In the paper "Planting Undetectable Backdoors in Machine Learning Models" by Goldwasser et al (arXiv:2204:06974), the authors establish the notion of "black-box undetectability" for machine learning models and prove it in many cases. This is a backdoor that is undetectable by merely looking at inputs and outputs of the model. The paper also introduces the concept of "white-box undetectability."  We aim to consider this stronger notion and outline how even with the knowledge of entire model weights, there may be undetectable backdoors in a model. More specifically, we establish an idea where one takes an innocuous model (say a Multi-Layer-Perceptron model) and enlarges it by adding "dummy" edges and using appropriate non-linear activation functions to effectively place a backdoor in the model. In our project, we establish a proof of concept by backdooring an MNIST classifier.

Traumatic spinal cord injuries (SCI) are devastating and lead to permanent and irreversible functional impairments. While the primary injury causes immediate damage, the progression of secondary injury is characterized by neuroinflammation. Microglia, the resident immune cells of the central nervous system, can further contribute to tissue damage. Although extensive research has been done focusing on microglial activation at the lesion site, their presence in regions distal to the injury at the chronic stage (4-6 weeks after injury) remains understudied. Here, we aimed to investigate the correlation between microglial activation in the lumbar region caudal to the injury site and cervical region rostral to the injury site with different grades of injury severity. We hypothesize that as injury severity increases, microglial activation in the surrounding region will increase as well. Contusion injuries were created at T8/9 in Long Evans rats using three impact forces: 200 kilodynes, 200 kilodynes and 2-second dwell time, and 250 kilodynes and 2-second dwell time. After 8 weeks post injury, our histological analyses revealed a significant increase in microglial activation in the caudal region, with activation levels reaching 136.03%, 205.08%, and 254.81% of sham levels in the 200, 200/2s, and 250/2s groups, respectively (n = 5/group). The most severe injury had the highest microglial inflammation. We anticipate a similar trend in the cervical region rostral to the injury. Combined, our data indicate a significant microglial response in regions distal to the injury, which correlates with impaired functional recovery. We believe that modulating microglial responses in the regions distal to the site of SCI could provide a novel approach to reducing chronic secondary injury and enhancing recovery following traumatic SCI.

The tongue base is a key structure in respiration and swallowing and morphological and functional adaptations to its volumetric changes are largely unknown. Thus, addressing this gap could enhance the understanding of breathing and swallowing disorders in the enlarged and reduced tongue base. Twelve Yucatan minipigs 8-to-9-month-old (half each sex) were analyzed. Six minipigs received a high-caloric chow pellet to reach a BMI>50 (enlargement group), while the others underwent surgical partial tongue base ablation (reduction group). Five weeks after surgery all minipigs were scanned using magnetic resonance imaging (MRI) synchronized with respiratory cycle gating. Mid-sagittal cross-sectional areas of the velopharyngeal and oropharyngeal airways, and retroglossal space during inspiration and expiration were quantified using ITK-SNAP. The volumes were also calculated using segmentation techniques. These measurements were compared between the enlargement and reduction groups in the inspiratory and expiratory cross-sectional areas to determine differences. Extrapolating from one minipig from the enlarged group observed larger mid-sagittal cross-sectional areas of the interested regions compared to the reduction group. The enlarged minipig observed greater differences in range and larger averages and medians for each cross-sectional volume. The enlargement group also had slower inspiratory and expiratory rates than the reduced group. Observations from one minipig from the reduced group were observed to have smaller cross-sectional areas, medians, and averages for all interested regions. Additionally, the reduced minipig had more frequent respiratory rates. The current analysis of the sagittal views from the obese enlarged tongue base versus the reduced tongue base minipigs revealed larger volumes within the enlarged group. This pattern currently suggests enlarged tongue base minipigs with larger cross-sectional volumes, but less inspiratory and expiratory rates. However, the reduced tongue base minipigs are anticipated to have smaller cross-sectional volumes and more frequent respiratory rates compared to the enlarged group.

The stimulation of the genioglossus muscle may prevent upper airway collapse in breathing disorders such as obstructive sleep apnea (OSA). Thus, the present study was to analyze the 3D-changes of the tongue base by electric stimulation of genioglossal muscle in relation to volumetric alterations of the tongue base in minipigs. Twenty 8-to-9-month-old Yucatan minipigs were used. Of them, 8 were controls, and 12 were experimental. Each experimental same-sex sibling pair was randomly assigned: 1. Normal-weight having surgical tongue base volumetric reduction. 2. Enlargement having significant obesity, BMI>50. All minipigs received surgical implantation of eight 2mm ultrasonic crystals in a cubic-shaped array in the tongue base. The distance change between each crystal pair indicated dimensional deformations for lengths, widths, and thicknesses responding to the stimulation. Increased distances indicated elongations while decreased indicated shortenings. Stimulations to the left genioglossal muscle were ramping up in range of 10-40V to reach the maximal amplitudes (tetany). Stimulation of the genioglossus muscle in controls induced left lengthening, anterior thickening and overall widening along with posterior thinning and right shortening. In contrast, the reduction group showed thickening and widening with left lengthening and minor right shortening. Elongations in the reduction group were larger than those in the control group (p<0.05). The enlargement group showed decreased dorso-ventral lengths compared to those of the control and reduction groups (p<0.05), along with antero-posterior thickening and widening. Stimulation of the genioglossus muscle induces distinctive deformational patterns between the normal and volumetric-altered tongue bases. For instance, shortening in length in the enlarged tongue due to obesity may suggest retraction of the tongue base inducing narrowing of the oropharyngeal airway. These results may contribute to understanding kinematic adaptations in the respiratory dynamics in relation to the volumetric alterations of the tongue base, a current approach to treat moderate and severe OSA. 

