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A Test of the Pioneer Factor Hypothesis for Silent Gene Activation
Get PDFTranscription factors (TFs) activate silent genes by binding to and opening heterochromatic instances of their motifs. While we rely on this process for cellular reprogramming, we have an incomplete understanding of which TFs are capable of recognizing inaccessible instance of their motifs and what parameters are important for this activity. My thesis work aimed to address these two questions. The leading model for silent gene activation is the pioneer factor hypothesis (PFH). The PFH states that pioneer factors (PFs) are qualitatively unique TFs that can bind to and open DNA and subsequently recruit non-pioneer factors (nonPFs) to activate expression. We tested the predictions of the PFH by ectopically expressing a canonical PF FOXA1 and nonPF HNF4A in K562 blood cells. While we expected that only FOXA1 would bind inaccessible motifs and that neither TF would activate tissue-specific gene expression, we found that both TFs independently bound, opened, and activated tissue-specific loci. When we examined what may control such “pioneer activity,” we found that motif content, TF concentration, and TF binding strength were all important factors. Having shown that pioneer activity may not be a qualitative trait restricted to just a few TFs, we sought to develop a quantitative metric. Because pioneer activity is essentially “TF binding at hard-to-bind sites,” we suggest that a measure of pioneer activity should capture the relative difference in a TF’s ability to bind at accessible versus inaccessible DNA. We estimated a parameter related to a TF’s Kd by using doxycycline (dox) induction as a proxy for TF concentration. We call this term the TF’s dox50. We propose that the average difference of a TF’s dox50 between accessible and inaccessible binding sites is a measure of its pioneer activity. We call this term the TF’s Δdox50. The lower a TF’s Δdox50, the stronger its pioneer activity. To demonstrate the feasibility of this metric, we induced FOXA1 and HNF4A across a 1,000-fold range, measured binding, fit binding curves at tens of thousands of loci, and then extracted dox50s. We show that HNF4A has a smaller Δdox50 than FOXA1, which suggests it has stronger pioneer activity. We also show that FOXA1 has a smaller Δdox50 at sites that have more copies of its motif, which suggests that strong motif content can boost pioneer activity. Altogether we propose that every TF likely has some degree of pioneer activity that depends on its affinity for any given location, the concentration at which it is expressed, and the motif content at each target site. We hope that future work will characterize more TFs’ pioneer activity, making Δdox50 a useful quantitative metric to describe pioneer activity
Colliding Worlds: Visual Culture in France and Colonial Algeria (1918-1962)
Get PDFThe decline of French colonialism in Algeria and the Algerian War lay at the fault line of several tectonic forces. World War I, World War II, and the Cold War challenged France’s global stature, destabilized the colonial apparatus, and fostered unprecedented intercolonial intellectual exchange. These events provided the global context for Algeria’s national revolution, a prolonged period of conflict that was all in one a civil war that redefined Algerian identity, a political and military scandal that led to the downfall of the French Fourth Republic in 1958, influenced Cold War politics, and continues to shape national identity in both countries today. Focused on this complicated milieu, this dissertation uses Algeria as a vantage point and visual culture as a lens to examine the phenomena of decolonization, nationalism, Pan-Arabism, African unity, and Third World internationalism, and demonstrates that, in the instance of Algerian independence, national sovereignty and visual sovereignty were correlated concepts
Characterizing the Causal Role of SVEP1 in Human Disease
Get PDFSushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is a poorly understood, putative extracellular matrix protein. Several human traits and diseases are associated with SVEP1, including coronary artery disease, hypertension, type 2 diabetes, glaucoma, dementia, longevity, and platelet reactivity. This dissertation establishes a causal link between SVEP1 and human disease using Mendelian randomization and mouse models. It also provides insights into the disease mechanisms of the protein, including a novel interaction between SVEP1 and the orphan receptor Platelet endothelial aggregation receptor 1. The relevance of this interaction to platelet biology and its potential role in cardiometabolic disease is discussed. The viability of inhibiting SVEP1 to treat or prevent disease is also evaluated
AI Assignment Repositories: Peer-Generated Teaching Activities You Can Actually Use
Get PDFLearn about the steps and challenges involved in piloting an open access repository for assignments that challenge students to use AI in intellectually rigorous ways. Whether you’re new to generative AI or a seasoned ChatGPT user, this session will give you the tools to facilitate peer-to-peer sharing of faculty-generated and reviewed teaching activities at your institution. Ask questions and discuss potential difficulties with an interdisciplinary team of presenters, including a graduate instructor and fellow at WashU’s CTL, an award-winning professor and director of the CTL, and an experienced academic librarian and expert in digital publishing and repository services.https://openscholarship.wustl.edu/lib_present/1039/thumbnail.jp
Learning to Disagree: The Surprising Path to Navigating Differences with Empathy and Respect
No full textAre you discouraged by our divided, angry culture, where even listening to a different perspective sometimes feels impossible? If so, you\u27re not alone, and it doesn\u27t have to be this way. Learning to Disagree reveals the surprising path to learning how to disagree in ways that build new bridges with our neighbors, coworkers, and loved ones--and help us find better ways to live joyfully in a complex society.
