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Association of the Commensal Fungus Candida albicans in Alzheimer's Disease
Get PDFCandida albicans is a common gastrointestinal (GI) tract commensal fungus in humans, yet under certain circumstances, it will adopt a pathogenic state and promote systemic infection and inflammation. One of the primary virulence factors of C. albicans is candidalysin, a cytolytic peptide secreted during hyphal growth that has been shown to induce disruption of epithelial barriers and trigger host immune responses. Current evidence suggests that intestinal barrier dysfunction and microbial dysbiosis can lead to the pathogenesis of Alzheimer's disease (AD) and C. albicans has been detected in AD patients' brains postmortem. However, less is known about the mechanisms through which gut fungi migrate to the brain and induce neuroinflammation. In this current study, we used in vitro and in vivo models to investigate if C. albicans virulence factors - hyphal morphogenesis and candidalysin secretion - increase intestinal permeability and systemic dissemination, and to identify how these occurrences might interact with AD-associated host susceptibility. In vitro, C. albicans induced significant barrier disruption in Caco-2 cell monolayers, dependent on hyphal formation and candidalysin secretion. Additionally, in our 3D cortical brain organoid models, organoids harboring the familial AD mutation (PSEN1 L435F), C. albicans infection did not significantly induce neuroinflammation when microglia were present. But when the organoids lacked glial cells or had astrocytes, a significant immune response was detected when challenged with yeast or hyphal Candida regardless of candidalysin, respectively. In vivo, candidalysin was required for C. albicans to translocate from the gut to the brain in CARD9-deficient mice. However, in APP-NLGF mice, a transgenic model of AD, GI colonization of C. albicans did not result in dissemination into the brain despite being predisposed to increased gut permeability and altered GI proinflammatory cytokine expression. Surprisingly, candidalysin was not required for colonization in our murine model of AD. Together, these findings identify candidalysin and hyphal morphology as key drivers of epithelial barrier dysfunction and fungal dissemination in susceptible hosts. While AD pathology correlates with increased gut permeability and immune dysregulation, candidalysin-independent colonization does not appear sufficient for fungal migration to the brain. These results underscore the complex interplay between fungal colonization, host defense/immunity, and neurodegenerative diseases and highlight candidalysin as a potential target for preventing fungal-mediated systemic and neurological pathologies.Molecular Microbiology and Immunolog
From Features to Feelings: How Media Platform Design Fosters Parasocial Experiences
Get PDFThis dissertation examines parasocial experiences and user engagement across evolving media platforms. Although conceptualized before Tukachinsky's (2023a) call to shift focus away from specific platforms, it aligned to directly address this challenge by highlighting the effects of media affordances and offering a framework to study parasocial phenomena across different mediums. Grounded in communication theories such as media richness and synchronicity, this study explores how design features enable affordances that align with users’ motivations, ultimately influencing their platform selection. Using the Multimotive Information Systems Continuance Model (MISC) by Lowry et al. (2015), we investigate how hedonic and intrinsic motivations influence platform usage, and how parasocial experiences contribute to users’ evaluations of platforms. Further, using the Needs-Affordances-Features perspective provided by Karahanna et al. (2018), we explain how users pursue features to fulfill the aforementioned (hedonic & intrinsic) motivational needs. Results demonstrate how parasocial relationships play a role in shaping users’ attitudes and expectations before system use, while parasocial interactions improve expectation disconfirmation. Ultimately, parasocial experiences have a positive indirect influence on platform continuance, through initial and revised attitudes and their expectation disconfirmation.Information Systems and Cyber Securit
Development of a Novel Compound Effective Against Juvenile, Adult, and Drug-Resistant Schistosoma Species
Get PDFSchistosomiasis, a neglected tropical disease affecting over 250 million people worldwide, relies on praziquantel (PZQ) as its sole treatment. However, PZQ has significant limitations, including inactivity against juvenile worms, inability to prevent reinfection, and emerging drug resistance. In this review, we outline the development of CIDD-0150303, a novel oxamniquine (OXA) derivative with pan-species and pan-stage activity against <i>Schistosoma mansoni</i>, PZQ-resistant <i>S. mansoni</i>, and <i>S. haematobium</i>. Using a structure-guided design approach, over 350 OXA analogs were synthesized and screened to identify leading drug candidate CIDD-0150303. CIDD-0150303 demonstrates 100% lethality in vitro and up to 80% reduction in worm burden in vivo. CIDD-0150303 is effective against both juvenile and adult parasites as well as PZQ-resistant <i>S. mansoni</i>. This compound represents a promising advance in schistosomiasis treatment to address urgent gaps in control/elimination strategies and PZQ resistance. However, dedicated safety and toxicity studies are still ongoing, and additional in vivo validation is required.Chemistr
Autonomous Construction in Extraterrestrial Environments: A Focus on Process Simulation and Resource Optimization for Lunar Sustainability
