Experimental Evidence of Generation and Reception by a Transluminal Axisymmetric Shear Wave Elastography Prototype

Experimental evidence on testing a non-ultrasonic-based probe for a new approach in transluminal elastography was presented. The proposed modality generated shear waves by inducing oscillatory rotation on the lumen wall. Detection of the propagated waves was achieved at a set of receivers in mechanical contact with the lumen wall. The excitation element of the probe was an electromagnetic rotational actuator whilst the sensing element was comprised by a uniform anglewise arrangement of four piezoelectric receivers. The prototype was tested in two soft-tissue-mimicking phantoms that contained lumenlike conduits and stiffer inclusions. The shear wave speed of the different components of the phantoms was characterized using shear wave elastography. These values were used to estimate the time-of-flight of the expected reflections. Ultrafast ultrasound imaging, based on Loupas' algorithm, was used to estimate the displacement field in transversal planes to the lumenlike conduit and to compare against the readouts from the transluminal transmission-reception tests. Experimental observations between ultrafast imaging and the transluminal probe were in good agreement, and reflections due to the stiffer inclusions were detected by the transluminal probe. The obtained experimental evidence provided proof-of-concept for the transluminal elastography probe and encouraged further exploration of clinical applications

Characterization of non‑linear mechanical behavior of the cornea

The objective of this study was to evaluate which hyperelastic model could best describe the nonlinear mechanical behavior of the cornea, in order to characterize the capability of the non-linear model parameters to discriminate structural changes in a damaged cornea. Porcine corneas were used, establishing two diferent groups: control (non-treated) and NaOH-treated (damaged) corneas (n= 8). NaOH causes a chemical burn to the corneal tissue, simulating a disease associated to structural damage of the stromal layer. Quasi-static uniaxial tensile tests were performed in nasaltemporal direction immediately after preparing corneal strips from the two groups. Three non-linear hyperelastic models (i.e. Hamilton-Zabolotskaya model, Ogden model and Mooney-Rivlin model) were ftted to the stress–strain curves obtained in the tensile tests and statistically compared. The corneas from the two groups showed a non-linear mechanical behavior that was best described by the Hamilton-Zabolotskaya model, obtaining the highest coefcient of determination (R2 > 0.95). Moreover, Hamilton-Zabolotskaya model showed the highest discriminative capability of the nonlinear model parameter (Parameter A) for the tissue structural changes between the two sample groups (p= 0.0005). The present work determines the best hyperelastic model with the highest discriminative capability in description of the non-linear mechanical behavior of the cornea.Ministry of Education DPI2017-83859-R DPI2014-51870-R EQC2018004508-P UNGR15-CE-3664Ministry of Health - Turkey DTS15/00093Junta de Andalucia PI16/00339 PI-0107-2017 PIN-0030-201

A synthetic-lethality RNAi screen reveals an ERK-mTOR co-targeting pro-apoptotic switch in PIK3CA+ oral cancers.

mTOR inhibition has emerged as a promising strategy for head and neck squamous cell carcinomas (HNSCC) treatment. However, most targeted therapies ultimately develop resistance due to the activation of adaptive survival signaling mechanisms limiting the activity of targeted agents. Thus, co-targeting key adaptive mechanisms may enable more effective cancer cell killing. Here, we performed a synthetic lethality screen using shRNA libraries to identify druggable candidates for combinatorial signal inhibition. We found that the ERK pathway was the most highly represented. Combination of rapamycin with trametinib, a MEK1/2 inhibitor, demonstrated strong synergism in HNSCC-derived cells in vitro and in vivo, including HNSCC cells expressing the HRAS and PIK3CA oncogenes. Interestingly, cleaved caspase-3 was potently induced by the combination therapy in PIK3CA+ cells in vitro and tumor xenografts. Moreover, ectopic expression of PIK3CA mutations into PIK3CA- HNSCC cells sensitized them to the pro-apoptotic activity of the combination therapy. These findings indicate that co-targeting the mTOR/ERK pathways may provide a suitable precision strategy for HNSCC treatment. Moreover, PIK3CA+ HNSCC are particularly prone to undergo apoptosis after mTOR and ERK inhibition, thereby providing a potential biomarker of predictive value for the selection of patients that may benefit from this combination therapy

Electrocatalytic hydrogen evolution using amorphous tungsten phosphide nanoparticles

Amorphous tungsten phosphide (WP), which has been synthesized as colloidal nanoparticles with an average diameter of 3 nm, has been identified as a new electrocatalyst for the hydrogen-evolution reaction (HER) in acidic aqueous solutions. WP/Ti electrodes produced current densities of −10 mA cm^(−2) and −20 mA cm^(−2) at overpotentials of only −120 mV and −140 mV, respectively, in 0.50 M H_2SO_4(aq)