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Whole-Blood RNA-seq in Adult-Onset Focal Dystonia: Differential Expression, Cell-Type Deconvolution, and Pathway Analyses
No full textBackground: Although adult-onset focal dystonia (AOFD) is the third most common movement disorder, its etiology remains poorly understood. Clinical diagnosis is performed solely based on clinical features, often leading to significant delays in diagnosis and treatment. While Genome-Wide Association Studies (GWAS) have identified specific genetic risk loci, these common variants explain only a fraction of the heritability and lack functional context. Consequently, identifying objective blood-based biomarkers that reflect the downstream biology of this disease is critical. Recent independent proteomic studies indicate immune and metabolic dysregulation in AOFD plasma; therefore, a comprehensive transcriptomic investigation is warranted to better characterize the systemic molecular footprint.
Methods: PAXgene whole-blood RNA-sequencing data from a large multicenter cohort recruited by the Dystonia Coalition were analyzed. To exclude potential Alzheimer’s disease (AD) co-pathology, controls were defined as “AT-negative” (confirmed negative for plasma amyloid-beta and phosphorylated-tau). Data processing followed a standardized STAR/Salmon bioinformatics workflow. Samples that failed to meet strict numeric quality control (QC) thresholds (such as mapping rate and RNA Integrity Number (RIN)) were excluded. Differential expression was modeled using DESeq2, incorporating Surrogate Variable Analysis (SVA) to correct for latent technical confounders, as SVA outperformed Principal Component Analysis (PCA) in capturing batch effects. Cell-type composition and functional contributions were inferred using CIBERSORTx-based deconvolution.
Results: Using a false discovery rate (FDR) \u3c 0.05, the analysis found 2,196 differentially expressed genes. The AOFD transcriptomic signature is characterized by the widespread downregulation of cytoplasmic translation and mitochondrial respiratory pathways (e.g., NDUFA7), along with significantly upregulated RNA splicing (e.g., FUS) and stress response signaling. Sensitivity analyses confirmed that these effects were robust across different QC strategies and racial backgrounds. Deconvolution revealed a significantly remodeled immune compartment, with expanded monocytes, and reduced CD4+ T cells and NK cells. Crucially, cell-type-specific enrichment indicated that the global translational suppression signal was largely driven by lymphopenia, while expanded neutrophils exhibited a suppressed functional signature (S100A8/A9).
Interpretation: In this study, we identified a robust systemic molecular footprint for AOFD in peripheral blood. By correcting for latent confounders and utilizing rigorous control definitions, we uncovered a complex interplay among metabolic suppression, splicing dysregulation, and myeloid-biased immune remodeling. These findings validate previous proteomic signals and suggest potential molecular biomarkers for future clinical applications
Antioxidative Copolymer for Ischemia-Reperfusion-Induced Flap Necrosis: Synthesis and Evaluation
No full textReactive oxygen species (ROS)-induced oxidative damage is a major cause of tissue necrosis during skin flap ischemia-reperfusion (I/R) injury. However, existing antioxidant materials often show limited scavenging efficiency, poor injectability, or inadequate controllability. Here, we synthesized an injectable copolymer, poly(eTEGA-co-LA), via AIBN-initiated free-radical copolymerization. By integrating α-lipoic acid (ALA), a ROS-responsive thioether antioxidant, into the polymer backbone, the material achieves active elimination of multiple ROS, while tri(ethylene glycol) ether units maintain thermoresponsive behavior and injectability. Poly(eTEGA-co-LA) exhibits an adjustable lower critical solution temperature (LCST), excellent cytocompatibility, and sustained scavenging activity against various ROS, including DPPH radicals, hydroxyl radicals (·OH), and hypochlorous acid (HClO). In a rat random-pattern skin flap I/R model, the material improved microcirculatory perfusion, reduced distal necrosis, and helped preserve tissue structure, indicating significant in vivo protection against oxidative injury. Overall, poly(eTEGA-co-LA) serves as a dual-functional material combining thermoresponsive phase transition with strong antioxidant capacity, offering a promising materials-based strategy for treating flap I/R injury and other oxidative stress-related conditions
Dual Networks of Dynamic Polymer and Conducting Polymer for Bioelectronics
No full textStretchable conducting polymers are promising candidates for soft bioelectronics due to their advantages in stretchability, conductivity, and biocompatibility. However, the inherent trade-off between electrical performance and mechanical elasticity limits the practical applications in bioelectronic devices. In this thesis, dual polymer networks comprising a conducting polymer and a dynamic polymer were designed to investigate strategies for balancing mechanical robustness and electrical conductivity. Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS) was selected as the conducting component while a PEG-based dynamic polymer with hydrogen-bonded cross-linking networks was synthesized to provide mechanical functions. Increasing the PEDOT: PSS content enhanced stiffness and conductivity by forming interconnected polymer networks, but this improvement was accompanied by a significantly reduced elongation at break due to increased brittleness. The results demonstrate that incorporating 40% PEDOT: PSS achieves a good balance between toughness (160 MPa) and conductivity (25 S/cm) compared with other polymer blending strategies. These findings indicate that dynamic polymers enable improved mechanical toughness and electrical performance, offering a promising materials design strategy for future soft bioelectronic applications
The Reach of Legal Cynicism: A Comment on Tommie Shelby’s The Idea of Prison Abolition
No full textIn The Idea of Abolition, Tommie Shelby traces the prison abolition movement in the U.S. to 1960s Black radical politics, a politics based in war metaphors and isolationist anti-state ideology. While an understandable response to government persecution of mid-twentieth century Black activists, anti-state ideology is a poor fit for the Black communities of the present. Something similar can be said about a prison abolition politics that broadly rejects the notion that criminal detention has a role to play—however limited—within the broader project of rehabilitating beleaguered Black residential communities
