Digital Commons Network^™

Metabolic Dependencies Of Acute Myeloid Leukemia Stem Cells, Xiangguo Shi, Mengdie Feng, Daisuke Nakada

Faculty, Staff and Students Publications

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy primarily driven by an immature population of AML cells termed leukemia stem cells (LSCs) that are implicated in AML development, chemoresistance, and relapse. An emerging area of research in AML focuses on identifying and targeting the aberrant metabolism in LSCs. Dysregulated metabolism is involved in sustaining functional properties of LSCs, impeding myeloid differentiation, and evading programmed cell death, both in the process of leukemogenesis and in response to chemotherapy. This review discusses recent discoveries regarding the aberrant metabolic processes of AML LSCs that have begun to change the therapeutic landscape of …

Global Presence And Penetrance Of, Jaroslaw Dulski, Matthew Baker, Samantha A Banks, Michael Bayat, Rose Bruffaerts, Gabriela Ortiz Cruz, Caio C Disserol, Kristen S Fisher, Jainy N Jose, Bernadette Kalman, Orhun H Kantarci, Dmytro Maltsev, Catherine Middleton, Gabriela Novotni, Dijana Plaseska-Karanfilska, Salmo Raskin, Josiane Souza, Helio A Teive, Zbigniew K Wszolek

Faculty, Staff and Students Publications

Objectives: To highlight the worldwide presence of CSF1R-related disorder (CSF1R-RD), discuss its penetrance, and provide the first haplotype analysis.

Methods: Data on patients worldwide were collected, including demographics, genotype, family history, and clinical status. For haplotype analysis, polymorphisms of short tandem repeats in 3 distinct families with CSF1R p.Ile794Thr variant were examined.

Results: Nineteen new patients were included, at a mean age of 38.7 years (ranging from 11 to 74 years), from 14 families from the Americas, Asia, Australia, and Europe, including the first from Mexico, North Macedonia, and Ukraine. Fifteen CSF1R variants were found, including 8 …

Sequential Early-Life Viral Infections Modulate The Microbiota And Adaptive Immune Responses To Systemic And Mucosal Vaccination, Yuhao Li, Jerome M. Molleston, Crystal Lovato, Jasmine Wright, Isabel Erickson, Duyen Bui, Andrew H. Kim, Harshad Ingle, Somya Aggarwal, Lila S Nolan, Ahmed O. Hassan, Lynne Foster, Michael S. Diamond, Megan T. Baldridge

2020-Current year OA Pubs

Increasing evidence points to the microbial exposome as a critical factor in maturing and shaping the host immune system, thereby influencing responses to immune challenges such as infections or vaccines. To investigate the effect of early-life viral exposures on immune development and vaccine responses, we inoculated mice with six distinct viral pathogens in sequence beginning in the neonatal period, and then evaluated their immune signatures before and after intramuscular or intranasal vaccination against SARS-CoV-2. Sequential viral infection drove profound changes in all aspects of the immune system, including increasing circulating leukocytes, altering innate and adaptive immune cell lineages in tissues, …

Thioredoxin: An Antioxidant, A Therapeutic Target And A Possible Biomarker, Tara Sudhadevi, Anantha Harijith

Faculty Scholarship

Study by Haga et al. on the utility of neonatal serum thioredoxin-1 (TRX-1) levels as a biomarker of bronchopulmonary dysplasia (BPD)/ retinopathy of prematurity (ROP) is the first of its kind. A biomarker is considered to enable the detection of a pathological condition or its severity and ideally, should have the capacity to be detected in the pre-disease state or during the diseased state. Premature infants who develop BPD are exposed to supplemental O2 and show marked evidence of oxidant stress as suggested by elevated glutathione disulfide (GSSG) concentrations.1 Upon preterm delivery, an infant breathing even atmospheric oxygen of 21% …

