Digital Commons Network^™

Phosphorylation Of Ahr By Plk1 Promotes Metastasis Of Luad Via Dio2-Th Signaling, Chaohao Li, Derek B. Allison, Daheng He, Fengyi Mao, Xinyi Wang, Piotr G. Rychahou, Ibrahim A. Imam, Yifan Kong, Qiongsi Zhang, Yanquan Zhang, Jinghui Liu, Ruixin Wang, Xiongjian Rao, Sai Wu, B. Mark Evers, Qing Shao, Chi Wang, Zhiguo Li, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Metastasis of lung adenocarcinoma (LUAD) is a major cause of death in patients. Aryl hydrocarbon receptor (AHR), an important transcription factor, is involved in the initiation and progression of lung cancer. Polo-like kinase 1 (PLK1), a serine/threonine kinase, acts as an oncogene promoting the malignancy of multiple cancer types. However, the interaction between these two factors and their significance in lung cancer remain to be determined. In this study, we demonstrate that PLK1 phosphorylates AHR at S489 in LUAD, leading to epithelial-mesenchymal transition (EMT) and metastatic events. RNA-seq analyses reveal that type 2 deiodinase (DIO2) is responsible for EMT and …

Determinants Of Business Organization’S Adoption Of Complex Innovative Product: A Case Of The Intelligent Iot System For Hog-Raising, Jingguan Cao

Dissertations and Theses Collection (Open Access)

With the development of science and technology, various opportunities emerged for the application of complex innovative products. However, not all business organizations are willing to adopt complex innovative products although these products can improve efficiency and reduce costs of the organizations, because there are bound to be various problems in the early application of new technologies. Hence, it is important to find the key influencing factors for the acceptance of complex innovative products by business organizations. The Internet of Things (IoT) is a typical complex innovative product, and this dissertation takes the intelligent IoT system for hog-raising as a case …

Examining The Externalities Of Highway Capacity Expansions In California: An Analysis Of Land Use And Land Cover (Lulc) Using Remote Sensing Technology, Serena E. Alexander, Bo Yang, Owen Hussey, Derek Hicks

Mineta Transportation Institute

There are over 590,000 bridges dispersed across the roadway network that stretches across the United States alone. Each bridge with a length of 20 feet or greater must be inspected at least once every 24 months, according to the Federal Highway Act (FHWA) of 1968. This research developed an artificial intelligence (AI)-based framework for bridge and road inspection using drones with multiple sensors collecting capabilities. It is not sufficient to conduct inspections of bridges and roads using cameras alone, so the research team utilized an infrared (IR) camera along with a high-resolution optical camera. In many instances, the IR camera …

November 2023 News Releases, University Of Montana--Missoula. Office Of University Relations

University of Montana News Releases, 1928, 1956-present

No abstract provided.

A New Ferrocene Derivative Blocks K-Ras Localization And Function By Oxidative Modification At His95, Kristen M Rehl, Jayaraman Selvakumar, Rhonda L Pitsch, Don Hoang, Kuppuswamy Arumugam, Sean W Harshman, Alemayehu A Gorfe, Kwang-Jin Cho

Faculty, Staff and Student Publications

Ras proteins are membrane-bound GTPases that regulate essential cellular processes at the plasma membrane (PM). Constitutively active mutations of K-Ras, one of the three Ras isoforms in mammalian cells, are frequently found in human cancers. Ferrocene derivatives, which elevate cellular reactive oxygen species (ROS), have shown to block the growth of non-small cell lung cancers harboring oncogenic mutant K-Ras. Here, we tested a novel ferrocene derivative on the growth of pancreatic ductal adenocarcinoma and non-small cell lung cancer. Our compound, which elevated cellular ROS levels, inhibited the growth of K-Ras-driven cancers, and abrogated the PM binding and signaling of K-Ras …

Symposium: Reimagining The Rules Of Evidence At 50, Edward K. Cheng

Vanderbilt Law School Faculty Publications

Prior to the eighteenth century, cartographers would often fill uncharted areas of maps with sea monsters, other artwork, or even rank speculation—a phenomenon labeled “horror vacui,” or fear of empty spaces. For example, in Paolo Forlani’s world map of 1565, a yet to-be-discovered southern continent was depicted with anticipated mountain chains and animals. The possible explanations for horror vacui are varied, but one reason may have been a desire “to hide [the mapmakers’] ignorance.” Not until “maps began to be thought of as more purely scientific instruments . . . [did] cartographers . . . restrain their concern about spaces …

