Medulloblastoma is the most common pediatric brain cancer and accounts for 20% of all pediatric brain tumors. Upon diagnosis, patients undergo tumor-resection surgery followed by intense chemotherapy and cerebrospinal irradiation (CSI) regimens. CSI therapy is highly toxic and poorly tolerated in pediatric patients and is known to cause long-term neurocognitive, endocrine, and developmental deficits that often diminish the quality of life for medulloblastoma patients. The development of targeted therapies is necessary for both increasing the chance of survival and reducing treatment-related morbidities. A potential therapeutic target of interest in medulloblastoma is the polyamine biosynthesis pathway. Polyamines are metabolites present in every living organism and are essential for cellular processes such as growth, survival, and differentiation. Recent studies have shown that polyamine production is dysregulated in several cancers, including brain cancers, and have highlighted polyamine biosynthesis as a potential cancer growth dependency. Dysregulated polyamine metabolism has also been linked to several oncogenic drivers, including the WNT, SHH, and MYC signaling pathways that characterize genetically distinct medulloblastoma subgroups. One way to target polyamine biosynthesis is through the inhibition of the rate-limiting enzyme ornithine decarboxylase with difluoromethylornithine (DFMO), an analog of the polyamine precursor ornithine. DFMO is well-tolerated in pediatric populations and exerts minimal toxicities, as shown through neuroblastoma clinical trials, and is a therapy of interest for medulloblastoma. While DFMO has been tested clinically in multiple cancers, few in vitro studies have been performed to understand the exact mechanisms of anti-proliferation and cytotoxicity. Our study screened two immortalized medulloblastoma cell lines, DAOY (SHH) and D283 (non-WNT/non-SHH), and three patient-derived medulloblastoma cell lines, SL00024 (SHH), SL00668 (non-WNT/non-SHH), SL00870 (Unknown subgroup), for DFMO sensitivity and profiled the immortalized medulloblastoma cell line metabolome to understand the interactions between inhibition of polyamine metabolism with other essential metabolic processes and tumor cell growth. We found that medulloblastoma cell lines are sensitive to DFMO and the adaptive response to DFMO in medulloblastoma may be caused by increased oxidative stress and free radical scavenging. Our study hopes to inform the use of DFMO as an anti-cancer therapy in medulloblastoma by understanding the drug’s single-agent anti-proliferative mechanisms.

Survivors of military sexual assault (MSA), which has been shown to be positively linked with negative posttraumatic cognitions (NPTCs), may be at an increased risk of engaging in sexual risk behaviors. However, the relation between sexual risk-taking and NPTCs among MSA survivors is understudied. In the present study, it was hypothesized that (1) there would be a significant positive association between sexual risk-taking and NPTCs among MSA survivors, and (2) sex would significantly moderate this association, such that the relation between NPTCs and sexual risk-taking would be stronger among male MSA survivors compared to female survivors. Secondary data came from the Military Social Science Laboratory (MiSSiLe) at Arizona State University (ASU). Participants (N = 400) completed surveys in Qualtrics, Inc. assessing military history, MSA exposure, sexual risk-taking, and NPTCs. Pearson’s correlation and simple linear regression with moderation were used to test the above hypotheses, covarying for age, marital status, military branch, and history of PTSD treatment. Results showed a significant positive association between sexual risk-taking and NPTCs among MSA survivors (p < .001); however, the interaction between sex and NPTCs only approached significance, such that the association was slightly stronger for male MSA survivors compared to female survivors (p = .055). These results suggest that the interplay between sexual risk-taking and NPTCs could be an important target for improving healthcare for MSA survivors. Furthermore, future research may consider utilizing study samples that more accurately reflect the distribution of service members across all military branches and the sex distribution of service members and veterans. Doing so would improve generalizability and better inform treatment.

After traveling to Spain to study abroad, I noticed a large amount of shops selling goods related to Japanese anime, which helped inspire the topic of my honors thesis. In this paper, the cultural impact of Japanese animation and comics on Spain is explored. The history/origin of anime in Spain, the early reception of these works in Spain, the importance of the anime fandom, the intersection between Spanish and Japanese culture in anime and anime-inspired films, and the positive representation of Spain in these works are all relevant topics that constitute the argument of this document. Sources in both English and Spanish are utilized.This paper explores the surprising connections between the two countries. The way in which their cultures interact through the consumption of this form of media was quite fascinating to look into.

Immediately following the Russian invasion of Ukraine, the European Union (EU) activated the Temporary Protection Directive (TPD) for Ukrainian refugees, contrasting with its inaction during the 2015 Syrian crisis. This inconsistency revealed double standards in EU refugee policy. This thesis explores the EU's Othering in its responses to the Syrian and Ukrainian refugee situations, showing how the EU portrays migrants to affirm its identity. While the response to Syrians in 2015 depicted refugees as a threat to European Christian identity, the response to Ukrainians in 2022 showed more solidarity due to shared "Europeanness." Using the TPD as a lens, this thesis exposes the EU's selective refugee protection based on racialized Othering, where more "European" groups receive favorable treatment. Media narratives further emphasize the differences between Syrian and Ukrainian refugees. The thesis calls for the EU to prioritize human rights over restrictive identity notions.

Histology, the microscopic examination of tissues, is a pivotal tool in research. By providing a detailed view of cellular structures and their organization, this technique allows researchers to advance knowledge in many different disciplines including women’s health and ovarian studies. Studying the female reproductive system is of utmost importance due to its multifaceted effects on aspects such as biological functions, cellular mechanisms, and complex behavioral patterns in women. Therefore, the aim of this honors thesis is to refine and adapt a set of protocols from the Mayer-Dyer Laboratory for ovarian and follicular processing so that they are optimal to use in the Bimonte-Nelson Laboratory of Memory and Aging in the Department of Psychology at Arizona State University. The subsequent aim for the thesis is to replicate and extend the new protocols to complete histology of the ovaries from an interdisciplinary study that evaluated the consequences of hysterectomy with and without estrogen replacement for brain and cognition. This dual-pronged approach will not only contribute to the ongoing discussion regarding the effects of hysterectomy, but also provides a valuable framework for future research endeavors in the field.

Cell immunotherapies have revolutionized clinical oncology. While CAR T cell therapy has been very effective in clinical studies, off-target immune toxicity limits eligible patients. Thus, NK cells have been approached with the same therapy design since NK cells have a more favorable safety profile. Therefore, the purpose of this research project is to explore DNA nanotech-based NK cell engagers (NKCEs) that force an immunological synapse between the NK cell and the cancer cell, leading to cancer death. DNA tetrabody (TB) and DNA tetrahedron (TDN) are fabricated and armed with HER2 affibody for tight adhesion to HER2+ cancer cell lines like SKBR3. Overall, relationship between TB-NK treatment and cancer cell apoptosis is still unclear. TB-NK treatment induces an apoptotic profile similar to PMA/IO stimulation. Pilot cell assay needs to be replicated with additional controls and a shortened treatment window. For DNA TDN fabrication, HER2 affibody polishing with Ni-NTA affinity chromatography achieves high purity with 20% to 100% high-imidazole elution gradient. ssDNA-HER2 affibody conjugation is optimal when ssDNA is treated with 40-fold excess sulfo-SMCC for 4 hours. In conclusion, the manufacturing of DNA-based NKCEs is rapid and streamlined, which gives these NKCEs the potential to become a ready to use immunotherapy.