The n-acetyl phenylalanine glucosamine derivative attenuates the inflammatory/catabolic environment in a chondrocyte-synoviocyte co-culture system

Osteoarthritis (OA), the most prevalent degenerative joint disease, still lacks a true disease-modifying therapy. The involvement of the NF-κB pathway and its upstream activating kinases in OA pathogenesis has been recognized for many years. The ability of the N-acetyl phenylalanine glucosamine derivative (NAPA) to increase anabolism and reduce catabolism via inhibition of IKKα kinase has been previously observed in vitro and in vivo. The present study aims to confirm the chondroprotective effects of NAPA in an in vitro model of joint OA established with primary cells, respecting both the crosstalk between chondrocytes and synoviocytes and their phenotypes. This model satisfactorily reproduces some features of the previously investigated DMM model, such as the prominent induction of ADAMTS-5 upon inflammatory stimulation. Both gene and protein expression analysis indicated the ability of NAPA to counteract key cartilage catabolic enzymes (ADAMTS-5) and effectors (MCP-1). Molecular analysis showed the ability of NAPA to reduce IKKα nuclear translocation and H3Ser10 phosphorylation, thus inhibiting IKKα transactivation of NF-κB signalling, a pivotal step in the NF-κB-dependent gene expression of some of its targets. In conclusion, our data confirm that NAPA could truly act as a disease-modifying drug in OA

Damage detection in composites by AI and high-order modelling surface-strain-displacement analysis

In the recent years, machine learning algorithms have been widely employed for structural health monitoring applications. As an example, Artificial Neu-ral Networks (ANN) could be useful in giving a precise and complete map-ping of damage distribution in a structure, including low-intensity or local-ized defects, which could be difficult to detected via traditional testing tech-niques. In this domain, Convolutional Neural Network (CNN) are employed in this work along with one-dimensional refined models based on the Carrera Unified formulation (CUF) for surface strain\displacement based damage detection in composite laminates. A layer-wise kinematic is adopted, while both an isotropic and orthotropic damage formulation is implemented. In de-tail, CUF-based finite element models have been exploited in combination with Monte Carlo simulations for the creation of a dataset of damage scenar-ios used for the training of the CNN. Therefore, the latter is fed with images of the strain or displacement field in a region of particular interest for each sample, which are subjected to the same boundary conditions. The trained ANN, given the strain\displacement mapping of an unknown structure, is therefore able to detect and classify all the damages within the structure, solving the so-called inverse problem

Component-wise damage detection by neural networks and refined FEs training

Multilayer perceptrons are utilized in this work for vibration-based damage detection of multicomponent aerospace structures. A back-propagation algorithm is utilized along with Monte Carlo simulations and advanced structural theories for training Artificial Neural Networks (ANN’s), which are able to detect and classify local damages in structures given the natural frequencies and the associated vibrations modes. The latter ones are feed into the network in terms of Modal Assurance Criterion (MAC), which is a scalar representing the degree of consistency between undamaged and damaged modal vectors. Dataset and ANN training process is carried out by means of Carrera Unified Formulation (CUF), according to which refined finite elements with component-wise capabilities can be implemented in a hierarchical and unified manner. The proposed results demonstrate that CUF-trained ANNs can approximate complete mapping of the damage distribution, even in case of low damage intensities and local defects in localized components (stringers, spar caps, webs, etc.

CUF-based Multiscale Analysis of Failure of Composite Laminates

The detection of failure onset and progression in composites requires the proper modeling of various mechanical behaviors at various scales. Furthermore, the necessity of virtual models of large structures and the nonlinear nature of failure demand computational efficiency without accuracy penalties. Over the last years, a set of modeling strategies based on refined structural theories has been developed via the Carrera Unified Formulation (CUF). Such developments range from Equivalent Single Layer (ESL) and Layer-Wise (LW) models for the macro- and mesoscale to the component-wise modeling of microscale. The computational efficiency and accuracy stem from the use of 1D or 2D models, node-dependent kinematics (NDK) and global-local strategies providing the complete 3D stress state necessary to capture failure in critical locations such as free-edges. The coupling with well-known models for micromechanics, progressive failure (including non-local methodologies based on peridynamics) and multiscale analyses led to promising outcomes with multifold reductions of computational times