Towards An Effective Transnational Regulation Of Ai, Daniel J. Gervais

Vanderbilt Law School Faculty Publications

Law and the legal system through which law is effected are very powerful, yet the power of the law has always been limited by the laws of nature, upon which the law has now direct grip. Human law now faces an unprecedented challenge, the emergence of a second limit on its grip, a new “species” of intelligent agents (AI machines) that can perform cognitive tasks that until recently only humans could. What happens, as a matter of law, when another species interacts with us, can be integrated into human minds and bodies, makes “real-world” decisions—not through human proxies, but directly—and …

The Independent Agency Myth, Neal Devins, David E. Lewis

Faculty Publications

Republicans and Democrats are fighting the wrong fight over independent agencies. Republicans are wrong to see independent agencies as anathema to hierarchical presidential control of the administrative state. Democrats are likewise wrong to reflexively defend independent agency expertise and influence. Supreme Court Justices also need to break free from this trap; the ongoing struggle over independent agencies should be about facts, not partisan rhetoric.

This Article seeks to reframe the fight over independent agencies. By surveying executive branch and independent agency department heads and supervisors during the Obama (2014) and Trump (2020) administrations, we have assembled unique and expansive data …

The Nightmare Of Dream Advertising, Dustin Marlan

William & Mary Law Review

Advertisers are attempting to market to us while we dream. This is not science fiction, but rather a troubling new reality. Using a technique dubbed “targeted dream incubation” (TDI), companies have begun inserting commercial messages into people’s dreams. Roughly, TDI works by: (1) creating an association during waking life using sensory cues (for example, a pairing of sounds, visuals, or scents); and (2) as the subject is drifting off to sleep, the association is again introduced with the goal of triggering related dreams with related subject matter. Based on a 2021 American Marketing Association survey, 77 percent of 400 companies …

Divergence: Toward A Neurodivergent Latinx Liberative Social Ethic, Rudolph P. Reyes Ii

Electronic Theses and Dissertations

A significant problem facing neurodivergent Latinxs is the invisibility of their marginalization and oppression. Neurodivergent Latinxs are invisible in dominant society and theological discourse. While neurodivergence and disability are not synonymous, the failure to recognize the marginalization of disability contributes to neurodivergent invisibility. Disability is depoliticized when disability is conceived as an issue of individual embodiment rather than a social issue of acceptance, accessibility, and equality. Neurodivergent Latinxs are erased, and the physical, epistemic, and institutional violence against them go unnamed.

This research project uses the hermeneutical circle for ethics in formulating praxis in combating the oppression of neurodivergent Latinxs. …

Alfred Russel Wallace Notes 28. Wallace's 'Change Of Mind', Revisited, Charles H. Smith

Faculty/Staff Personal Papers

Alfred Russel Wallace (1823−1913) is best known for his work on the theory of evolution by natural selection, and studies on biogeography. This fame has not, however, prevented appraisals of his work that sometimes depart from rational interpretations of his actual words. In this study, the frequently-offered notion that his adoption of spiritualism in late 1866 caused him to reverse himself on the universality of natural selection is taken to task, with arguments linked to his own words on the subject.

The Human Affectome, Daniela Schiller, Alessandra N.C. Yu, Nelly Alia-Klein, Susanne Becker, Howard C. Cromwell, Florin Dolcos, Paul J. Eslinger, Lauren A. J. Kirby, 166 Additional Co-Authors

Psychology Faculty Publications and Presentations

Over the last decades, theoretical perspectives in the interdisciplinary field of the affective sciences have proliferated rather than converged due to differing assumptions about what human affective phenomena are and how they work. These metaphysical and mechanistic assumptions, shaped by academic context and values, have dictated affective constructs and operationalizations. However, an assumption about the purpose of affective phenomena can guide us to a common set of metaphysical and mechanistic assumptions. In this capstone paper, we home in on a nested teleological principle for human affective phenomena in order to synthesize metaphysical and mechanistic assumptions. Under this framework, human affective …