Upregulation Of Fatty Acid Synthase Increases Activity Of Β-Catenin And Expression Of Notum To Enhance Stem-Like Properties Of Colorectal Cancer Cells, Courtney O. Kelson, Josiane Weber Tessmann, Mariah E. Geisen, Daheng He, Chi Wang, Tianyan Gao, B. Mark Evers, Yekaterina Y. Zaytseva

Markey Cancer Center Faculty Publications

Dysregulated fatty acid metabolism is an attractive therapeutic target for colorectal cancer (CRC). We previously reported that fatty acid synthase (FASN), a key enzyme of de novo synthesis, promotes the initiation and progression of CRC. However, the mechanisms of how upregulation of FASN promotes the initiation and progression of CRC are not completely understood. Here, using Apc/VillinCre and ApcMin mouse models, we show that upregulation of FASN is associated with an increase in activity of β-catenin and expression of multiple stem cell markers, including Notum. Genetic and pharmacological downregulation of FASN in mouse adenoma organoids decreases the activation of β-catenin …

The Absence Of Cxcl10 Activity Does Not Affect The Capability Of Cd8+ T Cells To Migrate And Eliminate The Tissue Cysts Of Toxoplasma Gondii From The Brains Of Chronically Infected Mice, Rajesh Mani, Yasuhiro Suzuki

Markey Cancer Center Faculty Publications

Toxoplasma gondii forms tissue cysts in neurons and astrocytes in the brain to establish chronic infection, and astrocytes express the CXCL10 chemokine in chronically infected mice. Since chemokines mediate the migration of T cells to attack their targets, and since CXCL10 plays key roles in T cell-mediated control of the proliferation of tachyzoites (the acute stage form) of T. gondii during the acute stage of infection, we examined whether CXCL10 is involved in recruiting anti-cyst CD8+ cytotoxic T cells to eliminate the cysts in their brains. We employed adoptive transfer of CD8+ immune T cells to infected, T cell-deficient SCID …

The Impact Of Pdcd4, A Translation Inhibitor, On Drug Resistance, Qing Wang, Hsin-Sheng Yang

Markey Cancer Center Faculty Publications

Programmed cell death 4 (Pdcd4) is a tumor suppressor, which has been demonstrated to efficiently suppress tumorigenesis. Biochemically, Pdcd4 binds with translation initiation factor 4A and represses protein translation. Beyond its role in tumor suppression, growing evidence suggests that Pdcd4 enhances the chemosensitivity of several anticancer drugs. To date, numerous translational targets of Pdcd4 have been identified. These targets govern important signal transduction pathways, and their attenuation may improve chemosensitivity or overcome drug resistance. This review will discuss the signal transduction pathways regulated by Pdcd4 and the potential mechanisms through which Pdcd4 enhances chemosensitivity or counteracts drug resistance.

An Examination Of Civil Asset Forfeiture In South Carolina, Jeffrey Trowbridge

Theses and Dissertations

Civil asset forfeiture allows the government to seize and forfeit property that is associated with criminal activity without arresting or charging the property owner. Although expansive in its potential application, little is understood about the characteristics of civil asset forfeiture cases, the property owners involved in forfeiture cases, or the characteristics of any criminal cases pursued parallel to the civil cases. Utilizing open-source, public court records, this dissertation provides an exploratory analysis of these gaps in the literature by examining the types of civil asset forfeiture used, the value of asset forfeiture cases, how money from asset forfeiture is divided …

Psci 102: Political Controversies: Democracy, Politics, And Freedom., Antonia Cucchiara

Open Educational Resources

This course aims to provide students with an introduction to the analysis of political controversies stemming from issues related to freedom and democracy in America today. Students will first engage with questions central to the understanding of the concepts above, such as: What is freedom? What is the relationship between freedom and democracy? How have thinkers, from the ancient to modern era, defined freedom? How can we compare and contrast the varied definitions of freedom put forward by thinkers across time? Students will then apply the theories of freedom and democracies to analyze a series of case studies from the …

