The Interplay between HGF/c-met Axis and Nox4 in BRAF Mutated Melanoma

Background: Melanoma is the leading cause of death due to cutaneous malignancy and its incidence is on the rise. Several signaling pathways, including receptor tyrosine kinases, have a role in the development and progression of melanocytic lesions and malignant melanoma. Among those, the hepatocyte growth factor (HGF)/c-met axis is emerging as a critical player because it can play a role in drug resistance. Indeed, 50% of melanoma patients present BRAF mutations, however, all responders develop resistance to the inhibitors typically within one year of treatment. Interestingly, BRAF inhibitors induce reactive oxygen species (ROS) in melanoma cells, therefore, the aim of this study was to investigate a possible interplay between HGF/c-met and ROS sources, such as NADPH oxidases (Nox). Methods: The expression of c-met and Nox were quantified in 60 patients with primary cutaneous melanoma. In vitro experiments on melanoma primary cells and the cell line were performed to dissect the underpinned molecular mechanism. Results: The outcome of interest was the correlation between the high positivity for both Nox4 and c-met and metastasis occurring at least 1 year later than melanoma diagnosis in BRAF mutated patients, in contrast to nonmutated. In vitro experiments demonstrated that the axis HGF/c-met/Nox4/ROS triggers the epithelial-mesenchymal transition. Conclusions: The observed correlation suggests an interplay between c-met and Nox4 in promoting the onset of metastasis. This study suggests that Nox4 inhibitors could be associated to the current therapy used to treat melanoma patients with BRAF mutations.     

Design of a Control System Using an Artificial Neural Network to Optimize the Energy Efficiency of Water Distribution Systems

Sustainable management of water supply systems is a major challenge within the framework of the water-energy nexus. The main strategies to improve the operation of these systems are related to increasing the hydraulic and energy efficiency of pumping systems. In this context, this work presents a new artificial neural network (ANN) controller to improve the operation of water distribution systems (WDSs) that includes in its algorithm the specific energy consumption (SEC) as a decision parameter. Therefore, pressure control at the measuring points is also based on the energy efficiency of the pumps. The technique was applied to control the pressures in an experimental setup that emulates a WDS with two consumption zones with different topographies. For this purpose, the controller acted on a conventional pump, a booster pump and a control valve. To analyze the performance under the controller action, tests were performed emulating water-demand scenarios, introducing perturbations and changing the pressure setpoints. The real-time control performance was proven based on the dynamic performance, steady-state performance and SEC. The experimental results showed that the proposed controller kept the pressures close to the setpoints and provided a reduction in the SEC between 15.1% and 17.8%, compared with the uncontrolled system, and an economy that varied from 2.5% to 8.1% compared with the performance of the ANN based only on pressure control.

     

Maskless Preparation of Spatially-Resolved Plasmonic Nanoparticles on Polydimethylsiloxane via In Situ Fluoride-Assisted Synthesis

Here, a fluoride-assisted route for the controlled in-situ synthesis of metal nanoparticles (NPs) (i.e., AgNPs, AuNPs) on polydimethylsiloxane (PDMS) is reported. The size and coverage of the NPs on the PDMS surface are modulated with time and over space during the synthetic process, leveraging the improved yield (10×) and faster kinetics (100×) of NP formation in the presence of F⁻ ions, compared to fluoride-free approaches. This enables the maskless preparation of both linear and step gradients and patterns of NPs in 1D and 2D on the PDMS surface. As an application in flexible plasmonics/photonics, continuous and step-wise spatial modulations of the plasmonic features of PDMS slabs with 1D and 2D AgNP gradients on the surface are demonstrated. An excellent spatially resolved tuning of key optical parameters, namely, optical density from zero to 5 and extinction ratio up to 100 dB, is achieved with AgNP gradients prepared in AgF solution for 12 minutes; the performance are comparable to those of commercial dielectric/interference filters. When used as a rejection filter in optical fluorescence microscopy, the AgNP-PDMS slabs are able to reject the excitation laser at 405 nm and retain the green fluorescence of microbeads (100 µm) used as test cases.     

