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Investigation of Protein-Ligand binding interactions through the computational methods of Molecular Dynamics and Graph Neural Networks
Get PDFStudies in protein ligand binding are a significant focus in the field of medicinal chemistry
and biochemistry, facilitating a greater understanding of the structure-function relationship
of the protein and controlling function via drug development. In this research, we identify
new binding sites for lipids on the microbial membrane protein, proteorhodopsin, and apply
machine learning approaches to accelerate the generation of binding affinity-like data for the
use in the identification of potential small molecule drugs. The platelet activating factor
receptor. Cardiolipin, a lipid in membranes, and proteorhodopsin, a microbial proton pump,
are both commonly found in microbial membranes, but little is known about their putative
interactions. Using the Martini force field with coarse grain, molecular dynamics (MD) simulations
were carried out on μs time scales to model the lateral interactions of cardiolipin and
proteorhodopsin in a bilayer environment. We managed to identify two potential cardiolipin
binding sites with long-lived residence times. Both of these binding sites are located near regions
critical to proteorhodopsin function, suggesting that cardiolipin may play a role in the
ability for proteorhodopsin to pump protons across the outer membrane. The second area of
research was the application of machine learning approaches as a substitute for the screening
of small-molecule hits on the platelet activating factor receptor. Graph neural networks
with attentive mechanisms were trained in a 50,000-ligand library using structural features
and docking scores as input. Several ML techniques were applied to the generation of the
GNN models, identifying the combination of features that maximized accurate prediction
docking scores while also prioritizing efficiency. Although there were issues with overfitting
using a relatively small dataset, this GNN model in combination with active learning has the
potential to accelerate screening of ligand libraries. Further developments of this approach
are likely to improve the accuracy of screening, as well
Kizuna
No full textKizuna is a personal essay collection about the connections we make with the world and people around us. In each essay, author Emily Yandel explores the bonds that she’s formed in her life with her family, pets, and even with her own understanding of self, and how these bonds develop and change with the passage of time. Most of the essays are set in and around Japan, where she moves shortly after her undergraduate graduation. Through an often-emotional, often-humorous narrative voice, Kizuna aims to explore the world of human connection while offering readers the chance to reflect on the bonds they’ve made in their own lives
How Seeing Rural America as a Commons Can (Re)Build Mutual Respect Across the Rural-Urban Divide
Get PDFThis Essay, written for a symposium that honors and amplifies Ann Eisenberg’s 2024 book, Reviving Rural America: Toward Policies for Resilience, contemplates benefits that could flow from taking seriously Eisenberg’s conceptualization of rural America as a commons. In particular, I argue that the mutual respect and collaboration necessary for a successful commons could help heal the rural-urban rift, which has widened dramatically in the last few decades. Recent studies suggest that rural residents have what scholars call a rural consciousnesses, which means that living in a rural place is a key aspect of their identity. One feature of this identity is a desire to be seen and valued in relation to their rurality, something prominent urban and elite voices increasingly fail to do. Indeed, those voices often depict rural America as a sort of “taker” territory, dependent on urban tax dollars. The analysis that supports this thinking, often framed in terms of “rural subsidies,” focuses on fiscal transfers from the federal government to each state. These calculations can be misleading about the degree of rural reliance, and the metrics are also manipulable, depending on what sorts of transfers, e.g., safety net payments, rural development investments, are taken into account. Conceptualizing rural America as a commons provides an alternative to thinking about the relationship between rural and urban in strictly monetary terms. Focusing on rural America as the source of resources and products vital to our commonwealth—resources and products that urban places are not able to produce themselves—should lead us to see and value rural communities and their denizens. While rural scholars often speak in terms of the food, fuel and fiber rural America supplies, I focus on two other illustrations of what urban gets from rural: water and outdoor recreation. This reframing of the relationship between rural and urban shows it to be a symbiotic one. Further, this valuing of rural America and its residents for what they steward and supply provides a justification of federal investments in rural infrastructure and services. Those investments, in turn, would respond to rural residents’ belief that they are not getting their fair share of government resources. Viewing rural America as a commons, then, should ameliorate the tension between rural and urban interests and provide a mutually respectful path forward
