Tumor-Suppressor Role of the α1-Na/K-ATPase Signalosome in NASH Related Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide, with an estimate of 0.84 million cases every year. In Western countries, because of the obesity epidemic, non-alcoholic steatohepatitis (NASH) has become the major cause of HCC. Intriguingly, the molecular mechanisms underlying tumorigenesis of HCC from NASH are largely unknown. We hypothesized that the growing uncoupled metabolism during NASH progression to HCC, manifested by lower cell redox status and an apoptotic ‘switch’ activity, follows a dysregulation of α1-Na/K-ATPase (NKA)/Src signalosome. Our results suggested that in NASH-related malignancy, α1-NKA signaling causes upregulation of the anti-apoptotic protein survivin and downregulation of the pro-apoptotic protein Smac/DIABLO via the activation of the PI3K → Akt pro-survival pathway with concomitant inhibition of the FoxO3 circuit, favoring cell division and primary liver carcinogenesis. Signalosome normalization using an inhibitory peptide resets apoptotic activity in malignant cells, with a significant decrease in tumor burden in vivo. Therefore, α1-NKA signalosome exercises in HCC the characteristic of a tumor suppressor, suggesting α1-NKA as a putative target for clinical therapy.     

Effect of Phosphorus Impurity on Tricalcium Silicate T1: From Synthesis to Structural Characterization

Alite is the major compound of anhydrous Portland cement: it is composed of tricalcium silicate Ca₃SiO₅ (C₃S) modified in composition and crystal structure by ionic substitutions. Alite is also the main hydraulic phase of cement and the most important for subsequent strength development. Using raw meals (rich in Ca₃P₂O₈) as alternative fuels in cement plants raises the question about the effect of phosphorus on C₃S and its consequences on reactivity with water. This paper deals with a systematic study of C₃S triclinic T₁ polymorph doped with P₂O₅ in the range 0–0.9 wt%. All the samples were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and electron-microprobe analysis. The appearance of a phase rich in phosphorus is shown. It displays a structure derivative of the α'_H–Ca₂SiO₄ polymorph, noted α'_H–C₂S(P). As phosphorus content increases, C₃S is more and more decomposed into free lime and α'_H–C₂S(P). The α'_H phase was detected from 0.1 wt% P₂O₅ and located at the interfaces of C₃S grains. Two identification keys are proposed in order to highlight the α'_H–C₂S(P) phase: the XRD angular window at 2θ_Cu=32.8°–33.2° and a smooth aspect on SEM micrographs.     

Fine-grained transparent MgAl2O4 spinel obtained by spark plasma sintering of commercially available nanopowders

A high transmittance/small grain size combination for pure spinel ceramics from commercially available nanopowders without sintering aids can be obtained by SPS sintering. By using a low heating rate ≤10 °C/min and a sintering temperature ≤1300 °C, a transparent polycrystalline MgAl₂O₄ spinel was fabricated by SPS with an in-line transmission of 74% and 84% for 550 nm (visible) and 2000 nm (NIR) wavelengths respectively. A small average grain size of about 250 nm was obtained and the pores located at the multiple grain junctions have a mean size of about 20 nm. The high in-line transmission is linked not only to the low residual porosity but particularly to the very small size of pores.     

Modeling the short-circuit current density of polymer solar cells based on P3HT:PCBM blend

We have investigated the short-circuit current density of organic solar cells based on poly (3-hexylthiophene)(P3HT)/6,6-phenyl C61-butyric acid methyl ester (PCBM) blend. In order to model charge collection efficiencies with respect to short circuit density in such blends, a full optical modeling of the cell is performed. From the distribution of the electromagnetic field, we compute the rate of exciton generation. This exciton generation rate is used as input in the transport equations of holes and electrons. Charge densities at steady state are obtained as solutions are used for computing short-circuit current densities generated in the cell. The dependence of short-circuit current densities versus the thickness of the blend is analyzed and compared with our experimental data and with data extracted from the literature.     

Electroactive biofilms: new means for electrochemistry

This work demonstrates that electrochemical reactions can be catalysed by the natural biofilms that form on electrode surfaces dipping into drinking water or compost. In drinking water, oxygen reduction was monitored with stainless steel ultra-microelectrodes under constant potential electrolysis at −0.30 V/SCE for 13 days. 16 independent experiments were conducted in drinking water, either pure or with the addition of acetate or dextrose. In most cases, the current increased and reached 1.5–9.5 times the initial current. The current increase was attributed to biofilm forming on the electrode in a similar way to that has been observed in seawater. Epifluorescence microscopy showed that the bacteria size and the biofilm morphology depended on the nutrients added, but no quantitative correlation between biofilm morphology and current was established. In compost, the oxidation process was investigated using a titanium based electrode under constant polarisation in the range 0.10–0.70 V/SCE. It was demonstrated that the indigenous micro-organisms were responsible for the current increase observed after a few days, up to 60 mA m⁻². Adding 10 mm acetate to the compost amplified the current density to 145 mA m⁻² at 0.50 V/SCE. The study suggests that many natural environments, other than marine sediments, waste waters and seawaters that have been predominantly investigated until now, may be able to produce electrochemically active biofilms.     

