Digital Commons Network^™

Eosinophils Protect Against Acetaminophen-Induced Liver Injury Through Cyclooxygenase-Mediated Il-4/Il-13 Production, Jong-Min Jeong, Elizabeth A Jacobsen, Hua Wang, Cynthia Ju

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: A better understanding of the underlying mechanism of acetaminophen (APAP)-induced liver injury (AILI) remains an important endeavor to develop therapeutic approaches. Eosinophils have been detected in liver biopsies of patients with APAP overdose. We recently demonstrated a profound protective role of eosinophils against AILI; however, the molecular mechanism had not been elucidated.

APPROACH AND RESULTS: In agreement with our previous data from experiments using genetic deletion of eosinophils, we found that depletion of eosinophils in wild-type (WT) mice by an anti-IL-15 antibody resulted in exacerbated AILI. Moreover, adoptive transfer of eosinophils significantly reduced liver injury and mortality …

State-Of-The-Art In Carbides/Carbon Composites For Electromagnetic Wave Absorption, Maureen D Mayes

Faculty, Staff and Student Publications

Fibrosis of the skin and internal organs is a hallmark of systemic sclerosis (SSc). Although the pathogenesis of SSc is poorly understood, increasing evidence suggests that interleukins (IL)-4 and - 13 contribute to the pathogenesis of skin fibrosis by promoting collagen production and myofibroblast differentiation. Signal transducers and activators of transcription 6 (STAT6) is one of the most important downstream transcription factors activated by both IL-4 and IL-13. However, it is not completely understood whether STAT6 plays a role during the pathogenesis of skin fibrosis in SSc. In this study, we observed increased STAT6 phosphorylation in fibrotic skin samples collected …

Malignant Transformation By Oncogenic K-Ras Requires Idh2-Mediated Reductive Carboxylation To Promote Glutamine Utilization, Rui Liu, Panpan Liu, Huichang Bi, Jianhua Ling, Huiqin Zhang, Yumin Hu, Peng Huang, Jinyun Liu

Faculty, Staff and Student Publications

No abstract provided.

Tissue-Resident Memory T Cells Trigger Rapid Exudation And Local Antibody Accumulation, Pamela C Rosato, Sahar Lotfi-Emran, Vineet Joag, Sathi Wijeyesinghe, Clare F Quarnstrom, Rebecca Nedellec, Lalit K Beura, Lars Hangartner, Dennis R Burton, David Masopust

Faculty, Staff and Student Publications

Adaptive immunity is didactically partitioned into humoral and cell-mediated effector mechanisms, which may imply that each arm is separate and does not function together. Here, we report that the activation of CD8+ resident memory T cells (TRM) in nonlymphoid tissues triggers vascular permeability, which facilitates rapid distribution of serum antibodies into local tissues. TRM reactivation was associated with transcriptional upregulation of antiviral signaling pathways as well as Fc receptors and components of the complement cascade. Effects were local, but evidence is presented that TRM in brain and reproductive mucosa are both competent to induce rapid antibody exudation. TRM reactivation in …

Expression And Functions Of Transient Receptor Potential Channels In Liver Diseases, Michael X Zhu

Faculty, Staff and Student Publications

Liver diseases constitute a major healthcare burden globally, including acute hepatic injury resulted from acetaminophen overdose, ischemia-reperfusion or hepatotropic viral infection and chronic hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Attainable treatment strategies for most liver diseases remain inadequate, highlighting the importance of substantial pathogenesis. The transient receptor potential (TRP) channels represent a versatile signalling mechanism regulating fundamental physiological processes in the liver. It is not surprising that liver diseases become a newly explored field to enrich our knowledge of TRP channels. Here, we discuss recent findings revealing TRP functions across the fundamental …

Positioning The Brainstem Within The Neural Network Of Threat Prediction

Faculty, Staff and Student Publications

In a recent study, Strickland and McDannald dissected the role of brainstem networks in threat prediction. Using probabilistic threat discrimination in rats, the authors demonstrated that brainstem neurons estimate threat probability and generate positive aversive prediction errors after unexpected outcomes. Their findings suggest that, beyond organizing defensive behaviors, brainstem neurons are involved in threat prediction computations.

