Connexin 43 and Connexin 26 Involvement in the Ponatinib-Induced Cardiomyopathy: Sex-Related Differences in a Murine Model

Cardiac connexins (Cxs) are proteins responsible for proper heart function. They form gap junctions that mediate electrical and chemical signalling throughout the cardiac system, and thus enable a synchronized contraction. Connexins can also individually participate in many signal transduction pathways, interacting with intracellular proteins at various cellular compartments. Altered connexin expression and localization have been described in diseased myocardium and the aim of this study is to assess the involvement of Cx43, Cx26, and some related molecules in ponatinib-induced cardiac toxicity. Ponatinib is a new multi-tyrosine kinase inhibitor that has been successfully used against human malignancies, but its cardiotoxicity remains worrisome. Therefore, understanding its signaling mechanism is important to adopt potential anti cardiac damage strategies. Our experiments were performed on hearts from male and female mice treated with ponatinib and with ponatinib plus siRNA-Notch1 by using immunofluorescence, Western blotting, and proteomic analyses. The altered cardiac function and the change in Cxs expression observed in mice after ponatinib treatment, were results dependent on the Notch1 pathway and sex. Females showed a lower susceptibility to ponatinib than males. The downmodulation of cardiac Cx43, Cx26 and miR-122, high pS368-Cx43 phosphorylation, cell viability and survival activation could represent some of the female adaptative/compensatory reactions to ponatinib cardiotoxicity.     

Use of mesoporous SBA-15 for nanostructuring titania for photocatalytic applications

SBA15–TiO₂ samples prepared by introducing titanium with a grafting method and having TiO₂ loadings below 15 wt.% have been characterized by XRF, XRD, IR, porosimetry, SEM, HRTEM, and UV–Visible diffuse reflectance. Differently from the samples reported in the literature characterized by a high TiO₂ loading, no evidences have been found for the presence of titania particles inside or outside the mesopores of SBA-15. Three different titanium species were instead evidenced to be present. The first two derive from the reaction of titanium with silanol groups in the corona area of inner SBA-15 walls leading to the formation of either TiO₄ tetrahedral sites (by reaction by hydroxyl nests of surface defect sites) and/or pseudo-octahedral surface sites anchored by two (or more) Si or Ti ions through bridging oxygens. The third species derives from the reaction of titanium in the regions with high sylanol density, e.g. in the micropores located in the corona of SBA-15 channels, leading to the formation of TiO₂-like nanoareas (probably Si-doped) with dimensions of around 1–2 nm maximum. The potential interest of these materials as photocatalysts, for the presence of a TiO₂-like nanoareas highly accessible by reactants, is discussed.     

Reflexive Planning as Design and Work: Lessons from the Port of Amsterdam

In recent years, planning theorists have advanced various interpretations of the notion of reflexivity, inspired by American pragmatism, complexity theory, hermeneutics, discursive and collaborative planning. Scholars agree that “reflexivity” has a strong temporal dimension: it not only aims to solve present planning problems, but to imagine and understand alternative trajectories for future action. This article explores the practical utility of reflexivity for planners, through a case study that focuses on a project to promote sustainable development in the Port of Amsterdam. Reflexivity in planning emerges as a new tool for generating critical knowledge and dialogue that can synthesise the perspectives of multiple actors in a common understanding, existing structural constraints and a collective imagination of alternative future possibilities. Such research highlights the potential of this approach to generate a creative reconfiguration of the present, and to build capacity for meaningful and considered change.     

Dynamic delayed detached eddy simulation of a multi‐inlet vortex reactor

The multi‐inlet vortex reactor (MIVR) is used for flash nanoprecipitation to manufacture functional nanoparticles. A validated computational fluid dynamics model is needed for the design, scale‐up, and optimization of the MIVR. Unfortunately, available Reynolds‐averaged Navier‐Stokes methods are unable to accurately model the highly swirling flow in the MIVR. Large‐eddy simulations (LES) are also problematic, as excessively fine grids are required to accurately model this flow. These dilemmas led to the application of the dynamic delayed detached eddy simulation (DDES) method to the MIVR. In the dynamic DDES model, the eddy viscosity has a form similar to the Smagorinsky sub‐grid viscosity in LES, which allows the implementation of a dynamic procedure to determine its model coefficient. Simulation results using the dynamic DDES model are found to match well with experimental data in terms of mean velocity and turbulence intensity, suggesting that the dynamic DDES model is a good option for modeling the turbulent swirling flow in the MIVR. © 2016 American Institute of Chemical Engineers AIChE J, 62: 2570–2578, 2016     

An index to characterize gas-solid and solid-solid mixing from average volume fraction fields

A mixing index based on solid volume fraction fields is developed for gas-solid flows. Conventional mixing indices are based on particle realizations of granular mixing and are applicable to experimental data or discrete element method simulations. However, these indices cannot be used as-is for multifluid models, and an index for characterizing mixing in gas-solid flows from continuous fields is needed. The performance of the new mixing index is tested in two applications. The first is a 3D simulation of the mixing of biomass and sand in a fluidized bed reactor, and the second is a 2D simulation of binary particle segregation in a fluidized bed. The simulations are performed using OpenFOAM®. The mixing index is used to quantify gas-solid mixing using solid volume fractions and solid-solid mixing using solid fractions. The formulation of conventional mixing indices is extended to be used with solid volume fractions fields, and methods for performance improvement are presented.     

Proton conducting membranes based on sulfonated PEEK-WC polymer for PEMFCs

Proton conducting membranes have been prepared from chloro-sulfonated polyetheretherketone with cardo group polymers at various sulfonation degree via casting solutions using dimethylformamide as a solvent. The proton conductivity of sulfonated polyetheretherketone with cardo group membranes has been evaluated in the temperature range between 80 and 120 °C and the best result of this work has been achieved at 120 °C and sulfonation degree equal to 60% with a value equal to 6.7·10⁻² S/cm. Furthermore, this sample shows an open circuit voltage varying from 0.881 V at 80 °C to 0.867 V at 120 °C, pointing out that the membrane performance is not greatly affected by a temperature variation. Nevertheless, an increase of temperature from 80 to 120 °C makes possible an increase of the cell resistance varying from 0.17 to 0.24 Ω cm². Thus, the present study investigates the performance of sulfonated polyetheretherketone with cardo group membranes in terms of polarization curves, open circuit voltage, cell resistance and proton conductivity in order to propose them for proton exchange membrane fuel cell applications, particularly at T > 100 °C.     

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.     

Influence of the structure in low-Pt loading electrodes for polymer electrolyte fuel cells

The influence of the structure and composition of the electrodes on a polymer electrolyte fuel cell (PEFC) performance has been investigated. Electrodes have been prepared by varying the composition of diffusion and/or catalyst layer. Improvements have been obtained by introducing a hydrophobic carbon layer between the carbon paper and the catalyst layer for the gas diffusion backing. High performance has been achieved with low Pt-loading electrodes (0.15 mg/cm²) by including the ionomer Nafion in the catalyst ink. Electrodes have been characterized by SEM-EDX analyses and electrochemical tests in a 50 cm² single cell.     

Morphological changes in the electrodes of phosphoric acid fuel cells operating under open circuit voltage conditions

This paper reports the experimental evidence for morphological changes that occur at the electrodes of phosphoric acid fuel cells (PAFC) under very severe (OCV) conditions. In addition, the dissolution of Pt-supported crystallites in H₃PO₄ is demonstrated by Transmission Electron Microscopy (TEM) confirming previous results already reported in the literature. Finally, the experimental data are discussed on the basis of an analysis of the reaction rates and models for the corrosion mechanism is postulated.