71446 research outputs found
Sort by
The Marianas Adrift: Indexing Modernity in The Archipelago Beyond Tourism
No full text“The Marianas Adrift” examines the cultural power of sight in the Pacific, questioning the authority of “complete vision” and its colonial origins. Engaging the oscillation between the illegible and the hyper-legible, the project interrogates how landscape is visualized, archived, and designed through the epistemic frameworks of islands and archipelagos.
Set across the island of Pagan, the project embraces an archipelagic approach to interconnection, intervening in episodes of manifestation and dissolution—where lava flows repopulate islands and bomb craters become foundations for cultural resurgence. Here, design operates as an index, simultaneously revealing the accumulated histories of landscape and reorienting its spectacle.Department of Landscape Architectur
Rational Design of Selective Protein Therapeutics for Structurally and Functionally Complex Targets
No full textProtein biologics have transformed modern drug discovery and development by offering high selectivity and reduced off-target effects, prolonged serum half-lives, and the ability to modulate cellular processes. However, many clinically relevant targets remain intractable due to limited structural or mechanistic information, selectivity issues, or the need to modulate multiple pathways simultaneously. This work presents two distinct case studies in engaging challenging targets using rationally designed bispecific protein therapeutics and Fc fusion proteins. In Chapter 1, I describe the successful design and characterization of the first non-EPO-based, bispecific agonists for the tissue-protective receptor, EPO-R/CD131. We generated a structural model of the EPO-R/CD131 complex using AlphaFold and available structures of EPO-R and CD131 individually bound to single chain variable fragments (scFvs). Using this model, we designed several tandem scFvs and a bispecific antibody that selectively activated EPO-R/CD131 and not the related receptor, EPO-R/EPO-R. These proteins serve as a foundation for future studies of EPO-R/CD131 biology or for the development of safer, more selective therapeutic candidates for cell-protection applications, such as neurodegenerative diseases. In Chapter 2, I detail the design and early stage testing of several mono- and bi-specific Fc fusion proteins for the treatment of dysfunctional and inflammatory pain. Using similar design principles, I generated Fc fusions to peptides that inhibit the voltage-gated sodium channels Nav1.7 and Nav1.8 and Fc fusions to neprilysin, an enzyme that degrades the neuroinflammatory peptide, substance P. Altogether, this work provides novel approaches to the modulation of these challenging targets and insights about future design considerations and possible solutions to further the development of protein therapeutics for cell-protection and chronic pain.Systems Biolog
Mechanistic Characterization of Acyltransferases that Modify the Bacterial Cell Envelope
No full textBacteria are surrounded by a complex macromolecular structure called the cell envelope, which is essential for survival. The cell envelope structure varies depending on the bacterial species; however, there are conserved features present in all cell envelopes, like peptidoglycan. Because of its conservation and essentiality, peptidoglycan has long been the target for antibiotics, such as beta-lactams. Unfortunately, bacteria have developed resistance to these antibiotics, and their broad-spectrum activity is considered detrimental to commensal bacteria. With this in mind, it is critical to explore new antibiotic targets within cell envelope biosynthesis. Furthermore, it would be beneficial for these new drugs to have more specific activity, which could be achieved by targeting features that are unique to specific bacterial clades. This work explores the potential of cell envelope-modifying acyltransferases as new targets for antibiotic development. We focus on understanding the basic mechanism of these acyltransferases to lay the groundwork for future drug development campaigns.