Vip152 Is A Selective Cdk9 Inhibitor With Pre-Clinical In Vitro And In Vivo Efficacy In Chronic Lymphocytic Leukemia, Steven Sher, Ethan Whipp, Janek Walker, Pu Zhang, Larry Beaver, Shelley Orwick, Brandi Walker, Elizabeth Perry, Charles Gregory, Matthew Purcell, Alexander Pan, Pearlly Yan, Lapo Alinari, Amy J Johnson, Melanie M Frigault, Joy M Greer, Ahmed Hamdy, Raquel Izumi, Xiaokui Mo, Deepa Sampath, Jennifer Woyach, James Blachly, John C Byrd, Rosa Lapalombella

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia (CLL) is effectively treated with targeted therapies including Bruton tyrosine kinase inhibitors and BCL2 antagonists. When these become ineffective, treatment options are limited. Positive transcription elongation factor complex (P-TEFb), a heterodimeric protein complex composed of cyclin dependent kinase 9 (CDK9) and cyclin T1, functions to regulate short half-life transcripts by phosphorylation of RNA Polymerase II (POLII). These transcripts are frequently dysregulated in hematologic malignancies; however, therapies targeting inhibition of P-TEFb have not yet achieved approval for cancer treatment. VIP152 kinome profiling revealed CDK9 as the main enzyme inhibited at 100 nM, with over a 10-fold increase in …

Phenomics Enables Measurement Of Complex Responses Of Developing Animals To Global Environmental Drivers, Oliver Tills, Luke A. Holmes, Elliot Quinn, Tony Everett, Manuela Truebano, John I. Spicer

School of Biological and Marine Sciences

Phenomics offers technological advances for high-dimensional phenotyping, facilitating rapid, high-throughput assessment of physiological performance and has proven invaluable in global research challenges including drug discovery and food security. However, this rapidly growing discipline has remained largely inaccessible to the increasingly urgent challenge of assessing organismal functional sensitivity to global change drivers. Here, we investigate the response of an ecologically important marine invertebrate to multiple environmental drivers using Energy Proxy Traits (EPTs), a new approach for measuring complex phenotypes captured on video as a spectrum of energy levels across different temporal frequencies in fluctuating pixel values. We imaged three developmental stages …

Overexpression Of Both Human Sodium Iodide Symporter (Nis) And Brg1-Bromodomain Synergistically Enhances Radioiodine Sensitivity By Stabilizing P53 Through Npm1 Expression, J Na, C-H Lee, J-K Chung, H Youn

Peninsula Medical School

Improved therapeutic strategies are required to minimize side effects associated with radioiodine gene therapy to avoid unnecessary damage to normal cells and radiation-induced secondary malignancies. We previously reported that codon-optimized sodium iodide symporter (oNIS) enhances absorption of I-131 and that the brahma-associated gene 1 bromodomain (BRG1-BRD) causes inefficient DNA damage repair after high-energy X-ray therapy. To increase the therapeutic effect without applying excessive radiation, we considered the combination of oNIS and BRG1-BRD as gene therapy for the most effective radioiodine treatment. The antitumor effect of I-131 with oNIS or oNIS+BRD expression was examined by tumor xenograft models along with functional …

Agreement In Languages That Do Not Agree: The Processing Of Accented Speech In Chinese-English Bilinguals, Stanley Chen

Dissertations, Theses, and Capstone Projects

Speech produced with an unfamiliar accent is quite commonly encountered, especially in higher education settings, in which a large number of international students are found. As a result, it is inevitable for students and teachers alike to be exposed to different varieties of English across multiple settings. The current study examines the effects of such accents on grammatical processing in bilinguals.

