35 research outputs found

    Isolation and partial characterization of Caribbean palytoxin /

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    Peripheral Blood Mononuclear Cell Mitochondrial Dysfunction in Acute Alcohol-Associated Hepatitis

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    Background: Patients with acute alcohol-associated hepatitis (AH) have immune dysfunction. Mitochondrial function is critical for immune cell responses and regulates senescence. Clinical translational studies using complementary bioinformatics-experimental validation of mitochondrial responses were performed in peripheral blood mononuclear cells (PBMC) from patients with AH, healthy controls (HC), and heavy drinkers without evidence of liver disease (HD).Methods: Feature extraction for differentially expressed genes (DEG) in mitochondrial components and telomere regulatory pathways from single-cell RNAseq (scRNAseq) and integrated \u27pseudobulk\u27 transcriptomics from PBMC from AH and HC (n = 4 each) were performed. After optimising isolation and processing protocols for functional studies in PBMC, mitochondrial oxidative responses to substrates, uncoupler, and inhibitors were quantified in independent discovery (AH n = 12; HD n = 6; HC n = 12) and validation cohorts (AH n = 10; HC n = 7). Intermediary metabolites (gas-chromatography/mass-spectrometry) and telomere length (real-time PCR) were quantified in subsets of subjects (PBMC/plasma AH n = 69/59; HD n = 8/8; HC n = 14/27 for metabolites; HC n = 13; HD n = 8; AH n = 72 for telomere length).Results: Mitochondrial, intermediary metabolite, and senescence-regulatory genes were differentially expressed in PBMC from AH and HC in a cell type-specific manner at baseline and with lipopolysaccharide (LPS). Fresh PBMC isolated using the cell preparation tube generated optimum mitochondrial responses. Intact cell and maximal respiration were lower (p ≤ .05) in AH than HC/HD in the discovery and validation cohorts. In permeabilised PBMC, maximum respiration, complex I and II function were lower in AH than HC. Most tricarboxylic acid (TCA) cycle intermediates in plasma were higher while those in PBMC were lower in patients with AH than those from HC. Lower telomere length, a measure of cellular senescence, was associated with higher mortality in AH.Conclusion: Patients with AH have lower mitochondrial oxidative function, higher plasma TCA cycle intermediates, with telomere shortening innonsurvivors

    Assessing managerial power theory: A meta-analytic approach to understanding the determinants of CEO compensation

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    Although studies about the determinants of CEO compensation are ubiquitous, the balance of evidence for one of the more controversial theoretical approaches, managerial power theory, remains inconclusive. The authors provide a meta-analysis of 219 U.S.-based studies, focusing on the relationships between indicators of managerial power and levels of CEO compensation and CEO pay-performance sensitivities. The results indicate that managerial power theory is well equipped for predicting core compensation variables such as total cash and total compensation but less so for predicting the sensitivity of pay to performance. In most situations where CEOs are expected to have power over the pay setting process, they receive significantly higher levels of total cash and total compensation. In contrast, where boards are expected to have more power, CEOs receive lower total cash and total compensation. In addition, powerful directors also appear to be able to establish tighter links between CEO compensation and firm performance and can accomplish this even in the face of powerful CEOs. The authors discuss the implications for theory and research regarding the determinants of executive compensation

    Including neurodiversity in computational thinking

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    IntroductionThe foundational practices of Computational Thinking (CT) present an interesting overlap with neurodiversity, specifically with differences in executive function (EF). An analysis of CT teaching and learning materials designed for differentiation and support of EF show promise to reveal problem-solving strengths of neurodivergent learners.MethodsTo examine this potential, studies were conducted using a computer-supported, inclusive, and highly interactive learning program named INFACT that was designed with the hypothesis that all students, including neurodivergent learners, will excel in problem solving when it is structured through a variety of CT activities (including games, puzzles, robotics, coding, and physical activities) and supported with EF scaffolds. The INFACT materials were used in 12 treatment classrooms in grades 3–5 for at least 10  h of implementation. Pre-post assessments of CT were administered to treatment classes as well as 12 comparison classes that used 10  h of other CT teaching and learning materials. EF screeners were also used with all classes to disaggregate student results by quartile of EF.FindingsStudents using INFACT materials showed a significant improvement in CT learning as compared to comparison classes. Students with EF scores in the lower third of the sample showed the greatest improvement.DiscussionThis study shows promising evidence that differentiated activities with EF scaffolds situated across several contexts (e.g., games, puzzles, physical activities, robotics, coding) promote effective CT learning in grades 3–5

    A Spatial, Temporal, and Geographic Analysis of the Increasing Incidence of Dengue Fever in Kenya and Africa

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    While many studies have focused on the causes of dengue fever and the occurrence of specific outbreaks, little research has focused on the increasing spatial range, increasing incidence of infected individuals, and the use of algorithms/models to increase risk mapping in Kenya and Africa. GIS incorporates methods to evaluate results, identify geographic locations, and incorporate risk when dengue occurrence data are limited. This dissertation first outlines the limitations to dengue mapping then examines the strengths, weaknesses, opportunities, and threats (SWOT) to determine the limitations for mapping. Next, a similarity search approach was used to map dengue risk in Kenya. This method estimated the high and low risk areas for dengue by evaluating the similarity between environmental layers, population density, and elevation with respect to dengue and mosquito occurrence points. This analysis identified the most cost-effective locations to target dengue prevention activities such as vector control and public awareness campaigns. Finally, a PAT approach was used to map dengue susceptibility across the African continent using the Query Expression Editor and QFit tools. High susceptible risk areas were estimated by comparing peer reviewed literature, determining susceptibility for risk, and then improving the visualization through mapping. The Query Expression Editor evaluated dengue susceptibility risk based on environmental high risk parameters. The QFit tool provided a methodology to estimate high susceptibility risk between points of occurrence and a set of raster datasets. This dissertation contributes to improving risk analysis and susceptibility risk for disease through the localized visualization of risk and situational awareness between health officials, geographers, epidemiologists, and entomologists

    Bioactive Substances from Marine Sources

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