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Abstract: Composite materials are largely used for structural applications, thanks to their high strength-to-weight ratios. However, it is difficult to make accurate estimations on their mechanical behavior, as it is affected by several factors, involved both in the manufacturing process and in the experimental testing. In this study, GFRP laminates, with different stacking sequences, are tested under static loading conditions. During testing, thermal analyses are also performed by means of a thermal camera, obtaining an energetic parameter (i.e. the temperature) useful for the evaluation of damage. The thermographic method allows both qualitative and quantitative analyses to be performed in a relatively short time. Besides thermal analyses, damage is also assessed by means of static tests, interrupted at different load levels, and followed by stiffness reduction measurements and microscopic analyses, allowing for a comparison of the obtained results. [Copyright &y& Elsevier]

Abstract: Basalt reinforced composites are recently developed materials. These mineral amorphous fibres are a valid alternative to carbon fibres for their lower cost, and to glass fibres for their strength. In order to use basalt reinforced composites for structural applications, it is necessary to perform a mechanical characterisation. With this aim in the present work experimental results of several static and fatigue tests are described. Two polymeric matrices are taken into account, vinylester and epoxy, to assess their influence on the evaluated parameters. In parallel to these mechanical tests, also the thermal answer of the specimens to mechanical loads is evaluated by means of thermography. This experimental technique allows defining the composite local heating during the application of mechanical loads and its behaviour in details. Final discussion on obtained results is proposed focussing the attention on basalt fibre composite behaviour, and comparing mechanical properties of BFRP with other composite materials in glass and carbon fibres. [Copyright &y& Elsevier]

Abstract: Aim of this work is to test and understand the mechanical behaviour, in multi-axial stress conditions, of a composite material (E-glass reinforce fibres and vinyl-ester matrix) used to build a structural component: a corner beam of bus cabin. A series of experimental tests is performed on specimens cut out from this beam. Different unidirectional (UD) fibres orientations with respect to the direction of load application are considered: longitudinal (0°), normal (90°), inclined at 30° and 45°. Static and fatigue characterization are carried out to identify the mechanical behaviour in terms of σ–N curves. Obtained fatigue data are then interpolated by fitting the parameters required for multi-axial models of fatigue life estimation. A final comparison with the literature data is included, proposing a simple tool to evaluate the damage evolution of E-glass reinforced composites during fatigue life. [Copyright &y& Elsevier]

Abstract: The mechanism underlying plasticity-induced shielding of a crack tip under fatigue loading has been already experimentally investigated by means of photoelasticity using a recently-developed mathematical model which considers stress field near the crack tip and along the flanks. Stress intensification factors have also been defined to describe shielding effects on the applied elastic field. In this paper a new application of this model is developed through a numerical simulation of the experimental tests, which were previously performed. The study is aimed to analyze the shielding effect related to constant amplitude cycling loading and a single overload peak, considering numerical simulation. By means of the models developed by XFEM technique, the plastic region is reproduced finding a good agreement with the experimental data, and a systematic procedure is proposed to evaluate the stress intensity factors. A good correspondence is found by comparing the numerical with the experimental parameters, obtained from the mathematical model. [Copyright &y& Elsevier]

Abstract: The aim of this work is the fatigue design of a structural component manufactured in composite materials. The use of composite materials in structural applications implies that the reliability and safety requirements are met, in particular from a point of view of the fatigue life. A bus component is considered: the composite material is obtained by means of the pultrusion technique: the longitudinal reinforcement is glass fibre, while the matrix is polyester resin. At first, a static and fatigue characterization of the pultruded composite is performed to identify the mechanical behaviour along the fibres and in the normal direction, following an extensive testing programme on specimens. During the fatigue tests, the variation of the elastic modulus and the residual strength are monitored to characterize the damage; further experimental tests are performed to fit parameters required for models of fatigue life prevision. Fatigue bending tests are performed on the component, showing crack propagation through the section: a check at the SEM is performed to identify the main internal type of damage. A final comparison with a numerical simulation is proposed: this numerical model will be useful for the optimal fatigue design of the section. [Copyright &y& Elsevier]

Abstract: This paper proposes a numerical approach devoted to the investigation of the sub-surface crack propagation mechanism in gear pairs having crossing axis (i.e. hypoid gears). Starting from an accurate 3D description of the complex gear tooth geometry, a numerical analysis carried out by means of an advanced contact solver allows obtaining, over the entire meshing cycle, the contact pressure distribution and the displacement field in the un-cracked tooth. Then, such displacements are applied as boundary conditions to a second finite element model of the cracked zone, being the aim the stress intensity factors calculation for the modes I, II, III along the crack front. At this point it is possible to examine the crack growth mechanism: the maximum shear SIF range and the maximum tensile SIF range are computed and considerations about direction of crack propagation are drawn. As application of this approach, a circular sub-surface crack in a real hypoid gear of a truck differential transmission is analysed. [Copyright &y& Elsevier]

The pathogenesis of amyotrophic lateral sclerosis (ALS) is poorly understood. Increased levels of free radicals derived from nitric oxide (NO), the product of nitric oxide synthase (NOS), may damage mitochondrial function leading to motor neurone death. Previous studies demonstrated a specific impairment of mitochondrial function in skeletal muscle of ALS patients. In order to verify a pathogenetic relationship between neuronal NOS (nNOS) and mitochondrial function, we studied nNOS expression by Western blot and mitochondrial enzyme activity by spectrophotometric assays in muscle biopsies of 16 sporadic ALS patients and 16 controls subjects. We observed a reduced activity of respiratory chain complexes with mitochondrial encoded subunits and a lower nNOS amount in ALS muscles. There was a direct correlation between levels of nNOS and values of mitochondrial enzymes function. In ALS muscles we found normal levels of manganese superoxide dismutase (SOD2) that is assumed as related to mitochondrial DNA abnormalities. Our data suggest a beneficial role for NO to mitochondrial function and lead to the hypothesis of a common oxidative damage in motor neurones and skeletal muscle in sporadic ALS patients. [ABSTRACT FROM AUTHOR]