Occupational Therapy’s Role in Driving Evaluations: Age-specific Driving Normative Data
No full textOccupational therapists and driving evaluators with limited experience may have difficulty interpreting off-road driving assessments, such as the Occupational Therapy–Driver Off-Road Assessment battery (OT-DORA) or a driving simulator. Normative data may assist evaluators with the interpretation of off-road driving assessments. Data was collected from 19 young adult drivers to establish age-specific normative data for several assessments in the OT-DORA and the DriveSafety Driving simulator. Normative performance was defined as scores within one standard deviation of the mean, and impaired performance was defined as scores greater than two mean standard deviations. The data was also analyzed to determine which questions were most frequently missed on the Road Law and Road Craft Test and the Mini-Mental State Exam. The normative data presented in the results of this study may be used to identify impairments in the skills assessed by each assessment (e.g., attention, visual scanning, reaction time, etc.) in young adult drivers compared to other healthy young adult drivers. Further research is needed before this data can be used to make decisions about whether a young adult is fit or unfit to drive
Artificial Intelligence in Governance
Get PDFThis section gives an overview of AI in Governance including how it might impact jobs and employment, the business and nonprofit sectors
“We Do Everything Together!”: Examining the Effect of a Multitasking Chore on Narrative Engagement and Parasocial Relationships with Podcast Hosts
Get PDFThis dissertation examined the link between media multitasking behaviors and the subsequent enhancement of narrative engagement and parasocial relationships with podcast hosts. Research on parasocial relationships has long established that people can develop strong pseudo relationships through aural media, such as radio and podcasts (e.g., Horton & Wohl, 1956). This has often been attributed to the charismatic nature of hosts on audio programs (e.g., Schlütz and Hedder, 2022; Perks & Turner, 2019; Heiselberg & Have 2023), however, the ability of people to listen while they engage in other tasks (e.g., driving or doing chores) can also enhance parasocial bonds. One path for parasocial relationships is narrative engagement. When people engage in visual or motor tasks, they can also listen without overburdening their attention (Lee & Taatgen, 2019; Baumgartner & Wiradhany, 2022). In fact, listeners may actively immerse themselves in audio narratives while they engage in order to cognitively escape from attending to other less pleasant tasks. Higher levels of narrative engagement should increase parasocial relationships (Tukachinksy et al., 2020; Shedlosky-Shoemaker et al., 2014; Gabriel et al., 2018; Erickson et al., 2019). Consistent with research on interpersonal relationships, (Girme et al., 2014; Farrell et al., 2014), this study examined the possibility that engaging shared experiences while listening to a podcast host can increase feelings of closeness to them. Multitasking was expected to exert a direct effect on parasocial relationships with podcast hosts. An experiment was conducted in which 98 participants were randomly assigned to a t-shirt-folding chore or control while listening to a clip from the podcast, Armchair Expert: Armchair Anonymous. Afterwards, participants completed a survey assessing their narrative engagement and parasocial relationship strength. The goal of this dissertation was to examine the effect of multitasking on PSRs with male and female podcast hosts, Dax Shephard and Monica Padman. Due to an inconsistency in the administration of the experiment between conditions that affected the extent to which participants were engaged, the internal validity of the study was compromised, and the results should be in interpreted with caution. These results showed that although the folding chore did increase people’s perception of their own multitasking, participants assigned to this condition were no more or less narratively transported than those who were not. There was, however, a direct effect of the multitasking condition on parasocial relationship strength—with the female podcast host but not the other. However, it was not in the predicted direction. Participants in the multitasking condition ended up reporting lower parasocial relationship strength with Monica compared to those in the no multitasking condition. Supplemental analyses showed that trait boredom moderated this effect, such that as people’s trait boredom increased, the negative effect of the multitasking condition on parasocial relationship strength with Monica decreased. However, this interaction was only significant at low to moderate levels of trait boredom. Contrary to prior research finding multitasking and narrative engagement to be ill-matched (Brumby et al., 2014; Zwarun & Hall, 2012), the lack of an effect of multitasking on transportation lends tentative support to the idea that multitasking is not necessarily incompatible with