English requires grammatical agreement between the subject and the verb (e.g., the 3rd person singular “s” on the verb in The dog jumps); that is, subject-verb (S-V) agreement is obligatory. S-V agreement must hold even in …

The Alzheimer’S Disease Risk Factor Inpp5d Restricts Neuroprotective Microglial Responses In Amyloid Beta-Mediated Pathology

Faculty, Staff and Student Publications

Stroke is a devastating cause of global morbidity and mortality. Ischemic brain injury triggers a profound local and systemic immune response that participates in stroke pathophysiology. In turn, this immune response has emerged as a potential therapeutic target. In order to maximize its therapeutic potential, it is critical to understand how the immune response to ischemic brain injury is affected by age - the strongest non-modifiable risk factor for stroke. The development of multi-omics and single-cell technologies has provided a more comprehensive characterization of transcriptional and cellular changes that occur during aging. In this review, we summarize recent advances in …

Upregulation Of Pd-L1 By Sars-Cov-2 Promotes Immune Evasion, Chun-Che Liao, Hui-Ying Ko, Yi-An Ko, Ming-Tsai Chiang, Jian-Jong Liang, Chun-Tse Kuo, Te-An Lee, Diego Morales-Scheihing, Chen-Yang Shen, Shih-Yu Chen, Louise D Mccullough, Lu Cui, Gerlinde Wernig, Mi-Hua Tao, Yi-Ling Lin, Yao-Ming Chang, Shu-Ping Wang, Yun-Ju Lai, Chia-Wei Li

Faculty, Staff and Student Publications

Patients with severe COVID-19 often suffer from lymphopenia, which is linked to T-cell sequestration, cytokine storm, and mortality. However, it remains largely unknown how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells. We adopted a reverse time-order gene coexpression network approach to analyze time-series RNA-sequencing data, revealing epigenetic modifications at the late stage of viral egress. Furthermore, we identified SARS-CoV-2-activated nuclear factor-κB (NF-κB) and interferon regulatory factor 1 (IRF1) pathways contributing to viral infection and COVID-19 severity through epigenetic analysis of H3K4me3 chromatin …

Glucocorticoid Therapy As First-Line Treatment In Primary Hypophysitis: A Systematic Review And Individual Patient Data Meta-Analysis, Anurag R Lila

Faculty, Staff and Student Publications

OBJECTIVES: High-dose glucocorticoids are associated with improved recovery of deficits in primary autoimmune hypophysitis (PAH), but optimal dosing, route, and duration are unclear.

DESIGN: We reviewed literature for first-line glucocorticoid treatment in PAH until December 2021 and performed an individual patient data meta-analysis to analyze clinical, hormonal, and radiological outcomes with respect to route, dose, and duration (12 weeks) of glucocorticoid treatment according to disease severity.

RESULTS: A total of 153 PAH patients from 83 publications were included. The median age at presentation was 41 (32.5-48) years with a female preponderance (70.3%). Visual field recovery was significantly better with i.v. …

2023-02-01 Starbucks Stalls Progress In Labor Negotiations, Leila Bunker

The Spectator Online

No abstract provided.

Hemoglobin Concentration Impacts Viscoelastic Hemostatic Assays In Icu Admitted Patients, Glenda Torres, Katherine Xu, Winni Yang, Azzurra Cottarelli, Ernest Moore, Angela Sauaia, Kirk Hansen, Angela Velazquez, Amelia Boehme, Athina Vrosgou, Shivani Ghoshal, Soojin Park, Sachin Agarwal, Jan Claassen, E Sander Connolly, Gebhard Wagener, Richard O Francis, Eldad Hod

Faculty, Staff and Student Publications

Objectives: Low hemoglobin concentration impairs clinical hemostasis across several diseases. It is unclear whether hemoglobin impacts laboratory functional coagulation assessments. We evaluated the relationship of hemoglobin concentration on viscoelastic hemostatic assays in intracerebral hemorrhage (ICH) and perioperative patients admitted to an ICU.

Design: Observational cohort study and separate in vitro laboratory study.

Setting: Multicenter tertiary referral ICUs.

