18525 research outputs found
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Supporting Book Sharing Engagement in Latino Toddlers: Child, Caregiver, and Environmental Factors
No full textCaregiver–child book sharing is a well-established context for promoting early language and literacy skills; however, little is known about how children with language delays engage in these interactions. This study examined engagement during a 5-minute book sharing session between Spanish-speaking caregivers and their toddlers with language delays. Seventy-five toddlers with bilingual language scores at least 1.5 standard deviations below the mean participated. Observations took place in participants’ homes using a standardized set of books. Child engagement was coded in 20-second intervals for the presence of verbal and nonverbal indicators. On average, children were engaged during 72% of intervals, and over 60% were engaged for at least 10 of 15 intervals. Girls were significantly more engaged than boys. Engagement was not significantly associated with bilingual language scores, number of verbal utterances, or conceptual word use. However, more observed challenging behaviors (e.g., crying, throwing books, leaving the room) were related to reduced engagement. Caregiver-reported executive functioning, education level, and household income were not associated with engagement. Among caregiver behaviors, only question-asking was significantly related to engagement for both boys and girls. Matched conversational turns were related to engagement for boys only, while target-level utterances were not significantly associated for either group. Caregiver-reported values about book sharing (e.g., reading frequency, child enjoyment, perceived importance, or viewing book sharing as a target for intervention) were not associated with observed engagement. These findings suggest that, in this population, immediate child behavior and specific caregiver interaction strategies may play a greater role in child engagement than language skills or demographic characteristics. For researchers, results underscore the importance of including behavioral measures of engagement in studies of early book sharing. For practitioners, the findings suggest there may be value in teaching caregivers book sharing strategies that include support for child engagement, such as positively managing challenging behavior and using interactive prompts such as book-focused questions with follow-up comments
Regulatory Mechanisms Governing Cell Wall Biogenesis in, and Host Immune Modulation Against, Acinetobacter baumannii
No full textThe emergence of multidrug-resistant Acinetobacter baumannii presents a critical threat to global health, driven by its capacity to evade antimicrobial therapies and persist in hostile environmental conditions. This dissertation explores the interconnected roles of bacterial zinc (Zn) homeostasis, cell wall biogenesis, and host immune responses, revealing how metal regulation influences both A. baumannii pathogenesis and host defense mechanisms. Central to this investigation are COG0523 family proteins, key mediators of Zn-dependent processes essential for bacterial fitness and virulence. ZigA coordinates Zn homeostasis with cell envelope integrity by interacting with the lytic transglycosylase SltB, linking metal availability to peptidoglycan remodeling. MigC, another COG0523 protein, functions as a Zn-dependent inhibitor of MurD, a critical enzyme in peptidoglycan synthesis. This regulation ensures cell wall integrity and bacterial survival under Zn-limiting conditions, while loss of MigC sensitizes A. baumannii to β-lactam antibiotics, identifying a novel therapeutic vulnerability. On the host side, Zn sequestration emerges as a pivotal factor in immune defense. The Zn-binding protein calprotectin, particularly its S100A9 component, regulates immune homeostasis during A. baumannii infection. S100A9 deficiency appears to disrupt this balance by enhancing ZNRF1 protein degradation activity, potentially reducing the abundance of its targets like Cav1, which may promote immune cell apoptosis, thereby contributing to increased bacterial colonization and tissue damage. Together, these findings elucidate the complex interplay between bacterial metal homeostasis, cell wall dynamics, and host immune regulation. By identifying critical regulatory nodes and potential therapeutic targets, this dissertation establishes a framework for novel strategies to combat multidrug-resistant A. baumannii, contributing to broader efforts in addressing the global challenge of antimicrobial resistance
CONTROL, ORDER REDUCTION, AND IDENTIFICATION OF NONLINEAR DIFFERENTIAL-ALGEBRIC MODELS OF RENEWABLES-HEAVY POWER SYSTEMS
No full textPower systems are transitioning toward a greener and more sustainable future through the widespread installation of renewable energy resources (RERs). These RERs, primarily wind and solar-based, are connected to the grid using advanced electronics and converter-based technologies. However, the uncertain, intermittent, and volatile nature of RERs has introduced unprecedented challenges, complicating the secure and reliable operation of modern power systems. Fortunately, the rapid advancements in phasor measurement units (PMUs) and remote-control technologies offer significant opportunities to address these issues. PMUs provide high-resolution, real-time snapshots of voltage and current measurements, which can be utilized for online control and health monitoring of power networks.
