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Angelic Introductions: The Utilization of Angels in the Epistle to the Hebrews
No full textA primary objective for the epistle to the Hebrews is to encourage the persecuted
audience to persevere. The message of perseverance begins with a comparison between
Jesus and the angels; and throughout the first two chapters of Hebrews angels are
mentioned multiple times. This thesis suggests the frequency of angelic mentions in the
introductory chapters of Hebrews utilizes the angels to introduce foundational themes
discussed throughout the remainder of Hebrews. This claim is supported by first
analyzing the utilization of angels in other New Testament epistles by separating the
verses that mention angels into the following four categories: angels utilized to describe
humanity’s relationship with God; angels utilized to elevate Christ and his message;
angels utilized to promote peaceful human relations; and angels utilized to provide
messages of warning. This categorical examination demonstrates there are similarities
between the New Testament epistles and Hebrews based on genre, but ultimately notes
the differences in the utilization of angels between the epistles and Hebrews. Secondly, a
description on the occasion, literary structure, and rhetorical nature of Hebrews is
provided in order to discuss the introductory nature of angels in regard to major themes in
Hebrews. Thirdly, the verses that mention angels in Hebrews are analyzed to demonstrate
the connection of angels to introducing major themes in Hebrews. This examination
separates the verses that mention angels into three categories: angels utilized to introduce
Christ; angels utilized to encourage humanity; and angels utilized to point towards the
future. The analyzation of angels within these categories demonstrate angels are utilized
in Hebrews to introduce major theological topics that are discussed throughout the
epistle
Principles of flux and concentration sensing in metabolic regulation
No full textTo efficiently regulate metabolism, cells must continuously monitor and respond to their metabolic state. Cells are generally thought to achieve this monitoring by sensing metabolite concentrations. However, many cellular responses do not correlate with metabolite concentrations but with the fluxes through metabolic pathways. The mechanisms with which cells sense these metabolic fluxes have largely remained unclear. In chapter 2 of this thesis, we report that one of the most–studied eukaryotic nutrient sensing pathways, galactose-responsive (GAL) signaling of Saccharomyces cerevisiae, is regulated by galactose flux and that this flux sensing is achieved by a simple mechanism: The enzyme that catabolizes galactose has a signaling activity that is coupled to its catalytic activity, resulting in the proportionality of signaling and flux. This flux sensing has the critical physiological role of maintaining GAL signaling when cells catabolize galactose. Additionally, the GAL pathway is regulated by the intracellular galactose concentration which is sensed by a dedicated sensor protein. This concentration sensing has the separate physiological role of activating GAL signaling when cells first encounter galactose. In chapter 3 of this thesis, we show that concentration sensing is tuned by cellular and evolutionary history, determining whether all or only some cells of a population respond to galactose. Overall, flux and concentration sensing underlie distinct regulatory behaviors in the GAL pathway and their combination could be a recurrent motif of metabolic regulation.Medical SciencesMedical Science
A Highly Soluble Iron‐Based Posolyte Species with High Redox Potential for Aqueous Redox Flow Batteries
No full textA novel iron‐based posolyte redox species are presented for an aqueous redox flow battery, (Tetrakis(2‐pyridylmethyl)ethylenediamine)iron(II) dichloride, which is obtained by a simple synthetic route, shows a high redox potential of 0.788 V versus SHE, and exhibits exceptional aqueous solubility of 1.46 M. Paired with bis(3‐trimethylammonio)propyl viologen tetrachloride at neutral pH, the battery demonstrates an open‐circuit voltage of 1.19 V and delivers good cycling performance, with a capacity fade rate of 0.28% per day and coulombic efficiency of 99.3%. Postmortem chemical and electrochemical analyses of the posolyte species suggest future routes for stabilization of the complex. Among all the iron complexes with a redox potential above 0.4 V versus SHE, this compound exhibits the highest solubility. These results offer valuable insights that can be applied to the development of future posolyte species for sustainable energy storage solutions.Version of Recor
Tissue-wide Responses to Airway Injury
