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Optimization of Research Pipeline to Characterize the Effects of ATP-sensitive Potassium Channels Mutations on Native Skeletal Muscle Fibers and Evaluate Potential Drug Therapy
No full textThe ATP-sensitive potassium (KATP) channel is a critical metabolic sensor in skeletal muscle, yet its definitive molecular composition and functional roles remain contested. In this study, I conclusively demonstrate that the Kir6.2/SUR2 complex forms sarcolemmal KATP channel in mouse fast-twitch muscle. Genetic knock-out (KO) of Kir6.2 (Kcnj11−/−) or SUR2 (Abcc9−/−) resulted in a similar phenotype with increased fatigue resistance and a pathological rise in unstimulated resting tension at high-frequency stimulation. In contrast, SUR1 (Abcc8−/−) KO was ineffective. Furthermore, a CRISPR/Cas9 knock-in mouse model of a human SUR2A truncation variant (KCGV/KCGV) recapitulated the abnormal force accumulation, demonstrating that even loss-of-function of this subunit specifically disrupts electromechanical stability. Crucially, the KV7 channel agonist retigabine (20 µM) partially prevented the increase in unstimulated tension, suggesting a potential therapeutic approach. I also have developed a same-day, suspension-mode fluorescence ion-flux assay that provides a greater than two-fold enhancement in signal intensity and can be used as a stable base for future high-throughput therapeutic screening. This would eliminate uncertainties in muscle KATP channel biology and create a pipeline from mechanistic discovery to potential therapeutic approach
Telling Melodies: Musical Agency in Narrative Film
No full textMost filmgoers feel the power of film music and its ability to “tell the story,” though few are able to describe how that power works. Through close analysis of several uses of music in a variety of Hollywood films, this thesis provides insights into the nature and degree of how the emotional power of film music serves the narration. Using neoformalist film-studies methods combined with recent ideas in philosophy, film-music narratology, and fields that study the mind and brain, I will demonstrate film music’s ability to relay narrative information, showing that film music is able to function as a primary contributor to our comprehension of film narratives as it increases knowledgeability and communicativeness thereby facilitating the construction of the fabula. Through close analysis of music’s role in the narration process, I argue for the necessity of expanding the type of knowledge that the narration shares as well as reconceptualizing ways of sharing and receiving it. The results suggest that we rethink the nature of narration and of hypothetical spectators’ activities as they interact with a film’s stylistic system in their active construction the fabula. That film music “moves us” is not just figuratively true but literally true as the spectator through embodied cognition engages with the film’s stylistic system that “hijacks” the evolutionary dispositions that function to monitor physical, emotional and social changes to the environment, including the mediated environment
From Desegregation to BLM: Racial Threat, Discourse, and Consolidation of Power in a Missouri Public School District
No full textThe re-emergence of the Black Lives Matter movement in 2020 and publication of the 1619 Project brought a cultural shift with how our nation talk about and understands racism. Within the K-12 public schools, this led to a review and reconsideration of how race has been addressed through curriculum, in staff representation, and programmatically through support of students of color (Dunivin et al, 2020). Yet within a few short years, over 560 measures aimed at limiting conversations around race were introduced in local and state governing bodies across the country (Clark, 2022). What does this shift say about how white power is negotiated and mobilized around during moments of perceived racial threat? I build upon critiques of traditional racial threat literatures (Brown, 2010; Cunningham, 2012) to offer a more expansive conceptualization of how racial threat is perceived, communicated, and navigated over time. In this paper, I examine one instance of contestation occurring in the political context of a Missouri school district from 2019-2024. Utilizing a qualitative content analysis, I draw upon election forums, interviews, and news reports to study the dynamics of threat-based mobilization as reflected in local school board elections. By integrating racial threat, contentious politics, and boundary work literatures, I find that white powerholders mobilized against perceived racial threat by utilizing discursive mechanisms to contract community boundaries, placing parents and education stakeholders in opposition to one another. Over time, elite movement victories become institutionalized and racial threat is suppressed, leading the community boundaries to appear expansive once again. While this positioning is discursively reflected as a movement towards unity and normalcy, we instead find a consolidation of power and return to colorblind discourse. Broadly, these findings suggest that the decline in extreme and divisive discourse was the product of suppression of opposition, rather than political positioning itself. Within our polarized political climate, this research encourages us to think critically about the power of discursive mobilization
Little Nights: A Novel
No full textJonathan has soft centers: he tends a garden, enjoys baking, crochets, collaborates on graphic novels and pop culture trivia with classmates. He enjoys long walks and watching people. Following the death of his mother, he is thrust into a world of hyper-masculinity. His father, a traveling civil engineer and in grief, leaves Jonathan and his younger brother Ikenna in the care of their older cousin, Chuka, and his friends. These men, in a new position of power over Jonathan, seek to remake him into a model man: straight, masculine, subservient to their pecking order.