ITER safety and licensing update

Safety files were submitted by the ITER Organization to the French nuclear safety authorities in March 2010 as a part of the licensing process. These included the preliminary safety report (RPrS) which presents the extensive safety analyses performed for ITER. The report has been the subject of examination by the authorities and their advisors, and discussions with them have been held on many topics. In the light of this process, this paper discusses some of the topics that remain prominent in the safety analysis of ITER. In particular, the provision of the two safety functions, confinement of radioactive material and limitation of exposure to radiation, is explained and some of the potential challenges to them are identified. Amongst these are the risks of fire and explosion, and external events such as earthquake and loss of all electric power. Provisions in the ITER design, together with the characteristics of fusion, ensure that a very good safety performance will be achieved.     

Synergistic antimicrobial activity of two binary combinations of marjoram,lavender, and wild thyme essential oils

The combination of essential oils (EOs) is a novel alternative to improve their preservative effects and to reduce their organoleptic impact in food. In this context, this work aims to investigate the antibacterial combined effect of two EOs combinations through the calculation of the fractional inhibitory concentration index. The combinations tested consists of Lavandula dentata/Origanum majorana EOs and Thymus serpyllum/Origanum majorana EOs. Their chemical compositions were identified by CG/MS analyses. The main compounds of O. majorana EO were (-) - terpinene-4-ol and trans-4-thujanol. Those of L. dentata EO were β-pinene and 1,8-cineole, and those of T. serpyllum EO were p-cymene and γ-terpinene. Regarding the outcomes, results highlighted partial synergistic and additive interactions. Two combinations of marjoram and thyme EOs had antibacterial activities against S. aureus. The first one corresponded to the quarter of the minimum inhibitory concentration of marjoram and half that of thyme. The second one was the mix of half and quarter of the minimum inhibitory concentration of respectively marjoram and thyme EOs. This last combination also showed an antibacterial effect against E. coli. The quarter and the half of their minimum inhibitory concentration of marjoram and lavender combination, respectively, gave a partial synergy against both strains. Henceforth, these findings could be largely exploited in food preservation through the use of minimal doses of these plant products without affecting the antibacterial and the organoleptic properties in foods.     

Fabrication of reducing atmosphere electrodes (fuel electrodes) by electroless plating of copper on BaZr0.9−xCexY0.1O3−δ – A proton-conducting ceramic

Copper appears to be an interesting fuel electrode material for proton-conducting ceramic electrolytes (such as BaZr_0.9?xCe_xY_0.1O_3?δ) because it is stable at high temperatures in reducing and hydrocarbon-containing atmospheres. However, when deposited using organometallic Cu pastes/inks, these electrodes suffer from poor performance due to delamination issues and coating thickness (10–20 μm). Alternatively, electroless plating (ELP) is a method of depositing metal films – without utilizing electric power – that can achieve much thinner coatings than with pastes. In this work ELP of Cu was shown to be an alternative to Cu pastes for electrode fabrication on the non-electrically conductive, proton-conducting ceramic BaZr_0.8Ce_0.1Y_0.1O_3?δ. Pd, Ru, and Cu were investigated as activation catalysts, on which Cu was then plated. All three were found to produce thin electrodes (～1 μm) with good electrode/electrolyte adhesion. Scanning electron microscopy coupled with energy dispersive x-ray spectroscopy, x-ray fluorescence and x-ray diffraction were used to characterize the Cu-based ELP electrodes. Additionally, the ELP process was shown to be transferable to tubular substrates without significant modification to the procedure.     

Microbubbles for optofluidics: controlled defects in bubble crystals

We use liquid–gas microfluidics as a low-cost, tunable microstructuring tool, for which applications can be envisioned in optics. In order to obtain relevant geometries for photonics, beyond simple self-assembled crystals, we propose an original approach that excludes bubbles from chosen zones thanks to tiny pillars. To assess the strength of the exclusion mechanism, we predict the behaviour of a single flattened bubble in front of a thin cylindrical pillar located in a rectangular microchannel. The model compares the hydrodynamic force F _fluid that pushes the bubble and the force F _s, due to surface tension, resulting from the surface augmentation when the bubble rises over the pillar. The resulting predictions have been confirmed by experimental results which showed that the bubble passes over the pillar if F _s < F _fluid and goes around it in other cases. Consistently with this model, dynamic bubble crystals with controlled lacuna defects of one, two, or a line of bubbles have been successfully produced. Defects can be switched on or off by changing the flow. Using a photosensitive polymer as a carrier liquid, static bubble crystals have also been produced.