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Remnants of Identity: Tracing Ancestry in the 19th-Century Rush Medical College Anatomical Collection
Get PDFThis research examines a 19th-century skeletal collection (Rush Medical College Collection) housed at the Field Museum of Natural History to explore whether the original documents designating the recorded “race” of each individual can be corroborated using a modern statistical program (FORDISC 3.1), since how museum workers would have known the ‘race’ of the individuals cannot be determined. The Rush Medical College Collection reflects society’s attitudes towards our nation\u27s most vulnerable individuals, even after death. This research allows us to gain a deeper understanding of the potential effects of marginalization and disenfranchisement in 19th-century Chicago
Motorola Solutions Foundation Cybersecurity Experiential Scholarship Program
Get PDFThis presentation includes the recipients of the Motorola Solutions cybersecurity scholarship. It also includes a summary of the program and the competitions recipients participated in
Analysis of β-glucosidase Mutant T352V
Get PDFThis study looks at mutant T352V Β-glucosidase B (BglB). The mutant product was hypothesized to show reduced kinetic activity and thermostability compared to the wild-type. This was determined through modeling of the mutation using the FoldIt software. The protein was then purified and expressed through SDS-PAGE and Western Blotting. The results indicate that there was no production of a soluble protein. However, the Western Blot indicates the production of an insoluble protein. FoldIt modeling helps to explain the insoluble protein, as it indicates that the proximity of molecules without binding could cause aggregates to form inclusion bodies
Völuspá: A New Translation with Commentary
No full textThis project attempts to translate the Völuspá – the poem of the Poetic Edda which narrates the beginnings and endings of the world in Norse religion – as primarily a religious text, and to provide commentary that elaborates Völuspá’s plot and major theological points in order to make it accessible for theological examination
“Buying Time or Doing Harm?”: Tracing Contestation and Consensus in Debates on Puberty Blockers for Trans Youth
No full textThe use of hormone blockers and other forms of gender affirming medical care for trans youth has emerged as a site of medical and political contestation, with 26 states passing legislation outlawing their use (Movement Advancement Project, 2024). Drawing from a multiple-methods approach, this dissertation examines the ways in which this contestation emerged and has been framed both in political case law and digital spaces, which a specific attunement toward how medical discourse is used to support arguments calling for either the allowance or ban of hormone blockers. This dissertation highlights the ways in which the families of trans youth respond to and make sense of the legislative ban on hormone blockers. Chapter One of this dissertation uses content analysis and case comparison in order to highlight how legislative documents generated in Arkansas and Texas have used medical rhetoric to both ban and appeal the ban of hormone blockers and other forms of gender affirming care. In Chapter Two, content analysis is used to examine how digital communities have formed to call for either the allowance or ban of hormone blockers for trans youth. Chapter Three uses interview data to understand how parents of trans youth frame and understand the political contestation of hormone blockers, and how these bans impact their families. This research has significant implications for sociological scholarship, as it is one of the first works to consider the use of medical rhetoric within on-going debates on the use of hormone blockers. Further, this work contributes to the fields of science and technology studies through an examination of the politicization of science, as well as works within medical sociology studying trans health
Uncovering the Mechanisms of the Anti-Cancer Activity of New Non-Covalent Thioredoxin Reductase inhibitors in Triple Negative Breast Cancer
No full textTriple negative breast cancer (TNBC) makes up only 15-20% of all breast cancer cases, yet it contributes to almost 50% of all breast cancer related mortalities. This highlights the urgent need to develop novel therapeutics for the treatment of TNBC. The thioredoxin (Trx) system is an important cellular antioxidant pathway supported by the enzyme thioredoxin reductase 1, TXNRD1. Upon reduction by TXNRD1, Trx regulates many cellular functions including redox homeostasis and DNA replication and repair through ribonucleotide reductase (RNR), which catalyzes the rate limiting step in the de novo synthesis of dNTPs. Notably, TXNRD1 is elevated in TNBC, thus presents a druggable vulnerability. We identified novel non-covalent inhibitors, TXNRD(i)s, that bind to a unique allosteric site, the “doorstop pocket”, and have previously shown they exhibit anti-cancer activity in TNBC. This study focuses on characterizing the mechanisms of anti-cancer effects elicited by these inhibitors to guide future drug optimization and development in TNBC. To identify major pathways affected, we conducted transcriptomics in TNBC cells treated with two lead TXNRD(i)s or siTXNRD1. Bioinformatic analysis revealed enrichment of oxidative stress (ROS) along with multiple proliferation and cell cycle pathways. Although TXNRD(i) treatment increased intracellular ROS levels, this elevation did not correlate with reduced cell viability. Furthermore, treatment with antioxidant ROS scavengers failed to rescue the TXNRD(i)-induced effects, indicating that elevated ROS is not the primary driver of their cytotoxic activity. We next evaluated the impact of TXNRD(i)s on TNBC cell proliferation and observed a marked reduction in DNA synthesis, accompanied by G1 phase cell cycle arrest. Given that Trx supports ribonucleotide reductase (RNR) activity, we tested whether exogenous supplementation with dNTPs, the products of RNR, could reverse these effects. Indeed, dNTP supplementation fully rescued the cell cycle arrest and significantly restored cell viability while reducing apoptosis and DNA damage. These findings strongly support the conclusion that disruption of RNR function is the key mechanism underlying the anti-cancer effects of TXNRD(i)s in TNBC. Overall, our study challenges the prevailing view that TXNRD1 inhibitors primarily act through pro-oxidant mechanisms and instead highlights a critical role for the TXNRD-Trx-RNR axis in sustaining TNBC cell proliferation and survival