In a tense cultural climate, is it possible to disagree productively and respectfully without compromising our convictions? Spanning a range of challenging issues--including critical race theory, sexual assault, campus protests, and clashes over religious freedom--highly regarded thought leader and law professor John Inazu helps us engage honestly and empathetically with people whose viewpoints we find strange, wrong, or even dangerous.
As a constitutional scholar, legal expert, and former litigator, John has spent his career learning how to disagree well with other people. In Learning to Disagree, John shares memorable stories and draws on the practices that legal training imparts--seeing the complexity in every issue and inhabiting the mindset of an opposing point of view--to help us handle daily encounters and lifelong relationships with those who see life very differently than we do.
This groundbreaking, poignant, and highly practical book equips us to: Understand what holds us back from healthy disagreement Learn specific, start-today strategies for dialoguing clearly and authentically Move from stuck, broken disagreements to mature, healthy disagreements Cultivate empathy as a core skill for our personal lives and our whole society
If you are feeling exhausted from the tattered state of dialogue in your social media feed, around the country, and in daily conversations, you\u27re not alone. Discover a more connected life while still maintaining the strength of your convictions through this unique, often-humorous, thought-provoking, and ultimately life-changing exploration of the best way to disagree
Materials are my Conduits
No full textThis text is a tangle as much as it is a trajectory—of a mother (me), of materials and matter, and of processes of making and becoming. It is a very long and also very short story about the genesis of my artistic practice and my material wanderings across fiber, sculpture, drawing, painting, and installation. I move freely across these materials and disciplines, and insatiable curiosity is my guide.
I use humble materials and provisional strategies to explore themes of fragility and resilience. Forms intersect and balance, are tethered and in tension, and are tangled, wrapped, and bound.
In this curated disparity, I foster beauty and curiosity, inclusivity and harmony. In my sculptures and installations, the overlooked and discarded find a home.
Materials help me make connections to the world around me. As I conduct research relative to my artistic practice, I weave across, together, and through anthropology, philosophy, material science, quantum physics, neuroscience, biology, and ecology. Expanding my understanding of being (in the world) and making (as an artist) helps me understand my place in the world I inhabit. These discoveries flow through me in the same way energy moves between me and my materials as I make work.
I elevate the mundane and discarded to offer beauty, even absurdity, through efficient and restrained gestures. The resulting works may be provisional and ephemeral and even risk being overlooked. I want to engage the viewer in the process of wondering, questioning, and slow-looking. With a delicate sleight of hand, I make a 25-foot beam a whisper and a piece of dangling thread the star of a backstage show. Each material gesture aims to lull the distracted mind and lift the human spirit.
I work with found objects and am in awe of my own entanglement with material systems and accumulations. Things have a magnetic pull. I draw on political theorist Jane Bennett, who uses the terms ‘vibrant matter’ and ‘thing power’ in my discussion of the agency of objects. Things taunt me and activate my studio practice.
