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Modifying Xanomeline’s Toxic Properties on Human Muscarinic Acetylcholine M1-M4 Receptors
No full textMuscarinic acetylcholine receptor agonists such as Xanomeline (C₁₄H₂₃N₃OS) have demonstrated therapeutic efficacy in schizophrenia by targeting M1 and M4 receptors, yet significant off-target interactions with M2 and M3 receptors contribute to adverse cardiovascular and urinary effects. Cobenfy is a particular drug that pairs Xanomeline with Trospium chloride to mitigate peripheral effects, yet limitations remain. This study applied computational docking and structure-based design to modify Xanomeline’s molecular architecture to enhance selectivity for M1 and M4 while reducing affinity for M2 and M3. Iterative modifications included heteroatom substitutions, polar cap additions, backbone constraints, and linker geometry adjustments. Binding affinities across receptor subtypes were evaluated using Maestro Schrodinger and ADMET analyses assessed predicted toxicity, absorption, and pharmacokinetics. Modified molecules demonstrated retained or enhanced M1/M4 binding and significantly reduced M2/M3 interactions with improved toxicity profiles. These findings suggest that rational multi-target drug design can optimize receptor selectivity and safety profiles in schizophrenia therapeutics and provide a framework for future computational and experimental follow-up
Innovative Temperature-Responsive Fluorescent Hydrogel for Smart Windows and Advanced Environmental Sensing
No full textThe presented study described the synthesis, characterization, and temperature-responsive fluorescence behaviour of a dual-chromophore double-network hydrogel (DNH) that incorporates poly(N-isopropylacrylamide) (PNIPAM) covalently crosslinked with fluorescein diacrylate (FL-DA), as a primary network, followed by the formation of a secondary poly(2-acrylamido-2-methylpropanesulphonic acid) (PAMPS) network incorporating fluorene diacrylate (FR-DA) as a second covalently-integrated chromophore. The thermoresponsive PNIPAM/PAMPS hydrogel had a dual-wavelength signaling and mechanically robust structure that could be used for environmental sensing, innovative thermal coatings, and smart surface applications. The temperature-dependent fluorescence spectra were recorded from 5 °C to 60 °C and exhibited two emission bands characteristic of the two chromophores. The increase in temperature produced a decrease in band intensity and a red shift. The short-wave emission characteristic of FR-DA exhibited wavelength shifts of 9 nm and 8 nm, corresponding to overall increases of 2.91% and 2.49%, respectively. FL-DA exhibited a long-wave emission peak that shifted to red by 14 nm, from 511 to 525 nm, corresponding to a 2.74% increase in wavelength over the 5 to 60 OC temperature range. The one-way ANOVA showed F(11, 3600) = 2.20, p \u3c 0.012. A post hoc Tukey test confirmed that the control condition (25 °C) differed across all temperature groups. The increase in temperature altered the degree of polymer hydration, increased chain mobility, and altered chromophore orientation, leading to enhanced non-radiative relaxation and spectral changes. The PNIPAM network undergoes a coil-to-globule transition, which produces a pronounced inflection in the overall fluorescence behavior
Designing a Low-Cost, Wearable System to Accurately Detect Ground Contact Time Asymmetries Between Each Foot During Outdoor Running
No full textRunning biomechanics, including ground contact time (GCT) and gait asymmetry, play crucial roles in performance and injury risk (Moore et al., 2019). GCT, in particular, is a critical metric for understanding stride efficiency, optimizing training, and preventing injuries (Weber et al., 2024). However, current methods for measuring these parameters, such as motion capture systems or stationary force plates, are expensive and poorly suited for real-world environments (Dunn et al., 2020). This study investigated whether a low-cost, outdoor-capable wearable system could accurately measure GCT and detect gait asymmetries during running. Two identical IMU-based devices were built and attached to each foot, and their GCT measurements were compared to high-speed video analysis across multiple terrains, distances, and running speeds. Device-measured GCT values were evaluated using one-sample z-tests for trials with at least 30 strides and independent t-tests for trials with fewer than 30 strides. Results showed that the device consistently overestimated GCT compared to video validation, with almost all z-tests producing extremely large z-scores (p \u3c .001), indicating statistically significant disagreement between the device and the validated measurements. Independent t-tests revealed inconsistent detection of left-right asymmetry, with only one trial showing comparable values between the left (M = .3275, SD = .0262) and right (M = .3314, SD = 0.0261) sides. Despite these outcomes, the project highlights clear areas for improving algorithmic thresholds, sensor placement, and hardware design in future low-cost wearable systems. The results contribute to the broader effort to develop accessible biomechanical tools for real-world environments