In this thesis, we determined the mechanism for teichoic acid D-alanylation in Gram-positive bacteria. We showed that the small membrane protein DltX uses a conserved C-terminal hexapeptide motif to help shuttle D-alanine across the membrane. This occurs through a cascade of covalent intermediates that promote thermodynamically favorable transfer. Additionally, we found that cell envelope modifying pathways that lack a DltX homolog use a similar hexapeptide motif; however, it is fused directly to a polytopic membrane protein akin to DltB. We then used cryoEM to structurally characterize the DltXBCD complex to further probe the mechanism. We developed a robust pipeline to determine this structure and applied it to a disulfide mutant that traps DltX in a DltB-bound state. Finally, we turned our attention to an acetyltransferase, TmaT, important for mycomembrane biogenesis in Mycobacteriales. We found that this acetyltransferase interacts with an arabinosyltransferase, AftD, involved in arabinogalactan biosynthesis. We also discovered that the acetyltransferase and the arabinosyltransferase regulate each other’s activities. This work led to a model where the TmaT/AftD complex serves to coordinate cell envelope assembly in Mycobacteriales. Taken together, this work uncovered fundamental mechanistic information about a range of cell envelope-modifying acyltransferases that will serve as a basis for future antibiotic development efforts.Chemical Biolog
Beyond Better Babies: Religion and Eugenic Maternalism in Progressive Era Child Welfare Reform
No full textThis dissertation explores the role of eugenic environmental reform in urban child and maternal welfare from 1900-1935. It centers on the New York City Babies Welfare Association (BWA), a federation of over one hundred private philanthropic and religious organizations, including settlement houses, education extension societies, clinical dispensaries, and educational clubs for children. Though its members reported to the hub, they remained relatively autonomous, and, as a result, much of the day-to-day work of public health programming was done not by public health officials alone but also by Protestant, Catholic, and Jewish women with religious missions.
I identify a vast network of reformers across these movements who collectively promoted and perpetuated the integration of public health and child welfare practices. I refer to these reformers as eugenic maternalists to demonstrate how eugenic ideas about heredity and the environment permeated discourses about religion, immigration, maternity, and child welfare in the first half of the twentieth century. This sprawling network of philanthropic, religious, and municipal organizations comprised a wide range of scientific, theological, and political views, offering a way of visualizing how eugenic maternalists created a unifying conception of American citizenship built around health and hygiene behavior and defined by perceived moral, mental, and physical fitness.History of Scienc
Uncle Moses: A Novel
No full textUncle Moses is an historical novel based on the 1955 kidnapping and murder of fourteen-year-old Emmett Till that occurred when he was visiting his great-uncle Moses Wright, a Black sharecropper and preacher in the Mississippi Delta. The fictionalized account begins the night Emmett whistles at the young white woman minding the country store where Emmett and his cousins go to buy candy.
The novel follows the tragic events that unfold after that encounter, told from the perspective of one of the murderer’s wives. In the novel, she is an autodidact—from a family of limited means with little formal education—inspired to read by the literary Percy family in Greenville, Mississippi where she grew up. She has been friends with 64-year-old Moses Wright since her childhood, when he helped with cotton harvest on the Percy plantation that her father managed.
The book places the fictionalized Moses at the center of the story as the first Black person to ever testify in open court against white defendants in a murder trial.Extension Studie
Image-Based Algorithms for Remote Surgical Site Infection Diagnosis in Rural Rwanda
No full textA key challenge in global health is the delivery of high-quality health care in low-resource settings. In sub-Saharan Africa, wound infections are physically and financially catastrophic for patients due to limited access to medical facilities, health professionals, and adequate follow-up care. Surgical Site Infections (SSIs) in rural Rwanda affect an average of 12.4% of women undergoing cesarean deliveries and significantly contribute to maternal morbidity and mortality.
A key challenge to SSI monitoring is that cesarean-associated SSIs often develop after hospital discharge and traveling back to a facility for follow-up care is burdensome for women. However, the widespread availability of mobile health technology among community health workers (CHWs) in rural regions presents a new opportunity for SSI care. In this thesis, we propose a CHW-led mobile health system for automated, home-based diagnosis of surgical site infections for mothers after C-section. The mobile health system takes a smartphone image of the wound site, uses a real-time computer vision algorithm for image preprocessing, and deploys an AI-based predictive model for image classification. The methodology eliminates the need for tedious manual preprocessing and the variability in the collected image data.
The utility of our method is demonstrated by testing on two image datasets -- visible and thermal -- of 621 wound photos collected from women at Kirehe District Hospital in Rwanda. The final model trained on visible images had an AUC=0.86 (sensitivity=0.83, specificity=0.75). The final model trained on the thermal images had an AUC=0.89 (sensitivity=0.94, specificity=0.81).