Jonathan is stubborn, insistent on a value in his queerness that is affirmed by the media he consumes and the internet. While he resists Chuka’s friends, his feelings grow complex once he starts to desire them sexually. As puberty begins, with an increasing sense of his alienation, Jonathan falls into the world of internet pornography, finding older men on Facebook and developing a physically- and psychically-painful masturbation addiction.
Set in Nigeria and the internet space of the mid-2010s, Little Nights is an exploration of the internet\u27s influence on the relationship between one\u27s self and community, and the quest towards a meaningful life
Reliability of Longitudinal Sleep Monitoring in Amyloid-Negative and Amyloid-Positive Older Adults.
No full textSleep disturbances are associated with Alzheimer’s disease (AD) pathology and cognitive symptoms, but longitudinal studies exploring sleep, AD biomarkers, and cognition are limited. Understanding changes in sleep among older adults with and without AD pathology is crucial for appropriately designing longitudinal studies of aging and AD. To assess this, sleep was longitudinally assessed (over ~3.5 years) in amyloid-negative and amyloid-positive older adults using self-reported logs, questionnaires, and at-home monitoring with a single-channel electroencephalography (EEG) device. Amyloid imaging and cognitive assessments were also performed. Test-retest reliability was evaluated using intraclass correlation coefficients, and power analysis determined sample sizes for longitudinal observational studies. In both amyloid groups, EEG spectral power measures demonstrated the highest test-retest reliability, followed by EEG-derived sleep staging and duration then self-reported measures. Spectral power required the smallest sample size to detect changes over time. These results indicate that objective EEG measures provide the most reliable longitudinal data for studying sleep and AD, aiding future study designs
Do all Components of Psychological Wellbeing Predict Cognitive Function?
No full textSense of purpose has been consistently associated with cognitive function. However, less is known about the associations between the other five components of wellbeing and cognitive outcomes. The current research aimed to establish which components of wellbeing are most strongly associated with cognitive function. Participants from the Midlife in the United States study (MAge=56.18, SD=12.38) completed the Ryff Psychological Wellbeing Scales (1989) and the Brief Test of Adult Cognition. Multiple regression analyses were used to examine the cross-sectional and prospective associations between wellbeing and cognitive function. All six components of wellbeing were significantly and positively associated with cognition cross-sectionally (bs=0.07-0.19). Moreover, higher levels of sense of purpose, personal growth, environmental mastery, and self-acceptance were associated with better cognitive function at nine-year follow-up when controlling for baseline cognition (bs=0.03-0.05). These findings extend past wellbeing research by demonstrating that, in addition to sense of purpose, other components of wellbeing are also associated with cognitive function and should be assessed as possible protective factors for cognitive function across the lifespan
Fabrication Process for Thin Film Solution Based Indium Galium Zinc Oxide (IGZO)
No full textOxide thin film transistors (TFTs) have gained popularity as a replacement silicon based TFTs, with indium gallium zinc oxide (IGZO) being the leading candidate. A solution-based fabrication method has been studied to replace the current fabrication method using radio frequency or direct current sputtering. However, the solution based fabrication method has shown to have low reliability in producing high quality IGZO films. Thus, the fabrication parameters to produce high quality IGZO films were studied. It was found that an IGZO solution with a 0.5M concentration of 2-methoxyethanol annealed at 300°C for 30 minutes with a prebake at 70°C for 10 minutes produced the best quality IGZO film
STEM and PDF Simulation of crystalline and amorphous materials
No full textThe aberration corrected scanning transmission electron microscope (STEM) is a powerful tool for nanoscale characterization, as it is capable of imaging structures with sub-angstrom resolution. An optical microscope uses visible light to magnify objects, which is limited to ~1000X due to the limited resolving power of light. Here, we applied STEM simulations via PRISMATIC and PY4DSTEM, in order to compute images of crystals, 2D materials, and metallic glasses. Practically, computational simulations are important due to the operating cost of STEM and time required to be trained on the equipment. More importantly, simulations provide a direct comparison between theory and experimental results. It assumes ideal crystal formation, with no defects, thus producing an easily interpretable image. In addition, Pair Distribution Function (PDF) algorithm of DiffPY-CMI are employed in order to probe into S/MRO of amorphous materials