Alterations In Salivary Biochemical Composition And Redox State Disruption Induced By The Anticonvulsant Valproic Acid In Male Rat Salivary Glands, Rayara Nogueira De Freitas, Lucas Guilherme Leite Da Silva, Gabriela Alice Fiais, Douglas Sandrac De Biagi Ferreira, Allice Santos Cruz Veras, Giovana Rampazzo Teixeira, Sandra Helena Penha Oliveira, Rita Cássia Menegati Dornelles, Ana Cláudia De Melo Stevanato Nakamune, Walid D Fakhouri, Antonio Hernandes Chaves-Neto

Faculty, Staff and Student Publications

Objective: To investigate the effects of the anticonvulsant valproic acid (VPA) on salivary glands in male rat using biochemical, functional, histomorphometric, and redox state parameters.

Materials and methods: Twenty-four male Wistar rats were randomly distributed into three groups (n = 8 per group): Control (0.9% saline solution), VPA100 (100 mg/kg), and VPA400 (400 mg/kg). After 21 consecutive days of treatment with by intragastric gavage. Pilocarpine-induced saliva was collected to determine salivary flow rate, pH, buffering capacity, and biochemical composition. Analyses of histomorphometric parameters and redox balance markers were performed on the parotid and submandibular glands.

Results: Salivary flow rate, pH, …

Clonal Hematopoiesis Of Indeterminate Potential (Chip) And Incident Type 2 Diabetes Risk, Deirdre K Tobias, Alisa K Manning, Jennifer Wessel, Sridharan Raghavan, Kenneth E Westerman, Alexander G Bick, Daniel Dicorpo, Eric A Whitsel, Jason Collins, Adolfo Correa, L Adrienne Cupples, Josée Dupuis, Mark O Goodarzi, Xiuqing Guo, Barbara Howard, Leslie A Lange, Simin Liu, Laura M Raffield, Alex P Reiner, Stephen S Rich, Kent D Taylor, Lesley Tinker, James G Wilson, Peitao Wu, April P Carson, Ramachandran S Vasan, Myriam Fornage, Bruce M Psaty, Charles Kooperberg, Jerome I Rotter, James Meigs, Joann E Manson

Faculty, Staff and Student Publications

OBJECTIVE: Clonal hematopoiesis of indeterminate potential (CHIP) is an aging-related accumulation of somatic mutations in hematopoietic stem cells, leading to clonal expansion. CHIP presence has been implicated in atherosclerotic coronary heart disease (CHD) and all-cause mortality, but its association with incident type 2 diabetes (T2D) is unknown. We hypothesized that CHIP is associated with elevated risk of T2D.

RESEARCH DESIGN AND METHODS: CHIP was derived from whole-genome sequencing of blood DNA in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) prospective cohorts. We performed analysis for 17,637 participants from six cohorts, without prior T2D, cardiovascular disease, …

Novel Academic Tabletop 2022 (Nat22): A Dynamic Dice-Based Emergency Medicine Education Tool, Adam Heilmann, Jessica Pelletier, Collyn Murray, Alexander Croft

2020-Current year OA Pubs

Gamification is an effective teaching tool that improves engagement and knowledge retention. Tabletop role-playing games are dynamic games that use random chance and foster player/leader partnership. To date, there are no teaching tools that mimic dynamic or unpredictable patient presentations. This style of game may work well as a tool for medical education in a simulation-based modality. In this report, we document the rules, materials, and training required to reproduce a hybrid game created to combine facets of simulation and tabletop role-playing games (TRPGs) to create a dynamic medical education tool. After testing the game for flaws and fluidity of …

Parenchymal Border Macrophages Regulate Tau Pathology And Tau-Mediated Neurodegeneration, Antoine Drieu, Siling Du, Michal Kipnis, Megan E Bosch, Jasmin Herz, Choonghee Lee, Hong Jiang, Melissa Manis, Jason D Ulrich, Jonathan Kipnis, David M Holtzman, Maud Gratuze