Cervical spinal cord injuries (SCIs) often result in impaired locomotion and forelimb mobility. Assessed with a forelimb locomotor scale (FLS), previous research demonstrated improved forelimb locomotion with task-specific physical therapy (PT) training following a unilateral 150 kdyne C6 SCI in a rat model. Improvement in locomotion was calculated using a recovery ratio, which measures the difference in FLS scores normalized to the animal’s baseline score. There was a significant improvement in the recovery ratio (3dpi-14wpi) for animals that underwent task-specific PT training (p ≤ 0.0014). The underlying molecular mechanisms behind this improvement are still unclear. A potential explanation for these functional changes is the task-specific PT-induced increase in brain-derived neurotrophic factor (BDNF) targeted at the injury site. Task-specific PT stimulates neurons, microglia, and astrocytes to release BDNF, promoting neuron survival, growth, and synaptic plasticity. These processes are crucial for mediating the effects of cervical SCI trauma. This study investigates whether BDNF expression in the spinal cord varies in rats that underwent task-specific PT training following cervical SCI. PT-trained rats are hypothesized to have increased BDNF within the spinal cord, especially proximal to the injury site, which would help mitigate SCI trauma and enhance forelimb locomotion and mobility. To this end, we performed immunohistochemistry staining and quantification of BDNF in the spinal cord and compared it across three groups: PT + SCI, SCI-only, and Sham. The expression levels of BDNF in neuronal cells, astrocytes, and microglia were then correlated with their FLS scores to determine if there was a positive correlation between BDNF expression and forelimb locomotion. This would indicate that BDNF supports synaptic plasticity and recovery from SCI-induced trauma.

The aim of this study was to examine the respiratory 3D deformational changes in the tongue base with normal weight and obesity in a minipig model. This study included 6 same-sex sibling pairs (3 pairs each sex) of Yucatan minipigs 8-to-9 months old. Of each pair, one minipig was normal weight with a BMI<35 and the other was fed a special diet reaching a BMI>50 (obese,). While under sedation, eight 2mm ultrasonic piezoelectric crystals with an extended skin button attached to the back were surgically implanted at the base of the tongue in a cubic-shaped arrangement. These crystals represented dorsoventral lengths, anteroposterior widths, and thicknesses. The 3D deformational changes of the tongue base were recorded during respiration using a Sonometric system together with synchronized electromyography and airflow recordings to identify respiratory phases. The amplitudes and durations of each dimensional change within the crystal-defined region concerning inspiration were calculated for 5- consecutive respiratory cycles per minipig. The total respiratory cycle duration was 1.87±0.38s in the normal-weight group and 3.2±1.01s in the obese group (p<0.05).  Similarly, the durations of the inspiratory phase in the normal and obese groups were 0.62±0.36s and 1.19±0.77s respectively (p<0.05). Deformational changes in the normal-weighted group included dorsoventral lengthening, anteroposterior ventral widening with dorsal shortening, and thickening in all dimensions. In contrast, the obese group showed dorsal lengthening with ventral shortening, widening in all dimensions, and anterior thickening with posterior shortening. Overall, larger dynamics were observed in the normal-weighted group compared to the obese group (p<0.05). These results demonstrate that obesity affects tongue base respiratory kinematics, with longer respiratory cycles and decreased deformational changes mainly ventrally and posteriorly. These findings enhance understanding of obesity's impact on the oropharyngeal function, with implications for breathing disorders.

Social expectations are constantly changing, and even subjects typically considered “taboo” are changing as well. Though sex is often seen as a private, maybe even secretive, discussion, this lack of public eye to the true nature of sex can lead to many difficulties in an individual's personal and intimate life through misunderstandings and social expectations. This literature review focuses on possible correlations between behavioral sex therapy treatment (such as guided open communication, and sensate focus) and aspects of unsustainable romantic relationships (such as stonewalling and criticism). Some sexual dysfunctions can arise from emotional difficulties, such as anxiety during or before sexual encounters, lack of enjoyment from one or both partners, or different perceived ideas of what is supposed to happen during sex. These difficulties can translate into daily life in the relationship outside of sex. By treating these dysfunctions there may be a domino effect which impacts the relationship outside of sexual relations, which can improve the relationship overall and lead to a relationship that is more sustainable for all parties involved. Through comparisons of articles on treatments typical in behavioral sex therapy and articles defining aspects of unsustainable relationships, like those published by John Gottman, initial findings support connections between the topics. These positive correlations indicate an innate connection between sexuality and relationships, which could lessen the social stigma that surrounds discussing sex or sexual topics

In this project, we study the order polytopes of generalized snake posets, a particular family of polytopes (geometric shapes with flat sides) defined in recent work by von Bell and coauthors. We specifically investigate triangulations of these polytopes, which are subdivisions of the polytopes into simplicies (arbitrary-dimensional generalizations of the triangle). To do so we examine their secondary polytopes. The secondary polytope of a polytope is a related polytope in which each vertex corresponds to a triangulation of the original polytope and each edge corresponds to a bistellar flip (a specific type of transformation between triangulations), capturing the combinatorial relationships between different triangulations in a geometric object. Von Bell and coauthors conjecture that the secondary polytopes of order polytopes of snake posets have multiple unusually nice properties similar to those of the associahedra, a well-known family of polytopes that admit nice combinatorial descriptions and appear in many areas of mathematics. The overall goal of this project is to prove these conjectures. Collaborating with fellow undergraduates Molly Bradley (University of Pennsylvania), Mario Tomba (Dartmouth), and Katherine Tung (Harvard), I have written code to compute details of the smallest examples of these secondary polytopes, proved related theorems/results, proposed some new conjectures based on observed patterns in the examined examples, and made partial progress towards proving multiple of the von Bell conjectures. This project is ongoing, and we continue to explore multiple ways to approach the conjectures and more broadly understand the secondary polytopes.