I also reference anthropologist Tim Ingold and his writing on making, which is informed by sensing, touch, and repetitive movements. These processes build bodily knowledge while simultaneously lulling and satisfying obsession and compulsion. Ingold also writes about the line that is integral to my work, whether weaving, writing, painting, drawing, walking, or working in architecture or installation.
Because I privileged expansion over iteration in this slice of academic time, the reader will experience the breadth of my exploration through connections to artists that span and elude movements: they are conceptual, minimalists, abstract expressionists, post-minimalists, contemporary (as in current) and taunt boundaries between art and craft. Those no longer living feel oddly contemporary as they are survived by my recent encounters with their ever-present work. Artists include but are not limited to: Michael Asher, Tamara Johnson, Mary Mattingly, Richard Tuttle, Cecilia Vicuña, and B. Wurtz. Phyllida Barlow, Shiela Hicks, Cy Twombly, Sol LeWitt, and Eva Hesse could be on this list, but as a sculptor and middle-aged mom, I don’t know where it all goes (in reference to material, the work, the pages, and last-but-not-least time)
The validity and challenges of third-party funding in the Saudi arbitration framework
No full textThird-party funding (TPF) is a new concept in which a third-party funds one of the disputing parties for potential share outcomes while the funded party is not obligated to repay the funds if the case is unsuccessful. In recent decades, the TPF has become more prominent for dispute parties in order who have facing financial obstacles to access to justice. However, the validity of the TPF agreements in Saudi Arabia remains to be determined. As the ruler of Saudi laws, Shariah prohibited agreements involving gharar (uncertainty) and usury as public policy concerns. Therefore, to break the silence surrounding TPF, this dissertation examined the validity of TPF from Shariah and Saudi perspectives. Consequently, the dissertation concluded that TPF complies with Shariah, based on the Muzara\u27ah partnership model, with sharing risks. This dissertation also introduces a Saudi roadmap for a TPF framework, which recommends the following (third-party funding arrangements in the Muzara\u27ah model comply with Saudi public policy. 2) Amendments to Saudi arbitration law require mandatory TPF disclosure to avoid conflicts of interest. 3) A code established by a supervisory body to monitor the TPF’s confidentiality and ethical practices in Saudi Arabia
Good Enough
Get PDFThe seven-foot-tall sculptural painting Good Enough explores the cultural significance of trophies in contemporary American society. As an ancient object representing achievement and reward, the irony of trophies’ current junk-status pokes at absurd contradictions embedded in American culture. I offer context on the evolution of “the readymade” from Dada to Pop Art to 90s assemblage, and position Good Enough’s handmade, tender approach as a celebratory twist to that lineage of cultural critique
Time-Dependent Charge of Water Droplets in Mineral Oil
No full textThis study investigates the behavior of water droplets acquiring an electrical charge in mineral oil, a non-polar environment. The experimental setup was developed and refined to improve control and understanding of droplet behavior and charge acquisition. Modifications included using a longer acrylic cube and longer electrodes, alongside a DC high-power supply. Droplet detachment was optimized, allowing for better observation of droplet interactions with the mineral oil. Analysis of experimental results revealed that droplet size influences movement dynamics and charge acquisition. The polarity of droplets changed throughout the experiment, which could indicate a time-dependent change in surface charges on the droplet. These findings contribute to understanding droplet behavior in non-polar oil environments
Introduction to 2D and 3D Nanomembrane Devices: Fabrication and Characterization
Get PDFThe goal of this independent study was to gain familiarity with research methods and fundamental concepts in 2D/3D materials research. To that end, two projects were completed – 1) the design, fabrication, and characterization of an in-vivo flexible piezoelectric antenna, and 2) the fabrication and characterization of a GaN-based, interdigitated (IDT), surface acoustic wave (SAW) strain sensor. The function of the in-vivo antenna was successfully demonstrated while implanted in a mouse brain. The SAW strain sensor’s basic functionality was also demonstrated, but performance was modest. Alongside in-lab work, the operating principles behind the devices and the state of 2D/3D nanomaterials research were studied at an introductory level through literature review. The following report documents important theoretical concepts learned, in-lab methods, and the testing results for the two devices