Electronic Thesis or Dissertation

In this study, we developed a new peptide motif called β-strap (strap = strand + cap) used to fold β-hairpins of varying length. β-Straps are mean to be short sequences (4 to 8 a-amino acids) forming β-sheets using a judicious combination of non-covalent interactions (NCI) to overcome the entropic penalty inherent to long loop closure. Among those, we proved that a couple of CH-π / NH-π interactions from a tryptophan zipper motif were critical to create a stable packing of the structure. To optimize these interactions, we incorporated unnatural tryptophan derivatives having functionalized indole side chains. Finally, the innate ability of the β-strap to bring β-stand in close contact was exploited to promote macrocyclization of long coiled peptides (up to 16 residues).
Then, we studied a more complex β-hairpin loop mimics found at the apex of monoclonal antibodies (mAb) complementary determining region 3 (CDR-H3). Using a set of bioinformatics tools, a search of PDB crystal structures revealed that a large set of mAb crystals possess a β-bulge, located at the edge of CDR-H3 loops. A cluster analysis revealed it has an impressive adaptability towards different H3-loop sizes and conformations. In order to evaluate its function in antibodies, we synthesized several β-hairpin models bearing a prototypical β-bulge. By combining short β-straps and the β-bulge, we were able to design β-hairpin peptides mimic of mAb with a variety of lengths and rigidity while retaining a high degree of folding. Starting from pembrolizumab, the most outstanding blocker of the PD-1/PD-L1 checkpoint currently available in clinic, we scoped ~30 CDR-H3 mAb mimics (H3 loop). As a result, several novel β-hairpin peptide inhibitors of the PD-1/PD-L1 pathway were identified (IC50 <0.3 μM).

In The Bahamas, the Princess Margaret Hospital is one of the main public facilities used to deliver babies. The hospital is divided into two maternity wards, public and private. This thesis aims to analyze the narratives of mothers’ experiences who have given birth in the hospital. Also, this thesis examines the difference in treatment between mothers’ first, second and third births. The data suggest that the way mothers were treated is based on their age and relationship status during delivery. Notably, mothers on the private ward had the advantage of a family member to witness the delivery pre-COVID, while mothers on the public ward did not experience this privilege. Mothers’ first, second and third birth experiences showed differences based on their increased knowledge of delivery. However, both wards were associated with common issues related to hospital resources, doctor-patient relationships, communication, and perceptions of treatment.

This narrative research study focuses on the lived experiences of Black female doctoral students navigating predominantly White colleges and universities (PWIs) and their connections within cultural safe spaces. Through the lens of Black Feminist Theory and the application of a Black Feminist-Ecological Perspective, this study investigates how Black female doctoral students are defining cultural safe spaces and how these safe spaces support their academic and personal lives. Specifically, this study explored the narratives of nine Black female doctoral students and how they define and locate cultural safe spaces.
This study expanded on the limited existing research on Black women in doctoral programs by delving into a more nuanced look into understanding the specific dynamics of Black female cultural safe spaces and the role they play in supporting Black women pursuing doctoral degrees at PWIs. Using the Rodgers 3-R Framework, three major themes unfold from this narrative, beginning with participants’ initial experiences in their doctoral programs (recognition phase), their journey towards finding a cultural safe space after recognizing that there was a deficit in their doctoral experience (reconciliation phase), and their recounts of how they interpreted their experience after becoming a part of a cultural safe space of their own (reflection phase). Implications for future research are discussed.

Despite the historical norm that businesses should refrain from making public political statements for fear of losing customers, recent history has shown an increase in firms wading into controversial sociopolitical topics. As politics become increasingly pervasive in everyday life, consumers, investors, employees, and the general public expect firms to engage in political topics and make their positions clear. However, the considerations and processes firms undertake in deciding whether to take political stands are largely unstudied.
This study examines the role of firm executives’ ideologies on their propensity to engage in corporate sociopolitical activism (CSA). Further, I examine how the ideologies of organizational, social, and capital market stakeholders also influence the decision to engage in CSA as executives weigh the desires and expectations of key stakeholders. Using stakeholder theory, I argue that CEOs and top management teams (TMTs) are responsive to the ideological leanings of multiple stakeholder groups, while also considering their own political opinions. Studying a random sample of 139 public firms, I find that CEO and TMT ideologies, on their own, are not reliable predictors of firm CSA. Firms are more likely to engage in CSA when the CEO’s ideology is aligned with that of employees or the region surrounding the firm headquarters. I also find that the volatility of the firm’s stock price reduces the propensity toward CSA, suggesting that the potential for adverse impacts on firm value can blunt firms’ CSA efforts. Further, I find that firm factors, such as B2B vs B2C markets, firm size, and firm reputation also predict the likelihood of CSA. The results have theoretical implications by adding to the nascent body of CSA literature, as well as managerial implications for perceptions of the business environment and political influences.