transportation (Woods et al., 2017; Riggs & Knoblock-Westerwick, 2024; Scherer & Cohen, 2024) Additionally, these findings shed light on the relationship PSR strength and multitasking. Because participants who sat without distraction had greater PSR than those who performed a chore while listening reported greater PSR, this indicates that having fewer attentional demands during media consumption can be more conducive to parasocial intimacy (Schlütz and Hedder, 2022; Lieberman et al., 2022). Finally, consistent with previous findings linking trait boredom to difficulty focusing (Struk et al., 2017; Drody et al., 2022), these results indicate that the negative effect of multitasking on PSR is limited to those who are relatively low in trait boredom. Presumably, those who exhibited higher levels of boredom had difficulty focusing to cultivate a sense of intimacy during listening, regardless of condition
Investigating the physiological, metabolomic, and transcriptomic changes in response to telomerase deletion in Saccharomyces cerevisiae
Get PDFTelomerase is an enzyme found in rapidly dividing cells that maintains chromosome ends and prevents the loss of genetic information during cell division. When telomerase is inactive, cells gradually lose their telomeres and eventually stop dividing. In yeast, a rare subset of cells can bypass this growth arrest by switching to a recombination-based mechanism to maintain telomeres. Therefore, yeast provides a powerful system to study this adaptation, as telomerase-deficient strains can generate \u27survivors\u27 that mimic the Alternative Lengthening of Telomeres (ALT) pathway observed in some human tumors. In this work, my goal was to examine how a telomerase-null (TLC1-deletion) strain of yeast adapts over time by tracking physiological, metabolic, and transcriptomic changes across serial passages. To do this, cultures were repeatedly diluted into fresh media, allowing them to undergo multiple generations of growth. Each passage captured a different stage of adaptation—from early crisis to full survivor formation. Early-passage cells showed physical signs of mitochondrial dysfunction, poor respiration, and increased oxidative stress, consistent with a crisis-like state. As survivors emerged, these cells displayed improved growth, restored respiration in a subset of the population, and changes in metabolite profiles, especially in amino acid and antioxidants. Transcriptome analysis revealed that genes involved in mitochondrial activity, DNA recombination, and stress response were strongly upregulated during this transition, while growth-related pathways were repressed. Although each culture followed a slightly different path through in-lab evolution, one theme remained consistent: mitochondria were central to the adaptation process. Together, these findings suggest that surviving telomerase loss is not just about maintaining telomeres, it also requires broad metabolic rewiring and stress management to support long-term proliferation
Resilience in Adolescents with Type 1 Diabetes: The Relation between Grit, Benefit-Finding, Diabetes Distress, HbA1c and Health-Related Quality of Life
Get PDFBackground: Type 1 diabetes (T1D) is a common pediatric chronic illness that requires complicated management by both the child and their caregiver. Research and clinical guidelines have highlighted adherence (as measured by HbA1c) and health-related quality of life (HRQOL) as important outcomes particularly in adolescents with T1D. Notably, diabetes distress has been identified as a risk factor contributing to poor adherence and HRQOL outcomes in this population. Given these considerations, understanding what resilience factors contribute to optimal outcomes is vitally important to inform future interventions. Grit and benefit-finding are two novel resilience factors that have yet to be fully evaluated in pediatric T1D. Methods: The current study investigated the relation between grit, benefit-finding, diabetes distress, HbA1c, and HRQOL using a cross-sectional design. Seventy participant dyads were recruited during regularly scheduled endocrinology appointments at WVU Medicine. Adolescents completed measures of diabetes distress, grit, benefit-finding, and HRQOL. Caregivers filled out measures of their own diabetes distress and grit. Adolescent HbA1c was collected from the medical chart. The study aims investigated the direct effect of grit and benefit-finding on both HRQOL and HbA1c using linear regression, as well as the moderating effect of grit and benefit-finding on the relation between diabetes distress, HRQOL, and HbA1c using the PROCESS macro. Results: Three significant findings were found in this study. First, adolescent grit was positively associated with adolescent HRQOL, F(1,68) = 6.44, p = .01. Second, adolescent grit moderated the relation between adolescent diabetes distress and HRQOL, F(3, 66) = 36.35, R2 = 0.62, p \u3c .001. Specifically, when an adolescent had less diabetes distress and more grit, HRQOL was better. However, when an adolescent had more diabetes distress and more grit, HRQOL was worse. Third, adolescent benefit-finding moderated the relation between diabetes distress and HRQOL, F(3,66) = 35.00, R2 = .61, p \u3c .001. Similar to our finding with grit, when there was less diabetes distress and more benefit-finding, HRQOL was better. However, when there was more diabetes distress and more benefit-finding, HRQOL was worse. Discussion: These findings highlight that grit and benefit-finding may not be universal protective factors in adolescents with T1D. Instead, it is important to consider these factors within the context of distress. Future studies should investigate how coping strategies, stigma, social support and distress tolerance may play a role in these findings to potentially inform future intervention
