In their books Pihkal and Tihkal, Dr. Alexander and Ann Shulgin describe their experiences ingesting 234 psychoactive compounds, most of them newly synthesized by Dr. Shulgin. The goal of this project is to use natural language processing techniques to map the semantic space of the Shulgins’ qualitative comments and determine what commonalities, if any, exist between compounds of similar molecular structures. I first created a TF-IDF matrix to determine the importance of each word for each compound. I then applied three clustering techniques (k-means, DBSCAN, and affinity propagation) to group compounds based on their meaning and used UMAP after each technique to graph the clusters in two dimensions. Unfortunately, despite attempting different combinations of pre/post processing and hyperparameter tuning, each method resulted in only weakly associated clusters. My next analytical method is using Sentence-BERT modeling to compare the semantic meanings at the sentence level. Since sentences hold more meaning than single words, I anticipate that this technique will differentiate the compounds to a greater extent, therefore leading to more visibly divided clusters. I also have the compounds clustered by similarity in molecular structure and determined the most common words associated within each group. By quantifying the subjective experiences of these psychoactive compounds and mapping them to molecular structures, this knowledge could allow us to synthesize molecules to obtain a desired effect on a patient’s consciousness. This could in turn aid in synthesizing new medications to treat mental health disorders.

Transient ischemic attack (TIA) patients can still experience a recurrent stroke due to platelet-rich thrombi despite being on dual antiplatelet therapy (DAPT) consisting of acetylsalicylic acid (ASA) and a P2Y12-inhibitor. One pattern these patients have was an elevated von Willebrand Factor level (VWF), a blood clotting protein that tethers platelets to the endothelium. VWF unfolds under shear, exposes its A1 domain to which surface receptor GPIb-IX-V of platelets can bind. DAPT targets platelet activation by inhibiting thromboxane A2 synthesis and blocking ADP binding to P2Y12, but it does not directly address shear-mediated activation of platelets via VWF. Even with DAPT, platelets can still bind to VWF via GPIb-IX-V under a high shear rate. To understand the interplay between elevated VWF levels, DAPT, and platelet thrombus formation under shear flow, we used a microfluidic device to analyze platelet-rich plugs for (1) platelet activation, (2) aggregation size, and (3) contractile versus drag forces to withstand embolization. Those characteristics are measured in a healthy platelet-plug control and a platelet-plug doped with 6-fold VWF level, both with and without DAPT. We found platelet-plugs with DAPT still maintain activation, and activation level becomes higher when DAPT is combined with elevated VWF level. Platelet-plugs with DAPT and/or elevated VWF have larger aggregate size than control, and aggregate size is highest when DAPT is combined with elevated VWF level. While contractile force dominates in control, it becomes similar to drag force with DAPT and/or elevated VWF. We suspect the large size, reduced contractile force and maintained activation of platelet-plugs with elevated VWF can make the plug prone to embolization caused by the drag force. This result can shed light on the limitations of DAPT when VWF level is elevated, and introduces the possibility of screening patients for high VWF to tailor antiplatelet therapies. 

Serotonin serves a vital role in the regulation of stress responses, and variance in the release of serotonin was found to contribute to various mental illnesses such as anxiety and depression. Current mental health treatments heavily rely on Selective Serotonin Reuptake Inhibitors (SSRIs). While these medications are generally effective, there are patient populations for whom SSRIs show limited efficacy. Recent studies found that in response to stress, the expression of the FKBP5 gene also increases and modulates many neuronal pathways including serotonin. This experiment determined whether manipulating FKBP5 gene expression in the dorsal raphe (DRN) directly correlates with serotonin release in the basolateral amygdala (BLA), an established neural circuit for fear. To manipulate FKBP5 gene expression, an adeno-associated FKBP5-Cre virus was injected into the DRN of Pet1-Cre transgenic mice, causing up or downregulation of FKBP5 in the DRN. To gauge the effects of FKBP5, fiber photometry was used to measure the release of serotonin following optogenetic activation of the DRN-BLA pathway using a 5HT GRAB sensor injected into the BLA. We hypothesize that increased FKBP5 expression in the DRN will increase serotonin release to the BLA, and as FKBP5 expression is decreased, the release of serotonin to the BLA will decrease. Success in modulating serotonin release using FKBP5 gene expression will expand therapeutic targets in mental illness research, mitigating the gap in treatment efficacy for patients who have undergone ineffective SSRI therapy.