The stories in Nameless in Z take place in the fictional city of Z, located on the northwestern coast of the US. The throughline of this collection tracks alternate versions of the same male narrator as he subconsciously pursues relationships in an attempt to supplant his own destructive addictions. The first half of this book dwells more in the relationship aspect, while the second half owns up to the consequences of the first half.
Each story involves the titular city tormenting the narrator in a way that physically and/or spiritually manifests his specific addiction. Speculative fiction elements hang around the fringes of each of these stories, typically through different forms of the supernatural. The purpose of this work is to give a voice to underrepresented aspects of addiction and to disentangle my own demons; the ones I’ve inherited as well as the ones I’ve created as a direct result.

This thesis is composed of a collection of essays on the themes of motherhood, loss, and grief. Through the use of innovative form, these essays thread together personal narratives and research to find language for complicated manifestations of loss. These essays experiment with structure and form to grapple with the illusive nature of memory, loss, and healing. The essays in this collection attempt to find healing and meaning through language and meditation. This collection is also an attempt at categorizing grief when normative societal ideas are challenged by complicated loss. This work serves as a call to action that there should be better recognition of uncommonly recognized manifestations of grief.

Talmy (2007) was the first to propose a language typology based on the lexicalization patterns of motion verbs. According to his typology, certain languages tend to encode certain elements within the main verb of motion event descriptions. It has been proposed that Spanish and English exist on opposites sides of this typology and Slobin (1996 & 2006) speculates these structural differences may affect what aspects of external events are more salient to speakers of these languages.
The present study investigates the verbal and nonverbal behavior of English monolinguals and Spanish-English bilinguals to see if any differences exist in the aspects of the motion event that they describe in an elicitation task or prefer in a similarity judgement task. This study provides evidence that Spanish-English bilinguals may be less likely to encode manner when speaking in English. The present study provides no evidence that this extends to nonverbal behavior as all groups showed a preference for categorizing motion events based on the manner (e.g., run, walk, crawl, etc.) of motion rather than the path (up, down, left, right, etc.).

Transgender identity and the concept of artificial intelligence are constructed and understood through dichotomies such as natural/unnatural and real/artificial, with each dichotomy informing the other; what is “unnatural” is often deemed to be a mimicry of the “natural,” therefore a false representation of what is “real.” By surveying various classic SF texts and their portrayal of AI characters through the lens of transgender studies—drawing upon scholars including Susan Stryker, Sandy Stone, and Florence Ashley—I assert that artificiality itself is a construction formed by cisnormative ideals and standards to exclude certain others (namely, transgender people) that requires reframing. I examine how these representations in works such as Richard Powers’s Galatea 2.2 reveal and articulate the constructed dichotomies and cultural narratives which surround transgender identity, as well as how contemporary, trans-authored works such as Annalee Newitz’s Autonomous can offer tools for responding to and reconfiguring those dichotomies.

The current work investigates the identification of novel drugs that have the potential to be suitable anti-malarials against Plasmodium falciparum-infected erythrocytes. The growing resistance to current therapeutic modalities necessitates the development of new emerging and effective compounds. The target of these compounds in this work will be PfGARP (P. falciparum glutamic-acid-rich protein), a surface antigen of infected erythrocytes (IEs) found only in P. falciparum that has been recently recognized as a valuable drug target and vaccine candidate. Using a two-step approach designed in our lab, we were able to efficiently screen large libraries of small molecules provided by ChemBridge and the Torrey Pines Institute for Molecular Studies (TPIMS). We base the current work on our preliminary results, obtained with a subset of 6,400 compounds of DIVERSet library, reasoning that there may be other individual compounds that can be identified as having equal or greater parasiticidal activity. In this work, initial screening of the ChemBridge DIVERSet library subset of other 3,600 compounds organized into compound mixtures using Bio-Plex technology resulted in the identification of the most active mixtures (HITS-1), which were further deconvoluted into simpler mixtures (HITS-2). Screenings of HITS-2 yielded two mixtures of interest that did not portray any noticeable binding inhibition, and the deconvolution process was thus forfeited.

Epilepsy is a prevalent brain disorder that affects more than 1 in 26 people in the United States. The recurring increased neuronal excitability during seizures results in sleep disturbances and muscle convulsions that reduce the quality of life and increase the healthcare costs for these patients. An epilepsy diagnosis is made when patients have had two or more seizures. There are many types of seizures and an individual can have more than one type. Seizures are classified into two groups, 1) generalized seizures that affect both sides of the brain and 2) focal seizures that are located in just one area of the brain. The causes of epilepsy vary by the age of the person, some with no clear cause may have a genetic form of epilepsy. Due to the various causes and types of seizures, many treatments including invasive surgeries and antiepileptic drugs (AEDs) do not work for all epileptic/seizure patients and are merely used to ease symptoms. The physiological complexity of the disorder and limited knowledge on its specific molecular mechanisms may contribute to the lack of effective treatment. In recent years, there has been an estimated average cost in billions of dollars to bring new medicine to the market; due to the lack of novel antiseizure targets and mechanism-based therapies on seizure phenotypes. In response to this, we utilized the electroconvulsive seizure behavioral assay to characterize one generalized seizure phenotype, tonic-clonic/grand mal seizures.