2020-Current year OA Pubs

Parenchymal border macrophages (PBMs) reside close to the central nervous system parenchyma and regulate CSF flow dynamics. We recently demonstrated that PBMs provide a clearance pathway for amyloid-β peptide, which accumulates in the brain in Alzheimer's disease (AD). Given the emerging role for PBMs in AD, we explored how tau pathology affects the CSF flow and the PBM populations in the PS19 mouse model of tau pathology. We demonstrated a reduction of CSF flow, and an increase in an MHCII

A Human Mitofusin 2 Mutation Can Cause Mitophagic Cardiomyopathy, Antonietta Franco, Jiajia Li, Daniel P Kelly, Ray E Hershberger, Ali J Marian, Renate M Lewis, Moshi Song, Xiawei Dang, Alina D Schmidt, Mary E Mathyer, John R Edwards, Cristina De Guzman Strong, Gerald W Dorn

2020-Current year OA Pubs

Cardiac muscle has the highest mitochondrial density of any human tissue, but mitochondrial dysfunction is not a recognized cause of isolated cardiomyopathy. Here, we determined that the rare mitofusin (MFN) 2 R400Q mutation is 15-20× over-represented in clinical cardiomyopathy, whereas this specific mutation is not reported as a cause of MFN2 mutant-induced peripheral neuropathy, Charcot-Marie-Tooth disease type 2A (CMT2A). Accordingly, we interrogated the enzymatic, biophysical, and functional characteristics of MFN2 Q400 versus wild-type and CMT2A-causing MFN2 mutants. All MFN2 mutants had impaired mitochondrial fusion, the canonical MFN2 function. Compared to MFN2 T105M that lacked catalytic GTPase activity and exhibited normal …

Protective Effects Of Epigallocatechin-3-Gallate Counteracting The Chronic Hypobaric Hypoxia-Induced Myocardial Injury In Plain-Grown Rats At High Altitude, Haotian Chen, Chen Chen, Yuhui Qin, Lei Wang, Jie Zheng, Fabao Gao

2020-Current year OA Pubs

Exposure to hypobaric hypoxia (HH) environment causes stress to the body, especially the oxygen-consuming organs. Chronic HH conditions have adverse effects on the myocardium. Thus, we conducted this experiment and aim to evaluate such adverse effects and explore the therapeutic role of epigallocatechin-3-gallate (EGCG) in rats' heart under chronic HH conditions. For that purpose, we transported rats from plain to a real HH environment at high altitude for establishing the HH model. At high altitude, animals were treated with EGCG while the salidroside was used as the positive control. General physiological data were collected, and routine blood test results were …

Steatosis Drives Monocyte-Derived Macrophage Accumulation In Human Metabolic Dysfunction-Associated Fatty Liver Disease, Mandy M Chan, Joseph W Beals, Marina Terekhova, Christina F Fu, Li He, Arick C Park, Gordon I Smith, Kathleen Byrnes, Wandy L Beatty, Shaina R Eckhouse, J Christopher Eagon, Daniel Ferguson, Brian N Finck, Samuel Klein, Maxim N Artyomov, Joel D Schilling, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common complication of obesity with a hallmark feature of hepatic steatosis. Recent data from animal models of MAFLD have demonstrated substantial changes in macrophage composition in the fatty liver. In humans, the relationship between liver macrophage heterogeneity and liver steatosis is less clear.

METHODS: Liver tissue from 21 participants was collected at time of bariatric surgery and analysed using flow cytometry, immunofluorescence, and H&E microscopy. Single-cell RNA sequencing was also conducted on a subset of samples (n = 3). Intrahepatic triglyceride content was assessed via MRI and tissue histology. …

Small Molecule Screen Identifies Pyrimethamine As An Inhibitor Of Nrf2-Driven Esophageal Hyperplasia, Chorlada Paiboonrungruang, Brittany Bowman, Julius Chembo, M Ben Major, Et Al.

2020-Current year OA Pubs

OBJECTIVE: NRF2 is a master transcription factor that regulates the stress response. NRF2 is frequently mutated and activated in human esophageal squamous cell carcinoma (ESCC), which drives resistance to chemotherapy and radiation therapy. Therefore, a great need exists for NRF2 inhibitors for targeted therapy of NRF2

DESIGN: We performed high-throughput screening of two compound libraries from which hit compounds were further validated in human ESCC cells and a genetically modified mouse model. The mechanism of action of one compound was explored by biochemical assays.

