Mutations in the DNA of somatic cells, resulting from inaccuracies in DNA<br/>replication or exposure to harsh conditions (ionizing radiation, carcinogens), may be<br/>loss-of-function mutations, and the compounding of these mutations can lead to cancer.<br/>Such mutations can come in the form of thymine dimers, N-𝛽 glycosyl bond hydrolysis,<br/>oxidation by hydrogen peroxide or other radicals, and deamination of cytosine to uracil.<br/>However, many cells possess the machinery to counteract the deleterious effects of<br/>such mutations. While eukaryotic DNA repair enzymes decrease the incidence of<br/>mutations from 1 mistake per 10^7 nucleotides to 1 mistake per 10^9 nucleotides, these<br/>mutations, however sparse, are problematic. Of particular interest is a mutation in which<br/>uracil is incorporated into DNA, either by spontaneous deamination of cysteine or<br/>misincorporation. Such mutations occur about one in every 107 cytidine residues in 24<br/>hours. DNA uracil glycosylase (UDG) recognizes these mutations and cleaves the<br/>glycosidic bond, creating an abasic site. However, the rate of this form of DNA repair<br/>varies, depending on the nucleotides that surround the uracil. Most enzyme-DNA<br/>interactions depend on the sequence of DNA (which may change the duplex twist),<br/>even if they only bind to the sugar-phosphate backbone. In the mechanism of uracil<br/>excision, UDG flips the uracil out of the DNA double helix, and this step may be<br/>impaired by base pairs that neighbor the uracil. The deformability of certain regions of<br/>DNA may facilitate this step in the mechanism, causing these regions to be less<br/>mutable. In DNA, base stacking, a form of van der Waals forces between the aromatic<br/>nucleic bases, may make these uracil inclusions more difficult to excise. These regions,<br/>stabilized by base stacking interactions, may be less susceptible to repair by<br/>glycosylases such as UDG, and thus, more prone to mutation.

The COVID-19 pandemic has resulted in preventative measures and has led to extensive changes in lifestyle for the vast majority of the American population. As the pandemic progresses, a growing amount of evidence shows that minority groups, such as the Deaf community, are often disproportionately and uniquely affected. Deaf people are directly affected in their ability to personally socialize and continue with daily routines. More specifically, this can constitute their ability to meet new people, connect with friends/family, and to perform in their work or learning environment. It also may result in further mental health changes and an increased reliance on technology. The impact of COVID-19 on the Deaf community in clinical settings must also be considered. This includes changes in policies for in-person interpreters and a rise in telehealth. Often, these effects can be representative of the pre-existing low health literacy, frequency of miscommunication, poor treatment, and the inconvenience felt by Deaf people when trying to access healthcare. Ultimately, these effects on the Deaf community must be taken into account when attempting to create a full picture of the societal shift caused by COVID-19.

The Founders lab is a year-long program that gives its students an opportunity to participate in a unique team-based, experiential Barrett honors thesis project to design and apply marketing and sales strategies, as well as business and financial models to start up and launch a new business. This honors thesis project focuses on increasing the rate of vaccination outcomes in a country where people are increasingly busy (less time) and unwilling to get a needle through a new business venture that provides a service that brings vaccinations straight to businesses, making them available for their employees. Through our work with the Founders Lab, our team was able to create this pitch deck.

Stardust grains can provide useful information about the Solar System environment before the Sun was born. Stardust grains show distinct isotopic compositions that indicate their origins, like the atmospheres of red giant stars, asymptotic giant branch stars, and supernovae (e.g., Bose et al. 2010). It has been argued that some stardust grains likely condensed in classical nova outbursts (e.g., Amari et al. 2001). These nova candidate grains contain 13C, 15N and 17O-rich nuclides which are produced by proton burning. However, these nuclides alone cannot constrain the stellar source of nova candidate grains. Nova ejecta is rich in 7Be that decays to 7Li (which has a half-life of ~53 days). I want to measure 6,7Li isotopes in nova candidate grains using the NanoSIMS 50L (nanoscale secondary ion mass spectrometry) to establish their nova origins without ambiguity. Several stardust grains that are nova candidate grains were identified in meteorite Acfer 094 on the basis of their oxygen isotopes. The identified silicate and oxide stardust grains are <500 nm in size and exist in the meteorite surrounded by meteoritic silicates. Therefore, 6,7Li isotopic measurements on these grains are hindered because of the large 300-500 nm oxygen ion beam in the NanoSIMS. I devised a methodology to isolate stardust grains by performing Focused Ion Beam milling with the FIB – Nova 200 NanoLab (FEI) instrument. We proved that the current FIB instrument cannot be used to prepare stardust grains smaller than 1 𝜇m due to lacking capabilities of the FIB. For future analyses, we could either use the same milling technique with the new and improved FIB – Helios 5 UX or use the recently constructed duoplasmatron on the NanoSIMS that can achieve a size of ~75 nm oxygen ion beam.