To design realtime control and monitoring (i.e., state estimation) algorithms, the consideration of an appropriate dynamic model is crucial. This model captures the electromechanical transients of power systems, detailing the time-evolution of critical physical quantities like frequencies, generator rotor angles, and voltages. Typically, this model is derived from nonlinear differential-algebraic equations (NDAE) that integrate generator dynamics with power flow equations. Ideally, real-time control and state monitoring algorithms implemented in control centers should consider the complete NDAE model of power systems, incorporating detailed models of synchronous machines and RERs. However, current literature often oversimplifies the NDAE model through linearization and neglects essential algebraic constraints that describe the relationship between generator dynamics and loads. Using a linearized model to study power system dynamics sacrifices accuracy, as it only considers system behavior around a specific equilibrium point. Consequently, the performance and stability of linearization-based estimators and controllers are limited to that point. Given the increasing complexity and uncertainty of electrical grids due to the aggressive deployment of RERs, it is crucial to account for the full NDAE model and the detailed dynamics of synchronous machines and RERs in control and estimation algorithms. Such comprehensive algorithms would ensure the stable and safe operation of future power systems in real time.
To that end, the main objectives of this dissertation are to: (1) develop techniques to effectively capture renewables, loads uncertainties, and grid dynamics; (2) build general theory for state/output feedback control and dynamic-algebraic state estimation for the complete NDAE representation of power system with high penetration of advanced power-electronics based RERs and composite loads dynamics; (3) pave a way for realtime and data-driven control/monitoring via model order reduction and system identification for the complete NDAE power system models; (4) design computationally efficient algorithms that can be implemented in the power systems control center for wide-area monitoring and control
The effect of active engagement on belief in and perceptions of social media posts
No full textAs people browse social media, they can actively engage with posts or passively read what’s presented. These choices may then change people’s beliefs and attitudes towards the content. Existing research finds that active engagement with persuasive messages increases belief change. Similar psychological processes likely occur with online news reading and sharing. In our study participants selected social media posts (true and false news headlines) that they would be willing to share online. They then typed hypothetical comments for half of the posts while passively viewing the others. In two pre-registered experiments (N=1798), we tested if active engagement influences belief and perceptions towards true and false headlines. Across both studies, engaged news items were judged to be more emotional intense. Furthermore, the influence of commenting on news perception varied depending on participants' initial motivations for engaging with the content. Our studies demonstrate that how individuals process and interpret news content
The Language & Mechanics of an Interview
No full textThe Language & Mechanics of an Interview is an educational resource developed by the Vanderbilt University English Language Center (ELC) in collaboration with the Career Center to support students who use English as an Additional Language (EAL) in developing effective interview skills. This resource addresses the unique linguistic and cultural challenges faced by multilingual students when navigating professional, academic, and formal interview contexts within English-speaking environments. The guide provides systematic instruction on linguistic components and structural mechanics essential for successful interview performance, including appropriate register, question interpretation strategies, and cultural expectations within American interview contexts. Designed as both a self-study tool and instructional supplement, this resource supports student success by building confidence and competence in high-stakes communication situations critical for academic and career advancement
Investigating DNA Methylation and Chromatin Accessibility Dynamics During Cell Fate Specification
No full textEpigenetic mechanisms govern the transcriptional activity of lineage-specifying enhancers; but recent work challenges the dogma that joint chromatin accessibility and DNA demethylation are prerequisites for transcription. To investigate DNA methylation function in dynamic processes, we developed and optimized ATAC-Me, a joint profiling method to measure DNA methylation and chromatin accessibility simultaneously. Through application of ATAC-Me, we established a highly-resolved timeline of DNA methylation and chromatin accessibility dynamics during neural progenitor cell differentiation. We discover that, while complete demethylation appears delayed relative to shorter-lived chromatin changes for thousands of enhancers, DNA demethylation actually initiates with 5-hydroxymethylation before appreciable accessibility and transcription factor occupancy is observed. The extended timeline of DNA demethylation creates temporal discordance appearing as epigenetic heterogeneity between these distinct layers of enhancer regulation. The gain of methylation is exceedingly rare and resulting enhancer hypomethylation persists long after chromatin activities have dissipated. We demonstrate that these timepoint specific methylation states predict past, present and future chromatin accessibility using machine learning models. Thus, chromatin and DNA methylation collaborate on different timescales to mediate short and long-term enhancer regulation during cell fate specification
Stories That Connect us: Supplement to the Martha Rivers Ingram Commons Summer Assignment 2025
No full textThe English Language Center (ELC) created this “Stories That Connect us: Supplement to the Martha Rivers Ingram Commons Summer Assignment 2025” resource for incoming multilingual first-year undergraduate students at Vanderbilt University who use English as an Additional Language (EAL) in support of the 2025 Summer Assignment
Molecular Basis for Ligand Activation of NR4A-RXR
No full textTwo members of the orphan nuclear receptor (NR) NR4A family, Nurr1 and Nur77, are essential for the development, regulation, and maintenance of several important aspects of mammalian brain development and homeostasis and have been shown to be associated with pathological development and progression, including Parkinson’s disease (PD) and Alzheimer’s disease (AD). Although NRs are considered to be ligand-dependent transcription factors, Nurr1 and Nur77 are thought to function independent of binding an endogenous ligand that is produced and present in cells. It also remains unknown in the field whether there are functional endogenous ligands that bind to the ligand-binding domains (LBD) of Nurr1 and/or Nur77 via their putative canonical ligand-binding pocket, a region within the core of the LBD conserved across the NR superfamily where endogenous ligands bind to other NRs.