No full textThe full text of this item is not available at this time because the author has placed this item under an embargo until August 26, 2027.Establishing a sustainable human presence on the Moon requires construction of essential infrastructure, notably a Lunar Launch and Landing Pad (LLP). A lunar base is considered a gateway for advancing deep space exploration by serving as a testing ground for technologies essential for long-duration space travel and a strategic launch location for missions to Mars and beyond. However, lunar construction is faced with challenges like extreme temperature variations and solar wind, vulnerability to meteorite bombardments due to its vacuum environment, and the absence of conventional construction materials. This necessitates an alternative construction method less dependent on human workers and traditional construction materials on Earth. An alternative construction method that relies on robotic construction equipment with in-situ resources utilized as construction materials is presented in this research. The overarching goal of this study is to assess the feasibility of autonomous construction of a lunar landing pad on the moon’s surface, develop a simulation framework to model the construction, and optimize the use of construction robots by eliminating system bottlenecks. By considering the extraction and processing of the in-situ construction materials, the power requirement of the construction equipment, and the impact of the lunar environment on the construction process, the intricate dynamics of the construction activities are assessed. The Findings of this research are expected to facilitate equipment quantification, resource optimization, project scheduling, and preliminary costing.Civil and Environmental Engineerin
MEASURING ADAPTABILITY IN U.S. ENVIRONMENTAL REGULATION: EVIDENCE FROM COMMAND-AND-CONTROL, INCENTIVE-BASED, AND HYBRID FRAMEWORKS
Get PDFThis study investigates the adaptive evolution of U.S. environmental regulatory policy by analyzing the structural behavior of three major frameworks: Command-and-Control (CAC), Incentive-Based (IB), and Hybrid models. While adaptability is widely acknowledged as a critical feature of effective environmental governance, most existing research lacks empirical tools to measure it systematically across regulatory systems. As a result, analyses of regulatory adaptability have been limited in scope, often case-specific, and lacking in longitudinal depth and empirical evidence. Using a longitudinal dataset of over 11,000 environmental regulatory subparts drawn from the Code of Federal Regulations (1970–2022), this study introduces a novel methodology to quantify regulatory adaptability. Each subpart was manually classified into CAC, IB, or Hybrid categories based on enforcement mechanisms and compliance structures. Time-series growth trends, Gini coefficients, kurtosis analysis, and Lorenz Curve modeling are employed to assess distributional balance, volatility, and structural evolution. The findings reveal that Hybrid frameworks exhibit the most stable, evenly distributed, and adaptable growth patterns. Unlike the episodic surges typical of CAC models or the volatility seen in IB approaches, Hybrid regulations evolve incrementally, balancing prescriptive enforcement with flexible, incentive-based compliance. These results provide the first large-scale, empirical evidence that Hybrid regulatory frameworks exhibit superior structural adaptability. The study contributes an empirical foundation for future policy analysis and advances the measurement of adaptability as a structural feature of governance. By developing empirical tools that operationalize theoretical concepts like enforcement rigidity, flexibility, and punctuated evolution, this study contributes a new methodological foundation for measuring adaptability.Political Scienc
Bias Mitigation in Recommendation Systems: A Multi-Platform Analysis Using Semantic Similarity
Get PDFRecommendation systems are critical in shaping user exposure to information across digital platforms, yet they often amplify sentiment biases intensifying polarization and limiting diverse perspectives. This thesis investigates sentiment bias in content recommendation systems through a multi-platform comparative study involving YouTube, Medium, and Reddit. Datasets were constructed via incognito-mode search experiments to minimize personalization and consisted of both evaluation and training data. The evaluation sets measured bias propagation by analyzing content recommended after user engagement with sentiment-polarized posts on controversial societal topics where the training sets are used in designing new recommendation system. The datasets were manually annotated into In-favor, Against, Neutral, and Off-topic. To mitigate bias, four content variations were explored: original content, lexicon-based neutralization, machine learning filtering using topic-specific classifiers, and a hybrid debiasing strategy. Sentence embeddings generated via the all-MiniLM-L6-v2 transformer were used to retrieve similar content. Performance was evaluated using nDCG@10 for ranking quality and cosine similarity-based neutrality scores to assess sentiment alignment between recommendations and platform-wide discourse. The findings indicate that the hybrid approach improves neutrality but at the cost of ranking quality, while machine learning filtering with topic-specific classifiers offers a more balanced trade-off between ranking performance and neutrality. However, outcomes demonstrated sensitivity to class imbalance, underscoring the necessity of sentiment-balanced datasets to achieve fairer, more reliable recommendations. This study contributes to understanding bias amplification dynamics and proposes actionable strategies toward equitable and balanced recommendation systemsComputer Scienc
Nanomaterial Solutions for Environmental Applications and Bacteriological Threats: The Role of Laser-Induced Graphene