Hydrogen sulfide (H₂S), known for its distinct smell of rotten eggs, is recognized as the third endogenous gaseous signaling molecule, alongside nitric oxide and carbon monoxide. Often described as a double-edged sword, H₂S exhibits both cytoprotective and cytotoxic properties depending on the biological context. A 2018 study suggested that H₂S enhances the efficacy of doxorubicin (Dox), an anticancer drug, by promoting apoptosis and reducing colony formation in HepG2 cells, even restoring drug sensitivity in resistant cells. However, my preliminary experiments indicated a protective role of H₂S in HepG2 cells under stress, particularly when treated with NaSH (an H₂S donor). Rather than inducing apoptosis, H₂S appears to support cell proliferation and regulate reactive oxygen species (ROS) production. My research project aims to identify H₂S -dependent pathways in HepG2 cells under oxidative stress. Using Dox as a stress inducer, I conducted viability and cytotoxicity assays, demonstrating that supplementation with 250 µM NaSH at 0 and 12 hours significantly restored cell survival. To investigate the molecular mechanisms, RNA-seq analysis identified 2,996 differentially expressed genes in the H₂S + Dox group compared to Dox alone. Principal component analysis (PCA) revealed distinct transcriptomic profiles, while KEGG enrichment analysis highlighted significant alterations in genes within the PI3K-Akt pathway. To further validate these findings, I plan to perform flow cytometry and western blot analysis. While the role of H₂S continues to be debated, my data suggest a protective function in liver cells against Dox-induced stress via the PI3K-Akt pathway. Understanding these mechanisms could pave the way for new therapeutic strategies aimed at maintaining or increasing H₂S levels to support cell health in diseases characterized by oxidative stress, such as cancer and diabetes.

The effectiveness of a drug candidate depends on its ability to distribute to its target site of action after administration. Thus, a primary concern for drug delivery labs like the Pun lab is preventing drugs from being cleared from the bloodstream by the body's renal system before they are able to accumulate to therapeutic levels at their site of action. In short, one important goal in drug delivery research is to find ways to extend a drug's blood circulation half-life. Conjugating drugs to the large molecular weight molecule polyethylene glycol (PEG) to slow their clearance kinetics is the current gold-standard method, but a crucial drawback is that PEG's large size leads to its potentially toxic buildup in tissues like the liver. To get around this problem, my project aims to develop a drug delivery platform that will allow small molecule drugs to reversibly bind, or in other words "hitchhike" onto human serum albumin (HSA), an abundant protein in blood plasma with an extraordinarily long half-life. At this point in my project, I have successfully synthesized a novel fatty acid monomer with a methacrylate functionality that can be used to copolymerize the monomer with therapeutic small-molecules or peptides to improve their circulation half-life. The next steps will be to copolymerize the fatty acid monomer with pGmMA, a water-soluble polymer, and use biolayer interferometry to test the fatty acid monomer's ability to coordinate to albumin, which will confirm its efficacy as a drug delivery platform. If successful, this project has the potential to provide a generalizable improvement to the pharmacokinetics of various kinds of small-molecule drugs or peptides, enhancing their potency and overall ease of treatment. 

Hypertrophic Cardiomyopathy is the most common form of hereditary heart disease affecting ~1:500 individuals, characterized by progressive thickening of the left ventricular wall. The first mutation linked to this disease was the heterozygous R403Q mutation in human beta-myosin heavy chain (β-MHC). Conflicting reports of contractile kinetics between human myectomy samples vs transgenic mouse and rabbit models motivated us to study the molecular mechanisms of altered contraction in a CRISPR/Cas9 gene edited human inducible pluripotent stem cell line. Following differentiation to cardiomyocytes (hiPSC-CMs) and maturation in culture, we isolated sub-cellular contractile organelles called myofibrils. Myofibril contractile kinetics from this line had slowed force development and cross-bridge detachment, with reduced maximal force compared to the WT line. hiPSC-CMs were cast into fibrin matrices to form three-dimensional, engineered heart tissue (EHT) for measures of twitch force and contractile kinetics. At 1Hz stimulation, heterozygous mutation EHT’s exhibited a hypercontractile phenotype compared to WT EHTs, with slowed relaxation kinetics. Since the penetrance of our heterozygous R403Q hiPSC-CMs is unknown, we are now studying a homozygous iPSC-CM line where 100% of the β-MHC is mutated. This will allow us to assess the direct contribution of the mutation to the disease contractile phenotype. We will repeat the myofibril and EHT measures of contractile properties and perform stopped flow kinetics analysis on isolated myosin to determine ATP turnover and ATP hydrolysis product release rates. This will provide molecular mechanistic insight of the contractile abnormalities, allowing development of therapeutic interventions that specifically target the mechanisms that alter contractile function. 

My project intends to discover a DNA aptamer, a single stranded DNA oligonucleotide, that binds selectively to the protein Interleukin-6 (IL-6). IL-6 has an important role in the immune system response and in excess it is known to cause inflammation. Aptamers exhibit binding affinities like that of antibodies but are ~50 times cheaper to produce. The method of aptamer discovery is through SELEX (Systematic Evolution of Ligands by Exponential Enrichment) which involves the selection from an aptamer library that contains 52N random nucleotide region and constant 5’ and 3’ 18 base pair regions for PCR amplification. Positive and negative selection are completed by incubating aptamer libraries with IL-6 or random protein immobilized on magnetic beads respectively. After each round selected aptamer sequences are amplified with a polymerase chain reaction (PCR) with primers that anneal to the constant regions. Reverse primer has biotin on 5’ end that is used later for strand separation with streptavidin agarose. After each round aptamer pool is going to be sequenced using nanopore sequencing platform till the enrichment of IL-6 specific sequences is observed. Binding will be tested through an enzyme-linked immunosorbent assay (ELISA) using the fam on 3’ end. The end goal of this project is to design a cost-effective method of IL-6 depletion from patients blood, allowing for cost-effective method of treatment for overactive immune system inflammation in sepsis patients.