Patients: Two acute ICH cohorts receiving distinct testing modalities: rotational thromboelastometry (ROTEM) and thromboelastography (TEG), and a third surgical ICU cohort receiving ROTEM were evaluated to assess the generalizability of findings across disease processes and testing platforms. A separate in vitro ROTEM laboratory …

Reduced Spag17 Expression In Systemic Sclerosis Triggers Myofibroblast Transition And Drives Fibrosis, Brian Skaug, Carlos Córdova-Fletes, Pei-Suen Tsou, Amr H Sawalha, Johann E Gudjonsson, Feiyang Ma, Priyanka Verma, Dibyendu Bhattacharyya, Mary Carns, Jerome F Strauss, Delphine Sicard, Daniel J Tschumperlin, Melissa I Champer, Paul J Campagnola, Maria E Teves, John Varga

Faculty, Staff and Student Publications

Systemic sclerosis (SSc) is a clinically heterogeneous fibrotic disease with no effective treatment. Myofibroblasts are responsible for unresolving synchronous skin and internal organ fibrosis in SSc, but the drivers of sustained myofibroblast activation remain poorly understood. Using unbiased transcriptome analysis of skin biopsies, we identified the downregulation of SPAG17 in multiple independent cohorts of patients with SSc, and by orthogonal approaches, we observed a significant negative correlation between SPAG17 and fibrotic gene expression. Fibroblasts and endothelial cells explanted from SSc skin biopsies showed reduced chromatin accessibility at the SPAG17 locus. Remarkably, mice lacking Spag17 showed spontaneous skin fibrosis with increased …

Legal Dispositionism And Artificially-Intelligent Attributions, Jerrold Soh

Research Collection Yong Pung How School Of Law

It is conventionally argued that because an artificially-intelligent (AI) system acts autonomously, its makers cannot easily be held liable should the system's actions harm. Since the system cannot be liable on its own account either, existing laws expose victims to accountability gaps and need to be reformed. Recent legal instruments have nonetheless established obligations against AI developers and providers. Drawing on attribution theory, this paper examines how these seemingly opposing positions are shaped by the ways in which AI systems are conceptualised. Specifically, folk dispositionism underpins conventional legal discourse on AI liability, personality, publications, and inventions and leads us towards …

Disentangling The Effects Of Smartphone Screen Time, Checking Frequency, And Problematic Use On Executive Function: A Structural Equation Modelling Analysis, Wei Xing Toh, Wee Qin Ng, Hwajin Yang, Sujin Yang

Research Collection School of Social Sciences

The pervasiveness of smartphone engagement among young adults has attracted growing interest regarding its impact on cognitive processes. However, research on the relation between smartphone use and executive function (EF)—a set of adaptive, goal-directed control processes—remains inconclusive due to imprecise estimation of EF dimensions and inconsistent operationalisation of smartphone use in past studies. Therefore, we examined how two indices of smartphone use—screen time and checking frequency—would predict EF (common EF, shifting-specific-, and working-memory-specific components), using a latent-variable approach based on a comprehensive battery of EF tasks. We also examined the moderating role of problematic smartphone use in the link between …

Australian Consumers’ Attitudes Towards Sustainable Diet Practices Regarding Food Waste, Food Processing, And The Health Aspects Of Diet: A Cross Sectional Survey, Janelle D. Healy, Satvinder S. Dhaliwal, Christina M. Pollard, Piyush Sharma, Clare Whitton, Lauren C. Blekkenhorst, Carol J. Boushey, Jane A. Scott, Deborah A. Kerr

Research outputs 2022 to 2026

Environmentally sustainable diets are increasingly aspired to in food-based dietary guidelines across the world. However, little is known about consumer attitudes toward these diets when making food decisions. This study aimed to identify the demographic characteristics of Australian adults based on the level of attention they paid to the healthfulness of their diet, their consideration of the level of food processing, and their concern about household food waste and sustainable packaging disposal. Adults aged from 18 to over 75 years (n = 540) were surveyed online. Thirty-seven percent were concerned about sustainable food waste, 28 % considered the level of …