An alternative way to target NR4A activity is through ligands that bind to the retinoid X receptor (RXR), which forms heterodimers with Nurr1 and Nur77. Interestingly, although RXR activates transcription of most NR-RXR heterodimers including PPARγ-RXRα, RXR heterodimerization represses Nurr1 and Nur77 transcription. Additionally, synthetic RXR ligands can activate transcription of Nurr1- and Nur77-RXR heterodimers and have been implicated in treating neurodegenerative disorders. However, the mechanism by which RXRα represses Nurr1 and Nur77 transcription, and the mechanism of action of ligands that activate NR4A-RXR transcription, remain poorly understood.
Here, I use a multidisciplinary approach combining structural biology, biochemistry, biophysics, and molecular and cellular pharmacology approaches to characterize the structure of Nurr1-RXRα LBD heterodimer, which uncovered a novel structural mechanism of ligand-dependent activation of NR4A-RXR heterodimers: RXR ligands can function as allosteric protein-protein interaction inhibitors that bind to the canonical orthosteric ligand-binding pocket within the RXR LBD and influence NR4A-mediated transcription via heterodimer dissociation. This dissertation provides fundamental insights into the structural mechanisms governing NR4A-RXR heterodimer function and ligand-dependent activation, which may inform the development of targeted therapeutic strategies for PD, AD, and other aging-associated neurodegenerative disorders
Deconvolution of Permeability-Activity Relationships for Verticilide-Inspired Cyclic (Depsi)Peptides and Progression of the Structure-Activity Relationship Campaign for ent- V erticilide
No full textThrough a cross-disciplinary collaboration, it was discovered that ent-verticilide is a selective inhibitor of RyR2-mediated calcium release, including a preliminary study of efficacy in vivo. As a 24-membered cyclic depsipeptide with a molecular weight of 853 Da, ent-verticilide falls outside of the category of a traditional small molecule drug. While “Beyond Rule of 5” compounds with in vivo activity are growing in number, an understanding of their pharmacokinetics (PK) has lagged, thereby requiring new chemical tools and creative tactics to advance the field. By methodical structural changes to ent-verticilide, we have created an SAR-based feedback loop between permeability, activity, structure, and conformation. A strength of this approach is the combination of rigorous tools to study passive membrane permeability, and cardiomyocyte-based functional studies using both permeabilized and non-permeabilized cells to achieve an overall hypothesis-driven approach to discover how analogues of ent-verticilide travel through cellular membranes and ultimately target RyR2. Another strength is our positioning to prepare diverse analogues that include ring-chain variants likely to exhibit contrasting permeability. With increased understanding of the mechanism of action, we hypothesize that we can design analogues of ent-verticilide with improved potency and selectivity, thereby providing a potential therapeutic against fatal ventricular arrhythmias. Key findings of this work include that a single ester-to-N-H- amide point modification can enhance cell permeability significantly but several backbone modifications exhibit low activity and permeability; N-permethylation of ent-verticilide is critical for activity and permeability but in less critical with the ent-B1 oligomer; backbone cyclization enhances permeability; nat-verticilide is significantly less active and permeable than ent-
verticilide; and several side chain or backbone modifications results in loss of activity
The Nature of Memory for Conversations: Questions and Organization
No full textThe focus of this dissertation was to investigate how multiple factors influence the memory for conversations. First, we hypothesized that questions are less well remembered than answers. This hypothesis is based on proposals surrounding the functional role of questions as temporary placeholders in communication (Heller & Brown-Schmidt, 2023) and theories that posit the meaning of a question is defined by the possible answers (Groenendijk & Stokhof, 1984). In Experiments 1-2 we tested this hypothesis by having pairs of participants engage in communication games where they named objects in either question and answer pairs or assertions. We found that recognition memory was best for second named items in pairs, whether that was an answer or part of an assertion. Memory for answers may be better than memory for questions, but future research will need to disentangle the effect from order of presentation. Second, we hypothesized that temporal, speaker, and topic contexts would each influence the organization of conversation recall. In word list paradigms, temporal, semantic, and source topics have all been shown to influence the order of recall (Polyn et al., 2009). This study thus tested relevant contexts to see if similar principles guided conversation recall. In Experiment 3, pairs of participants engaged in 15 minute conversations about a list of six topics. They independently recalled these conversations after a 20 minute delay, a ~4 day delay, and a ~10 day delay. We found temporal contiguity at each delay. Participants were more temporally organized within self-produced idea units than partner-produced idea units, reflecting the memorial benefit for self-produced idea units in conversation. We find recall patterns to support the theory that there is a temporal context for topics and a separate temporal context for idea units within each topic. Across all three experiments, we find that elements of a given utterance, such as the role it plays in communication, the serial order, the speaker, and the content discussed all influence what is recalled and/or in what order it is recalled