Car T-Cell Therapy In Acute Myeloid Leukemia, Alhomidi Almotiri

Saudi Medical Journal

ABSTRACT Acute myeloid leukemia (AML) is an aggressive leukemic malignancy that affects myeloid lineage progenitors. Relapsed or refractory AML patients continue to have poor prognoses, necessitating the development of novel therapy alternatives. Adoptive T-cell therapy with chimeric antigen receptors (CARs) is an intriguing possibility in the field of leukemia treatment. Chimeric antigen receptor T-cell therapy is now being tested in clinical trials (mostly in phase I and phase II) using AML targets including CD33, CD123, and CLL-1. Preliminary data showed promising results. However, due to the cellular and molecular heterogeneity of AML and the co-expression of some AML targets on …

Daily Stress, Problematic Social Media Use, And Executive Functions: A Daily Diary Approach, Wee Qin Ng

Dissertations and Theses Collection (Open Access)

A growing body of research suggests that daily stress may be a risk factor for problematic social media use. However, findings concerning the relation between stress and social media use are mixed, suggesting the presence of moderators that may buffer the relation between stress and problematic social media use. Further, previous studies have relied on either cross-sectional designs or longitudinal designs that may not fully capture daily experiences of stressors and social media use. To overcome these limitations, the present study utilized a 7-day daily diary study to investigate the within-individual associations between daily stress and problematic social media use. …

Construction And Empirical Assessment Of An Employee Health Management Index System For Chinese Enterprises, Ming Dong

Dissertations and Theses Collection (Open Access)

Purpose: Employee health management is critical for enhancing corporate productivity, and scientific evaluation is core to effective health management practices. This study aims to construct an evaluation index system for assessing the employee health management effectiveness tailored to China’s national conditions (Hereinafter called “evaluation system”), and to empirically assess its differentiation, accuracy, and universality.

Methodology: (1) Grounded in literature and policy analysis, the study adopts the PDCA theory as a foundational framework and employs a modified Delphi method to finalize the evaluation system's structure. Indicator weights were determined using the Analytic Hierarchy Process, and a standard scale was created for …

Visual Parsing Algorithms For An Equitable Augmented Reality Learning System, Pushpita Saha '25, Matthew L. Furber Mfa, Paul W. Bible

Annual Student Research Poster Session

Giving instructions for a character to navigate around a scene provides a simple analog for the planning needed in computer programming. While many children’s navigation games exist, most require the child to use a combination of input devices such as keyboard, mouse, and controllers for play. Children under the age of five may struggle to use a mouse, but they can easily construct the plans needed for such a game. This research explores layout and graph connectivity algorithms to connect tactile game pieces for a navigation game. A web camera identifies the position of action cards and numerical modifiers (card: …

Antitrust After The Coming Wave, Daniel A. Crane

Articles

A coming wave of general-purpose technologies, including artificial intelligence ("AI"), robotics, quantum computing, synthetic biology, energy expansion, and nanotechnology, is likely to fundamentally reshape the economy and erode the assumptions on which the antitrust order is predicated. First, AI-driven systems will vastly improve firms' ability to detect (and even program) consumer preferences without the benefit of price signals, which will undermine the traditional information-producing benefit of competitive markets. Similarly, these systems will be able to determine comparative producer efficiency without relying on competitive signals. Second, AI systems will invert the salient characteristics of human managers, whose intentions are opaque but …

Leveraging Imitation Learning In Agricultural Robotics: A Comprehensive Survey And Comparative Analysis, Siavash Mahmoudi, Amirreza Davar, Pouya Sohrabipour, Ramesh Bahadur Bist, Yang Tao, Dongyi Wang

Biological and Agricultural Engineering Faculty Publications and Presentations

Imitation learning (IL), a burgeoning frontier in machine learning, holds immense promise across diverse domains. In recent years, its integration into robotics has sparked significant interest, offering substantial advancements in autonomous control processes. This paper presents an exhaustive insight focusing on the implementation of imitation learning techniques in agricultural robotics. The survey rigorously examines varied research endeavors utilizing imitation learning to address pivotal agricultural challenges. Methodologically, this survey comprehensively investigates multifaceted aspects of imitation learning applications in agricultural robotics. The survey encompasses the identification of agricultural tasks that can potentially be addressed through imitation learning, detailed analysis of specific models …

