18525 research outputs found
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Machine Learning on Single-Cell RNA-Seq to Advance our Understanding of Clonal Hematopoiesis
No full textClonal Hematopoiesis of Indeterminate Potential (CHIP) is characterized by genetic mutations within blood-forming stem cells, leading to the emergence of mutated blood cell populations. Associated with elevated risks of various diseases, including malignancies and cardiovascular ailments, CHIP's intricate relationship between genetics and health underscores the need for comprehensive investigation and understanding. Current methodologies for the identification of CHIP cells are time-consuming and cost intensive. Utilizing single-cell RNA sequencing (scRNA-seq) data, this study aims to delve deeper into the complex genomic landscape of CHIP, harnessing the power of machine learning classifiers and techniques to build a more cost-effective pipeline for the identification of CHIP cells and enhance our understanding. A specialized machine learning classifier is tailored within a pipeline specifically for the nuances of CHIP-related single-cell RNA expression data, meticulously analyzing critical features. Using model-agnostic methods such as permutation importance, the model refines hundreds of features down to the most critical ones while maintaining a high level of accuracy. Exploration with the TET2 dataset successfully pinpoints 13 key genes that play a pivotal role in the identification of CHIP cells vs. non-CHIP cells using a model that accurately classifies CHIP cells 91% of the time. Exploration with the DNMT3A dataset successfully pinpoints 3 key features using a model that accurately classifies CHIP cells 81% of the time. The classifier developed within the pipeline holds the potential to assist in the precise identification of CHIP cells and unveil distinct RNA expression profiles. This research endeavors to illuminate the genetic and functional facets of CHIP cells, paving the way for advancements in disease prediction, diagnostics, and potential therapeutic interventions
Guyane et Polynésie : de l’enfer vert au paradis, construction des espaces coloniaux tropicaux et émergence des voix autochtones
No full textMy dissertation project takes an ecocritical approach towards literature in the francophone world by exploring the French colonial underpinnings of environmental perceptions and policies. While the ecocriticism approach in literature has been particularly exploited in North America, it has recently made its appearance in the francophone world. I am interested in exploring how vast spaces, like the Pacific Ocean and its islands as well as the Amazonian jungle, have been depicted in French literature. For example, I explore how the breadfruit tree plays a crucial role in the mutiny of the Bounty in the works of Jules Verne or the way that the jaguar figure and other representations from a fantastical bestiary in the adventure novels of Louis-Henri Boussenard serve to complete French heroism.
The first part of the project undertakes a comparative study of French Guyana and Polynesia and show how literary depictions contributed to the Othering of the Tropics as either a paradise or l'enfer vert in the Western collective consciousness. The second part centers on contemporary indigenous voices in these regions and their tactical, even radical, refashioning of the imposed ecological outlook of the French colonial gaze. The interdisciplinary nature of my research draws from an array of perspectives, from literary and historical to anthropological and socio-economic, to shed light on the cultural dimensions of environmental representations and prevailing biases
Designing for Their Joy: An ethnographic investigation of middle school students’ joyful mathematical learning
No full textThis is an empirical, ethnographic study about middle school students’ mathematical joy in a formal math classroom. This study is situated in a year-long Research Practice Partnership with 6th grade mathematics teacher and 21 students in her 3rd block class. Through this collaboration, the teacher and I sought to design tasks to support students’ unique joyful mathematical engagement. We did this through an iterative design approach involving three phases of data collection and three analytic cycles. Qualitative open coding, case studies, and abductive postcoding analysis were conducted to determine: 1. what are some characteristics of joyful mathematical engagement? and 2. what conditions support students’ joyful mathematical engagement in a formal math classroom? Findings revealed that sociomathematical norms of this classroom characterized knowing and doing mathematics as product-oriented, competitive, compliant, and a complex negotiation of fun and stressful. Additionally, when students engaged in tasks that were intentionally designed to support mathematical reciprocity, many students across the class demonstrated joy while engaging in math learning in multifaceted ways (for example through humor, movement, debate, and encouragement) that represented their multifaceted well-being. This is not to generalize to say that we can design for all students’ mathematical joy by incorporating reciprocity or in fact any single dimensions of design. Joy that emerged for these students resulted from listening to students varied ways of communicating their experience with both humanizing and dehumanizing mathematical experiences in this cultural environment. It was by attending to them, treating them as human, listening to their stories, watching their grins and winces that we could see more clearly, albeit imperfectly, learn how to design more humanizing formal mathematical learning experiences that supported their unique joy
