its sensitivity and specificity for abnormality detection. The interindividual RNFLT peak location variability contribution to this wide normative range has not been directly evaluated. The purpose of this study is to assess the effect of RNFLT peak normalization (PN) on normative variability.

METHODS: Circumpapillary RNFLT profiles at 1.7 mm radius from the optic nerve head (ONH) were re-sampled from optical coherence tomography (OCT) volumes (Cirrus HD-OCT, 200 × 200) obtained from one eye of 83 healthy individuals. Fovea-ONH axis (FOA) was calculated from corresponding …

Assessment Of H2s-Induced Cracking Susceptibility In Steam Line Pipes And Weld Zones During Geothermal Well Construction, Riene Kaelamanda Pragitta, Yudha Pratesa

Journal of Materials Exploration and Findings

The susceptibility of steam line pipes, especially in the HAZ (heat-affected zone) and weldment areas, to hydrogen sulfide in the geothermal industry is crucial to understand from the early stages, particularly during construction. The combination of tensile stress from residual stresses after welding and metallurgical phase transformation makes the joint areas vulnerable to sulfide stress cracking. This condition becomes even more extreme when the equipment operates during the well stimulation phase. This research assesses the severity of H₂S-induced cracking using NACE MR0175 and ISO 15156-1 standards, focusing on the effects of pH and partial pressure of H₂S (p_{H₂S …}

Impact Of Tumor Cell Expressed Cd38 On Metastasis And Immune Evasion In Breast Cancer, Tanvi Visal

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype. The epithelial-to-mesenchymal transition (EMT) of cancer cells is a key feature of the metastatic cascade and is not a binary process but often generates malignant cells with both epithelial (E) and mesenchymal (M) traits known as hybrid EM cells. Recent studies highlight the enhanced metastatic potential of the hybrid EM cells. However, molecular insights and targetable vulnerabilities within hybrid EM remain elusive. We discovered that hybrid EM murine tumors are enriched in CD38, an immunesuppressive molecule associated with worse clinical outcomes in liquid malignancies but relatively understudied in solid …

Investigating Prefrontal Cortex Neuronal Signatures Of Opioid-Induced Risk-Taking Behavior, Cana Quave

Dissertations and Theses (Open Access)

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of …

Effectiveness Of Maternal Bovine Appeasing Substance Administered To Newly Received, High-Risk Stocker Calves, Elle Johnston

Animal Science Undergraduate Honors Theses

Stocker cattle purchased at auction can be susceptible to disease due to the stressors associated with the auction process. These cattle are labeled “high-risk” due to their compromised immune system during transportation, handling, and vaccination processes. The objective of this study was to determine the efficacy of a maternal bovine appeasing substance, FerAppease, on growth performance and behavior of stocker cattle. Male beef calves (n=80) were purchased at auction and transported to the University of Arkansas Division of Agriculture Savoy Research Complex Beef Stocker Unit. Steers and bulls were of varying age, breed, and temperament. Upon arrival to the facility …

Biophysical Studies Of Nucleic Acid - Small Molecule Recognition, Andrea Conner

All Dissertations

The presented work is a collection of studies performed to examine small molecule recognition of nucleic acids. Recognition of nucleic acids was examined using two types of small molecules: aminoglycosides and Hoechst dyes. Chapter One focuses on established experimental techniques (i.e. absorbance, isothermal titration calorimetry, flow cytometry, cell microscopy, etc.) in small molecule recognition of nucleic acids. The emphasis of studies in the group has been on two focus areas. (i) Thermodynamic characterization of mixed A-form and B-form DNA or RNA conformation with aminoglycosides, particularly neomycin-class. (ii) Characterization of new Hoechst-morpholine (HT-MO) derivatives’ interactions with nucleic acids.

Focus area (i) …

A Strategic Audit: Eli Lilly & Company, Natalie Karrels, Ethan Heinemann, Jonathan Patton, Meg Williams

Honors Program: Senior Projects (Public)

This strategic audit assesses the external and internal forces impacting Eli Lilly & Company’s strategic decision-making strategies. All information has been gathered from industry reports and company reports, including reports for investors, analyst calls, financial statements, and news reports. The report highlights the quantitative, qualitative, performance, strategy, and leadership decisions that have allowed Eli Lilly & Company to succeed for the past 150 years.

