1,2,4-Oxadiazole Topsentin Analogs with Antiproliferative Activity against Pancreatic Cancer Cells,Targeting GSK3β Kinase

A new series of topsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,2,4-oxadiazole moiety, was efficiently synthesized. All derivatives were pre-screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. The five most potent compounds were further investigated in various pancreatic ductal adenocarcinoma (PDAC) cell lines, including SUIT-2, Capan-1, and Panc-1 cells, eliciting EC₅₀ values in the micromolar and sub-micromolar range, associated with significant reduction of cell migration. These remarkable results might be explained by the effects of these new topsentin analogues on epithelial-to-mesenchymal transition markers, including SNAIL-1/2 and metalloproteinase-9. Moreover, flow cytometric analysis after Annexin V-FITC and propidium iodide staining demonstrated that these derivatives enhanced apoptosis of PDAC cells. Keeping with these data, the PathScan intracellular signaling and ELISA array revealed cleavage of caspase-3 and PARP and a significant inhibition of GSK3β phosphorylation, suggesting this kinase as a potential downstream target of our novel compounds. This was further supported by a specific assay for the evaluation of GSK3β activity, showing IC₅₀ values for the most active compounds against this enzyme in the micromolar range.     

One-step synthesis of graphene supported platinum nanoparticles as electrocatalyst for PEM fuel cells

Here in, we describe an ultrafast, single-step microwave irradiation route (MW) to prepare graphene supported Pt nanoparticles, during which the small Pt nanoparticles are distributed uniformly on a reduced graphene oxide surface. This route provides evident advantages namely low cost, easiness, low time consuming and high yield in comparison to actual chemical methods to develop efficient Pt/rGO catalyst with Pt content close to state-of-the-art commercial composition. The structure and composition of prepared samples have been studied by specific techniques, while the electrocatalytic stability has been studied using ex-situ and in-situ measurements. High performance and electrochemically stable catalyst for PEM fuel cells was developed using the sample with highest loading and good dispersion. The fabricated Pt-rGO-based MEA was investigated for durability under fuel starvation in comparison with commercial Pt/C-based MEA. The electrocatalytic activity was investigated and the electrochemical response revealed the higher stability during accelerated degradation test under fuel starvation in comparison with commercial Pt/C. This study promotes the applicability of described preparation method to noble or transition metal nanoparticles embedded on graphene-based materials.     

Oncogenic MicroRNAs Characterization in Clear Cell Renal Cell Carcinoma

A key challenge for the improvement of clear cell renal cell carcinoma (ccRCC) management could derive from a deeper characterization of the biology of these neoplasms that could greatly improve the diagnosis, prognosis and treatment choice. The aim of this study was to identify specific miRNAs that are deregulated in tumor vs. normal kidney tissues and that could impact on the biology of ccRCC. To this end we selected four miRNAs (miR-21-5p, miR-210-3p, miR-185-5p and miR-221-3p) and their expression has been evaluated in a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) tissues from 20 ccRCC patients who underwent surgical nephrectomy resection. miR-21-5p and miR-210-3p resulted the most significantly up-regulated miRNAs in this patient cohort, highlighting these onco-miRNAs as possible relevant players involved in ccRCC tumorigenesis. Thus, this study reports the identification of specific oncogenic miRNAs that are altered in ccRCC tissues and suggests that they might be useful biomarkers in ccRCC management.     

Functionalised hybrid Poly(ether ether ketone) containing MnO2: Investigation of operative conditions for hydrogen sorption

A composite material synthesis, based on Manganese oxide (MnO₂) anchored to a functionalized polymeric matrix, was optimized. For this investigation two different MnO₂ loadings were selected (16 and 80 wt%) in order to understand the relation between the oxide content, chemical-physical characteristic and the H₂ sorption properties. SEM, XRD were carried out and the obtained results were correlated to the H₂ sorption/desorption characterizations by Sievert apparatus.From these measurements at 50 °C/40 bar, the sample containing 16 wt% of metal oxide content has revealed a low H₂ sorption capability (0,04 wt%), while the 80 wt% sample showed a very high H₂ storage value (3 wt%). A short sorption/desorption cycles were carried out and a good reversibility was revealed.A modelling study, ab-initio Density Functional Theory (DFT) calculations, was carried out. The starting unit cell was MnO₂ while Mn₂₄O₄₈ was considered as a supercell. The number of H atoms was gradually increased and desorption energy was calculated. Desorption energy starts from 366 kJ/mol and decreases by increasing the number of H atoms. For the experimental H₂ sorption value (1,7 wt%) it was calculated the number of the respective H atoms (36) and the corresponding desorption energy (150 kJ/mol).     