Political Polarization
No full textThis working paper covers some of the various causes of political polarization, maps the current problem landscape, and attempts to categorize and examine these problems. Furthermore, the paper provides some potential solutions for political polarization in the United States using a systems thinking approach.The United States is currently navigating a landscape deeply scarred by political polarization, a phenomenon that has quintupled since 1930 (Cinolesi et al., 2022). This escalating division is not merely a divergence of political ideologies but has evolved into affective polarization - characterized by increasing animosity and distrust between major political parties, Democrats and Republicans. A crucial aspect of this divide is the demographic shift, with the Democratic Party becoming more diverse while the Republican Party maintains a predominantly white and conservative base. Political elites play a significant role in amplifying group identities, thereby activating stereotypes and reinforcing partisan understanding. This trend fuels the increasing affective polarization among the public (Wilke et al., 2022).The goal of our research is to explore and begin mapping the complex web of political polarization in the United States. Collectively, this information will help us create a series of concept maps and ultimately, identify levers for change
Design, Sensing, and Control for Safe Human-Robot Interaction in Confined Spaces
No full textWorkers across multiple sectors of industry are often put at risk of developing musculoskeletal disorders such as carpel tunnel syndrome, tendinitis, and lower back pain. These work-related musculoskeletal disorders stem from repeatedly lifting heavy equipment, resisting tool vibrations, and exerting forces in non-ergonomic postures. While full automation could completely alleviate the issue, many industrial tasks such as equipment maintenance and repair require human sensory presence. For these scenarios, researchers have developed collaborative robots that can offset the physiological strain from the worker while still being safe enough to operate in close physical proximity to the worker. Despite their potential benefits, there are still areas of industrial work for which no collaborative robot has been designed. One such area is industrial operation inside confined spaces. Human-robot collaboration in confined spaces presents a host of difficult technical challenges to ensure worker safety during complex industrial tasks.
This dissertation aims to address a few of these technical challenges in the areas of design, sensing, and control. We first present the mechanical design of a robot intended for human-robot collaboration in confined spaces. This robot consists of a statically balanced, rigid-linked base, two continuum segments lined with contact and proximity sensors, and a wrist for a total of 11 active degrees of freedom. The static balancing of this robot is achieved using a spring-loaded wire-wrapped cam mechanism. When designing this mechanism, we noticed several gaps in the literature. To address these limitations, we present an optimization-based design strategy for two-degree of freedom wire-wrapped cam mechanisms that 1) respects the deflection limits of springs, 2) ensures the cams are convex, and 3) minimizes the effect of unmodeled changes in spring constant. We also present a model of the effect of wire-cam friction and evaluate the method experimentally. Next, we present what we believe is the first adaptation of the generalized momentum observer contact detection/estimation approach for variable curvature continuum robots. We also present a model for the effect of dynamic state uncertainty on the performance of the observer and evaluate the method experimentally. After this, we present a redundancy resolution and end-effector compliance modulation strategy for robots with bracing constraints. This redundancy resolution strategy can be used to enable the design of long-reach robots with minimal torque actuators. Lastly, we present the software and control framework of the aforementioned collaborative robot. We also present a preliminary system evaluation user study that explores the benefits and tradeoffs of human sensory presence for mock industrial tasks. Specifically, the user study explores controlling the robot using admittance control and using teleoperation with and without virtual fixtures.