I investigate the effects of scopolamine-induced cholinergic disruption on the working memory performance of rhesus macaques. Working memory plays a critical role in cognitive function and relies heavily on cholinergic signaling in the brain. To explore this relationship, I designed and implemented a delayed match-to-sample (DMTS) task to optimize the accuracy and reliability of the data collected. The DMTS trials involve three phases: stimulus, delay, and choice. Monkeys are presented with a sample stimulus they must memorize. After a variable delay period of 5 to 30 seconds, they select the target image from a set of options. Performance is tracked by calculating the percentage of correct, incorrect, and omitted responses. Daily DMTS sessions provide longitudinal data on memory performance, allowing me to analyze patterns before and after scopolamine administration. I am also learning to analyze spike-spike coherence to investigate changes in neuronal synchronization associated with memory performance. Upon inducing amnesia-like conditions under scopolamine, an M1 muscarinic antagonist, the delayed match-to-sample task evaluates memory performance under baseline and drug-induced conditions. The primary objective of my project is to understand how scopolamine-induced disruptions affect working memory performance and to investigate the underlying cortical mechanisms involved. Based on existing literature and preliminary observations, I anticipate observing a measurable decline in memory performance following scopolamine administration, with older macaques likely exhibiting more pronounced deficits compared to younger macques. This project aims to contribute to the understanding of how cholinergic mechanisms influence working memory performance and to provide insights into the cognitive impairments associated with neurodegenerative diseases.

Somatosensory neurons innervate the skin, where their peripheral axons detect signals like touch and pain. The neurons relay stimuli to the brain via peripheral axons in the skin and spinal cord axons in the spinal cord. Given their superficial location, somatosensory axons are susceptible to damage. Axon damage can cause tingling, increased pain, or sensory inhibition, and reinnervation in mammals is often slow or incomplete. I use injury models in zebrafish to study the mechanisms of successful axon regeneration in an adult vertebrate with optically accessible skin. I aim to reveal conserved regeneration patterns of somatosensory neurons. Furthermore, I seek to understand the extent of reinnervation success and observe the prevalence of hyperinnervation post-injury. Using in vivo confocal microscopy and adult zebrafish skin models, I created a methodology to capture somatosensory reinnervation over a three-week span following a scale pluck injury. Zebrafish scales separate epidermal and dermal layers of skin, and scale removal induces regeneration of epidermal skin and surrounding dermal tissue. I use transgenic zebrafish with fluorescent labels for dorsal root ganglion DRG neurons and osteoblast cells Tg(p2rx3a:mCherry);Tg(sp7:EGFP). DRG neurons are the primary somatosensory neuron in adult zebrafish, and osteoblasts allow me to view the scale alongside axon reinnervation. For image acquisition, I designed a 3d-printed chamber for zebrafish mounting and intubation within our confocal microscope. For analysis, I developed Image J macros which use threshold analysis to quantify changes in axon density of specific regions of regenerating axons. Dermal axons tend to regenerate first while superficial axons in the epidermis regenerate secondarily in conjunction with the novel scale. To examine skin layer differences, I separate epidermal and dermal layers to compare the reinnervation trends between superficial and dermal axons. With this data, I can gain insight in the regeneration potential of somatosensory neurons.

The tumor microenvironment (TME)—the ecosystem surrounding a tumor—is an important factor that influences the growth of a tumor. Specifically, features of TME may be associated with patients’ survival time, which suggests that further study of TME structures is warranted. This study used the existing METABRIC breast cancer dataset which contains spatial data of cells from tissue samples. Using cox regression, a statistical method, we aimed to analyze general patterns in TME structures to model the relationship between TME and patient survival time. Log cell type proportion and Ripley’s K function, which quantifies cell clustering, were compared in cox regression. We found that log immune cell proportion was associated with decreased patient survival time. These findings suggest that further research to determine the exact relationship between TME structures in breast cancer and patient survival outcomes is important.

VLA-4 is an integrin expressed on immune cells that plays an important role in their extravasation into tissues during an immune response. In the autoimmune disease multiple sclerosis (MS), pathogenic T cells extravasate and attack nerve cells by using VLA-4 to bind to VCAM-1, a cell adhesion molecule on endothelial cells that line blood vessels. Current treatments for MS rely on antibodies to bind VLA-4 and block its interaction with VCAM-1, thus preventing a pathogenic immune response. However, antibodies are expensive to manufacture, and their binding cannot be easily regulated to control drug-induced side effects. Aptamers are single-stranded DNA or RNA molecules that fold into sequence-defined structures capable of binding to their targets with affinities and specificities comparable to antibodies. Being chemically synthesized, they are much cheaper to manufacture and offer minimal batch-to-batch differences. Unlike antibodies, their binding in vivo can be rapidly reversed using a reversal agent, which could alleviate the side effects of disease treatments. However, aptamers have limitations in vivo: degradation by nucleases in blood serum, and rapid clearance into urine through the glomerular filtration barrier. This project focuses on the development of a VLA-4 aptamer for treating MS. We found that the VLA-4 aptamer prevents soluble VCAM-1 from binding to VLA-4-expressing leukocytes by flow cytometry. We then showed that the aptamer blocks VLA-4/VCAM-1 mediated leukocyte adhesion in vitro. We are currently assessing aptamer blockade of leukocyte transendothelial migration. We are also designing modifications to improve the stability of the aptamer for in vivo uses. Successful development of the aptamer will lead to an alternative treatment modality for MS with a potentially improved safety profile.