Statin Effects On The Lipidome: Predicting Statin Usage And Implications For Cardiovascular Risk Prediction, Changyu Yi, Kevin Huynh, Yvette Schooneveldt, Gavriel Olshansky, Amy Liang, Tingting Wang, Habtamu B. Beyene, Aleksandar Dakic, Joanne E. Curran, John Blangero

School of Medicine Publications

Statin therapy is a highly successful and cost-effective strategy for the prevention and treatment of cardiovascular diseases (CVD). Adjusting for statin usage is crucial when exploring the association of the lipidome with CVD to avoid erroneous conclusions. However, practical challenges arise in real-world scenarios due to the frequent absence of statin usage information. To address this limitation, we demonstrate that statin usage can be accurately predicted using lipidomic data. Using three large population datasets and a longitudinal clinical study, we show that lipidomic-based statin prediction models exhibit high prediction accuracy in external validation. Furthermore, we introduce a re-weighted model, designed …

Assessing The Behavioral Impact Of Pyridostigmine Bromide In Rats, Noah A. Martin

Honors Theses

Pyridostigmine bromide (PB) is an organophosphate (OP) nerve agent prophylactic used to protect warfighters against chemical warfare agents. OPs inhibit the neural enzyme acetylcholinesterase (AChE) in the brain. This leads to the buildup of acetylcholine, causing respiratory failure, seizures, and death. PB functions by inhibiting ~30% of peripheral AChE temporarily, protecting the enzymes so that the body is able to restore sufficient cholinergic function post-exposure. PB does not cross the blood-brain barrier, though it may still indirectly affect toxicity in the brain due to repeated AChE inhibition throughout treatment, or by inhibition of non-target ChE’s in the blood. The aim …

The Impact Of Biomaterial Characteristics On Macrophage Phenotypes In Tissue Engineering: A Review, Julian Jackson, Hani Samarah, William Palmer, Zachary Kaplan, Marianna Nicodem, Parvesh Kumar, Spenser Short, Kelly Bridgham, Larry Harshyne, Joseph Curry

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Macrophages are highly plastic cells central to pathogen removal, tissue regeneration, and inflammation, making them key targets in biomaterial design for improved clinical outcomes. Foreign body responses (FBRs) to implanted biomaterials often involve excessive macrophage-mediated inflammation, leading to fibrotic encapsulation, infection, and implant failure. Advances in tissue engineering demonstrate that macrophage polarization - the transition from pro-inflammatory M1 to anti-inflammatory M2 phenotypes - can be influenced by biomaterial properties to mitigate these responses and enhance regeneration. This review synthesizes the relationship between biomaterial properties, such as surface chemistry, structure, and stiffness, and their ability to modulate macrophage behavior. Key innovations, …

A Mean Field Theory For Pulse-Coupled Neural Oscillators Based On The Spike Time Response Curve, Carmen C. Canavier

School of Medicine Faculty Publications

A mean field method for pulse-coupled oscillators with delays used a self-connected oscillator to represent a synchronous cluster of N - 1 oscillators and a single oscillator assumed to be perturbed from the cluster. A periodic train of biexponential conductance input was divided into a tonic and a phasic component representing the mean field input. A single cycle of the phasic conductance from the cluster was applied to the single oscillator embedded in the tonic component at different phases to measure the change in the cycle length in which the perturbation was initiated, that is, the first-order phase response curve …

Determining The Bioaccumulation Of Minor Cannabinoids In Zebrafish Larvae, Kamdyn A. Holt

Honors Theses

Due to the increasing prevalence of cannabis product availability and usage in the modern United States, particularly among pregnant individuals, evaluating the bioaccumulation of minor cannabinoids to further understand the adverse effects of cannabinoids during early development is critical. This study quantitated the uptake of eight minor cannabinoids ((∆8-tetrahydrocannabinol (∆8-THC), ∆9-THC, ∆10-THC, cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), tetrahydrocannabivarin (THCV), and hexahydrocannabinol (HHC)) in zebrafish larvae following water-borne 2 µM exposures from 6 to 96 hours post fertilization (hpf). Larvae were homogenized at 96 hpf and analyzed using a gas chromatography- mass spectrometry (GC-MS) method developed in this study. Bioconcentration …

Fluorescent Labeling And Size-Dependent Uptake Of Mesoporous Silica Nanoparticles In Ovarian Cancer Tumor Spheroids, Kimberly R. Berardis

Honors Scholar Theses

Ovarian cancer is the most lethal gynecologic malignancy, with most patients presenting at an advanced stage. While surgical debulking improves survival, nonresectable tumors (<1 cm) contribute significantly to morbidity and remain difficult to treat. Nanocarrier-based drug delivery systems offer an innovative approach to targeted therapy and palliation. In vivo models have demonstrated that intraperitoneally delivered mesoporous silica nanoparticles (MSNs) preferentially accumulate in tumors with low systemic exposure, enabling targeted chemo- and radiotherapy.

MSNs are particularly suited for radiotherapeutic delivery, as their strong interactions with tumor extracellular matrices drive selective uptake. Additionally, they exhibit excellent stability under neutron flux, allowing for loading with stable isotopes and irradiation immediately prior to administration. High radionuclide retention after dilution further minimizes systemic exposure and toxicity.

