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Lyons Werner posted an update 3 days ago
The results indicate that ultrasound has obvious augmentation effects on flow boiling heat transfer even though the intensification effects will be limited with the heat flux increases. The higher ultrasonic power, the lower ultrasonic frequency and the higher ultrasonic radiation angle, the better intensification efficiency. The maximum enhancement ratio of have in the saturated boiling section reaches 1.88 at 50 W, 23 kHz and 45° under the experimental conditions. This study will be beneficial for future applications of ultrasound on flow boiling heat transfer in micro/mini-channels.Breakpoint cluster region-Abelson (Bcr-Abl) kinase is a key driver in the pathophysiology of chronic myelogenous leukemia (CML). Broadening the chemical diversity of Bcr-Abl kinase inhibitors with novel chemical entities possessing favorable target potency and cellular efficacy is a current medical demand for CML treatment. In this respect, a new series of ethynyl bearing 3-aminoindazole based Bcr-Abl inhibitors has been designed, synthesized, and biologically evaluated. The target compounds were designed based on introducing the key structural features of ponatinib, alkyne spacer and diarylamide, into the previously reported indazole II to improve its Bcr-Abl inhibitory activity and overcome its poor cellular potency. All target compounds elicited potent activity against Bcr-AblWT with sub-micromolar IC50 values ranging 4.6-667 nM. In addition, certain derivatives exhibited promising potency over the clinically imatinib-resistant Bcr-AblT315I. Among the target molecules, compounds 9c, 9h and 10c stood as the most potent derivatives with IC50 values of 15.4 nM, 4.6 nM, and 25.8 nM, respectively, against Bcr-AblWT. Interestingly, 9h showed 2 folds and 3.6 times superior potency to the lead indazole II and 10c, respectively, against Bcr-AblT315I. Molecular docking of 9h pointed out its possibility to be a type II kinase inhibitor. Furthermore, all compounds, except 9b, showed highly potent antiproliferative activity against the Bcr-Abl positive leukemia K562 cell (MTT assay) surpassing the modest activity of lead indazole II. Moreover, the most potent members 9h and 10c exerted potent antileukemic activity against NCI leukemia panel, particularly K562 cell (SRB assay) with GI50 less than 10 nM, being superior to the FDA approved drug imatinib. Further biochemical hERG and cellular toxicity, phosphorylation assay, and NanoBRET target engagement of 9h underscored its merits as a promising candidate for CML therapy.Aggregation of α-synuclein (α-syn) is one of the central hypotheses for Parkinson’s disease (PD), therefore, its inhibition and disaggregation is an optimistic approach for the treatment of PD. Here, we report design, synthesis and in-vitro efficacy studies of a series of diphenyl triazine hybrids as potential inhibitors of α-syn fibrillogenesis. From the docking studies, we concluded that compounds A1, A2, A4, A8 and A9 display promising binding affinity with the essential residues of α-syn with binding energy values -6.0, -7.0, -6.3, -6.6 and -6.7 kcal/mol respectively. The target compounds were synthesized using multistep organic synthesis reactions. Compounds A1, A2 A4, A8 and A9 showed a significant lowering of the α-syn fibril formation during Thioflavin-T assay and fluorescence microscopy. In addition, these compounds A1, A2, A4, A8 and A9 also proved to be good disaggregators in the pre-aggregated form of α-syn. Most of the compounds exhibited no cytotoxicity in mouse embryonic fibroblast (MEF) and human adenocarcinomic alveolar basal epithelial cells (A549) except A2. Overall, diphenyl triazine-based compounds can be further investigated for the treatment of synucleinopathies and for Lewy body dementia in which α-syn is predominantly observed.Olive trees are often subjected to a prolonged dry season with low water availability, which induces oxidative stress. Arbuscular mycorrhizal (AM) symbioses can improve olive plant tolerance to water deficit. This study investigated several aspects related to drought tolerance in AM fungi olive plants. Non-AM and AM plants were grown under well-watered or drought-stressed conditions, and mycorrhizal growth response, neutral lipid fatty acid (NLFA)161ω5 and phospholipid fatty acid (PLFA) 161ω5 in roots (intraradical mycelium) and in soil (extraradical mycelium), carbohydrates (monosaccharides, disaccharides and polyols) and phenolic compounds (phenolic alcohols, flavonoids, lignans, secoiridoids and hydroxycinnamic acid derivatives) were determined. Results showed that the amounts of PLFA 161ω5 and NLFA 161ω5 were significantly influenced by drought stress conditions. see more The NLFA 161ω5/PLFA 161ω5 ratio showed a dramatic decrease (-62%) with the application of water deficit stress, indicating that AM fungi allocated low carbon to storage structures under stress conditions. Mannitol and verbascoside are the main compounds detected in the roots of well-watered plants, whereas oleuropein and mannitol are the main compounds differentially accumulated in the roots of water-stressed plants. The oleuropein/verbascoside ratio increased in the case of drought-stressed AM plants by 30%, while the mannitol/oleuropein ratio was decreased by 46%, when compared to the non-AM stressed plants. Mycorrhization therefore oriented the flux toward the biosynthetic pathway of oleuropein and the data suggest that sugar and phenolic compound metabolism may have been redirected to the formation of oleuropein in roots of AM stressed plants, that may underlie their enhanced tolerance to drought stress.The generative adversarial network (GAN) is a good example of a strong-performing, neural network-based generative model, even though it does have some drawbacks of its own. Mode collapsing and the difficulty in finding the optimal network structure are two of the most concerning issues. In this paper, we address these two issues at the same time by proposing a neuro-evolutionary approach with an agile evaluation method for the fast evolution of robust deep architectures that avoid mode collapsing. The computation of Pareto set approximations with GANs is chosen as a suitable benchmark to evaluate the quality of our approach. Furthermore, we demonstrate the consistency, scalability, and generalization capabilities of the proposed method, which shows its potential applications to many areas. We finally readdress the issue of designing this kind of models by analyzing the characteristics of the best performing GAN specifications, and conclude with a set of general guidelines. This results in a reduction of the many-dimensional problem of structural manual design or automated search.