Alternative-technology (alt-tech) platforms like Telegram, Truth Social, and Rumble have emerged as self-proclaimed free speech hubs, appealing to distrust in governments and tech companies. While alt-tech platforms remain niche, they play a growing role in political communication and have contributed to real-world events, such as the January 6 Capitol attack. Despite their influence, research on these platforms remains limited compared to mainstream social media studies. This study develops a typology of five right-wing alt-tech platforms—Rumble, Truth Social, Gab, Gettr, and Telegram—analyzing their ownership structures, monetization models, and content moderation policies. By examining how these platforms’ designs and financial incentives influence content production and user behavior, the study aims to provide insights into their role in shaping online information ecosystems. Prior research has examined individual alt-tech platforms, such as Bitchute, and broader comparisons between mainstream and alt-tech platforms. However, this study offers a comparative analysis focused exclusively on alt-tech platforms, identifying patterns in governance, incentive structures, and policy enforcement. Findings from this research could inform policymakers on potential regulatory approaches, including ownership transparency, antitrust interventions, and content accountability measures. Additionally, technologists and platform developers may leverage these insights to design more transparent governance frameworks for alternative digital spaces. By addressing gaps in current social media research, this study enhances public understanding of alt-tech platforms and their growing influence in digital discourse and political communication.

Political satire is often viewed as a form of indirect political expression commonly employed in authoritarian states like China. When social media is heavily regulated, satire serves as a rhetorical tool to circumvent censorship. However, satire might vary across various types of political discussion, including housing, unemployment, and the overwork culture. While prior research has extensively examined political satire and censorship in China, there is little research comparing how satire functions differently across political discussion themes. This study hypothesizes a correlation between themes of political discussion and the role and characteristics of satire in political discourse by analyzing content on Zhihu, a Chinese Q&A platform. Specifically, it examines (1) the correlation between discussion themes and stance to assess whether satire is a necessary feature for expressing dissent, (2) the prevalence of satire, measured by the proportion of satirical posts within each theme, and (3) the relationship between linguistic ambiguity and satire to determine whether ambiguity is a key strategy for evading censorship. The methodology consists of three main steps: (1) Construct a dataset by creating a random sample from a list of select political discussion themes and scraping the top discussion forums, recommended by the platform's algorithms, to ensure the sample reflects the overall user experience. (2) Qualitative text annotation based on the post's stance, ambiguity, and the presence of satire. (3) Applying natural language processing techniques to examine cross-topic variations in the use of satire and other rhetorical strategies. This approach facilitates a systematic exploration of how different types of public political discussions utilize satire to evade censorship. This research contributes to the broader understanding of political discourse under authoritarianism, offering insights into how citizens navigate the boundaries of permissible speech. 

The kidney plays an important role in blood filtration, regulation of blood pressure, acid/base homeostasis, and electrolyte balance. Studying the different kidney compartments provides critical insights into the metabolic mechanisms underlying these essential functions. Ziyu Guo, my research mentor has recently developed a highly multiplexed fluorescence microscopy using semiconducting polymer dots (Pdots) that allows one round of immunostaining and imaging of up to 21 targets. However, this technique is restricted to thin samples (50-100 µm), which may oversimplify biological systems by lacking depth and structural integrity. To overcome this limitation, my research integrates multiplexed fluorescence imaging with ELAST, a technology to transform thick tissues into elastic hydrogels, reinforcing the tissue's structure while allowing for better antibody penetration. This approach allows for simultaneously labeling multiple targets in the thick tissue while preserving tissue architecture. Overall, my project seeks to improve our understanding of kidney architecture in their natural spatial 3D context and further provide insights into disease mechanisms and potential therapeutic targets.

This research project is my English Honors thesis. I am researching Asian American history and feminism, taking stock of current Asian American depictions in media, drawing off existing Asian American literature, and theorizing and practicing comedy as a way forward. I want to push past the Model Minority stereotype and the current sad, intergenerational conflict heavy tone of Asian American literature. To do so, I’ll draw off sources like the UW Press published Asian American Feminism and Women of Color Politics book and employ Asian American feminism and comedy to bring a lighter tone to Asian American Literature. Asian American Feminism is characterized by an “invisible” yet active praxis of mobilizing the diverse, heterogenous Asian American community and constantly occupying and pushing to improve conflicting perceptions such as the submissive, assimilated female caretaker and the threatening yet sexualized foreign agent. I am textually analyzing books like Interior Chinatown (Charles Yu) and Minor Feelings (Cathy Park Hong). I am analyzing how raunchy and unconventional comedians like Ali Wong layer their jokes into a stand-up comedy special form. All of this will come together in a scrapbook. Drawing together book arts and the resilience of Asian American identity against fragmentation driven by oppressive laws, I will dive into prejudiced legislature and significant Asian American novels. My scrapbook will chronicle uncovering Asian America together and look towards the future. The scrapbook will serve as a meeting place to first condense historical context, then honor existing Asian American works, and put them in conversation with each other across time and medium. After my scrapbook facilitates these scraps becoming something new together as a whole, I will shift to comedy. I will theorize what makes Asian American comedians like Ali Wong so effective at reaching wide audiences, and I will write comedic bits myself.