Clinical Epigenomic Explanation Of The Epidemiology Of Cannabinoid Genotoxicity Manifesting As Transgenerational Teratogenesis, Cancerogenesis And Aging Acceleration, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

As global interest in the therapeutic potential of cannabis and its’ derivatives for the management of selected diseases increases, it is increasingly imperative that the toxic profile of cannabinoids be thoroughly understood in order to correctly assess the balance between the therapeutic risks and benefits. Modern studies across a number of jurisdictions, including Canada, Australia, the US and Europe have confirmed that some of the most worrying and severe historical reports of both congenital anomalies and cancer induction following cannabis exposure actually underestimate the multisystem thousand megabase-scale transgenerational genetic damage. These findings from teratogenic and carcinogenic literature are supported by …

Effect Of Deferoxamine On Post-Transfusion Iron, Inflammation, And In Vitro Microbial Growth In A Canine Hemorrhagic Shock Model: A Randomized Controlled Blinded Pilot Study, Melissa A. Claus, Lisa Smart, Anthea L. Raisis, Claire R. Sharp, Sam Abraham, Joel P. A. Gummer, Martin K. Mead, Damian L. Bradley, Rachel Van Swelm, Erwin T. G. Wiegerinck, Edward Litton

Research outputs 2022 to 2026

Red blood cell (RBC) transfusion is associated with recipient inflammation and infection, which may be triggered by excessive circulating iron. Iron chelation following transfusion may reduce these risks. The aim of this study was to evaluate the effect of deferoxamine on circulating iron and inflammation biomarkers over time and in vitro growth of Escherichia coli (E. coli) following RBC transfusion in dogs with atraumatic hemorrhage. Anesthetized dogs were subject to atraumatic hemorrhage and transfusion of RBCs, then randomized to receive either deferoxamine or saline placebo of equivalent volume (n = 10 per group) in a blinded fashion. Blood was sampled …

Psychological Profiles Of South African Smallholder Farmers, Navjot Bhullar, Nkhanedzeni B. Nengovhela, Livhuwani Mudau, Renato A. Villano, Isaac Koomson, Heather M. Burrow

Research outputs 2022 to 2026

The present study examined smallholder farmer profiles based on key psychological variables associated with farm business performance in the South African context. A sample of 471 beef farmers (mean age = 54.15 years; SD = 14.46; men = 76 %) and 426 poultry farmers (mean age = 47.28 years; SD = 13.53; women = 54.5 %) provided data on a range of measures assessing attitudes, subjective norms, perceived behavioral control, personality characteristics, present and future time orientation, expected benefits of, and efficacy to perform the farm business tasks, and farm-related concerns. Latent profile analysis identified three distinct profile segments of …

Site Selection Of Combined Offshore Wind And Wave Energy Farms: A Systematic Review, Shabnam Hosseinzadeh, Amir Etemad-Shahidi, Rodney A. Stewart

Research outputs 2022 to 2026

Growing energy demand worldwide and onshore limitations have increased interest in offshore renewable energy exploitation. A combination of offshore renewable energy resources such as wind and wave energy can produce stable power output at a lower cost compared to a single energy source. Consequently, identifying the best locations for constructing combined offshore renewable energy farms is crucial. This paper investigates the technical, economic, social, and environmental aspects of Combined Offshore Wind and Wave Energy Farm (COWWEF) site selection. Past literature was evaluated using a systematic review method to synthesize, criticize, and categorize study regions, dataset characteristics, constraints, evaluation criteria, and …

Executive Function Deficits And Borderline Personality Disorder Symptomatology In A Nonclinical Adult Sample: A Latent Variable Analysis, Keisha D. Veerapandian, Gabriel X. D. Tan, Nadyanna M. Majeed, Andree Hartanto