fatigue crack propagation in a helicopter component subjected to impact damage

Abstract Damage tolerant methodology is increasingly used in aeronautical components, especially due the fact that the Aviation Regulation requires such an assessment in case an accidental damage occurs. At present, there is a strong and actual interest in applying such procedures to helicopter components that are subjected to high frequency cyclic loads. In this paper, an investigation on a damaged transmission shaft for a tail rotor transmission of an actual helicopter has been carried out focusing on the fatigue crack propagation. A complete sequence of experimental tests was performed in order to create an actual ballistic damage and to subsequently check the damage tolerant behaviour. The shaft was damaged by oblique ballistic impact and was subsequently subjected to torsional fatigue loading. During the fatigue cycles several cracks propagated from the ballistic damages. Both of these steps (impact and fatigue loading) were also simulated by a complex modelling approach based on Finite Element Models and fracture mechanics theory. The comparison between the experimental and numerical results shows a good agreement but it underlines the need for a very refined modelling technique capable to replicate all the features associated with the damage in order to reliably simulate the subsequent propagation phase

Free vibration analysis of simply supported beams with solid and thin-walled cross-sections using higher-order theories based on displacement variables

Solutions for undamped free vibration of beams with solid and thin-walled cross-sections are provided by using refined theories based on displacement variables. In essence, higher-order displacement fields are developed by using the Carrera unified formulation (CUF), and by discretizing the cross-section kinematics with bilinear, cubic and fourth-order Lagrange polynomials. Subsequently, the differential equations of motion and the natural boundary conditions are formulated in terms of fundamental nuclei by using CUF and the strong form of the principle of virtual displacements. The second-order system of ordinary differential equations is then reduced into a classical eigenvalue problem by assuming simply supported boundary conditions. The proposed methodology is extensively assessed for different solid and thin-walled metallic beam structures and the results are compared with those appeared in published literature and also checked by finite element solutions. The research demonstrates that: (i) the innovative 1D closed form CUF represents a reliable and compact method to develop refined beam models with solely displacement variables; (ii) 3D-like numerically exact solutions of complex structures can be obtained with ease; and (iii) the numerical efficiency of the present method is uniquely robust when compared to other methods that provide similar accuracies

The orbifold cohomology of moduli of genus 3 curves

In this work we study the additive orbifold cohomology of the moduli stack of smooth genus g curves. We show that this problem reduces to investigating the rational cohomology of moduli spaces of cyclic covers of curves where the genus of the covering curve is g. Then we work out the case of genus g=3. Furthermore, we determine the part of the orbifold cohomology of the Deligne-Mumford compactification of the moduli space of genus 3 curves that comes from the Zariski closure of the inertia stack of M_3.Comment: 29 pages, 2 figures. Minor changes, to appear in Manuscripta Mat

Stochastic characterization of multiscale material uncertainties on the fibre-matrix interface stress state of composite variable stiffness plates

This work analyses the stochastic response of fibre and matrix scale stresses of Variable Angle Tow (VAT) laminates affected by multiscale uncertainty defects. The aim is to evaluate the influence of the innermost constituents on the overall structural response via an accurate mechanical characterization of both macro- and microscales. The Carrera Unified Formulation (CUF) is employed to obtain two-dimensional (2D) and one-dimensional (1D) models for both scales. Indeed, 2D layer-wise (LW) and 1D component-wise (CW) approaches are adopted for the macroscale and the microscale, respectively. The use of 2D and 1D models proves to be convenient as a superior computational efficiency is reached, this aspect being of great importance as many analyses are necessary for uncertainty quantification. The numerical results demonstrate the validity of the proposed methodology to obtain an accurate description of the 3D stress state at the different scales. A special focus is made on the fibre-scale stresses and how they may vary when affected by multiscale uncertainty

Flour from sprouted wheat as a new ingredient in bread-making

Despite the nutritional and sensory improvements associated with sprouted grains, their use in baking has been limited until recently. Indeed, severe and uncontrolled grain sprouting induces high accumulations of enzymatic activities that negatively affect dough rheology and baking performance. In this study, wheat was sprouted under controlled conditions and the effects of enrichment (i.e. 15%, 25%, 33%, 50%, 75% and 100%) of the related refined flour (SWF) on dough rheological properties, baking performances and starch digestibility were assessed. Adding SWF to flour significantly decreased dough water absorption, development time, and stability during mixing, which suggests a weakening of the gluten network. However, no significant changes in mixing properties and gluten aggregation kinetics were measured from 25 to 75% SWF. Regardless of the amount added, SWF improved dough development and gas production during leavening. Decreases in gas retention did not compromise bread-making performances. The best result – in terms of bread volume and crumb porosity – was obtained with 50% SWF instead of using SWF alone. Interestingly, in 100 % SWF bread the slowly digestible starch fraction significantly increased