We believe the contributions to the design, sensing, and control of collaborative robots in confined spaces presented in this dissertation will help improve the health of industrial workers and increase the adoption of collaborative robots
Executive functioning in Huntington’s Disease and Major Depressive Disorder: Moderators and associations with emotion regulation
No full textElucidating disorder- and domain-specific deficits within psychiatric and medically ill
populations is a primary focus in the field of neuropsychology. Comparing overlapping and distinct patterns of cognitive functioning across psychiatric disorders may improve our understanding of brain–behavior relationships and either support or challenge existing diagnostic boundaries. Executive functioning (EF) has been proposed as a transdiagnostic factor underlying risk for psychopathology, and EF is important for dealing with stress and negative emotions that accompany many psychiatric disorders. The present study compared EF impairments using a common methodology and shared metrics in two samples affected by psychiatric disorders: adults with Huntington’s disease (HD; n = 82; 58.5% female, M age = 42.17 ± 12.43 years; 97.6% White) and adults with a history of major depressive disorder (MDD; n = 105; 89.3% female, M age = 42.77 ± 6.33 years; 70.5% White, 9.5% Black/African American, 10.5% Multiracial). Results indicated that individuals with HD are at risk for impairments equal to or greater than one standard deviation below the normative mean across core domains of EF (inhibitory control, working memory, shifting). Individuals with a history of MDD evidenced much lower risk for EF impairments compared to normative data and outperformed individuals with HD on all three domains of EF. Between-group differences remained after accounting for current depression symptom, and relatively low inhibitory control scores drove within-group differences. Results did not provide support for EF domains and processing speed entered simultaneously as predictors of secondary control coping. Findings suggest that individuals with HD may benefit from interventions targeting all core EFs, but that EFs may not be a primary target of intervention for individuals remitted from depression
Exploring the Impact of Support Systems & Instructor Practices on Course Completion at Virtual Learning Academy Charter School
No full textLeadership and Learning in Organizations capstone projectVirtual Learning Academy Charter School (VLACS) is a non-profit virtual public charter school in Southern New Hampshire that serves over 10,000 K-12 and adult learners, with nearly 400 students attending full-time in grades 9-12. With a 70% four-year graduation rate below the state’s 88% average, this project aimed to identify elements of the VLACS program model and instructor practices that contribute to or serve as barriers to course completion for its full time high school students. Grounding our work in Social and Academic Integration Theory, Self-regulation Theory, and User Experience Design Theory, we explored student engagement and support within online learning environments, development of self-regulation skills, and application of user-centered design principles to online learning. This study utilized a sequential mixed methods approach, incorporating empathy interviews with staff, analysis of school documentation, surveys of students and instructors, student focus groups, and instructor interviews. Key findings highlight the importance of instructor responsiveness and constructive feedback, the utility of the Canvas learning management system and support features such as pace charts and Tutor.com, the promotion of self-regulation skills, and the crucial role that the instructor-student relationship plays in facilitating course completion. Challenges identified include communication barriers, a desire for social connections, and user experience issues with technical support in Canvas. Recommendations include standardizing expectations and protocols for improving communication and responsiveness, fostering social and academic connections, supporting self-regulation skills, refining the Canvas user experience, and strengthening instructor-student relationships to improve student engagement and course completion
Stress and Coping in Siblings of Individuals with Intellectual and/or Developmental Disabilities
No full textPSY-PC 4999 - Honors Seminar - Dr. Jessika Boles
Millions of children are living with intellectual and developmental disabilities worldwide, yet
little is known about this experience from the vantage point of neurotypical siblings. Therefore,
the purpose of this mixed-methods study was to explore the coping mechanisms and stressors of
adult siblings of individuals with intellectual and/or developmental disability to identify
opportunities for better supporting this population. Twenty-seven adults who identified as a
sibling of a person with intellectual and/or developmental disabilities completed a series of
electronic instruments including a demographic questionnaire, the Coping Resources Inventory,
the Brief Coping Orientation to Problems Experienced Inventory, and the Perceived Stress Scale.