Allura Red Ac Is A Xenobiotic. Is It Also A Carcinogen?, Lorne J. Hofseth Ph.D., James Hébert Scd, Elizabeth Angela Murphy, Erica Trauner, Athul Vikas, Quinn Harris, Alexander A. Chumanevich

Faculty Publications

Merriam-Webster and Oxford define a xenobiotic as any substance foreign to living systems. Allura Red AC (a.k.a., E129; FD&C Red No. 40), a synthetic food dye extensively used in manufacturing ultra-processed foods and therefore highly prevalent in our food supply, falls under this category. The surge in synthetic food dye consumption during the 70s and 80s was followed by an epidemic of metabolic diseases and the emergence of early-onset colorectal cancer in the 1990s. This temporal association raises significant concerns, particularly given the widespread inclusion of synthetic food dyes in ultra-processed products, notably those marketed toward children. Given its interactions …

Allura Red Ac Is A Xenobiotic. Is It Also A Carcinogen?, Lorne J. Hofseth, James R. Hébert Scd, Elizabeth Angela Murphy, Erica Trauner, Athul Vikas, Quinn Harris, Alexander A. Chumanevich

Faculty Publications

Merriam-Webster and Oxford define a xenobiotic as any substance foreign to living systems. Allura Red AC (a.k.a., E129; FD&C Red No. 40), a synthetic food dye extensively used in manufacturing ultra-processed foods and therefore highly prevalent in our food supply, falls under this category. The surge in synthetic food dye consumption during the 70s and 80s was followed by an epidemic of metabolic diseases and the emergence of early-onset colorectal cancer in the 1990s. This temporal association raises significant concerns, particularly given the widespread inclusion of synthetic food dyes in ultra-processed products, notably those marketed toward children. Given its interactions …

Benefits Of Calorie Restriction In Mice Are Mediated Via Energy Imbalance, Not Absolute Energy Or Protein Intake, Daniel L Smith, Sharon E Mitchell, Maria S Johnson, Victoria K Gibbs, Stephanie Dickinson, Beate Henschel, Rui Li, Kathryn A Kaiser, Daniella E Chusyd, Andrew W Brown, David B Allison, John R Speakman, Tim R Nagy

Children’s Nutrition Research Center Staff Publications

Caloric restriction (CR) results in reduced energy and protein intake, raising questions about protein restriction's contribution to CR longevity benefits. We kept ad libitum (AL)-fed male C57BL/6J mice at 27°C (AL27) and pair-fed (PF) mice at 22°C (22(PF27)). The 22(PF27) group was fed to match AL27 while restricted for calories due to cold-induced metabolism. The 22(PF27) mice had significantly lower body weight, lean mass, fat mass, leptin, IGF-1, and TNF-α levels than AL27 mice (p< 0.001 for all). Manipulations over ~11 weeks resulted in significant differences in body temperature, physical activity, and expression of key genes linked to hunger in the hypothalamus. Survival was significantly greater in 22(PF27) compared to AL27 overall (p< 0.001). CR in the context of equivalent energy and protein intake resulted in hormonal, metabolic, and physiological benefits and extended longevity. Hence, energy imbalance, rather than low energy or protein intake per se, mediates the benefits of CR.

