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anjing University (14913414), and the Natural Science Foundation of Jiangsu Province of China (BK20171098).<br /><br />This work was supported by the National Natural Science Foundation of China (81773255, 81472820, and 81700037), the Science and Technology Innovation Foundation of Nanjing University (14913414), and the Natural Science Foundation of Jiangsu Province of China (BK20171098).<br /><br /> Acute lymphoblastic leukaemia with mixed lineage leukaemia gene rearrangement (MLL-ALL) frequently affects infants and is associated with a poor prognosis. Primary refractory and relapsed disease due to resistance to glucocorticoids (GCs) remains a substantial hurdle to improving clinical outcomes. In this study, we aimed to overcome GC resistance of MLL-ALL.<br /><br /> Using leukaemia patient specimens, we performed bioinformatic analyses to identify target genes/pathways. To test inhibition of target pathways in vivo, we created pre-clinical therapeutic mouse patient-derived xenograft (PDX)-models by transplanting human MLL-ALL leukaemia initiating cells (LIC) into immune-deficient NSG mice. Finally, we conducted B-cell lymphoma-2 (BCL-2) homology domain 3 (BH3) profiling to identify BH3 peptides responsible for treatment resistance in MLL-leukaemia.<br /><br /> Src family kinases (SFKs) and Fms-like tyrosine kinase 3 (FLT3) signaling pathway were over-represented in MLL-ALL cells. PDX-models of infant MLL- ALL recapitulateAgency for Medical Research and Development (the Basic Science and Platform Technology Program for Innovative Biological Medicine for FI and by NIH CA034196 for LDS. The funders had no role in the study design, data collection, data analysis, interpretation nor writing of the report.<br /><br />This study was supported by RIKEN (RIKEN President's Discretionary Grant) for FI, Japan Agency for Medical Research and Development (the Basic Science and Platform Technology Program for Innovative Biological Medicine for FI and by NIH CA034196 for LDS. The funders had no role in the study design, data collection, data analysis, interpretation nor writing of the report.The upcoming end-of-life solar photovoltaics (PV) waste stream is a huge concern before solid waste professionals due to presence of hazardous metals like lead or cadmium. The objective of present study was to understand the metal dissolution from PVs under four standard waste characterization regulatory tests of U.S., Germany, and Japan and their representativeness with actual landfill leachate. Modules were exposed to real municipal solid waste (MSW) landfill leachate for extended extraction duration, agitation and diluted leachate to investigate the effect of various parameters on metal dissolution. The results indicated that extractions using landfill leachates resulted in lower metal release than standard methods. The leached metal concentrations were found to be within the threshold limits except for cadmium, copper, lead and selenium, with maximum lead release from amorphous-PV of 8.68 mg/L and 6.91 mg/L with respect to TCLP and WET tests, respectively. Arsenic showed negligible release with maximum concentration of 0.046 mg/L from copper indium gallium de-selenide(CIGS) PV. Regardless of small size (1-2 cm pieces) and agitation, Germany and Japan's standard tests resulted in minimal release except of copper from copper indium gallium de-selenide PV. Leaching without agitation, showed negligible release from all photovoltaics whereas when agitation is applied to diluted leachate, significant release was observed with aluminum and copper leached up to 145.32 mg/L (multi-crystalline silicon) and 139.01 mg/L (amorphous-PV), respectively. CIGS was found to be most hazardous with a Metal Hazard Score (calculated on the basis of magnitude of leached metals with respect to their threshold limit and subsequent health effects) of 23.19, when exposed to standard tests. For all scenarios, increased metal release was observed with decrease in sample size and increase in leachate dilution and thus, leaching in highly acidic conditions are by no means representative for modules dumping in realistic conditions.Biogas production is a relatively novel and developing branch of the renewable fuel sector, which allows agricultural waste, and more, to be used as a feedstock. New technologies have been integrated into the process to improve its efficiency. In this study, a pump-mixed anaerobic digestion concept is considered for both experimental and modeling approaches. The experiment included a total of nine configurations with the same geometry (140 dm3 of total reactor volume) but different hydraulic retention times and mixing intervals. The measurements were used to create and optimize a mathematical model. The complete-stirring assumption, which underlies most anaerobic digestion (AD) simulations, is no longer valid in this case. Thus, the novel concept is developed by assuming that the liquid phase is split into three separate sections, which approximates the concentration gradient in a real reactor. [https://www.selleckchem.com/products/gdc-0068.html Ipatasertib chemical structure] This method allows partial differential equations to be avoided, which could potentially affect the calculation efficiency. The final mean accuracy of the model in the tested range was estimated to be 86.60% while, in selected parts of the scope, was close to 90%. The pump-mixed anaerobic digestion technique in the experiment achieved high production performance (above 8 dm3 of product per 1 dm3 of feedstock) while maintaining a high methane content (approximately 65%). The comparison between the reactor stirred by an impeller, and the pump-mixed, indicated that the proposed configuration ensures better production stability. Additionally, it was possible to achieve a higher biogas production rate with the same feedstock concentration.Pollutants in real aquatic systems commonly occur as chemical mixtures. Yet, the corresponding risk assessment is still mostly based on information on single-pollutant toxicity, accepting the assumption that pollutant mixtures exhibit additive toxicity effect which is often not the case. Therefore, it is still better to use the experimental approach. Unfortunately, experimental determination of toxicity for each mixture is practically unfeasible. In this study, quantitative structure-activity relationship (QSAR) models for the prediction of toxicity of binary mixtures towards bioluminescent bacteria Vibrio fischeri were developed at three toxicity levels (EC10, EC30 and EC50). For model development, experimentally determined toxicity values of 14 pollutants (pharmaceuticals and pesticides) were correlated with their structural features, applying multiple linear regression together with genetic algorithm. Statistical analysis, internal validation and external validation of the models were carried out. The toxicity is accurately predicted by all three models.