Thirteen participants also completed a semi-structured telephone interview following survey
completion. Results demonstrated that participants most often used Self-Blame, Instrumental
Support, and Acceptance coping mechanisms, and that, overall, emotional and social were the
most commonly endorsed coping resources. Interview responses highlighted four major themes:
1) caretaking across the lifespan, 2) negotiating normalcy inside and outside the household, 3)
parental transparency about sibling diagnosis and 4) reframing the sibling experience. Taken
together, the results of this study suggest that providers and caregivers can better support siblings
of individuals with intellectual and/or developmental disabilities by recognizing and supporting
them through the negotiation of normalcy that comes with their unique stressors and experiences.Thesis completed in partial fulfillment of the requirements of the Honors Program in Psychological Science
Consequences of WDR5 Targeted Degradation in Human Cancer Cells
No full textWDR5 is a highly-conserved nuclear protein which facilitates the assembly of histone-modifying complexes involved in a variety of chromatin-based, gene regulatory processes. WDR5 is best known for its role in scaffolding the assembly of MLL/SET histone methyltransferase complexes that catalyze histone H3 lysine 4 (H3K4) di– and tri-methylation (Me2/Me3), but WDR5 acts outside this setting to promote ribosomal protein gene transcription and recruit the oncogenic transcription factor MYC to chromatin. WDR5 is also a target for pharmacological inhibition in cancer, and most drug discovery efforts aim to block the WIN site of WDR5, an arginine binding cavity that engages MLL/SET enzymes. Therapeutic application of WIN site inhibitors is complicated by the disparate functions of WDR5, but is generally guided by two assumptions—that WIN site inhibitors disable all functions of WDR5, and that changes in H3K4me drive the transcriptional response of cancer cells to WIN site blockade. Here, we test these assumptions by comparing the impact of WIN site inhibition versus WDR5 degradation on H3K4me and transcriptional processes in Burkitt lymphoma and neuroblastoma cell lines. We show that WDR5 regulates transcription widely, yet WIN site inhibition disables only a specific subset of WDR5 activity, and that H3K4me changes induced by WDR5 depletion do not explain accompanying transcriptional responses. Additionally, WDR5 degradation results in the collateral loss of SET1/MLL proteins. These data recast WIN site inhibitors as selective loss-of-function agents, contradict H3K4me as a relevant mechanism of action for WDR5 inhibitors, and point to distinct clinical applications of WIN site inhibitors and WDR5 degraders
Efficiently Mining the B cell Repertoire for Cross-Reactive Coronavirus Antibodies
No full textCoronaviruses (CoVs) are single-stranded, positive-sense RNA viruses that infect a wide variety of species including birds, reptiles, and mammals. SARS-CoV-2 is only the latest coronavirus to jump from animals into humans in the last 20 years, and it has highlighted the necessity of developing our defenses against these threats before the next pandemic emerges. Antibodies are one of the most promising therapeutic and prophylactic drugs that we have against viruses, and they have been utilized extensively throughout the COVID-19 pandemic, however due to the rapid evolution of SARS-CoV-2, many lost effectiveness. This emphasizes the need for antibodies that are more cross-reactive and target more conserved epitopes of the spike protein. This dissertation contains my research efforts in characterizing novel, cross-reactive coronavirus antibodies, as well as developing techniques that will allow for the efficient discovery of rare, epitope-specific antibodies. In chapter 2, I characterize cross-reactive, potently neutralizing antibodies isolated from children, highlighting that antibodies from children may be an underutilized source for the discovery of cross-reactive CoV antibodies. In chapter 3, I present the discovery, characterization, and structure of an S2-specific, pan-betacoronavirus antibody to a novel epitope. Finally, I detail my work developing LIBRA-seq with antibody blocking, a high-throughput antibody discovery technology that will allow for the enrichment of antibodies that target rare epitopes that are difficult to identify through currently available technologies. Overall, my thesis work will contribute to the discovery and development of protective coronavirus antibodies, and epitope-specific antibody discovery tools in general