The prevalence of food allergies in the United States has increased dramatically, affecting 4 in every 100 children under the age of 18. There are 8 main categories of food that make up the most common food allergies. These foods include eggs, fish, milk, crustacean shellfish, wheat, tree nuts, soy, sesame, and peanuts. Together, these foods create the "Big 8" list: a priority list for the US Food Allergen Labeling and Consumer Protection Act (FALCPA). In this literature review of current treatments for food allergies, we will select the peanut allergy for further research due to the often fatal complications that arise from anaphylaxis following exposure. This review will seek to provide a comprehensive overview of the current types of food allergy treatments and to discuss a cure for peanut allergies. The current solutions available today to treat food-induced allergic reactions include medical treatment (epinephrine), immunotherapy (e.g., "allergy shots'), nutritional support, and simply avoidance. While these solutions are great aids to help alleviate allergic reactions, they do not cure the food allergies themselves. This means that people who have food allergies are not able to consume the foods they want or need. This begs the question, "Is it possible to make a cure for peanut allergies?" The origin of food-induced intolerances stems from the failure of the immune system to ignore, or be tolerant of, food antigens. Previous studies have identified specific peanut antigens that promote allergic responses. Food allergic immune responses are primarily driven by T cells. Potentially, these antigens can be used to isolate peanut-specific T cells in allergic individuals. These T cells could then be analyzed and used to generate cell-based therapies to suppress allergic responses (bystander suppression). This solution could permanently prevent peanut-induced allergic reactions from occurring. 

Alzheimer's Disease (AD) is a neurodegenerative disorder with classical behavioral and pathophysiological presentations such as memory impairment, cerebral vascular alterations, and most notably, the accumulation of amyloid-beta plaques and tau fibers in humans. While these symptoms are hallmark signs of AD, the severity of these symptoms differs for individual patients. As such, clinicians face challenges in misdiagnosing or giving a late diagnosis using a few of these AD markers. My research project aims to characterize AD through 3 concurrent modalities with the goal of early diagnosis and better quality of care for AD patients: [1] motor activity using a motion capture chamber, [2] spatial memory and learning using Barnes Maze Trials, and [3] real-time cerebral hemodynamics with ultrafast contrast-enhanced ultrasound (CEUS) in a rat model of AD. This project utilized control wild-type (WT; n=3) and transgenic (AD; n=3) rats. We hypothesize that the WT and AD rats will express similar movement and cognitive metrics measured until they are 12 months old, whereas the AD rats show a gradual motor decline and cognitive impairment. The 12-month metric is used as a benchmark set by prior research using this rat model. Intravital CEUS imaging will be conducted at 16-19 months old. We expect CEUS imaging will reveal that cerebral blood flow in the parietal and hippocampal regions of the brain is reduced, and microvascular response is impaired in AD rats. The expected outcome of all 3 experiments is that there is a strong correlation between motor and cognitive decline with impaired hemodynamics in AD rats. Results from our study will allow for systematically chronologizing the progression of AD in greater detail than before which allows for greater diagnostic ability.  

The orofacial sensorimotor cortex plays an important role in controlling tongue and jaw movements, such as speaking and eating. Being able to reliably perform these movements has critical implications for people suffering from neurological diseases such as stroke and Alzheimer’s disease, which are known to affect orofacial functions. However, the features of the complex lingual function that drive motor cortical activity are still poorly understood. Here, we investigate how information in the orofacial primary motor cortex (MIo) varies based on factors such as availability of tactile sensation, axis of motion, and specific regions of the tongue. To answer this question, we tracked marker-based movements of the tongue and jaw while recording neural activity from implanted microelectrode arrays in the MIo of two rhesus macaques (Macaca mulatta) engaged in feeding. Decoding accuracies of models based on (i) axis of motion, i.e., antero-posterior (x-axis), supero-inferior (y-axis), medio-lateral (z-axis), (ii) tongue marker region (superficial vs. deep, anterior vs. intermediate vs. posterior), and (iii) local anesthesia applied to sensory branches of the trigeminal nerve, were then compared to evaluate the ability to predict marker position. Generally, decoding performance was best using the y-axis and worst with the z-axis. Additionally, model performance was best in the x-axis of posterior tongue markers. Lastly, we found significant differences in model performance between control and nerve block conditions across all motion axes, with the x-axis showing the largest decrease in performance post-nerve block. These findings indicate that information carried by MIo neurons differ as a function of the tongue's motion axis, region, available tactile information, and varying combinations of these factors. These have important implications for the development of evaluation tools, rehabilitation strategies, and neural prostheses to restore orolingual function in particular and limb sensorimotor function in general.

6PPD-Quinone (6PPD-Q) is a toxic transformation product of the tire rubber additive, 6PPD, that has been identified as the primary cause of Coho Salmon (Oncorhynchus kisutch) mortality in watersheds impacted by roadway runoff. Recent studies have focused on quantifying the lethal concentration of 6PPD-Q, identifying the major sources, and predicting the environmental release from rubber products. Organic chemical release from solids is typically evaluated with solvent extraction where organic solvent and solid are contacted, releasing the leachable chemicals for measurement. However, different solvents and methods introduce inconsistencies in leaching data from different laboratories. This study evaluates the impact of solvent choice on 6PPD-Q extraction from crumb rubber. I will quantify 6PPD-Q concentrations in methanol, ethyl acetate, or acetone during storage after rubber extractions. Determining the best solvent for 6PPD-Q that promotes the most recovery and stability is essential for data quality. After this study, desorption and resorption rates of 6PPD-Q onto various crumb rubbers will be measured.  These studies aim to improve study design for leaching assessments and enhance our understanding of the persistence and mobility of 6PPD-Q in the environment.

