Synthesis,Molecular Docking,and Preliminary Evaluation of 2-(1,2,3-Triazoyl)benzaldehydes As Multifunctional Agents for the Treatment of Alzheimer's Disease

We described here our results on the use of thiourea as a ligand in the copper catalysed azide-alkyne cycloaddition (CuAAC) of 2-azidobenzaldehyde with alkynes. Reactions were performed reacting 2-azidobenzaldehyde with a range of terminal alkynes using 10 mol % of copper iodide as a catalyst, 20 mol % of thiourea as a ligand, triethylamine as base, DMSO as solvent at 100 °C under nitrogen atmosphere. The corresponding 2-(1H-1,2,3-triazoyl)-benzaldehydes (2-TBH) were obtained in moderated to excellent yields and according our experiments, the use of thiourea decreases the formation of side products. The obtained compounds were screened for their binding affinity with multiple therapeutic targets of AD by molecular docking: β-secretase (BACE), glycogen synthase kinase (GSK-3β) and acetylcholinesterase (AChE). The three compounds with highest affinity, 5 a (2-(4-phenyl-1H-1,2,3-triazol-1-yl)benzaldehyde), 5 b (2-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)benzaldehyde), and 5 d (2-(4-(4-(tert-butyl)phenyl)-1H-1,2,3-triazol-1-yl)benzaldehyde) were selected and evaluated on its antioxidant effect, in view of select the most promising one to perform the in vivo validation. Due the antioxidant potential ally to the affinity with BACE, GSK-3β and AChE, compound 5 b was evaluated in a mouse model of AD induced by intracerebroventricular injection of streptozotocin (STZ). Our results indicate that 5 b (1 mg/kg) treatment during 20 days is able to reverse the cognitive and memory impairment induced by STZ trough the modulation of AChE activity, amyloid cascade and GSK-3β expression.     

Experimental and Computational Fluid Dynamics Validation of Correlations for Dry Pressure Drop in Trays without Downcomer

The dry tray pressure drop (ΔP_d) is a design parameter that provides preliminary information about the total pressure drop. This work aimed to assess correlations for ΔP_d prediction for different types of trays without downcomer and to evaluate the effects of the free area ratio (φ) and the hole diameter (d) on ΔP_d. Assessment was performed by comparing results of several correlations with those from an experimentally validated computational fluid dynamics simulation. The study shows that the correlations of Červenka and Kolář, Bennett, Agrawal and Cook, and Stichlmair and Mersmann predicted the dry pressure drop satisfactorily. The correlation of Bennett, Agrawal and Cook can be recommended for the prediction of ΔP_d for a wide range of geometries and operation conditions. Also, φ has a higher influence on ΔP_d than d.     

Sclerotinia Sclerotiorum (White Mold): Cytotoxic,Mutagenic, and Antimalarial Effects In Vivo and In Vitro

This work aimed includes performing the sclerotia chemical profile and evaluates their biological effects on mutagenesis, oxidative stress, cancer, and malaria. A chemical profile was determined by ultraperformance liquid chromatography mass spectrometry (UHPLC–HRMS) analysis dereplicating norditerpenoid dilactone, sclerolide, and other compounds. The GI₅₀ values to cancer cells (19.8 to 277.6 µg/mL) were higher than normal (16.05 µg/mL), meaning high cytotoxicity. Regarding the oxidative stress, the results showed that the all AcOET fraction concentrations tested on IMR90 noncancer cell increased reactive oxygen species (ROS) production in more intense way (by fivefold) than in tested cancer cells. The in vivo study showed an increase of the following biomarkers (by 296.00%): % DNA in comet tail in peripheral blood and liver cells; micronucleated erythrocytes and colon cells and lipid serum peroxidation. These results indicate the sclerotia as genotoxic and mutagenic agent and its contamination may lead to fungal toxic effects with a risk to human health.     

Thermal bridging of graphene nanosheets via covalent molecular junctions: A non-equilibrium Green’s functions–density functional tight-binding study

Nano Research - Despite the uniquely high thermal conductivity of graphene is well known, the exploitation of graphene into thermally conductive nanomaterials and devices is limited by the...     

Model-based process capability indices: The dry-etching semiconductor case study

Process capability indices are widely used to check quality standards both at the production level and for business activity. They consider the location and the deviation from specification limits and targets. The literature contains many contributions on this topic both in the univariate and the multivariate context. Motivated by a real semiconductor case study, we discuss the role of rational subgroups and the challenge they present in the computation of capability indices, especially when data refer to lots of products. In addition, our context involves a mix of problems: unilateral specification limit, nonsymmetric distribution of the data, evidence of data from a mixture of distributions, and the need to filter one component of the mixture. After solving the previous issues and because of the peculiar characteristics of semiconductor processes based on the so called “wafers,” we contribute to the literature a proposal on how to compute capability indices in the case of heteroscedastic spatial processes. With a generalized additive model, we show that it is possible to estimate a capability surface that allows the identification of regions expected to not be fully compliant with the desired quality standards.     

Improving security in NoSQL document databases through model-driven modernization

Knowledge and Information Systems - NoSQL technologies have become a common component in many information systems and software applications. These technologies are focused on performance, enabling...