Novel ferrofluids coated with a renewable material obtained from cashew nut shell liquid

In this work, we present the synthesis and characterization of a new surfactant molecule obtained from a byproduct of the cashew nut processing (diphosphorylated cardol, DPC). It is herein used to overcoat magnetic nanoparticles showing spinel structures in order to create new ferrofluids. The nanoparticle structure and magnetic properties have been deeply investigated. DPC-functionalized Fe₃O₄ and NiFe₂O₄ samples exhibit higher magnetic saturation than DPC–CoFe₂O₄. These new ferrofluids reveal appealing as possible nanoparticle stabilizing molecules, magnetic resonance imaging agents, storage systems or in any material science field that requires the employment of biocompatible magnetic stable fluids.     

The structure of toluene-doped counterflow gaseous diffusion flames

The structure of gaseous counterflow diffusion flames perturbed with the addition of hundreds of ppm of prevaporized toluene is studied in two distinct flame environments: a blue methane flame stabilized on the fuel side of the gas stagnation plane and an incipiently sooting ethylene flame stabilized on the oxidizer side. The goal is to provide a well-defined testbed in terms of temperature–time history, major species and part of the radical pool, for the examination of reference fuels that are critical components of practical fuel blends. Gas samples are extracted from the flame with fused silica microprobes for subsequent GC/MS analysis and thermocouples and thin filament pyrometry are used to characterize the temperature field. Profiles of critical toluene pyrolysis products and stable soot precursors are compared with computational models using two semi-detailed chemical mechanisms. Results show that in the methane flame some oxygen containing radicals like O and OH are contributing early on to the toluene destruction path. In the incipiently sooting ethylene flame, the primary attack is from H alone. This finding confirms the different challenges that such flames pose to the validation of a chemical kinetic mechanism. The onset of toluene decay in these flames begins at relatively modest temperatures, on the order of 800 K. This reactivity is captured reasonably well by both chemical mechanisms in the methane flame, in the absence of reactants larger than C2, but not so in the ethylene flame, in the presence of a richer, more complex mixture. The aromatic ring opening mechanisms are not adequately modeled in either case. This discrepancy has implications for the modeling of practically relevant fuel blends with both aliphatic and aromatic compounds. The dominant species larger than toluene in the doped methane flame is ethylbenzene, which at least one of the mechanisms reproduces quite well. The largest measured species in the incipiently sooting flame is indene, whose concentration increase due to toluene addition is properly captured by one of the models. The experimental dataset reported here may help identifying future improvements to chemical kinetic mechanisms and complement other reactor datasets lacking the coupling of kinetics and transport of flame environments.     

An improvement of the response surface method

The coupling of the Monte Carlo method and the finite element method for the reliability analysis of structures leads often to a prohibitive computational cost. The response surface method is a powerful reliability method that approximates the limit state function with a polynomial expression using the values of the function at specific points. This type of analytical function replaces the exact limit state function in the Monte Carlo simulation. Therefore, the computational effort required for the assessment of the reliability of structural systems can be reduced significantly. The position of the sample points and the type of polynomial response surface have been investigated by several authors and the performance of the response surface method is still under discussion. In this paper an improvement of the response surface method is proposed. An iterative strategy is used to determine a response surface that is able to fit the limit state function in the neighbourhood of the design point. The locations of the sample points used to evaluate the free parameters of the response surface are chosen according to the importance sensitivity of each random variable. Several analytical and structural examples are considered to demonstrate the advantages of the proposed improvement.     

Modeling and analysis of landing collision dynamics for a shipborne helicopter

A Lagrange dynamic model is established based on small-angle approximation to improve the simulation model for shipborne helicopter landing collision. To describe fuselage motion effectively, the proposed model considers ship motion, the interaction of the tires with the deck, and tire slippage. A mechanism of sliding motion is built, and a real-time reliability analysis of the algorithm is implemented to validate the proposed model. Numerical simulations are also conducted under different operation conditions. Results show that the proposed dynamic model can simulate the collision motion of helicopter landing in real time. Several suggestions for helicopter pilot landing are likewise provided.     

1.5 kWe HT-PEFC stack with composite MEA for CHP application

In this work, the performance of a High Temperature (HT) Polymer Electrolyte Fuel Cell (PEFC) stack for co-generation application was investigated. A 3 kW power unit composed of two 1.5 kW modules was designed, manufactured and tested. The module was composed of 40 composite graphite cell with an active area of 150 cm². Composite Membrane Electrode Assemblies (MEAs) based on Nafion/Zirconia membranes were used to explore the behavior of the stack at high temperature (120 °C). Tests were performed in both pure Hydrogen and H₂/CO₂/CO mixture at different humidification grade, simulating the exit gas from a methane fuel processor. The fuel cells stack has generated a maximum power of 2400 W at 105 A with pure hydrogen and fully hydrated gases and 1700 W at 90 A by operating at low humidity grade (95/49 RH% for H₂/Air). In case the stack was fed with reformate simulated stream fully saturated, a maximum power of 2290 W at 105 A was reached: only a power loss of 5% was recorded by using reformate stream instead of pure hydrogen. The humidification grade of Nafion membrane was indicated as the main factor affecting the proton conductivity of Nafion while the addition of the inert compound like YSZ, did not affectthe electrochemical properties of the membrane but, rather has enhanced mechanical resistance at high temperature.