Audio Description Customization, Rosiana Natalie, Ruei-Che Chang, Sheshadri Smitha, Anhong Guo, Kotaro Hara

Research Collection School Of Computing and Information Systems

Blind and low-vision (BLV) people use audio descriptions (ADs) to access videos. However, current ADs are unalterable by end users, thus are incapable of supporting BLV individuals’ potentially diverse needs and preferences. This research investigates if customizing AD could improve how BLV individuals consume videos. We conducted an interview study (Study 1) with fifteen BLV participants, which revealed desires for customizing properties like length, emphasis, speed, voice, format, tone, and language. At the same time, concerns like interruptions and increased interaction load due to customization emerged. To examine AD customization’s effectiveness and tradeoffs, we designed CustomAD, a prototype that enables …

The Middle Domain Of Hsp104 Can Ensure Substrates Are Functional After Processing, Hannah Buchholz, Jane E. Dorweiler, Sam Guereca, Brett T. Wisniewski, James Shorter, Anita L. Manogaran

Biological Sciences Faculty Research and Publications

Molecular chaperones play a central role in protein disaggregation. However, the molecular determinants that regulate this process are poorly understood. Hsp104 is an AAA+ ATPase that disassembles stress granules and amyloids in yeast through collaboration with Hsp70 and Hsp40. In vitro studies show that Hsp104 processes different types of protein aggregates by partially translocating or threading polypeptides through the central pore of the hexamer. However, it is unclear how Hsp104 processing influences client protein function in vivo. The middle domain (MD) of Hsp104 regulates ATPase activity and interactions with Hsp70. Here, we tested how MD variants, Hsp104^A503S and …

Taking The Law Into Their (Virtual) Hands: Facebook And Digital Vigilantism, Christine Anne R. Cox

Department of Communication Faculty Publications

Digital vigilantism is an emerging phenomenon whereby netizens engage in forms of targeted surveillance, naming and shaming through new media, supposedly for social justice ends. The multi-layered case of Christine Dacera, the Filipina flight attendant who was found dead on New Years Day 2021, is one such case that warrants the critical investigation of the role of Facebook in vigilant behaviors of Filipino users. Using netnographic data and an affordances approach, this study asks the following: What are the dominant affordances associated with the use of Facebook for digital vigilantism, and how does surveillance enable the new normal of community …

Regulation Of Fibrinogen Synthesis, Dre'von A Dobson, Richard J Fish, Paul S De Vries, Alanna C Morrison, Marguerite Neerman-Arbez, Alisa S Wolberg

Faculty, Staff and Student Publications

The plasma protein fibrinogen is encoded by 3 structural genes (FGA, FGB, and FGG) that are transcribed to mRNA, spliced, and translated to 3 polypeptide chains (Aα, Bβ, and γ, respectively). These chains are targeted for secretion, decorated with post-translational modifications, and assembled into a hexameric “dimer of trimers” (AαBβγ)2. Fully assembled fibrinogen is secreted into the blood as a 340 kDa glycoprotein. Fibrinogen is one of the most prevalent coagulation proteins in blood, and its expression is induced by inflammatory cytokines, wherein circulating fibrinogen levels may increase up to 3-fold during acute inflammatory events. Abnormal …

Ficture: Scalable Segmentation-Free Analysis Of Submicron-Resolution Spatial Transcriptomics, Yichen Si, Changhee Lee, Yongha Hwang, Jeong H Yun, Weiqiu Cheng, Chun-Seok Cho, Miguel Quiros, Asma Nusrat, Weizhou Zhang, Goo Jun, Sebastian Zöllner, Jun Hee Lee, Hyun Min Kang

Faculty, Staff and Student Publications

Spatial transcriptomics (ST) technologies have advanced to enable transcriptome-wide gene expression analysis at submicron resolution over large areas. However, analysis of high-resolution ST is often challenged by complex tissue structure, where existing cell segmentation methods struggle due to the irregular cell sizes and shapes, and by the absence of segmentation-free methods scalable to whole-transcriptome analysis. Here we present FICTURE (Factor Inference of Cartographic Transcriptome at Ultra-high REsolution), a segmentation-free spatial factorization method that can handle transcriptome-wide data labeled with billions of submicron-resolution spatial coordinates and is compatible with both sequencing-based and imaging-based ST data. FICTURE uses the multilayered Dirichlet model …

Hippocampal Gray Matter Volume In Young Adulthood Varies With Adolescent Alcohol Use, Juliann B Purcell, Nathaniel G Harnett, Sylvie Mrug, Marc N Elliott, Susan Tortolero Emery, Mark A Schuster, David C Knight

