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Apocalyptic Masculinity: Messiahs, Monsters, and Men Out of Time
No full textWith their often other-worldly settings and larger-than-life themes, apocalyptic texts are regularly thought of as “dramatic” texts. These texts have inspired large swaths of popular media considering the end times, but rarely have performance critical projects within biblical studies considered how these texts would have been received in performance in antiquity. To expand thinking around performance and apocalypse, this project examines not only these categories, but also adds in a consideration of gender. This work is concerned with answering the question “is there such a thing as apocalyptic masculinity?” This project uses performance and performativity as a method to read apocalyptic texts to delineate a particular masculinity distinctive to apocalypses. I bring these threads together through three themes: (1) messianic figures in apocalypses, (2) the relationship between the monstrous and the masculine, and (3) the place of pseudepigraphy and what happens when major male historical figures are pulled out of their historical locations to be used in other contexts. This book argues that there is a particular strand of masculinity that is prevalent in apocalypses: one that is fluid and unstable. In talking about fluid apocalyptic masculinity, we can make sense of the shifting and reframing of the masculinity standards that were a part of the culture at-large when the narratives were created
Cyclical Matters: Black Labor, Temporality, and the Incomplete Reconstructions within African American Literature
No full textThis dissertation examines the role literature plays in understanding black life post-reconstruction and post-civil rights movement. Specifically, I explore the continuation of injustices and mistreatment for black workers, the role black labor plays during the first and second post-reconstructions, and how literature can be used in framing this discussion. The similarities between these periods help us to better understand the cycle of racist societal expectations and the challenges black workers face integrating into society, discriminatory mandates required of black workers, the unfair job market, and forced labor. These periods interact cyclically in that the second post-reconstruction models the first post-reconstruction. Both periods contain moments of hope and progression as demonstrated through nationwide ordinances and moments of hopelessness and regression due to minimal or no change. I argue that literature is a complex aesthetic construction whose relation to social reality must be investigated. My focus on temporality and narratives provides a way that literature uniquely speaks to the questions regarding black labor and workers
Perverse Convergences: Aelred of Rievaulx and the Queerness of Waiting
No full textABSTRACT Using Aelred of Rievaulx’s (1110-1167) treatise Spiritual Friendship and his fundamental insight, “God is friendship,” this dissertation seeks to understand how the divine arrives woven into the dynamics of human relationships. I bring together social media research, critical theories of language, queer phenomenology, queer temporalities, and liberation theologies into a cross-temporal erotic narrative between Aelred and me. The first part establishes the imaginative distemporal space of Sodom, based on a shared homosexual identity. It critiques historical and theological disciplines as familiarizing discourses that compel arrivals of the other through structures authentication and the social magic of professionalization. In the second part, Aelred’s own desires confront me when I wander the ruins of his twelfth-century abbey. Listening to these ‘echoes of the past,’ I find myself complicit in familiarizing discourses. The final chapter situates all definitive claims about the other, whether theological, historical, or relational, within temporal structures of teleological stability, as if we already know to be true what will be true about God, Aelred, or another. Desiring stability, we risk leaving behind others, whose experiences of the divine may disalign with what theologians already know to be true. They become remainders to our systems and ideological claims, and, in leaving these persons in the past, we ignore when the divine fails to act according to our desires for liberation. I propose a method of theological wandering (pervagatio) following Aelred’s dialogical method that flips the roles of student and teacher, that prefers and gives voice to the opinions, needs, concerns, and (failed) desires of the non-professional. It is, in brief, about noticing those who remain silent
Genetic Architecture of Complex Traits in African Ancestries Across Diverse Environments
No full textGiven genetic and environmental diversity, genetic prediction based on African- ancestries individuals in the US or UK may not transfer well to other African diaspora regions. The Modeling the Epidemiological Transition Study (METS) is a longitudinal study of cardiometabolic health in five African-ancestry populations. We performed genome-wide genotyping in METS participants from the US, Jamaica, South Africa, and Ghana. We aimed to explore how genetic models for the transcriptome and body mass index (BMI) built using US- based African-ancestries populations perform in these four diverse populations. A subset of METS participants also had whole blood RNA-Seq data. For these, we predicted gene expression from genotypes using published African-ancestries transcriptome models, which were built in the US-based TOPMed MESA study. Next, we used the three largest populations in All of Us to build cross-validated polygenic risk score (PRS) models for BMI with PRS-CSx, a Bayesian method that combines genetic effects across populations via a continuous shrinkage prior. We then tested our PRS models in METS participants. PRS performance varies between these four groups, roughly following the trend in their countries’ human development index levels, suggesting the influence of environmental differences in genetic prediction of BMI. Transcriptome prediction performance also varies significantly between the US and Ghana. Overall this work supports the importance of global representation in genetics research for more accurate healthcare
Examining Pyroptosis in Neutrophil-Like Differentiated Hl-60 Cells