Traumatic brain injury (TBI) is a widespread health issue that affects approximately 1.7 million lives per year. The effects of TBI go past the incident of primary injury, as chronic damage can follow for years and cause irreversible neurodegeneration. A potential strategy for repair that has been studied is cell transplantation, as neural stem cells improve neurological function. While promising, neural stem cell transplantation presents challenges due to a relatively low survival rate post-implantation and issues with determining the optimal method of transplantation. Shear-thinning hydrogels are a type of hydrogel whose linkages break when under shear stress, exhibiting viscous flow, but reform and recover upon relaxation. Such properties allow them to be easily injected for minimally invasive delivery, while also shielding encapsulated cells from high shear forces, which would normally degrade the function and viability of such cells. As such, it is salient to research whether shear-thinning hydrogels are feasible candidates in neural cell transplantation applications for neuroregenerative medicine. In this honors thesis, shear-thinning hydrogels were formed through guest-host interactions of adamantane modified HA (guest ad-HA) and beta-cyclodextrin modified HA (host CD-HA). The purpose of the study was to characterize the injection force profile of different weight percentages of the HA shear-thinning hydrogel. The break force and average glide force were also compared between the differing weight percentages. By understanding the force exerted on the hydrogel when being injected, we could characterize how neural cells may respond to encapsulation and injection within HA shear-thinning hydrogels. We identified that 5% weight HA hydrogel required greater injection force than 4% weight HA hydrogel to be fully delivered. Such contexts are valuable, as this implies that higher weight percentage gels impart higher shear forces on encapsulated cells than lower weight gels. Further study is required to optimize our injection force system’s sensitivity and to investigate if cell encapsulation increases the force required for injection.

There are many challenges in designing neuroprostheses and one of them is to maintain proper axon selectivity in all situations. This project is based on an electrode that is implanted into a fascicle in a peripheral nerve and used to provide tactile sensory feedback of a prosthetic arm. This fascicle can undergo mechanical deformation during every day motion. This work aims to characterize the effect of fascicle deformation on axon selectivity and recruitment when electrically stimulated using hybrid modeling. The main framework consists of combining finite element modeling (FEM) and simulation environment NEURON. A suite of programs was developed to first populate a fascicle with axons followed by deforming the fascicle and rearranging axons accordingly. A model of the fascicle with an implanted electrode is simulated to find the electrical potential profile through FEM. The potential profile is then used to compare which axons are activated in the two conformations of the fascicle using NERUON.

Colorimetric assays are an important tool in point-of-care testing that offers several advantages to traditional testing methods such as rapid response times and inexpensive costs. A factor that currently limits the portability and accessibility of these assays are methods that can objectively determine the results of these assays. Current solutions consist of creating a test reader that standardizes the conditions the strip is under before being measured in some way. However, this increases the cost and decreases the portability of these assays. The focus of this study is to create a machine learning algorithm that can objectively determine results of colorimetric assays under varying conditions. To ensure the flexibility of a model to several types of colorimetric assays, three models were trained on the same convolutional neural network with different datasets. The images these models are trained on consist of positive and negative images of ETG, fentanyl, and HPV Antibodies test strips taken under different lighting and background conditions. A fourth model is trained on an image set composed of all three strip types. The results from these models show it is able to predict positive and negative results to a high level of accuracy.

This research endeavor explores the 1964 reasoning of Irish physicist John Bell and how it pertains to the provoking Einstein-Podolsky-Rosen Paradox. It is necessary to establish the machinations of formalisms ranging from conservation laws to quantum mechanical principles. The notion that locality is unable to be reconciled with the quantum paradigm is upheld through analysis and the subsequent Aspect experiments in the years 1980-1982. No matter the complexity, any local hidden variable theory is incompatible with the formulation of standard quantum mechanics. A number of strikingly ambiguous and abstract concepts are addressed in this pursuit to deduce quantum's validity, including separability and reality. `Elements of reality' characteristic of unique spaces are defined using basis terminology and logic from EPR. The discussion draws directly from Bell's succinct 1964 Physics 1 paper as well as numerous other useful sources. The fundamental principle and insight gleaned is that quantum physics is indeed nonlocal; the door into its metaphysical and philosophical implications has long since been opened. Yet the nexus of information pertaining to Bell's inequality and EPR logic does nothing but assert the impeccable success of quantum physics' ability to describe nature.

This analysis explores what the time needed to harden, and time needed to degrade is of a PLGA bead, as well as whether the size of the needle injecting the bead and the addition of a drug (Vismodegib) may affect these variables. Polymer degradation and hardening are critical to understand for the polymer’s use in clinical settings, as these factors help determine the patients’ and healthcare providers’ use of the drug and estimated treatment time. Based on the literature, it is expected that the natural logarithmic polymer mass degradation forms a linear relationship to time. Polymer hardening was tested by taking video recordings of gelatin plates as they are injected with microneedles and performing RGB analysis on the polymer “beads” created. Our results for the polymer degradation experiments showed that the polymer hardened for all solutions and trials within approximately 1 minute, presenting a small amount of time in which the patient would have to remain motionless in the affected area. Both polymer bead size and drug concentration may have had a modest impact on the hardening time experiments, while bead size may affect the time required for the polymer to degrade. Based on the results, the polymer degradation is expected to last multiple weeks, which may allow for the polymer to be used as a long-term drug delivery system in treatment of basal cell carcinoma.

The use of enzyme-catalyst interfaces is underexplored in the field of biocatalysis, particularly in studies on enabling novel reactivity of enzymes. For this thesis, the HaloTag® protein tagging platform was proposed as a bioconjugation method for a pinacol coupling reaction using lipases, as a model for novel reactivities proceeding via ketyl radical intermediates and hydrogen-bonding-facilitated redox attenuation. After an initial lipase screening of 9 lipases, one lipase (Candida rugosa) was found to perform the pinacol coupling of p-anisaldehyde under standard conditions (fluorescein and 530nm light, 3% yield). Based on a retrosynthetic analysis for the photocatalyst-incorporated HaloTag® linker, the intermediates haloamine 1 and aldehyde 6 were synthesized. Further experiments are underway or planned to complete linker synthesis and conduct pinacol coupling experiments with a bioconjugated system. This project underscores the promising biocatalytic promiscuity of lipases for performing reactions proceeding through ketyl radical intermediates, as well as the underdeveloped potential of incorporating bioengineering principles like bioconjugation into biocatalysis to overcome kinetic barriers to electron transfer and optimize biocatalytic reactions.