Research Collection School of Social Sciences

While borderline personality disorder (BPD) symptomatology has been studied extensively in clinical populations, the mechanisms underlying its manifestation in nonclinical populations remain largely understudied. One aspect of BPD symptomatology in nonclinical populations that has not been well studied is cognitive mechanisms, especially in relation to executive functions. To explore the cognitive mechanisms underlying BPD symptomatology in nonclinical populations, we analysed a large-scale dataset of 233 young adults that were administered with nine executive function tasks and BPD symptomatology assessments. Our structural equation modelling did not find any significant relations between latent factors of executive functions and the severity of BPD …

Natural Disasters And Corporate Philanthropy: A Double Movement Perspective, Guoguang Wan, Heli Wang, Xuesong Geng, Kenneth G. Huang

Research Collection Lee Kong Chian School Of Business

This study examines Chinese corporations’ responses to a sudden natural disaster in terms of their philanthropic donations. We apply Polanyi’s double movement perspective to argue that rapid market expansion in an emerging economy causes social problems such as large-income disparities and environmental degradation. This calls forth counterforces advocating social responsibility and sustainability. Such countermovements can be strengthened by a major disaster, especially in the domain of corporate philanthropy. The resulting increase in corporate philanthropy persists long after the disaster, especially for those firms with large intra-firm pay disparities, operating in socially contested industries and located in regions with more social …

Oria Stage Ii Expansion: Keep River Post-Development Aquatic Fauna And Targeted Sawfish Survey - 2022, Indopacific Environmental, Department Of Primary Industries And Regional Development, Western Australia

Irrigated Agricultural Development in the North

This report presents the results of the 2022 Keep River Aquatic Fauna and Targeted Sawfish Survey which represents the final post-development survey required as per the project conditions of the Goomig Irrigation Development. Unlike the 2021 survey, which was affected by pandemic related travel restrictions that prohibited some sites from being surveyed, all regular monitoring sites were able to be sampled in 2022. Field work was undertaken September 2022 and sampling and analyses undertaken during the current study aligned with standardised methodologies set forth in the Ord River Irrigation Area – Weaber Plain Development Project Aquatic Fauna Management Plan.

Real-Time Hierarchical Map Segmentation For Coordinating Multi-Robot Exploration, Tianze Luo, Zichen Chen, Budhitama Subagdja, Ah-Hwee Tan

Research Collection School Of Computing and Information Systems

Coordinating a team of autonomous agents to explore an environment can be done by partitioning the map of the environment into segments and allocating the segments as targets for the individual agents to visit. However, given an unknown environment, map segmentation must be conducted in a continuous and incremental manner. In this paper, we propose a novel real-time hierarchical map segmentation method for supporting multi-agent exploration of indoor environments, wherein clusters of regions of segments are formed hierarchically from randomly sampled points in the environment. Each cluster is then assigned with a cost-utility value based on the minimum cost possible …

An Analysis Of The Effects Of Demographic Variables And Perceptions On The Safety Reporting Behavior In Collegiate Flight Programs, Daniel Kwasi Adjekum, Micah Walala, Julius Keller, Cody Christensen, Randal J. Demik, John P. Young, Gary J. Northam

International Journal of Aviation Sciences (IJAS)

The purposes of this study were to assess the perceptions of respondents on scale items that measure safety culture in collegiate aviation programs in the United States (U.S.) and establish levels of interactions between demographic variables and safety reporting behavior. A convenience sample (n = 259) of flight students inclusive of those who are flight instructors from five collegiate aviation programs in the U.S. responded to scale items adopted from the Collegiate Aviation Perceptions of Safety Culture Assessment Survey (CAPSCAS) online. The highest perception mean score was on Safety Fundamentals (4.2) and the lowest perception mean score was on Safety …

Law Schools Under Siege: The Challenge To Enhance Knowledge,Creativity, And Skill Training, Robert I. Reis

Ohio Northern University Law Review

No abstract provided.

Comment On The Use Of “Cy Pres” In Class Actions In Ohio, Geoffrey J. Ritts

Ohio Northern University Law Review

No abstract provided.