As the life expectancy for global populations rises, the prevalence of people affected by age-related morbidity has also increased. Although therapies and treatments are available to alleviate such diseases, they do not effectively address the fundamental cause of all such diseases age. One hallmark of age is cellular senescence. Senescence refers to the state of a cell in which it cannot divide anymore due to factors such as stress or damage to DNA. Although this mechanism is naturally preventative there can be many undesirable consequences. As senescent cells accumulate within aging tissues, inflammatory responses are promoted and may even spread senescence to neighboring cells. This causes more inflammation and elevates the risk of illnesses. Targeting these cells with therapeutics such as senolytic drugs presents a potential solution. A combination of senolytic drugs, Dasatinib + Quercetin (D+Q), has been shown to target and lyse senescent cells, thus increasing lifespan and reducing frailty in mice. This research study involves two groups of mice: old and old treated with D+Q, where D+Q was administered for 24 months. Mandibles were collected to evaluate levels of senescence (CDKN1A and CDKN2A, genes coding for p21 and p16, respectively) through RNA extraction and QRTPCR. Inflammation markers, IL1a and IL1b, were also examined as inflammation is frequently associated with senescence. Preliminary observations have shown decreased transcription of CDKN1A and CDKN2A in treated male mice in comparison to controls (p < 0.05 and p < 0.001, respectively) within aging alveolar bone. In addition, IL1a and IL1b were shown to have decreased expression in the treated male mice in comparison to the controls (p < 0.001, p < 0.05, respectively). This project was funded by the SenNET Grant (AG079753) and funded in part by the Dr. Douglass L. Morell Dentistry Research Fund.

Recent research suggests an association between comprehensive sex education and improved sexual health–demonstrated by lowered rates of STIs and teen pregnancy and higher rates of contraceptive use in states with comprehensive sex education as compared to states without comprehensive sex education. However, there is still an overall dearth of literature regarding the association of sex education legislation and relationship health. Some data suggests that education programs can have effects on relationship health, such as gender equality education programs that predict lower levels of intimate partner violence. Our project aimed to provide insight into how sex education legislation is associated with relationship health indicators by examining the relationship between legislative requirements and relationship health outcomes. We ran a series of t-tests and point biserial correlations, comparing states with comprehensive sex education and those with abstinence only education requirements, and found significant group differences in teen birth rates and STI rates. We also analyzed the association between legislation requiring medically accurate sex education and sexual health outcomes, and found no significant associations. We similarly did not find any significant associations between the requirement of consent in sex education legislation and intimate partner violence rates. Our significant results align with prior literature indicating that comprehensive sex education is associated with lower rates of sexual health outcomes like teen pregnancy and STI rates. Our non-significant findings are more difficult to interpret and could be influenced by limitations in our research, including inadequate sample size and a lack of publicly available databases on variables that accurately operationalize relationship health. Future research might conduct new surveys on relationship health indicators such as happiness, trust, and satisfaction within each state to better operationalize relationship health. These results can inform policy development around sex education in a direction that promotes higher-quality public health outcomes.