Modulating Micrococcus luteus Biofilm Repopulation via Aloe vera-Infused Silica Aerogels and Red Light Exposure
No full textChronic wounds present a significant healthcare burden, increasing infection risk, mortality, and healthcare costs (Parnell & Volk, 2019; Sen, 2025). Micrococcus luteus is a non-pathogenic bacterium that can inhibit pathogenic bacterial colonization of the skin\u27s epithelial layer through microbial competition and promote healthy skin function, underscoring its appropriate use in various healing environments (Heo et al., 2023; McLoughlin et al., 2024). The purpose of this study was to determine whether the combination of Aloe-vera-infused silica aerogels and 660nm red light therapy would enhance M. luteus repopulation in a modified scratch-based biofilm regrowth assay. M. luteus cultures were diluted in Tryptic Soy Broth and aspirated into 96-well plates for uniform biofilm formation. A scratch was made into the biofilm using a sterile micropipette tip, and wells were put into four groups: control, Aloe-vera infused aerogel only, red light therapy only, and combined red light + aerogel. Plates were incubated at 25°C, and images were taken at 0 and 24 hours for ImageJ analysis to determine the percent change in scratch width during biofilm repopulation. A one-way ANOVA showed a statistically significant difference in mean percent change in scratch across groups, F(3, 116) = 61.34, p \u3c 0.001. The combined treatment of aerogel and red light exhibited the highest percent change in scratch, followed by red light therapy alone, aerogel alone, and the control. These findings suggest that porous aerogel scaffolds combined with photobiomodulation of a skin commensal may support the development of microbiome-based, non-invasive wound care modalities
Discover the Heartburn Difference
No full textHeartburn is a big problem in the US, about 60 million people experience it at least once a month. The hypothesis states that at least one average time it takes the solution to reach neutral is different from the others. While experimenting, multiple antacids were tested to see how long it would take to neutralize an artificial stomach acid solution. This artificial stomach acid consists of 450 mL of distilled water, 50 mL of hydrochloric acid (0.1M), and 4.3 g of sodium chloride (0.150M), the pH measures within the range of the acid found in the stomach, 2.6-2.9. The dosage of the antacid listed on the bottle was added to the solution, pH was then measured every 3 minutes using an electronic pH sensor. It was measured until it reached neutralization, which is a pH of 7. The results have shown that not every antacid tested was successful at neutralizing the pH, some remained at 2.6-2.9 the entire time. The successful ones were TUMS, Equate TUMS, Pepto Bismol, and baking soda. After performing an ANOVA statistics test, results showed that there was a significant difference between test subjects. This means the hypothesis is supported, some antacids work faster than others at neutralizing the solution. Overall, baking soda was the fastest with an average of 13 minutes. This shows that a household ingredient works faster than medication to relieve heartburn. Future work includes testing more medications labeled for treating heartburn and household remedies
CycleGuard
No full textThe main problem we all found was storage of bikes in small spaces, especially in urban areas where finding room for the bike is always a problem. The existing wall-mounted racks among other solutions rarely help in utilizing space in small environments. By researching products and patents, we sought to design a space-saving bike storage solution that works in apartments, bedrooms, and garages. A compact design, easily adjustable, more affordable, and adaptable in various spaces is our design. Testing 3D printed prototypes, improvements will be designed upon users\u27 feedback. The problem it solves: Our solution addresses the growing need for bike storage as bike ownership increases in cities
Sizzle - Free Survival
No full textCurrent safety devices that aid with escaping upper-level house fires are becoming less accessible to vulnerable populations. The purpose of this project is to create a device that is efficient and accessible to the elderly, disabled, and children to provide a safer and more efficient alternative to current escape method
Defining the Role of Sphingosine Kinase 2 (SphK2) in Gastric Signet Ring Cell Carcinoma (GSRCC)