RESULTS: Using high-throughput screening of two small molecule compound libraries, we identified 11 hit compounds as …

Cux1-Related Neurodevelopmental Disorder: Deep Insights Into Phenotype-Genotype Spectrum And Underlying Pathology, Henry Oppermann, Christina A Gurnett, Et Al.

2020-Current year OA Pubs

Heterozygous, pathogenic CUX1 variants are associated with global developmental delay or intellectual disability. This study delineates the clinical presentation in an extended cohort and investigates the molecular mechanism underlying the disorder in a Cux1

P2y2 Purinergic Receptor Gene Deletion Protects Mice From Bacterial Endotoxin And Sepsis-Associated Liver Injury And Mortality, Athis R Arunachalam, Sanju S Samuel, Arunmani Mani, Janielle P Maynard, Kelsey M Stayer, Eric Dybbro, Subapradha Narayanan, Aalekhya Biswas, Saliha Pathan, Krishnakant Soni, Abu Hena Mostafa Kamal, Chandra Shekar R Ambati, Nagireddy Putluri, Moreshwar S Desai, Sundararajah Thevananther

Faculty, Staff and Students Publications

The liver plays a significant role in regulating a wide range of metabolic, homeostatic, and host-defense functions. However, the impact of liver injury on the host's ability to control bacteremia and morbidity in sepsis is not well understood. Leukocyte recruitment and activation lead to cytokine and chemokine release, which, in turn, trigger hepatocellular injury and elevate nucleotide levels in the extracellular milieu. P2Y2 purinergic receptors, G protein-coupled and activated by extracellular ATP/UTP, are expressed at the cell surface of hepatocytes and nonparenchymal cells. We sought to determine whether P2Y2 purinergic receptor function is necessary for the maladaptive host response to …

Tet2 Modulates Spatial Relocalization Of Heterochromatin In Aged Hematopoietic Stem And Progenitor Cells, Tingting Hong, Jia Li, Lei Guo, Maryn Cavalier, Tianlu Wang, Yaling Dou, Aaron Delafuente, Shaohai Fang, Anna Guzman, Katherina Wohlan, Chiraag Kapadia, Carina Rosas, Yaling Yang, C Cameron Yin, Shaoying Li, M James You, Xiaodong Cheng, Margaret A Goodell, Yubin Zhou, Yun Huang

Faculty, Staff and Student Publications

DNA methylation deregulation at partially methylated domains (PMDs) represents an epigenetic signature of aging and cancer, yet the underlying molecular basis and resulting biological consequences remain unresolved. We report herein a mechanistic link between disrupted DNA methylation at PMDs and the spatial relocalization of H3K9me3-marked heterochromatin in aged hematopoietic stem and progenitor cells (HSPCs) or those with impaired DNA methylation. We uncover that TET2 modulates the spatial redistribution of H3K9me3-marked heterochromatin to mediate the upregulation of endogenous retroviruses (ERVs) and interferon-stimulated genes (ISGs), hence contributing to functional decline of aged HSPCs. TET2-deficient HSPCs retain perinuclear distribution of heterochromatin and exhibit …

Mmp-2 Associates With Incident Heart Failure And Atrial Fibrillation: The Aric Study, Leo F Buckley, Ali M Agha, Pranav Dorbala, Brian L Claggett, Bing Yu, Aliza Hussain, Vijay Nambi, Lin Yee Chen, Kunihiro Matsushita, Ron C Hoogeveen, Christie M Ballantyne, Amil M Shah

Faculty, Staff and Student Publications

BACKGROUND: MMP (matrix metalloproteinase)-2 participates in extracellular matrix regulation and may be involved in heart failure (HF), atrial fibrillation (AF), and coronary heart disease.

