PTCH1+/− Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts

Gorlin's or nevoid basal cell carcinoma syndrome (NBCCS) causes predisposition to basal cell carcinoma (BCC), the commonest cancer in adult human. Mutations in the tumor suppressor gene PTCH1 are responsible for this autosomal dominant syndrome. In NBCCS patients, as in the general population, ultraviolet exposure is a major risk factor for BCC development. However these patients also develop BCCs in sun-protected areas of the skin, suggesting the existence of other mechanisms for BCC predisposition in NBCCS patients. As increasing evidence supports the idea that the stroma influences carcinoma development, we hypothesized that NBCCS fibroblasts could facilitate BCC occurence of the patients. WT (n = 3) and NBCCS fibroblasts bearing either nonsense (n = 3) or missense (n = 3) PTCH1 mutations were cultured in dermal equivalents made of a collagen matrix and their transcriptomes were compared by whole genome microarray analyses. Strikingly, NBCCS fibroblasts over-expressed mRNAs encoding pro-tumoral factors such as Matrix Metalloproteinases 1 and 3 and tenascin C. They also over-expressed mRNA of pro-proliferative diffusible factors such as fibroblast growth factor 7 and the stromal cell-derived factor 1 alpha, known for its expression in carcinoma associated fibroblasts. These data indicate that the PTCH1+/− genotype of healthy NBCCS fibroblasts results in phenotypic traits highly reminiscent of those of BCC associated fibroblasts, a clue to the yet mysterious proneness to non photo-exposed BCCs in NBCCS patients

Validation of a Novel Fluorescent Lateral Flow Assay for Rapid Qualitative and Quantitative Assessment of Total Anti-SARS-CoV-2 S-RBD Binding Antibody Units (BAU) from Plasma or Fingerstick Whole-Blood of COVID-19 Vaccinees

Background: Limited commercial LFA assays are available to provide a reliable quantitative measurement of the total binding antibody units (BAU/mL) against the receptor-binding domain of the SARS-CoV-2 spike protein (S-RBD). Aim: This study aimed to evaluate the performance of the fluorescence LFA FinecareTM 2019-nCoV S-RBD test along with its reader (Model No.: FS-113) against the following reference methods: (i) the FDA-approved GenScript surrogate virus-neutralizing assay (sVNT); and (ii) three highly performing automated immunoassays: BioMérieux VIDAS®3, Ortho VITROS®, and Mindray CL-900i®. Methods: Plasma from 488 vaccinees was tested by all aforementioned assays. Fingerstick whole-blood samples from 156 vaccinees were also tested by FinecareTM. Results and conclusions: FinecareTM showed 100% specificity, as none of the pre-pandemic samples tested positive. Equivalent FinecareTM results were observed among the samples taken from fingerstick or plasma (Pearson correlation r = 0.9, p < 0.0001), suggesting that fingerstick samples are sufficient to quantitate the S-RBD BAU/mL. A moderate correlation was observed between FinecareTM and sVNT (r = 0.5, p < 0.0001), indicating that FinecareTM can be used for rapid prediction of the neutralizing antibody (nAb) post-vaccination. FinecareTM BAU results showed strong correlation with VIDAS®3 (r = 0.6, p < 0.0001) and moderate correlation with VITROS® (r = 0.5, p < 0.0001) and CL-900i® (r = 0.4, p < 0.0001), suggesting that FinecareTM can be used as a surrogate for the advanced automated assays to measure S-RBD BAU/mL.This work was made possible by grant number UREP28-173-3-057 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors

The Usability of E-learning Platforms in Higher Education: A Systematic Mapping Study

The use of e-learning in higher education has increased significantly in recent years, which has led to several studies being conducted to investigate the usability of the platforms that support it. A variety of different usability evaluation methods and attributes have been used, and it has therefore become important to start reviewing this work in a systematic way to determine how the field has developed in the last 15 years. This paper describes a systematic mapping study that performed searches on five electronic libraries to identify usability issues and methods that have been used to evaluate e-learning platforms. Sixty-one papers were selected and analysed, with the majority of studies using a simple research design reliant on questionnaires. The usability attributes measured were mostly related to effectiveness, satisfaction, efficiency, and perceived ease of use. Furthermore, several research gaps have been identified and recommendations have been made for further work in the area of the usability of online learning

A study of low-temperature CO oxidation over mesoporous Cuo-TiO\u3csub\u3e2\u3c/sub\u3e nanotube catalysts

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. Supported copper oxide nanoparticles have attracted considerable attention as active and non-precious catalysts for many catalytic oxidation reactions. Herein, mesoporous xCuO-TiO2 nanotube catalysts were fabricated, and their activity and kinetics toward CO oxidation were studied. The morphology and structure of the prepared catalysts were systematically studied using SEM, TEM, EDS, EDX, XRD, TGA, BET, XPS, H2-TPR, and Raman techniques. The BET surface area study revealed the effect of the large surface area of the mesoporous TiO2 nanotubes on promoting the catalytic activity of prepared catalysts. The results also revealed the existence of strong metal-support interactions in the CuO-TiO2 nanotube catalyst, as indicated by the up-shift of the E2g vibrational mode of TiO2 from 144 cm-1 to 145 cm-1 and the down-shift of the binding energy (BE) of Ti 2p3/2 from 458.3 eV to 458.1 eV. The active phase of the catalyst consists of fine CuO nanoparticles dispersed on a mesoporous anatase TiO2 nanotube support. The 50-CuO-TiO2 nanotube catalyst demonstrated the highest catalytic activity with 100% CO conversion at T100 = 155°C and a reaction rate of 36 µmole s-1 g-1. Furthermore, the catalyst demonstrated excellent long-term stability with complete CO conversion that was stable for 60 h under a continuous stream. The enhanced catalytic activity is attributed to the interplay at the interface between the active CuO phase and the TiO2 nanotubes support