Faculty, Staff and Student Publications

Adolescent substance use is linked with negative future outcomes (e.g., depression, anxiety, substance use disorder). Given that the brain undergoes significant maturation during adolescence, this developmental period may represent a time of particular vulnerability to substance use. Neuroimaging research has largely focused on heavy or binge patterns of substance use; thus, relatively less is known about the neural impact of a broader range of adolescent substance use. Characterizing the neural impact of a broader range of adolescent substance use may inform prevention and treatment efforts. The present study investigated relationships between adolescent substance use trajectories (i.e., alcohol, tobacco, and cannabis) …

Pparγ/Etv2 Axis Regulates Endothelial-To-Mesenchymal Transition In Pulmonary Hypertension, Dong Hun Lee, Minseong Kim, Sarah S Chang, Raham Lee, Andrew J Jang, Juyoung Kim, Jing Ma, Michael J Passineau, Raymond L Benza, Harry Karmouty-Quintana, Wilbur A Lam, Benjamin T Kopp, Roy L Sutliff, C Michael Hart, Changwon Park, Bum-Yong Kang

Faculty, Staff and Student Publications

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells. Etv2 +/- mice spontaneously developed PH and right …

Psychological And Social Well-Being Of Bony Fishes In Zoos And Aquariums, Ronald G. Oldfield, Patrick Bonano

Animal Sentience

Research on the behaviour of animals in zoos has been conducted for decades, and observations have provided information that has improved the psychological and social well-being of animals. However, research on fishes in zoos and aquariums seems to be lacking. Here, we assess the current state of research on fishes in zoos and aquariums by surveying the peer-reviewed literature. Our assessment differs from previous surveys in that we examine the taxonomic classes Chondrichthyes (sharks and rays) and Osteichthyes (bony fishes) separately. Our survey finds that bony fishes have been drastically underrepresented in zoo journals, more drastically than chondrichthyans, revealing an …

Social Emotional Learning (Sel) Instruction: The Effects On Students With Learning Disabilities (Ld), Courtney Schulte

Master's Theses & Capstone Projects

Social Emotional Learning (SEL) has been researched for over 20 years, yet it has become the focus of policy makers over the last several years. SEL competency has proven to increase student relationship building skills, emotional control, academic success and overall self-esteem. Research has shown SEL instruction benefits all students, even students in special education when taught in an explicit and direct manner.

Classifying Open Access Business Models, Tasha Mellins-Cohen

Copyright, Fair Use, Scholarly Communication, etc.

The proliferation of open access (OA) business models has been rapid, presenting challenges for stakeholders in communicating and working effectively with one another. This article aims to clarify terminologies and address the inconsistencies and gaps in previous attempts to categorize OA models, supporting informed decision-making. It presents five core types, each with distinct characteristics and implications for funding, equity, and implementation. Operating at the level of individual pieces of content, transactional models expose authors to the financial implications of their decisions to make content OA; they often must pay out of their own funds. Driven by negotiations between libraries or …

Course Schedule 2024-2025, William & Mary Law School

Course Information

No abstract provided.

The Accurate Conversion Of Biological Experiments From Cesium Irradiation To X-Ray Irradiation: The Significance, Problems, And The Future Of Experimental Radiation Research, Gretchen Carpenter

Dartmouth College Master’s Theses

Preclinical small animal irradiation studies, once conducted on Cesium irradiators, are increasingly being performed with X-ray-based irradiators. The transition stems from concerns regarding national security risks, making X-ray irradiators which are compact and easy to operate an enticing alternative. However, questions regarding the relative biological effectiveness between the two sources have revealed a lack of adequate dosimetric characterization of X-ray beams, standardized protocol for dose calibration, and thorough understanding of experimental biological parameters. A literature review conducted on orthovoltage irradiators has revealed that there are over 54 different types of beam structures used, a dramatic departure from the one uniform …