METHODS: Among the 4693 ARIC study (Atherosclerosis Risk in Communities) participants (mean age, 75±5 years; 42% women) without prevalent HF, multivariable Cox proportional hazard models were used to estimate associations of plasma MMP-2 levels with incident HF, HF with preserved ejection fraction (≥50%), HF with reduced ejection fraction (

RESULTS: Compared with the 3 lower quartiles, the highest MMP-2 quartile associated with greater risk of incident HF overall (adjusted hazard ratio, 1.48 [95% CI, 1.21-1.81]), incident …

Big Boned: How Fat Storage And Other Adaptations Influenced Large Theropod Foraging Ecology, Cameron Pahl, Luis A. Ruedas

Biology Faculty Publications and Presentations

Dinosaur foraging ecology has been the subject of scientific interest for decades, yet much of what we understand about it remains hypothetical. We wrote an agent-based model (ABM) to simulate meat energy sources present in dinosaur environments, including carcasses of giant sauropods, along with living, huntable prey. Theropod dinosaurs modeled in this environment (specifically allosauroids, and more particularly, Allosaurus Marsh, 1877) were instantiated with heritable traits favorable to either hunting success or scavenging success. If hunter phenotypes were more reproductively successful, their traits were propagated into the population through their offspring, resulting in predator specialists. If selective pressure favored scavenger …

Does Chronic Obstructive Pulmonary Disease Originate From Different Cell Types?, Yohannes Tesfaigzi, Jeffrey L Curtis, Irina Petrache, Francesca Polverino, Farrah Kheradmand, Ian M Adcock, Stephen I Rennard

Faculty, Staff and Students Publications

The onset of chronic obstructive pulmonary disease (COPD) is heterogeneous, and current approaches to define distinct disease phenotypes are lacking. In addition to clinical methodologies, subtyping COPD has also been challenged by the reliance on human lung samples from late-stage diseases. Different COPD phenotypes may be initiated from the susceptibility of different cell types to cigarette smoke, environmental pollution, and infections at early stages that ultimately converge at later stages in airway remodeling and destruction of the alveoli when the disease is diagnosed. This perspective provides discussion points on how studies to date define different cell types of the lung …

Staff Matters: How Can We Be More Creative With Our Benefits?, Jodi Schafer Sphr, Shrm-Scp

The Journal of the Michigan Dental Association

As open enrollment for health benefits approaches, this column discusses creative and cost-effective benefit offerings to attract and retain employees. The focus is on innovative benefits beyond traditional health, life insurance, and retirement plans. Suggestions include pet insurance, paid volunteer time, lunch and learn sessions, and flexible scheduling to accommodate employees' needs, particularly working parents and those with caregiving responsibilities. The importance of seeking employee input in benefit planning is emphasized for discovering practical, employee-desired options.

Jurisdiction Beyond Our Borders: United States V. Alcoa And The Extraterritorial Reach Of American Antitrust, 1909–1945, Laura Phillips Sawyer

Scholarly Works

Chapter in the book Antimonopoly and American Democracy by Daniel A. Crane and William J. Novak, eds., Oxford University Press, 2023.

In 1945, Judge Learned Hand wrote one of the most influential opinions in modern antitrust law. In declaring that the Aluminum Company of America (Alcoa) had illegally monopolized the industry for virgin aluminum and had participated in an illegal international cartel, Hand both revived and extended American antitrust law. The ruling is famous for several reasons: it narrowly defined the relevant market in favor of the government; it expanded the category of impermissible dominant firm conduct; it interpreted congressional …

Students' Attitudes Towards Animals Influences Youth Development Constructs Based On Interactions With Different Animal Species Prior To College, Allison K. Pachunka

Department of Animal Science: Dissertations, Theses, and Student Research

Human-animal interactions (HAI) are commonplace in society and play a consequential role in a variety of situations such as companion animal ownership, agriculture, or youth programs such as 4-H or FFA. Interacting with animals has been shown to provide developmental benefits to children. Positive youth development (PYD), measured by the Five Cs Model, is a framework that focuses on fostering youth’s potential through positive activities which has been studied specifically in 4-H. However, this framework has not been applied to other organizations such as the National FFA Organization (FFA) or to other young adults with less formal interactions with animals. …

I Can’T Believe It’S Not Butter: Supply Management And The Constitutionality Of Carbon Budget Legislation In Canada, Andrew Leach

UBC Law Review

No abstract provided.