Overall, we demonstrate the first smartphone-based methodology for surgical site infection diagnosis. Further, the thermal model provides a new opportunity to help identify wound infections without dependence on skin color. We believe this new diagnostic tool will reduce barriers to accessing post-partum follow-up care, and takes a promising first step toward improving maternal health in low-resource settings. Further, we hope this advancement paves the way for the practical implementation of image-based machine learning models and represents an important milestone for the adoption of artificial intelligence for global health.Computer Scienc
The Weaver of Stories
No full textThe title of this short story collection is The Weaver of Stories. Why, The Weaver
of Stories? The word weaver is not a simple word, it is a rather complex word that
intersects all aspects of life. For many, the word weaver is most commonly associated
with threading material together. For others, the word weaver may be related to the
weaverbird, which is part of the finch family. While for others, the word weaver may
conjure up a variety of thoughts, perceptions, impressions, and ideas, specific to bringing
people together. My stories strive to implement many aspects of this word, by
meticulously layering them together to create a unique and individualized experience.
While my collection of short stories may not overlap, there is a cohesive idea of
overcoming, surviving, and proving personally resilient. The thematic intent of this
collection has been to ballast as many perspectives around survival, implicit and explicit,
and to extrapolate an underlying tone of resilience, persistence, and resistance.
My thesis is a journey through the lives of a variety of characters, both human and
non. It explores their angst, heartache, sorrow, and love. As you voyage through my
stories, you will witness how I have chosen to weave the very fabric of my unique stories
together. The stories are as much about the characters’ lives as they have to do with the
stories themselves.
Ultimately, the ambition of each of these stories has been to drive home a similar
theme of triumph, overcoming and the integrity of the human condition. You’ll be cast
into a rich environment of homesickness, nostalgia, friendship, loss, and love. My stories
intend to explore the very nature of the biopsychosocial makeup of the human
experience, while also examining the intrinsic drive to prove victorious
Transcript-specific enrichment enables profiling rare cell states via scRNA-seq
No full textSingle-cell genomics technologies have accelerated our understanding of cell-state heterogeneity in diverse contexts. Although single-cell RNA sequencing (scRNA-seq) identifies many rare populations of interest that express specific marker transcript combinations, traditional flow sorting limits our ability to enrich these populations for further profiling, including requiring cell surface markers with high-fidelity antibodies. Additionally, many single-cell studies require the isolation of nuclei from tissue, eliminating the ability to enrich learned rare cell states based on extranuclear protein markers. To address these limitations, we describe Programmable Enrichment via RNA Flow-FISH by sequencing (PERFF-seq), a scalable assay that enables scRNA-seq profiling of subpopulations from complex cellular mixtures defined by the presence or absence of specific RNA transcripts. Across immune populations (n = 141,227 cells) and fresh-frozen and formalin-fixed paraffin-embedded brain tissue (n = 29,522 nuclei), we demonstrate the sorting logic that can be used to enrich for cell populations via RNA-based cytometry followed by high-throughput scRNA-seq. Our approach provides a rational, programmable method for studying rare populations identified by one or more marker transcripts.Accepted Manuscrip
Bridging the Gap Between Imagined and Plausible Futures for Refugees: What Students Wish Their Teachers Knew
No full textThere is a gap between the futures that refugee young people imagine will be possible through their education and the plausible futures in exile, where opportunities are truncated by social, economic, and political exclusions. Our study examines how education can narrow this gap. Through interviews with Syrian students in Lebanon, we document fixed and malleable elements of education that refugee students identify as bridging their current education and their futures. Students experience the structures and content of schooling in Lebanon as both exclusionary and immutable, yet their teachers use what we call relational pedagogies rooted in predictability, explaining, fairness, and care to support students' learning and navigation toward future opportunities. While our research focuses on refugees, it has conceptual implications for educators and school systems in other settings where teachers support their marginalized students to make sense of disconnects between what they imagine is possible through school and their future opportunities.Version of Recor