No full textGastric signet ring cell carcinoma (GSRCC) is a particularly aggressive subtype of gastric cancer (GC) that is defined by its distinct signet ring cell morphology. GSRCC is associated with being more common in younger patients, its advanced stages by the time of diagnosis, and a poor prognosis compared to other GC subtypes. Additionally, GSRCC is somewhat resistant to standard chemotherapy treatments, highlighting the need for novice approaches to its treatment. Sphingosine kinase 2 (SphK2), a tumor promoting enzyme has emerged as a potential therapeutic target due to its role in boosting cancer cell proliferation, migration, and survival. This study aimed to investigate the role of SphK2 in GSRCC using shRNA-mediated knockdown (KD). We generated stable SphK2 KD AGS and KATO III GSRCC cell lines using lentiviral shRNA transduction. The efficacy of shRNA targeting was confirmed by antibiotic screening and western blot analysis, demonstrating a significant reduction in SphK2 protein levels. The effects of SphK2 loss on cell proliferation, migration, and invasion were assessed using in vitro assays, including MTT assays to measure cell viability and proliferation, wound healing assays to evaluate cell migration, and transwell assays to assess invasive capacity. Our results demonstrate that SphK2 loss significantly reduces GSRCC cell proliferation, migration, and invasion compared to control cells. These findings highlight the potential of targeting SphK2 as a novel therapeutic strategy for GSRCC, warranting further investigation into the efficacy of SphK2 inhibitors, such as Opaganib, in preclinical and clinical settings
The Impact of the pH on the Concentration of the Released Ogremorphin-Mimic Dye from Double-Network Hydrogels for Glioblastoma Localized Treatment
No full textGlioblastoma (GBM), a highly aggressive brain cancer, poses significant treatment challenges due to its complex microenvironment and low therapeutic efficacy of current approaches. Localized drug delivery systems hold promise for improving therapeutic outcomes. This study investigated the release of an Ogremorphin (OGM)-mimic dye from a double-network hydrogel (DNH) designed for GBM therapy, hypothesizing that the hydrogel would have a steady release of the mimic drug at a lower pH. A polyacrylamide alginate DNH was synthesized, and its swelling behavior, drug-loading efficiency, and release dynamics were evaluated. The hydrogel’s swelling degree was calculated after 72 hours of immersion in distilled water. Drug loading efficiency was determined by UV-Vis spectroscopy, measuring the residual concentration of a fluorescein solution. Dye release was assessed under various pH conditions from 4-8, simulating the tumor microenvironment (TME), with cumulative release profiles analyzed over 228 hours. The hydrogel exhibited a swelling degree of 135.8% and a drug loading efficiency of 87.4%. Drug release was pH-dependent, with minimal release at acidic pH (4 and 5) due to a compact polymer network and an increased release at alkaline pH 8, driven by network swelling. Statistical results from the one-way ANOVA test showed that F(4, 85) = 17.72, p \u3c .001. A post-hoc Tukey test showed a significant difference between the different pH levels. Optimized formulations at pH 4- 6 could minimize burst release, sustain therapeutic levels, and improve patient outcomes. These findings demonstrated the hydrogel’s pH-responsive properties made it a strong candidate for GBM therapy
Designing a UV-C Powered Self-Disinfecting Makeup Applicator
No full textMakeup is an important part of many women’s lives. However, the applicators used to apply these products harvest a lot of bacteria, causing skin infections, acne, and other harmful effects. Washing these applicators is essential, however, data has shown that many users fail to do so. UV-C disinfection systems have become increasingly popular for their fast, effective nature. The purpose of this study was to expand on these systems by placing one inside a UV-C transparent silicone makeup applicator to ensure more complete, frequent disinfection. It was hypothesized that when this applicator was used, bacteria levels on the applicator would decrease by at least two log reductions because UV-C has been shown to decrease bacteria over four log reductions, and the silicone used has UV-C transparency levels between 90-95%. To test this, a prototype was created by soldering a 16-chip UV-C LED to a set of wires and pulling them through the barrel of the applicator. They were soldered to a power cord and the UV-transparent silicone tip was glued to the top. 60 total trials were performed: 30 trials were tested by infecting the applicator tip with Escherichia coli, and 30 trials were tested by disinfecting the tip with UV-C. The results showed an 85.6% reduction in bacteria. A one-way ANOVA test revealed a statistically significant reduction in mean CFUs between the two groups (F(1, 58) = 27.36, p= \u3c0.001). However, the applicator did not reach 99% reduction, meaning the alternate hypothesis was only partially supported