Polycystin-2 Is Cardioprotective Against Myocardial Infarction by Regulating the Calcium-Mediated Er-Stress Response
No full textPatients with autosomal polycystic kidney disease (ADPKD) have an increased risk and worse outcomes after acute myocardial infarction, but the mechanism for this is unknown. Polycystin 2 (PC2), one of the two main proteins mutated in ADPKD, is a calcium permeant channel that localizes to the ER/SR. In non-cardiac cells, PC2 regulates the unfolded protein response (UPR) pathway under ER stress. However, whether PC2 is cardioprotective against ER stress is unknown. We found that PC2 expression increased in cardiomyocytes from human ischemic hearts and infarcted murine hearts. Cardiomyocyte-specific PC2 KO (PC2 KO) mice had worsened cardiac function after myocardial infarction (MI) compared to control (CTL) mice. The UPR arm PERK and its downstream target CHOP were decreased in PC2 KO mice and myoblast PC2 KO cells. The ER stress activator tunicamycin increased ER calcium leak and mitochondrial calcium in CTL cells, but not in PC2 KO cells or isolated PC2 KO cardiomyocytes. Consequently, there was impaired mitochondrial membrane potential and increased cell death in PC2 KO cells. Tunicamycin induced a rapid increase in PC2 expression with enhanced localization to ER-mitochondrial contact sites. Importantly, restoration of functional PC2 in vitro enhanced PERK phosphorylation and the calcium leak in PC2 KO cells. These data suggest that the upregulation of PC2 with ER stress facilitates its function as a leak channel under ER stress, regulating UPR-mitochondrial crosstalk in the early adaptive phase of ER stress. Loss of PC2 impairs the early adaptation and results in worsened cardiac dysfunction with AMI
Episodes in Computing History - Salon Talk
Get PDFThis talk (first given in 2004) presents a concise overview of key developments in the history of computing. It begins with early methods of counting and recordkeeping, such as tally sticks and the Inca quipu. It then traces the evolution of numeric systems, including Roman and Hindu-Arabic notation, and the mathematical contributions of figures like Al-Khwarizmi. Mechanical computing devices such as the abacus, Napier’s bones, and the Pascaline are examined, along with the Jacquard loom and its use of punch cards.
The talk continues through the rise of electronic computing, highlighting milestones such as ENIAC, the work of Alan Turing, and the stored-program concept advanced by John von Neumann. It concludes with reflections on Vannevar Bush’s vision of the memex and its connection to today’s information systems. The goal is to provide historical context for the ideas and technologies that define modern computing, which made the present era of AI possible
Family Matters: Experiences of Family Stigma, Addiction Recovery & The Role of Self-Compassion
Get PDFAddiction and substance use is currently one of the most stigmatized disorders in society, creating a barrier to treatment and recovery. This study explored the role of family stigma, the stigmatization processes of family members of otherwise stigmatized individuals, within families of substance users to examine how stigma might affect family support behaviors. Two hundred and twenty-two U.S. adults who have a substance using family member completed an online survey regarding their experiences of family stigma, attributions of responsibility for addiction, self-compassion, and any supportive recovery behaviors they engage in to help their family member’s addiction. Results of correlation analysis provide evidence that experiencing greater stigma, low trait self-compassion, and greater internal attributions of responsibility are related to lower engagement in recovery support behaviors. However, results from moderated mediation pathways did not support self-compassion as a moderator nor attributions of responsibility as a mediator between family stigma and recovery support behaviors. Additional findings from exploratory analysis and possible directions for future research are outlined
Regulation of Spermatogenesis by the Notch Signaling Pathway
Get PDFThe Notch signaling pathway plays a significant role in gonad development and spermatogenesis, but little is known about its specific targets in the testis. The Drosophila testis contains two populations of stem cells: germline stem cells and cyst stem cells, which give rise to differentiating germline and somatic cyst cells, respectively. Notch signaling is activated in the somatic cyst cells by the Delta ligand from the germline in a region of the testes coined the “transition zone”, where somatic cyst cells progress from early cyst cells surrounding gonialblasts and 2-cell germline cysts to late cyst cells surrounding 16-cell spermatocyte cysts. We have found that increased Notch signaling in somatic cyst cells prevents their complete transition from early to late cyst cell fate, leading to an arrest in late spermatogenesis and sterility. These results suggest Notch signaling is required to enter the transition state, but too much Notch signaling inhibits a complete transition to the late cyst cell fate. To explore the downstream effectors through which Notch mediates these effects, RNA-sequencing was performed on testes overexpressing activated Notch and 1535 potential Notch targets were identified. Through genetics and gene expression analysis, we identified two members of the Enhancer of Split Complex (E(spl)m3-bHLH and E(spl)m-bHLH) and groucho (gro) as downstream targets of the Notch signaling pathway in spermatogenesis. To investigate the direct effects of gro activation in the testes, we expressed overactive Gro protein in the somatic cyst cells using the Gal4/UAS system. Overexpression of activated Gro resulted in a decrease of cells in the transition state and a delayed onset of the transition zone when compared to the control. These results suggest too much Gro results in continued repression of Notch targets in somatic cells, preventing the transition of somatic cells from early to late cyst cell fate. Knocking down E(spl)m3-bHLH and E(spl) E(spl)m-bHLH also causes a delayed onset of the transition zone, suggesting that Notch activation of these targets is required to promote the transition state. Our results support a model in which Notch signaling is required for the transition state but must be turned off for somatic cells to completely transition to the late cyst cell fate to promote the late stages of sperm development