Sustainable multi-trip periodic redesign-routing model for municipal solid waste collection network: the case study of Tehran.

Daily transportation of wastes due to its environmental, financial, and social aspects has been considered a challenging issue in developing countries' municipal solid waste management systems. The location of transfer stations as intermediate nodes in municipal solid waste management network affects optimal collection frequency. A sustainable multi-period and multi-trip vehicle routing problem integrated with relocation models was developed to redesign the intermediate transfer stations and find optimal vehicle routes and the best collection frequency for each municipal solid waste generation point. Regarding the social aspects of a sustainable solid waste management system, an extended social life cycle assessment methodology for redesign and routing operations was developed based on the UNEP guidelines. The social life cycle assessment methodology evaluated the probable social effects of the system throughout the entire life cycle using an iterative policy. In this study, selected impact subcategories and inventory indicators for the routing and redesign system were utilized to quantify the system social score. Besides, the developed model was solved for different problem instances. The results indicated that system social score was affected by collection frequencies decisions, redesign policy, and the number of demand nodes. Furthermore, the model was applied to a real-world case study resulting in a total cost reduction of 66% that occurred by a 86% reduction in weekly traveled distance and a 12% decrease in routing social score.

Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia.

The chromatin reader eleven-nineteen leukemia (ENL) has been identified as a critical dependency in acute myeloid leukemia (AML), but its therapeutic potential remains unclear. We describe a potent and orally bioavailable small-molecule inhibitor of ENL, TDI-11055, which displaces ENL from chromatin by blocking its YEATS domain interaction with acylated histones. Cell lines and primary patient samples carrying MLL rearrangements or NPM1 mutations are responsive to TDI-11055. A CRISPR-Cas9-mediated mutagenesis screen uncovers an ENL mutation that confers resistance to TDI-11055, validating the compound's on-target activity. TDI-11055 treatment rapidly decreases chromatin occupancy of ENL-associated complexes and impairs transcription elongation, leading to suppression of key oncogenic gene expression programs and induction of differentiation. In vivo treatment with TDI-11055 blocks disease progression in cell line- and patient-derived xenograft models of MLL-rearranged and NPM1-mutated AML. Our results establish ENL displacement from chromatin as a promising epigenetic therapy for molecularly defined AML subsets and support the clinical translation of this approach. SIGNIFICANCE: AML is a poor-prognosis disease for which new therapeutic approaches are desperately needed. We developed an orally bioavailable inhibitor of ENL, demonstrated its potent efficacy in MLL-rearranged and NPM1-mutated AML, and determined its mechanisms of action. These biological and chemical insights will facilitate both basic research and clinical translation. This article is highlighted in the In This Issue feature, p. 2483.

The effect of sevoflurane versus propofol anesthesia on troponin I after congenital heart surgery, a randomized clinical trial.

BACKGROUND: The ischemic preconditioning phenomenon can save myocardium against move severe ischemic damages and reduce infarction size and furthermore a heart rhythm disturbance. In this study we examine relationship between troponin I (as a structural myocardial protein) level and anesthetic agents in the children. MATERIALS AND METHODS: In this study 84 children under 12 years age before cardiac surgery were divided randomly into two groups of 42 each. For anesthetic maintenance sevoflurane with dose of 0.5-1 MAC was used in Group 1 and 100-150 mg/kg/min of intravenous propofol in Group 2 for maintenance of anesthesia. Troponin I level was assessed 2 before and 1 hour after anesthetic induction. Outcome measures included the serum cardiac troponin I level in children before and after surgery in two study groups. RESULTS: There was no significant difference between two groups in indices and both groups were homogenous in this point of view. The troponin I level after surgery was significantly increased in two groups. In the sevoflurane group it was 0.04 ± 0.12 to 0.05 ± 0.09 ng/ml (P value = 0.003) and the propofol group was 0.12 ± 0.26 to 0.19 ± 0.38 ng/ml (P value = 0.001). CONCLUSIONS: In this study two Anesthetic regimens were compared to assess the mean troponin I level before and after pediatric closed heart surgery, and it was shown that mean troponin level before and after surgery in the sevoflurane group was less than the propofol group. But this result was not statistically significant. These results indicate that although more protective effects of sevoflurane on myocardial injuries during pediatric cardiac surgery is predominant but this effect has no significant difference in the propofol group.