834 research outputs found

    Reliability of stored river water as an alternative for consumption in Ekpoma, Nigeria: a human health risk assessment

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    With looming global water-related issues, the monitoring of water quality for household and industrial consumption has become more pertinent. Rivers in nearby towns serve as primary water sources for Ekpoma town. 123 samples of stored river water were collected from 41 sampling locations and physical properties - pH, electrical conductivity (EC), salinity, temperature, and total dissolved solids (TDS) - were measured in situ using the Hanna edgeÂŽ Multiparameter EC/TDS/Salinity Meter-HI2030. Atomic absorption spectrophotometry (AAS) was used to detect and measure the concentration of potentially toxic metals (PTMs): Al, Cr, Cu, Fe, Mn, Ni, Pb, and Zn. The measured concentrations were compared to the WHO, US EPA, and NSDWQ regulatory standards, and a spatiotemporal health risk analysis was performed using HERisk software. Twenty-five percent of the tested samples contained PTM concentrations within the allowable regulatory limits. Spatiotemporal health risk analysis showed that 98.8% of the cumulative carcinogenic risks (CRcum) were entirely from Pb contamination via oral ingestion. PTM concentrations in the samples suggest the degradation of river water quality due to agricultural activities, crude oil exploration activities, and soil composition in the region. Best management practices (BMPs) and treatment processes for the removal of detected contaminants are recommended to improve water quality

    HIF1/2-exerted control over glycolytic gene expression is not functionally relevant for glycolysis in human leukemic stem/progenitor cells

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    Background Hypoxia-inducible factors (HIF)1 and 2 are transcription factors that regulate the homeostatic response to low oxygen conditions. Since data related to the importance of HIF1 and 2 in hematopoietic stem and progenitors is conflicting, we investigated the chromatin binding profiles of HIF1 and HIF2 and linked that to transcriptional networks and the cellular metabolic state. Methods Genome-wide ChIPseq and ChIP-PCR experiments were performed to identify HIF1 and HIF2 binding sites in human acute myeloid leukemia (AML) cells and healthy CD34(+) hematopoietic stem/progenitor cells. Transcriptome studies were performed to identify gene expression changes induced by hypoxia or by overexpression of oxygen-insensitive HIF1 and HIF2 mutants. Metabolism studies were performed by 1D-NMR, and glucose consumption and lactate production levels were determined by spectrophotometric enzyme assays. CRISPR-CAS9-mediated HIF1, HIF2, and ARNT(-/-) lines were generated to study the functional consequences upon loss of HIF signaling, in vitro and in vivo upon transplantation of knockout lines in xenograft mice. Results Genome-wide ChIP-seq and transcriptome studies revealed that overlapping HIF1- and HIF2-controlled loci were highly enriched for various processes including metabolism, particularly glucose metabolism, but also for chromatin organization, cellular response to stress and G protein-coupled receptor signaling. ChIP-qPCR validation studies confirmed that glycolysis-related genes but not genes related to the TCA cycle or glutaminolysis were controlled by both HIF1 and HIF2 in leukemic cell lines and primary AMLs, while in healthy human CD34(+) cells these loci were predominantly controlled by HIF1 and not HIF2. However, and in contrast to our initial hypotheses, CRISPR/Cas9-mediated knockout of HIF signaling did not affect growth, internal metabolite concentrations, glucose consumption or lactate production under hypoxia, not even in vivo upon transplantation of knockout cells into xenograft mice. Conclusion These data indicate that, while HIFs exert control over glycolysis but not OxPHOS gene expression in human leukemic cells, this is not critically important for their metabolic state. In contrast, inhibition of BCR-ABL did impact on glucose consumption and lactate production regardless of the presence of HIFs. These data indicate that oncogene-mediated control over glycolysis can occur independently of hypoxic signaling modules.</p

    The short term debt vs. long term debt puzzle: a model for the optimal mix

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    This paper argues that the existing finance literature is inadequate with respect to its coverage of capital structure of small and medium sized enterprises (SMEs). In particular it is argued that the cost of equity (being both conceptually ill defined and empirically non quantifiable) is not applicable to the capital structure decisions for a large proportion of SMEs and the optimal capital structure depends only on the mix of short and long term debt. The paper then presents a model, developed by practitioners for optimising the debt mix and demonstrates its practical application using an Italian firm's debt structure as a case study

    How Substitutional Point Defects in Two-Dimensional WS2_2 Induce Charge Localization, Spin-Orbit Splitting, and Strain

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    Control of impurity concentrations in semiconducting materials is essential to device technology. Because of their intrinsic confinement, the properties of two-dimensional semiconductors such as transition metal dichalcogenides (TMDs) are more sensitive to defects than traditional bulk materials. The technological adoption of TMDs is dependent on the mitigation of deleterious defects and guided incorporation of functional foreign atoms. The first step towards impurity control is the identification of defects and assessment of their electronic properties. Here, we present a comprehensive study of point defects in monolayer tungsten disulfide (WS2_2) grown by chemical vapor deposition (CVD) using scanning tunneling microscopy/spectroscopy, CO-tip noncontact atomic force microscopy, Kelvin probe force spectroscopy, density functional theory, and tight-binding calculations. We observe four different substitutional defects: chromium (CrW_{\text{W}}) and molybdenum (MoW_{\text{W}}) at a tungsten site, oxygen at sulfur sites in both bottom and top layers (OS_{\text{S}} top/bottom), as well as two negatively charged defects (CDs). Their electronic fingerprints unambiguously corroborate the defect assignment and reveal the presence or absence of in-gap defect states. The important role of charge localization, spin-orbit coupling, and strain for the formation of deep defect states observed at substitutional defects in WS2_2 as reported here will guide future efforts of targeted defect engineering and doping of TMDs
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