Are human rights non-governmental organizations (HRNGOs) incorporating climate-based rhetoric and actions in their overall agenda, to what extent, and what is driving any shift in that direction? I focus on three main explanations. First, protectionary theory suggests that given the global democracy recession, NGOs have incentives to market themselves as environmental organizations to protect against the persecution faced by human rights groups. Second, financial theory suggests that NGOs could be motivated to incorporate the climate agenda to appeal to larger donor pools for funding. Third, need-based theory suggests that NGOs must solve quality of life challenges (of which climate change is an integral part) before human rights challenges. I hypothesize the transition over to climate rhetoric and action is negatively associated with NGOs’ revenue, and more likely among NGOs working in countries that restrict human rights work. To test my hypotheses, I utilize the Charity Navigator Data set to randomly select a sample of NGOs, both advocacy and service delivery, across four levels of revenue. I then create an original dataset where I code the mission and activities of these organizations as published on their websites using the Wayback Machine for 2010, 2015, 2020, and 2025.  Finally, I test whether this transition is more likely among NGOs working in poor countries with serious quality of life challenges. My preliminary findings provide some evidence in support of my hypotheses, with variation in climate rhetoric uptake based in part on organization size and region of action.

Democratic backsliding has become a prominent and undeniable feature of contemporary world politics while greatly affecting international criminal law. This raises a question of what elements of the justice system and global politics have the most effect on incentivizing international cooperation in pursuit of global justice. This thesis answers this dilemma through analysing case studies of significant past international criminal tribunals, namely the International Military Tribunal and the International Criminal Tribunal for Former Yugoslavia. Through examining the nature and effect of complementarity, criminal procedure, and political motivations, on the level of international cooperation, this research provides policy and reform recommendations for the International Criminal Court to enhance its ability to serve justice with the stable and continuous support of the international community amid the many challenges that come with the global rise of authoritarianism.

Heart disease remains the leading cause of death in the United States, with the limited regenerative capacity of cardiac tissue resulting in long-term functional deficits following injury or defects. There is a critical need to develop physiologically relevant engineered heart tissues (EHTs) for disease modeling, drug discovery, and even cardiac surgery. Extrusion-based bioprinting offers a promising approach to generate EHTs with high spatial precision using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). However, most extrusion-based bioprinting methods rely on hydrogel-rich bioinks to achieve desirable rheological properties, often leading to low cell densities that limit tissue functionality. Here, we show that the cell’s properties can be leveraged to form high cell density bioinks with suitable rheological properties, without the need for excessive hydrogel content. Using these boinks, we bioprinted cardiac tissues (400 M cells/mL) around flexible polydimethylsiloxane (PDMS) posts (2mm diameter) to assess contractile force output and electrophysiological characteristics. The printed cells began spontaneously beating after two days, maintained high viability (>80%), and formed mechanically robust tissues with strong structural integrity. These findings highlight the feasibility of high cell-density bioprinting for cardiac tissue engineering and provide a foundation for future work aimed at generating complex, functional EHTs with high cell-density and spatial precision.

Clathrin mediated endocytosis (CME) is a cellular process that is critical for internalizing nutrients, molecules, and involved in drug delivery and viral infection. During CME, individual actin proteins assemble into filaments that produce force to help internalize clathrin coated pits against membrane tension. It has previously been shown that in vivo actin networks assemble non-uniformly around an endocytic vesicle. However, there is little understanding of how the cell leverages this non-uniformity and the variables that influence the degree of non-uniformity. Due to the small scale of the molecules involved in endocytosis, we used a stochastic, agent-based simulation to test what conditions impact actin network formation at a high resolution. We studied how varying the distribution of the actin branch nucleator Arp2/3 complex affects CME progression. We hypothesized that non-uniform localization of the Arp2/3 complex around sites of CME would drive the formation of a non-uniform actin network. To test this idea, we analyzed data from simulations with varied distributions of Arp2/3 around the endocytic vesicle (n=50 runs for each condition). We utilized the Wasserstein Distance between distributions as a quantitative metric of the non-uniformity in actin networks, studied the change in uniformity over time, and correlated this property with internalization amount. We found that median internalization was robust to varying the distribution of Arp2/3, but that with smaller regions of Arp2/3, non-uniform networks were able to internalize more. While our findings provide a deeper understanding of the conditions under which non-uniform networks assemble in CME, they also prompt further exploration of the underlying mechanisms of non-uniform networks.