No full textThe innate immune system is the first line of defense against pathogens. Innate immune cells, such as macrophages and neutrophils, recognize pathogens through the recognition of pathogen associated molecular patterns or damage associated molecular patterns (PAMPS & DAMPS). When a pathogen is recognized, innate immune cells will start clearing the pathogen and secreting pro-inflammatory cytokines, such as interleukin-1β (IL-1β) to initiate the innate immune response. Release of IL-1β occurs through an unconventional secretory pathway triggered by inflammasome activation. Activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome cleaves both pro-IL-1β into mature IL-1β, and full length gasdermin-D (GSDMD) into a pore-forming N-terminal fragment (NT-GSDMD). In macrophages, the secretion of IL-1β is mediated through NT-GSDMD pores that form on the plasma membrane. Plasma membrane NT-GSDMD pores also allow the influx of water leading to cell lysis in a process called pyroptosis. In macrophages, pyroptosis occurs rapidly after inflammasome activation due to the immediate localization of NT-GSDMD to the plasma membrane. However, in neutrophils, pyroptosis is not a rapid process, rather they seem to be resistant to pyroptosis even under the same inflammasome activation conditions as macrophages. Previous studies have shown that NT-GSDMD localizes to intracellular vesicles in neutrophils directly after inflammasome activation and not the plasma membrane. The regulation of pyroptosis and NT-GSDMD subcellular localization is poorly characterized in neutrophils. To investigate the basis of neutrophil pyroptosis resistance and NT-GSDMD trafficking, we first identified a genetically tractable cell line model that mimics the pyroptosis phenotype observed in primary neutrophils. We determined that the HL60 cell line, when differentiated into neutrophil-like cells, recapitulates the pyroptosis-resistance phenotype observed in primary neutrophils upon NLRP3 inflammasome activation. We then employed pharmacological inhibition of secretory pathways and microscopy-based localization studies to characterize NT-GSDMD localization and trafficking in differentiated HL60 cells. We also established a doxycycline-inducible, flag-tagged NT-GSDMD expressing HeLa cell line, to investigate NT-GSDMD trafficking in a reductionist setting independent of upstream inflammasome activation. These complementary cell line tools now allow for dissection of NT-GSDMD localization and pyroptosis regulation. Determining how neutrophils regulate NT-GSDMD localization and resist lytic death may reveal novel approaches of therapeutic intervention for controlling neutrophil-driven inflammation in pathological contexts
Role of Coronavirus Envelope Protein on Infectivity
No full textCoronaviruses infect a wide range of hosts and have caused recent human pandemics. While much has been learned, gaps remain in understanding viral assembly and egress, particularly the role of the envelope (E) protein in specific infectivity. To study this, recombinant MHV viruses were created with E gene deletions and HiBiT-tagged spike (S) proteins to monitor virion release. In mouse cells, MHV∆E S-HiBiT secreted less spike and fewer infectious particles, indicating reduced specific infectivity. Comparisons between human HeLa-CEACAM and mouse DBT cells showed species-specific support for virus production. TMED10, a host membrane protein, was tested as a potential E-interacting partner via CRISPR knockout, but results showed it was not required for E-mediated assembly. Additionally, E proteins increased IL-1β secretion, with variability among coronavirus strains. Overall, the study enhances understanding of E protein roles in coronavirus egress, infectivity, and host interactions
Investigating Whether Txnrd2 Is a Therapeutic Target Against Triple Negative Breast Cancer Using African American-Derived Models
No full textDespite similar breast cancer incidence rates, African American (AA) women experience a 40% higher mortality rate compared to Caucasian American (CA) women. This disparity is multifactorial and particularly pronounced in the Chicago area. AA women are twice as likely to be diagnosed with triple-negative breast cancer (TNBC), often at a younger age and with more aggressive disease. TNBC is a heterogeneous subtype lacking targeted therapies and is associated with the poorest prognosis among breast cancer types. Therefore, there is an urgent need for novel therapeutic strategies for TNBC, especially those tailored to AA patients. The thioredoxin pathway is essential for maintaining redox homeostasis and supports various cellular processes, including proliferation, cell death, and signaling. In cancer, the heightened reliance on this pathway presents a druggable vulnerability. In this study, we investigated the role of thioredoxin reductases (TXNRDs), with a particular focus on the mitochondrial isoform TXNRD2, in AA-derived TNBC cell models. We first observed that TXNRD2 levels are highest in breast tumors from AA patients. We then evaluated the therapeutic potential of targeting TXNRD2 using a new class of non-covalent TXNRD inhibitors, TXNRD(i)s, which bind an allosteric site rather than relying on traditional covalent inhibition. To distinguish the activity of TXNRD2 from its close homologue TXNRD1, we developed a dual-labeling live-cell microscopy approach. Silencing TXNRD2 using siRNA significantly impaired TNBC cell growth. While TXNRD1 also plays a role in supporting TNBC cell viability, dual silencing of TXNRD1 and TXNRD2 had a markedly stronger inhibitory effect, with minimal impact on non-tumorigenic MCF-10A control cells. Treatment of AA-derived TNBC cells with our TXNRD(i)s phenocopied this dual silencing, and our imaging data confirmed that these compounds act as pan-TXNRD1/2 inhibitors. Together, these findings support TXNRD2 as a viable therapeutic target in TNBC and suggest that simultaneous inhibition of both TXNRD1 and TXNRD2 may represent a more effective therapeutic strategy especially for treating AA-patients with lethal breast cancers
Episodes in Computing History - Salon Talk
Full text linkThis 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
Full text linkAddiction 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
Full text linkThe 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