A study of low-temperature CO oxidation over mesoporous Cuo-TiO2 nanotube catalysts

Supported copper oxide nanoparticles have attracted considerable attention as active and non-precious catalysts for many catalytic oxidation reactions. Herein, mesoporous xCuO-TiO2 nanotube catalysts were fabricated, and their activity and kinetics toward CO oxidation were studied. The morphology and structure of the prepared catalysts were systematically studied using SEM, TEM, EDS, EDX, XRD, TGA, BET, XPS, H2-TPR, and Raman techniques. The BET surface area study revealed the effect of the large surface area of the mesoporous TiO2 nanotubes on promoting the catalytic activity of prepared catalysts. The results also revealed the existence of strong metal-support interactions in the CuO-TiO2 nanotube catalyst, as indicated by the up-shift of the E2g vibrational mode of TiO2 from 144 cm-1 to 145 cm-1 and the down-shift of the binding energy (BE) of Ti 2p3/2 from 458.3 eV to 458.1 eV. The active phase of the catalyst consists of fine CuO nanoparticles dispersed on a mesoporous anatase TiO2 nanotube support. The 50-CuO-TiO2 nanotube catalyst demonstrated the highest catalytic activity with 100% CO conversion at T100 = 155 C and a reaction rate of 36 mmole s-1 g-1. Furthermore, the catalyst demonstrated excellent long-term stability with complete CO conversion that was stable for 60 h under a continuous stream. The enhanced catalytic activity is attributed to the interplay at the interface between the active CuO phase and the TiO2 nanotubes support.made possible by the grant number NPRP 6?351?1?072 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility.Scopu

Near-surface mechanical heterogeneities in a dissimilar aluminum alloys friction stir welded joint

International audienceThe local mechanical properties of a dissimilar friction stir welded AA-2024-T3/AA-2198-T3 joint were documented during a uniaxial tensile test. High-resolution digital image correlation was performed during monotonic tensile tests to capture the local in-plane strain fields of the heterogeneous macrostructure of the weld. In the shoulder-affected region, banded macrostructures with heterogeneous mechanical properties were found. They were related to pronounced textures regions, which can be associated to strain-rate gradient during one rotation of the tool. The banded macrostructures in the nugget region were observed to be responsible for early plasticity in the joint and ultimately to be the fracture location of the weld. The heterogeneous mechanical response of the joint was also investigated by microhardness measurements. Differences were found between hardness and local tensile properties, demonstrating microhardness measurements can be misleading and only direct high-resolution digital image correlation techniques can document the mechanical behavior of materials having complex and heterogeneous micro-/macrostructures

Heterogeneous mechanical behavior of dissimilar aluminum alloys FSWed joints assessed by OHR-DIC characterization

International audienceFriction stir welding of dissimilar heat treatable 2139-T8 and 7020-T651 aluminum alloys was investigated in a large operating window of industrials welding parameters. Detailed microstructural and local mechanical characterizations have shown that despite consistency in the macroscopic tensile behavior of the different processed joints, local discrepancies in hardness highlighted the sensitivity of the two aluminum alloys to the welding process parameters. For this reason, a local characterization of the joint was undertaken. The local tensile behavior of the joints was investigated at the microstructure scale thanks to the use of an optical high-resolution digital image correlation (OHR-DIC) technique. The aim of this in-situ microtensile technique was to accurately calculate the local strain fields in the cross-weld section from kinematic field measurements. OHR-DIC micro-mechanical analysis demonstrated that strain localization first appears in the nugget region, then in the HAZ leading to fracture in this latter region. This study gives the opportunity to get an overall view of the welding parameters influence on the microstructural and mechanical characteristics of the welded joints and thus, make the right industrial choice according to the application. Keywords: FSWed dissimilar aluminum joint, Hybrid lightweight design, Digital image correlation, Tensile behavior Introduction Currently, reducing the weight of transport structure is an important challenge. The aluminum alloys (AA) 7020 comply with this constraint. AA7020 is a medium strength Al-Zn-Mg alloy well known for its good mechanical performance [1]. However, Al-Cu-Mg alloys, such as AA2139, will progressively replace 7XXX alloys because of the conjunction of higher mechanical strength and lower density [2]. Unfortunately, the intensive use of AA2139 is limited due to the production cost. Building hybrid structure by assembling medium-performance and high-performance aluminum alloys as a function of the local stresses in the structure is an attractive solution for cost-effective design strategies. In order to assemble these dissimilar alloys, Friction Stir Welding (FSW) is particularly suitable. Several process parameters, such as speeds [3], axial force [4], plates position [5], were reported to influence both the material flow of the weld and the mechanical behavior. In the present study, various dissimilar joints AA2139-T8/AA7020-T651 were produced with a large range of industrial welding parameters in order to correlate these parameters with the local mechanical behavior