Everyday Virtue Expressions as a Function of Virtue Traits and Situational Affordances
No full textInterdisciplinary virtue theories have conceptualized virtues as contextualized personality traits that may only be expressed in the presence of virtue-relevant situational affordances (Fowers et al., 2023; Wright et al., 2020). However, there have been no systematic efforts to determine which situations create opportunities for virtuous actions and what role these situational affordances should play in the conceptualization and measurement of virtues. Across two crowdsourcing studies and two daily life studies, we developed a taxonomy of virtue- affording situation features, tested competing predictions about how virtue traits and situational affordances work in tandem to explain momentary virtue enactments, and investigated measurement implications of including information about relevant affordances. We found little evidence that people’s virtue enactments were more consistent with their trait levels when these virtue-relevant affordances were present. Instead, we primarily found main effects of affordances on virtue enactments. Additionally, comparisons of intercorrelations between virtue enactments during situations where virtue affordances were present vs. absent suggested that self-reports of virtue states during virtue-relevant situations may be less affected by response biases. In sum, these findings support an additive model of trait and situational effects on virtues and provide insights into potential methods for improving the measurement of virtues in everyday life
Baubles
No full textBaubles is a nonfiction collage of flash prose exploring how obsession has shaped and transformed my experience of the world. As a child suffering from obsessive compulsive behavior, likely as a result of my father developing dementia when I was in elementary school, I found reprieve in what became a feverish obsession with music, namely Bob Dylan. Memorizing Dylan’s lyrics quelled the urge to hoard my memories, and tracing his many evolutions allowed me to emulate the construction of my own identity. My interest in such an icon unavoidably led to others, like Edie Sedgwick, whose fleeting fame and early demise evokes the melancholia of American girlhood. As the project unfolds in prose blocks, themes and patterns emerge kaleidoscopically to create a central narrative under the hum of musical language. In short, this manuscript chronicles the transformation of disruptive obsessions into life-giving ones, of murky memories into textured fragments of color and light
Investigating Ionic Liquid (IL)-based Electrolytes in Li-CO2 Battery Performance
No full textThis report discusses the results of an independent study that investigates the impact of ionic-liquid (IL) based electrolytes on Li-CO₂ battery performance. Three electrolytes were compared in this study at two temperatures: room temperature and 60 °C. The electrolytes tested were BMIM-DMSO (an IL-based electrolyte), TEGDME, and DMSO. The results indicate that the IL-based electrolyte enables better electrochemical reactions and achieves a higher discharge capacity than the other two electrolytes. This study also compared cathodes with different catalysts, emphasizing the importance of catalyst choice. The comparison showed that bismuth oxide combined with Vulcan carbon may serve as a strong catalyst for future cathode designs. To further characterize discharge product formation, cathodes were neutron-imaged at Oak Ridge National Laboratory, and image processing has begun using Dragonfly 3D, although additional analysis is still needed. Overall, these findings demonstrate that electrolyte and catalyst selection play key roles in advancing Li-CO₂ battery performance and lay the groundwork for optimizing next-generation CO₂-utilizing energy systems
MEMS 4110: The Scissor Arm Extender
No full textThe widespread adoption of electric vehicles is limited by the inconvenience and physical demands of manually connecting charging cables, particularly for individuals with mobility impairments. Existing automated charging solutions are either insufficient in reach, overly bulky, or cost-prohibitive. There is a need for a compact, affordable, and fully automated charging connector extender that can deliver a standard J1772 charging plug to a vehicle’s port with minimal human interaction, enabling accessible and efficient EV charging for all users
MEMS 4110: Arduino-Controlled Precise Water Distribution System
No full textChristina Youngepeter is a Graduate Student of Archaeology at Washington University in St. Louis. She is studying an ancient plant that fell out of use after 1400 CE, whose ideal watering conditions are lost to time. To better characterize the plant, Christina is running an experiment to determine the ideal watering conditions for plant development. This involves watering sets of the plant with different volumes of water twice a day. The different volumes of water received by the groups of plants are 933 mL, 833 mL, 733 mL, 617 mL, 517 mL, and 417 mL. The acceptable percent error in this delivered volume is 5%. Water is currently measured and delivered to plants by hand, but as the project expands to hundreds of plants (150-360 plants), this watering method is no longer feasible. To facilitate expansion, Christina wants a modular water delivery system that is designed to water 36 plants automatically, providing different amounts of water to watering groups of six plants. Furthermore, the watering schedule followed by the system must have the ability to be changed and set by the user. To accomplish this, a unique and precise water distribution system (PWD) was designed. The PWD will be implemented in the WashU greenhouse and will have access to water lines and power outlets. The University City tap water lines supply the water to the PWD. This water is currently used to water the plants and is an approved source of water for the PWD. In addition, the greenhouse houses structures such as cross beams which can provide support to the PWD. Any load applied to the greenhouse structure must be approved by the greenhouse manager, Benjamin Wolf, PhD. The following work is a detailed record of the design process and final product
MEMS 4110: Soft Boiled Egg Peeler
No full textThis report outlines the design and evaluation of a hard-boiled egg–peeling device developed for the Saint Louis restaurant Neon Greens. The restaurant prepares an average of 150 soft-boiled eggs daily for dishes such as the Protein Salad. They requested a device able to autonomously peel 150 eggs per hour with minimal employee involvement