Thermal and Stress Analysis of Mass Concrete Elements Using Elmer Finite Element Software
No full textIn large concrete structures, significant temperature gradients can develop due to the low thermal conductivity of concrete. This causes thermal stresses on the concrete’s surface which can lead to thermal cracking if it exceeds the concrete’s tensile strength. Therefore, researchers have extensively studied thermal stress in mass concrete structures. Often, commercially available finite element programs such as ABAQUS and ANSYS are used to implement the material properties of concrete using user subroutines. In this study, ELMER, an open-source finite element program, is used to predict the early-age thermal stress behavior of concrete. The time, temperature and location dependent material properties of concrete are implemented in ELMER using user functions and a UMAT subroutine. In thermal analysis, the concrete’s temperature distribution was modelled using user functions for thermal conductivity, specific heat and heat generation. In stress analysis, the degree of hydration dependent mechanical properties such as compressive strength and elastic modulus were incorporated using the UMAT subroutine. Creep deformation at early-age was also considered. A rectangular prism was used to validate the creep calculation under loading and unloading in the UMAT subroutine. Results indicate that ELMER can be effectively used as a tool to model early-age thermal and stress behavior of concrete.
Additionally, a comprehensive study of the thermal properties of soil samples obtained from four districts in West Virginia was conducted. The properties analyzed in this study include the soils’ moisture content, specific gravity, specific heat, compaction, and thermal conductivity. The soil samples were also classified using the Unified Soil Classification system (USCS). These properties of soil were measured in different conditions namely: non-compacted dry, compacted moist (16% moisture) and compacted dry. A three-dimensional heat conduction Green’s function solution for a rectangular prism developed in this study was shown to be able to accurately determine the thermal conductivity of soil in an experimental cube. The results indicate that the thermal conductivities of the compacted moist soil samples were the highest, followed by the compacted dry soil samples, with the non-compacted dry soil samples having the lowest thermal conductivities. The measured thermal properties of the four soil samples, namely, density, specific heat and thermal conductivity were used as a boundary condition in the thermal-stress analysis of mass concrete rectangular bridge footings in a parallel study
The effect of cerebellar feedback on the spatial processing of conspecific signals in the electrosensory system
Get PDFAnimals have evolved sensory systems to help decipher important environmental signals that are vital for their survival. Feedback pathways are necessary to allow these signals to stand out in a noisy background, enabling the animal to focus on them more effectively. The electrosensory system of Apteronotus leptorhynchus allows the fish to sense the modulations caused by other conspecifics to allow for proper responses during social interactions. Electroreceptors detect these EODs, and afferent nerves project these signals to the ELL, where electrosensory information is projected to other parts of the brain. Cerebellar feedback to the ELL allows the suppression of lower frequency stimuli. However, little has been studied about the role of feedback in the spatial decoding of realistic, conspecific signals. This research was conducted to investigate the impact of feedback on the spatial processing of conspecific stimuli. We hypothesize that feedback enhances spatial coding by implementing background suppression and thereby enhancing spatial contrast. To test this hypothesis, a fish-pole was used to emit realistic stimuli to a receiver fish from three different positions, and the responses of pyramidal cells in the ELL were recorded. We found that cancellation occurs significantly with the gain of the beat and envelope while keeping the population\u27s firing rate unaffected. Responses of the pyramidal cells were analyzed using a weighted Euclidean distance model, and we found that the overall efficiency of spatial discrimination increased when cancellation was present. Finally, the amount of cancellation and the efficiency of spatial discrimination is dependent on the history of the previous cycle of the beat. Feedback is shown to significantly improve spatial discrimination by suppressing background responses and thereby enhancing the spatial processing of communication signals