Diabetes is characterized by hyperglycemia, which is exacerbated by the inappropriate storage and mobilization of hepatic glycogen. Incretin drugs, specifically GIP and GLP1 agonists, have been clinically successful. In the islet, GIP stimulates insulin and glucagon, while GLP1 stimulates insulin and inhibits glucagon production. Incretin receptors are not in the liver, suggesting that any effect of incretins on liver metabolism is through indirect islet hormone effects. Preclinical studies show the benefits of increasing hepatic glycogen storage in diabetes models, yet no drugs currently target this important source of carbohydrate metabolism. Therefore, my study aims to investigate how incretin drugs interact with hepatic glycogen stores to modulate islet hormone action. I hypothesized that increased hepatic glycogen will amplify islet hormone action and GIPR agonism will increase glycogen metabolism, while GLP1R agonism will have little effect on hepatic glycogen. I used hepatocyte-specific AAVs to overexpress the PPP1r3b protein in mice (PPP1r3bOE), resulting in a significant increase in hepatic glycogen compared to the control. Post-incretin injection (GIPR agonist, D-Ala2-GIP or GLP1R agonist, Ex4), I measured blood glucose and collected plasma to quantify circulating insulin and glucagon by ELISA. I collected liver to measure glycogen by glucose oxidase reaction and glycogen signaling intermediates by western blot. My results have indicated that GIP is less effective at glucose lowering in PPP1r3bOE compared to controls, while there is no effect on GLP1R-mediated glucose-lowering. This supports that elevated hepatic glycogen is likely altering glucagon action in response to GIP, with no effect on GLP1 action. I am currently analyzing plasma insulin and glucagon and will be assessing post-receptor insulin and glucagon signaling in the liver in response to GIP. This study will provide a better understanding of hepatic glycogen regulation, and offer an opportunity to investigate how incretin action can be optimized as a diabetes treatment.

Mutations, which arise spontaneously, are the foundation of genetic variation and play a key role in evolution. Understanding mutation dynamics has relevance for public health, as antibiotic resistance in bacteria often results from genetic mutations that allow them to thrive in the presence of drugs that would typically inhibit their growth. Our research builds on the Luria-Delbrück method, originally designed to estimate mutation rates phenotypically, by using Next-Generation Sequencing (NGS) to measure base-level mutation rates in Escherichia coli that confer resistance to rifampicin. Rifampicin targets the β-subunit of RNA polymerase, and resistance arises from single nucleotide mutations in the rpoB gene. My team and I conducted experiments by inoculating E. coli populations, exposing them to rifampicin at specific times, and sequencing resistant mutants to calculate mutation rates for each base change. Interestingly, our data revealed that identical base changes at different genomic positions can have significantly different mutation rates. However, our mutation rate estimation does assume that every mutant cell has the same probability of establishing a lineage in the presence of rifampicin. If a certain mutant has a lower probability of lineage survival, its mutation rate will be underestimated. Thus, to determine whether the mutation rate variability we found is due to actual differences and not survival differences, I developed an assay to measure the probability that a mutant fails to establish a lineage. To date, I have isolated nine distinct rifampicin-resistant mutants and tested the extinction rates of two, finding no observable extinction, supporting the accuracy of our mutation rate estimates for these mutants. This research refines mutation rate calculations and enhances our understanding of bacterial adaptation, with implications for developing strategies to predict and mitigate antibiotic resistance. Additionally, it contributes to evolutionary biology by revealing the complexities of mutation and survival in microbial populations

As the aorta ages, the risk of cardiovascular diseases like high blood pressure, aortic aneurysms, and heart failure increases. Previous research has shown that both mitochondrial dysfunction and cellular aging (senescence) contribute to these problems. However, how these two processes interact is not well understood. We hypothesize that the interactions between mitochondrial dysfunction and senescence in aortic smooth muscle cells (SMCs) can lead to harmful changes that promote disease. To test this, we study SMCs from patients undergoing heart surgery. We will measure mitochondrial function using high-resolution respirometry (Oroboros Oxygraph), assess senescence through gene expression (qPCR) and β-galactosidase staining, and examine cell changes using qPCR and immunofluorescence. Understanding this connection could help identify new ways to prevent or treat age-related aortic diseases. Early data shows significant difference in mitochondrial function and cell expression function in different aging disease groups. We are currently studying the effects of mitochondrial targeted and senescence targeted drugs. 

According to the Centers for Disease Control and Prevention, the U.S. has more than 2.8 million antibiotic-resistant infections each year. The rise of multidrug resistance in bacteria poses an urgent clinical threat contributing to these various infections. UPAB1 is a specific strain of a notoriously drug-resistant bacteria Acinetobacter baumannii associated with catheter-associated urinary tract infections (CAUTI). UPAB1 infects the urinary tract through the introduction of a foreign object, such as a catheter. In response, the immune system coats the catheter with fibrinogen, a glycoprotein complex that assists in wound healing. UPAB1 uses its bacterial adhesin proteins, such as Abp2D, to bind to fibrinogen, deplete essential nutrients, and infect the urinary tract. By designing Abp2D inhibitors as de novo miniproteins, we hypothesize that A. baumannii will be prevented from establishing a bacterial infection and allow us to offer a potential alternative in combating antibiotic resistance in CAUTIs. Targeting UPAB1 Abp2D, we first developed designs of Abp2D inhibitors utilizing computational software like RoseTTAFold Diffusion (RFdiffusion) for miniprotein backbone design, ProteinMPNN for sequence design, and AlphaFold2 (AF2) for structure prediction of the sequences to validate and filter. Afterwards, in the laboratory, we expressed and purified the miniprotein designs. We are currently testing these designs as Abp2D inhibitors via E. coli cultures to determine their success in binding to UPAB1 Abp2D.

Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling. One key feature of airway remodeling is the thickening of the subepithelial basement membrane zone (BMZ) beneath the airway epithelium, which has been identified in severe asthma relative to milder severity asthma and other airway diseases. We aim to characterize the relationship between BMZ thickness, airway physiology, and airway immune cell populations. I am utilizing design-based stereology to precisely measure BMZ thickness in endobronchial biopsies obtained from 30 individuals with asthma and 10 healthy individuals. These individuals underwent extensive characterization for asthma airway physiology, profiling of airway immune cell populations, and airway inflammatory gene expression. Stereology provides unbiased thickness estimates that have greater reproducibility and overcome the limitations of two-dimensional measurements. I am measuring BMZ thickness using the orthogonal intercept method, which involves averaging the lengths of lines extended perpendicularly from the epithelial surface across the thickness of the BMZ at systematically sampled points. I am correlating BMZ thickness with clinical characteristics (allergic sensitization), airway physiology (baseline lung function, measurements of airway hyperresponsiveness), densities of both mast cells and eosinophils in the airway wall, and gene expression profiles obtained from airway epithelial brushings. I hypothesize that individuals with asthma patients will have more BMZ thickening in comparison to healthy controls. I also anticipate that there will be a positive correlation between the thickness of the BMZ and the expression of type-2 (T2) inflammatory genes (IL4, IL5, IL13). Finally, I hypothesize that there will be a positive correlation between BMZ thickness and the density of mast cells in the airway epithelial compartment. This research study provides new insights into the potential mechanisms responsible for airway remodeling in individuals with asthma and how they connect with airway inflammatory endotypes, which may guide further development of targeted therapeutics. 

Hypoxic ischemic encephalopathy (HIE) is a neurological condition resulting from reduced blood and oxygen flow to the brain and is a leading cause of morbidity and mortality in neonates. Limited treatment options necessitate accessible and scalable interventions to improve outcomes in newborns impacted by HIE. Extracellular vesicles (EVs) have been previously shown to attenuate oxidative stress and inflammation in the brain. Further research suggests that EVs secreted by astrocytes, a brain cell type involved with the inflammatory and injury response, may elicit neurotrophic or neuroprotective properties. In this study, I isolated, characterized, and evaluated the therapeutic potential of astrocyte-derived EVs (AEVs) in an ex vivo model of hypoxic-ischemic (HI) brain injury. AEV characterization via protein assays and nanoparticle tracking analysis showed that we were able to produce AEV particles about 100 nm in size at concentrations up to 10^11 particles/mL. To assess their therapeutic efficacy, I administered AEVs at varying doses (5, 12.5, 25, and 50 µg) to neonatal rat brain slices exposed to oxygen-glucose deprivation (OGD), an ex vivo model for HI injury. Following 24h of exposure, I evaluated cell viability. Our results indicate that AEVs decrease cytotoxicity in a dose-dependent manner. To further elucidate AEVs’ mechanisms of action, we conjugate AEVs with quantum dots to track AEV localization and cell-type specific uptake in brain tissues. Understanding AEV interactions with neural cells provides insight into both the roles of AEVs and different brain cells in modulating inflammatory responses and promoting neuroprotection. By characterizing AEVs and their therapeutic potential, these findings contribute to the growing body of research on EV-based therapeutics and lay a foundation for developing reliable and scalable therapies with the potential to advance treatments for neurodevelopmental disorders and aid brain injury recovery. 

The purpose of this research is to examine myoregeneration and tissue effects on the tongue base following surgical injury and adipose tissue accumulation in minipigs. Twenty, 8-9 months old Yucatan minipigs were studied. Eight minipigs were assigned as the control group, and other 6 same-sex pairs were used as intervention groups. In each pair, one was intentionally fed to obesity (BMI>50) and the other one with normal weight (BMI < 35) received surgical ablation of the tongue base. BrdU was administered intravenously to track muscular cell proliferation and myofiber formation, with injections given 15 days and 2 days before the termination, respectively. Tongue base samples were paraffin-embedded and cut into 7µ sections for routine H&E, Trichrome, and immunohistochemical staining. Quantitative cell counts and semi-quantitative analysis of labeled cell density and differentiation were performed using the grid system and coding approach to examine muscular responses to the injury and adipose tissue infiltration. The anticipated result will be: 1) fewer muscle satellite cells in the control group; 2) increased adipose cells occupying the spaces between myofiber; 3) significantly more active myoregeneration, with a higher presence of satellite cells in the surgical group. The outcome of this study will elucidate the potential capacity of the tongue base to respond to wound injury and adipose tissue infiltration.

Individuals with diabetes experience a unique set of challenges as metabolic disease impairs the proper regulation of glucose homeostasis. Glycogen stores in the liver are mobilized in response to islet hormones, insulin and glucagon, to address changes in circulating blood glucose levels. Individuals with diabetes are known to have lower hepatic glycogen levels and repairing these levels in preclinical mouse models of metabolic disease improves the diabetic state, suggesting hepatic glycogen storage may be a rational therapeutic target. With the use of a mouse model of increased hepatic glycogen by overexpression of a protein called Ppp1r3b ( Ppp1r3bhepOE), I explored the hypothesis that increasing hepatic glycogen levels affects the hormonal response and hepatic post-receptor signaling in response to nutrient feeding. Using oral gavage mixed-nutrient meals (consisting of varying glucose and/or alanine), I monitored plasma glucose and hormone levels from mice under different feeding conditions. I collected blood glucose and plasma samples from the tail vein and used ELISA to quantify circulating insulin and glucagon levels. In comparison to a control AAV group, the Ppp1r3b OE mice showed significantly elevated glycogen levels and following an overnight fast increased blood glucose levels. Furthermore, after conducting a 5 hour fast, the Ppp1r3b OE group had lower insulin levels without changes in glucose, signifying increased insulin sensitivity.  Yet, after an insulin tolerance test, Ppp1r3bhepOE mice did not decrease blood glucose to the same extent as controls, perhaps due to increased liver-derived glucose output. Lastly, to measure post-receptor signaling I administered either insulin or glucagon to control and Ppp1r3bhepOE mice and measured the glycemic response and activation of relevant hepatic signaling intermediates. My preliminary evidence reveals the importance of hepatic glycogen in energy metabolism and lays the foundation for future studies investigating how the alteration of glycogen storage could optimize energy expenditure in metabolic disease.