Two-step sinter-crystallization of K2O–CaO–P2O5–SiO2 (45S5-K) bioactive glass

Bioactive glasses and glass-ceramics (GCs) effectively regenerate bone tissue, however most GCs show improved mechanical properties. In this work, we developed and tested a rarely studied bioactive glass composition (24.4K₂O-26.9CaO-46.1SiO₂-2.6P₂O₅ mol%, identified as 45S5-K) with different particle sizes and heating rates to obtain a sintered GC that combines good fracture strength, low elastic modulus, and bioactivity. We analyzed the influence of the sintering processing conditions in the elastic modulus, Vickers microhardness, density, and crystal phase formation in the GC. The best GC shows improved properties compared with its parent glass. This glass achieves a good densification degree with a two-step viscous flow sintering approach and the resulting GC shows as high bioactivity as that of the standard 45S5 Bioglass®. Furthermore, the GC elastic modulus (56 GPa) is relatively low, minimizing stress shielding. Therefore, we unveiled the glass sintering behavior with concurrent crystallization of this complex bioactive glass composition and developed a potential GC for bone regeneration.     

Optimization methods in inverse problems and applications to science and engineering

Optimization and Engineering -     

Parametric study for tensile properties of molded high-density polyethylene for applications in additive manufacturing and sustainable designs

Test specimens following ASTM D638 standards are frequently used to measure the tensile properties of reinforced and unreinforced polymers machined with traditional machining and emerging manufacturing methods (additive manufacturing/3D printing). However, designs of large engineering structures may rely on mechanical properties based on ASTM D3039 for fiber-reinforced polymer composites. This parametric study examines the scaling effects present in uniaxial tensile test specimens of molded high-density polyethylene (HDPE), with geometries ranging from Types I to IV of ASTM D638 to ASTM D3039. HDPE is a thermoplastic polymer that is recyclable, can be 3D-printed, and has a wide range of engineering applications, from bottles to pipes to radiation protection shielding. The mechanical properties test results for the molded HDPE samples are validated using a Monte Carlo simulation to estimate uncertainties for the probability distribution of maximum stress at the yield point. A Finite Element study based on the empirical model shows how the proposed approach can be adopted for design purposes. The results of this work are a useful tool to enhance confidence in the tensile mechanical properties of ASTM D638 Types II and IV geometries as statistically similar to those of ASTM D3039 samples, impacting engineering designs with traditional and emerging manufacturing methods.     

Application of the novel Droplet digital PCR technology for identification of meat species

The authenticity and traceability of meat products are issues of primary importance to ensure food safety. Unfortunately, food adulteration (e.g. the addition of inexpensive cuts to minced meat products) and mislabelling (e.g. the inclusion of meat from species other than those declared) happens frequently worldwide. The aim of this study was to apply a droplet digital PCR assay for the detection and quantification (copies μL⁻¹) of the beef, pork, horse, sheep, chicken and turkey in meat products. The analysis conducted on commercial meat showed the presence of traces of DNA from other animal species than those declared. We show that the method is highly sensitive, specific and accurate (accuracy = 100%). This method could be adopted by competent food safety authorities to verify compliance with the labelling of meat products and to ensure quality and safety throughout the meat supply chain, from primary production to consumption.     

Residents’ evaluation of advantages and disadvantages of golf community living in Alicante,Spain

The growing numbers of golf communities are attracting a diverse group of homebuyers who experience varying levels of neighborhood satisfaction. A multinomial logistic regression analysis with follow-up ANOVA reveals that homeowners in one region of Spain who believe there are more advantages than disadvantages to living in a golf community are more likely to be older, Spanish, and evaluate the natural environment, sports facilities, and water supply of their community as better. Meanwhile, those who perceive more disadvantages cite the limitations on using the golf course for non-golf activities, high housing costs, automobile dependence, and lack of services and shops. Thus, satisfaction with the golf community varies depending on the residents’ personal characteristics as well as their evaluation of the neighborhood’s characteristics, but is not directly attributable to whether they play golf or whether the course was a decisive factor in choosing the house.     

Self-Assembly and Neurotoxicity of β-Amyloid (21–40) Peptide Fragment: The Regulatory Role of GxxxG Motifs

The three GxxxG repeating motifs from the C-terminal region of β-amyloid (Aβ) peptide play a significant role in regulating the aggregation kinetics of the peptide. Mutation of these glycine residues to leucine greatly accelerates the fibrillation process but generates a varied toxicity profile. Using an array of biophysical techniques, we demonstrated the uniqueness of the composite glycine residues in these structural repeats. We used solvent relaxation NMR spectroscopy to investigate the role played by the surrounding water molecules in determining the corresponding aggregation pathway. Notably, the conformational changes induced by Gly³³ and Gly³⁷ mutations result in significantly decreased toxicity in a neuronal cell line. Our results indicate that G³³xxxG³⁷ is the primary motif responsible for Aβ neurotoxicity, hence providing a direct structure–function correlation. Targeting this motif, therefore, can be a promising strategy to prevent neuronal cell death associated with Alzheimer's and other related diseases, such as type II diabetes and Parkinson's.