Get PDFLaser-induced graphene (LIG) is a high-quality graphene material produced by laser scribing. It has garnered significant attention as a solution to various growing global concerns, such as biological threats, energy scarcity, and environmental contamination due to its high conductivity, tunable surface chemistry, and ease of synthesis from a variety of carbonaceous substrates. This review provides a survey of recent advances in LIG applications for energy storage, heavy metal adsorption, water purification, and antimicrobial materials. As a part of this, we discuss the most recent research efforts to develop LIG as (1) sensors to detect heavy metals at ultralow detection limits, (2) as membranes capable of salt and bacteria rejection, and (3) antimicrobial materials capable of bacterial inactivation efficiencies of up to 99.998%. Additionally, due to its wide surface area, electrochemical stability, and rapid charge conduction, we report on the current body of literature that showcases the potential of LIG within energy storage applications (e.g., batteries and supercapacitors). All in all, this critical review highlights the findings and promise of LIG as an emerging next-generation material for integrated biomedical, energy, and environmental technologies and identifies the key knowledge gaps and technological obstacles that currently hinder the full-scale implementation of LIG in each field.Biomedical Engineering and Chemical Engineerin
Differential Effects of Hazardous Drinking on Post-Traumatic Stress Disorder Outcomes Across Two Prolonged Exposure Treatment Formats
Get PDFIndividuals with post-traumatic stress disorder (PTSD) are at increased risk for hazardous drinking, which often complicates treatment and affects trauma-focused psychotherapy outcomes. The present study is an exploratory, secondary analysis investigating differential effects of prolonged exposure (PE) among those with and without hazardous drinking and whether treatment outcomes varied across these groups as a function of PE format. Data used were from a randomized controlled trial that examined two daily, compressed formats of PE treatment for PTSD (massed and intensive outpatient program) in military personnel and veterans (N = 234). Individuals without hazardous drinking had greater PTSD symptom reductions compared to those with hazardous drinking (<i>d</i> = 0.42, <i>p</i> = 0.001). However, the hazardous drinking group also demonstrated significant reductions in PTSD (<i>d</i> = 1.46, <i>p</i> &lt; 0.001) following treatment, as well as in the number of drinks per week (<i>d</i> = 0.63, <i>p</i> = 0.025) at the 6-month follow-up. There was no significant difference in treatment engagement based on drinking classification and outcomes did not vary based on PE format. The findings suggest that PE is an appropriate treatment for individuals with PTSD and hazardous drinking. However, group differences in PTSD symptom reductions indicate concurrent hazardous drinking reduces treatment benefits of PE.Psycholog
Developing an Energy-Efficient Electrostatic-Actuated Micro-Accelerometer for Low-Frequency Sensing Applications
Get PDFMicro-accelerometers are in high demand across many due to their compact size, low energy consumption, and excellent precision. Since gravity causes a large movement when the device is positioned vertically, measuring low gravitational acceleration is challenging. This study examines the intrinsic relationship between applied voltage levels and displacement in micro-accelerometers. The study introduces a novel design that integrates hybrid flexures, comprising both linear and angular configurations, with an out-of-plane overlap varying (OPOV) electrostatic actuation mechanism. This design aims to measure the micro-accelerometer&rsquo;s movement and low frequency response. The proposed device with silicon material is designed and simulated using the IntelliSuite<sup>&reg;</sup> software, considering its small dimensions and 25 &micro;m thickness. The norm value of 28.0916 &mu;N from gravity&rsquo;s reaction forces on the body, a resonant frequency of 179.668 Hz at the first desired mode, and a maximum stress of 24.7 MPa were obtained through the electro-mechanical analysis. A comparison of the proposed design was conducted with other configurations, measuring a frequency of 179.668 Hz at a minimum downward displacement of 7.69916 &micro;m under the influence of gravity without electrostatic mechanisms. Following this, an electrostatic actuation mechanism was introduced to minimize displacement by applying different voltage levels, including 1 V, 1.5 V, and 3 V. At 3 V, a significant improvement in displacement reduction was observed compared to the other applied voltages. Additionally, dynamic and sensitivity analyses were carried out to validate the performance of the proposed design further.Electrical and Computer Engineerin
AI Judging Architecture for Well-Being: Large Language Models Simulate Human Empathy and Predict Public Preference
Get PDFLarge language models (LLMs) judge three pairs of architectural design proposals which have been independently surveyed by opinion polls: department store buildings, sports stadia, and viaducts. A tailored prompt instructs the LLM to use specific emotional and geometrical criteria for separate evaluations of image pairs. Those independent evaluations agree with each other. In addition, a streamlined evaluation using a single descriptor &ldquo;friendliness&rdquo; yields the same results while offering a rapid screening measure. In all cases, the LLM consistently selects the more human-centric design, and the results align closely with independently conducted public opinion poll surveys. This agreement is significant in improving designs based upon human-centered principles. AI helps to illustrate the correlational effect: living geometry &rarr; positive-valence emotions &rarr; public preference. The AI-based model therefore provides empirical evidence for a deep biological link between geometric structure and human emotion that warrants further investigation. The convergence of AI judgments, neuroscience, and public sentiment highlights the diagnostic power of criteria-driven evaluations. With intelligent prompt engineering, LLM technology offers objective, reproducible architectural assessments capable of supporting design approval and policy decisions. A low-cost tool for pre-occupancy evaluation unifies scientific evidence with public preference and can inform urban planning to promote a more human-centered built environment.Mathematic