A key …

Optimization Of Reaction Conditions For Synthesizing Kasa-Targeting Drug Candidates For Tuberculosis Treatment, Megan A. Baxter

Research and Creativity Symposium

Tuberculosis (TB) remains a global health challenge, with increasing drug resistance pressing for the development of novel treatments. KasA, a key enzyme in mycobacterial fatty acid biosynthesis, is a promising drug target for TB treatment. This research focuses on the design and synthesis of potential KasA inhibitors, specifically optimizing reaction conditions to efficiently produce 1-methyl-6-aminoindazole. This molecule is an intermediate in the synthesis of drugs targeting TB. Characterization of synthesized compounds is performed using NMR, mass spectrometry, and gas chromatography to confirm structure and purity. The first step involved optimizing the solvent and base for the methylation of nitroindazole. We …

Structural Insights Into The Function, Dysfunction And Modulation Of Kv3 Channels, Manuel Covarrubias, Qiansheng Liang, Linh Nguyen-Phuong, Kyle J. Kennedy, Tyler D. Alexander, Ms, Andrew Sam

Department of Neuroscience Faculty Papers

The third subfamily of voltage-gated K⁺ (Kv) channels includes four members, Kv3.1, Kv3.2, Kv3.3 and Kv3.4. Fast gating and activation at relatively depolarized membrane potentials allows Kv3 channels to be major drivers of fast action potential repolarization in the nervous system. Consequently, they help determine the fast-spiking phenotype of inhibitory interneurons and regulate fast synaptic transmission at glutamatergic synapses and the neuromuscular junction. Recent studies from our group and a team of collaborators have used cryo-EM to demonstrate the surprising gating role of the Kv3.1 cytoplasmic T1 domain, the structural basis of a developmental epileptic encephalopathy caused by the …

Lateral Flow Immunoassay Test Strips And Vibrational Spectroscopy For Mobile Detection Of Fentanyl, Sophia Rau

D.U.Quark

There is an increasing number of opioid-related crime scenes, resulting in more evidence that must be tested in a forensic laboratory. New fentanyl analogs are constantly being created, posing significant challenges for drug identification. This increase in drug-related crime and new substances cannot be effectively managed using current forensic technologies. There is a need for on-scene substance testing of unknown substances to improve the speed of testing of collected evidence and for the safety of responders. This review evaluates the impacts of fentanyl test strips, infrared absorption spectrometers, and surface-enhanced Raman scattering spectrometers as portable forensic instruments. The development and …

Studies To Understand The Stability And Liabilities Of Legumain-Cleavable Antibody-Drug Conjugates, Michele Yi

Undergraduate Honors Theses

Antibody-drug conjugates (ADCs) offer targeted drug delivery of potent cytotoxic payloads, minimizing systemic toxicity. However, the stability of the linker is integral to ensure that there is minimal off-target payload release and little systemic toxicity. This study analyzes the physical and biological stability of our new legumain-cleavable vs traditional cathepsin-cleavable antibody-drug conjugates (ADCs), with a focus on hydrophobicity, thermal stability, aggregation, and biological payload release. Our findings indicate that decreased hydrophobicity of the legumain-cleavable ADCs compared to cathepsin-cleavable ADCs is correlated with decreased aggregation (predicting lower uptake by liver macrophages and therefore slower clearance and less systemic toxicity) and lower …

The Analysis Of Reference Standard Storage Failures Through The Use Of Ibuprofen, Hope Vonder Brink

Honors Projects

Reference standards are commonly used in drug chemistry. They are used to calibrate the instruments and serve as a known point of reference for analysts’ ability to compare unknowns. Drugs can degrade over time or through environmental factors, causing contaminants to be present. In the event of environmental degradation while in storage, such as the exposure to high heat, it would be beneficial to have a database of known breakdown products in common drug reference standards for analysts’ reference. Using ibuprofen as an exemplar drug, this study attempted to identify the thermal breakdown products of ibuprofen and introduce the proposed …

Editorial: Women In Science: Allergy Research, Gemma Carreras-Badosa, Vanesa Esteban, Vivian Hernandez-Trujillo, Elina Toskala, Manali Mukherjee, Saba Al Heialy, Karin Fieten

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

No abstract provided.

5-Ht Receptors: Pharmacology And Functional Selectivity, Benjamin R. Cummins, Gerald B. Billac, David E. Nichols, Charles D. Nichols

School of Medicine Faculty Publications

Serotonin 5-HT receptors were one of the first serotonin receptors to be pharmacologically characterized. In mammals, they are expressed throughout the body in nearly every cell and tissue type, with the highest density in cortical layer V of the brain. They are involved in several aspects of normal physiological processes and behaviors and have been implicated in the etiology of neuropsychiatric diseases such as schizophrenia. Atypical antipsychotics have targeted blockade of 5-HT receptors as part of their therapeutic mechanism. More recently, 5-HT receptors have come to prominence for their role as the primary target for psychedelic drugs, which activate this …