No full textThe lungs contain numerous types of epithelial cells lining the trachea, bronchi (large airways), and bronchioles (small airways), which work in succession to transport air to alveoli, the sites of gas exchange. Acute injury in the airways or the lung activates local progenitors and stimulates changes in cell-cell interactions to restore homeostasis, but it is not appreciated how more distant niches are impacted by injury restricted to one region. We utilized mouse models of airway-specific epithelial injury to examine secondary tissue-wide alveolar, immune, and mesenchymal responses. Single-cell transcriptomics and in vivo validation revealed transient, tissue-wide proliferation of alveolar type 2 (AT2) progenitor cells after club cell-specific ablation in the airways. The AT2 cell proliferative response was reliant on alveolar macrophages (AMs) via upregulation of Spp1, which encodes the secreted factor Osteopontin. A previously uncharacterized mesenchymal population we termed Mesenchymal Airway/Adventitial Niche Cell 2 (MANC2) also exhibited dynamic changes in abundance and a pro-fibrotic transcriptional signature after club cell ablation in an AM-dependent manner. Although aberrant responses in the lung were observed to resolve after a single acute injury, future studies could elucidate how these responses intersect or become exacerbated with more severe, durable, or complex lung injuries and disease states. Overall, these results demonstrate that acute airway damage can trigger distal lung responses including altered cell-cell interactions that may contribute to potential vulnerabilities for further dysregulation and disease.Medical SciencesMedical Science
Modeling Item-Level Heterogeneous Treatment Effects With the Explanatory Item Response Model: Leveraging Large-Scale Online Assessments to Pinpoint the Impact of Educational Interventions
No full textAnalyses that reveal how treatment effects vary allow researchers, practitioners, and policymakers to better understand the efficacy of educational interventions. In practice, however, standard statistical methods for addressing heterogeneous treatment effects (HTE) fail to address the HTE that may exist within outcome measures. In this study, we present a novel application of the explanatory item response model (EIRM) for assessing what we term “item-level” HTE (IL-HTE), in which a unique treatment effect is estimated for each item in an assessment. Results from data simulation reveal that when IL-HTE is present but ignored in the model, standard errors can be underestimated and false positive rates can increase. We then apply the EIRM to assess the impact of a literacy intervention focused on promoting transfer in reading comprehension on a digital assessment delivered online to approximately 8,000 third-grade students. We demonstrate that allowing for IL-HTE can reveal treatment effects at the item-level masked by a null average treatment effect, and the EIRM can thus provide fine-grained information for researchers and policymakers on the potentially heterogeneous causal effects of educational interventions.Accepted Manuscrip
Explaining the Model, Protecting Your Data: Revealing and Mitigating the Data Privacy Risks of Post-Hoc Model Explanations via Membership Inference
No full textPredictive models using machine learning algorithms are becoming increasingly deployed in high-states contexts in various fields, such as medicine, finance, and law. Since these models rely heavily on sensitive personal data, regulatory principles that protect the privacy of training data are important. Concurrently, given the inherent complexity of models used in these high-stakes settings, model explanations are necessary in informing users about how models make decisions on data. Explainability and privacy are often viewed as conflicting: explainability promotes transparency, and privacy is a limit on transparency.
In this thesis, not only do we systematically study the under-addressed trade-off between deep learning explainability and privacy, but we push the boundaries of this trade-off: with a focus on foundation models for image classification tasks, we reveal unforeseen privacy risks of post-hoc model explanations and subsequently offer mitigation strategies for such risks. First, we construct VAR-LRT and L1-LRT/L2-LRT, two novel membership inference attacks based on model predictions and explanations that are significantly more successful than existing attacks, particularly in the low false-positive rate regime that allows an adversary to identify specific training set members with high confidence. Second, we find empirically that optimized differentially private fine-tuning of foundation models substantially diminishes the success of the aforementioned attacks, while maintaining competitive model accuracy. This portion of our work fills a gap in literature—there is no prior work that thoroughly quantifies the relationship between differential privacy and the subsequent privacy risks of model explanations in the deep learning setting. Third, we compare the quality of explanations from differentially private models with that of their non-private counterparts. We propose statistical estimators for the consistency and prediction gap fidelity metrics that are suitable for high-dimensional, quantitative data settings, and empirically, we find evidence of a trade-off between privacy strength and explanation quality; this trade-off bears meaningful implications to researchers, policymakers, and legal scholars alike. Although differential privacy has potential as a training data leakage method, further work is important for better understanding how to optimize for this privacy versus quality trade-off.
Overall, we carry out a rigorous empirical analysis with 2 novel membership inference attack types, 4 benchmark datasets, 4 state-of-the-art post hoc explanation methods, 3 new estimators of two explanation quality metrics, and 4 privacy strength settings. Our work addresses the lack of trust in post-hoc explanation methods that has contributed to the slow adoption of machine learning in high-stakes domains
Making Every Study Count: Learning From Replication Failure to Improve Intervention Research
No full textWhy, when so many educational interventions demonstrate positive impact in tightly controlled efficacy trials, are null results common in follow-up effectiveness trials? Using case studies from literacy, this article suggests that replication failure can surface hidden moderators—contextual differences between an efficacy and an effectiveness trial—and generate new hypotheses and questions to guide future research. First, replication failure can reveal systemic barriers to program implementation. Second, it can highlight for whom and in what contexts a program theory of change works best. Third, it suggests that a fidelity first and adaptation second model of program implementation can enhance the effectiveness of evidence-based interventions and improve student outcomes. Ultimately, researchers can make every study count by learning from both replication success and failure to improve the rigor, relevance, and reproducibility of intervention research.Accepted Manuscrip
Enshrining the Message: A Comparative Study of the Translatability of Islam and Christianity through Two West African Pilgrimage Traditions
No full textThis dissertation undertakes a comparative assessment of the translatability of Islam and Christianity in Senegal by studying two pilgrimages, one Muslim, the other Catholic. The Muslim pilgrimage practice under consideration is the Grand Magal of Touba, the annual festival of the Murid Brotherhood, which takes place every year on 18 Safar. The Catholic pilgrimage practice studied here is the Marian pilgrimage to Notre Dame de la Délivrande in Poponguine, which takes place every year on Pentecost Monday. Three main features of these pilgrimages are assessed, namely, narrative, sacred space, and ritual. The dissertation shows that these pilgrimages foster the enshrinement of Islam and Christianity in Senegal, and their comparison brings to the fore similarities and differences that offer lessons germane to the understanding of the processes through which Islam and Christianity have become “African religions.
A Multimodal Molecular View of Human Cartilage Development
No full textThe skeletal system is the foundation of human mobility. Human joint development and function relies on the proper specification and differentiation of hyaline cartilage, including growth plate cartilage that forms the template for developing bones and articular cartilage that provides lubrication and resilience for joint movement. Despite their vital role, the molecular mechanisms driving these distinct cartilage types in humans remain unclear. Our lab has pioneered an in vitro model of chondrogenesis, using human pluripotent stem cells (hPSCs) to generate articular and growth plate-like chondrocytes by recapitulating developmental processes. Using this system and human donor tissue, we investigated the transcriptomic and epigenetic signatures underlying human chondrogenesis.
Articular and growth plate cartilage represent two distinct lineages of hyaline cartilage developing in the appendicular skeleton. We used bulk RNA and ATAC sequencing to build transcriptomic and epigenetic profiles of hPSC-derived articular and growth plate-like cartilage. Transcriptomic comparison to human fetal epiphyseal and growth plate cartilage tissues highlighted similarities and differences between these lineages developing in vivo and those being differentiated in vitro. Integrating the transcriptomic and epigenetic profiles of in vitro articular and growth plate cartilage uncovered lineage specific differences and revealed putative transcription factors (TFs) that drive these lineage-specific changes. We validated the function of two of these transcription factors, RELA in articular cartilage and RUNX2 in growth plate cartilage, in binding regulatory elements, predicted by integrating both motif enrichment and target gene expression, in the genome of chondrocytes. This bulk multiomic atlas of in vitro chondrogenesis therefore enabled us to identify both known and novel putative regulators of these two functionally different cartilage types in human development.
Developing human cartilage is a continuum of hyaline cartilage with multiple subtypes of chondrocytes contained within it. We therefore employed single cell multiomic sequencing to characterize the transcriptomic and epigenetic profiles of individual cells from the developing human distal femur at two developmental timepoints. Using these data, we built enhancer-based gene regulatory networks that predicted regulators of chondrogenic differentiation. In addition to identifying some of the gene regulatory networks that we discovered in our bulk sequencing approach, we also identified novel regulators of chondrogenesis and defined the specificity of each regulatory network within different computationally-defined cell types. We used our in vitro chondrogenic differentiation model to test the function of gene regulatory networks identified from in vivo human fetal chondrocyte data. One such TF, NFATC2, was predicted to be highly active in epiphyseal and superficial zone chondrocytes during fetal development. Consistent with this, we found that overexpression of NFATC2 in the in vitro chondrocytes induced articular-like epiphyseal chondrocyte gene programs, even in the presence of culture conditions that promote growth plate differentiation. In addition to uncovering this role for NFATC2, we demonstrated the utility of the in vitro hPSC-based platform to study the effect of regulators on chondrogenesis. This work therefore represents a step towards comprehensively understanding the molecular mechanisms driving human cartilage development