Abstract: Aim of this paper is to propose a numerical tool able to compute the stress intensity factor for the Mode I, II and III along the front of any subsurface cracks found in spiral and hypoid gear teeth, allowing to assess the criticality of the crack itself. The described approach is based on two steps: firstly the contact pressures in the un-cracked teeth are efficiently computed by an advanced contact solver; in this way the complex tooth geometry and the intricate meshing condition can be accurately considered; then, the displacements field due to those pressures is applied as boundary conditions to a finite element model of the cracked zone and the SIFs are efficiently computed. This information, together with the knowledge of the ΔK threshold value of the material, makes possible to decide whether the defect is acceptable and to evaluate the conditions of propagation. [Copyright &y& Elsevier]

Shelling is the term used to describe the loss of part of the tread of a railway wheel as the result of the initiation and growth of a fatigue crack from an internal defect in the rim. Shelling makes the wheel unserviceable and to prevent it, railway wheels are periodically subjected to non-destructive testing. However in order to assess the criticality of any cracks found, it is necessary to know the modes I, II and III stress intensity factors of the crack.In this paper a versatile approach for the analysis of internal cracks in wheels under Hertzian loads is described. It is based on the analytical calculation of the displacement field in the wheel and on imposing it as boundary condition in a finite element analysis of the wheel zone close to the crack.Experimental tests were executed on photoelastic models to validate the results. A new technique was developed to naturally obtain an internal crack in the epoxy resin model. The stress-freezing technique was employed to elaborate the photoelastic fringes and to obtain the stress intensity factors. The numerical and the experimental results are critically discussed and their comparison shows an interesting and encouraging agreement. [Copyright &y& Elsevier]

In this paper the problem of predicting and optimising the fatigue strength of shot peened specimens is dealt with. A series of notched cylindrical specimens, peened by using different parameters, was fatigue tested, being the aim to determine the improvement of the fatigue limit of the treated specimens. After the tests, the specimens were observed at the SE microscope and non-propagating microcracks were found. On the basis of this experimental evidence it was considered that the fatigue alleviation due to shot peening is mainly due to the ability of stopping crack propagation. A finite element procedure of the cracked notched specimens was established, with the aim of calculating the stress intensity factor including the applied load, the residual stresses and the contact between the crack faces. The results enable the prediction of the improvement of fatigue strength due to shot peening. [Copyright &y& Elsevier]

The most recent trend in power transmission design considers the damage-tolerant approach as one of the methods to obtain safe, reliable and light systems. This means that components containing cracks must be considered and analysed to understand the conditions that cause critical cracks and defects and their dimensions. In this paper a cracked tooth of an automotive gearwheel is considered. A numerical procedure (based on the slice synthesis weight function method) to calculate the stress intensity factors of curved cracks due to bending loads is illustrated. The results are compared with those obtained by expensive finite element calculations. The agreement is satisfactory and the proposed technique proves to be very attractive from the point of view of time saving. One example of an application to fatigue design practice is provided, namely the analysis of fatigue crack propagation in surface-treated gears. The results show the role played by residual stresses induced by carburizing and shot peening. [ABSTRACT FROM AUTHOR]

The present work aims to model the fracture mechanical behavior of a high-strength low carbon steel, AISI 4130 operating in hydrogen contaminated environment. The study deals with the development of 2D finite element cohesive zone model (CZM) reproducing a toughness test. Along the symmetry plane over the crack path of a C(T) specimen a zero thickness layer of cohesive elements are implemented in order to simulate the crack propagation. The main feature of this kind of model is the definition of a traction-separation law (TSL) that reproduces the constitutive response of the material inside to the cohesive elements. Starting from a TSL calibrated on hydrogen non-contaminated material, the embrittlement effect is simulated by reducing the cohesive energy according to the total hydrogen content including the lattice sites (NILS) and the trapped amount. In this perspective, the proposed model consists of three steps of simulations. First step evaluates the hydrostatic pressure. It drives the initial hydrogen concentration assigned in the second step, a mass diffusion analysis, defining in this way the contribution of hydrogen moving across the interstitial lattice sites. The final stress analysis, allows getting the total hydrogen content, including the trapped amount, and evaluating the new crack initiation and propagation due to the hydrogen presence. The model is implemented in both plane strain and plane stress configurations; results are compared in the discussion. From the analyses, it resulted that hydrogen is located only into lattice sites and not in traps, and that the considered steel experiences a high hydrogen susceptibility. By the proposed procedure, the developed numerical model seems a reliable and quick tool able to estimate the mechanical behavior of steels in presence of hydrogen. [ABSTRACT FROM AUTHOR]

The sandwich panel structures have been widely used in many industrial applications because of their high mechanical properties. The middle layer of these structures is very important factor in controlling and enhancing their mechanical performance under various loading scenarios. The re-entrant lattice configurations, are prominent candidates that can be used as the middle layer in such sandwich structures because of several reasons namely the simplicity in tuning their elastic (e.g., values of Poisson's ratio and elastic stiffness) and plastic (e.g., high strength-to-weight ratio) properties by only adjusting the geometrical features of the constituting unit cells. Here, we investigated the response of a three-layered sandwich plate with a re-entrant core lattice under flexural bending using analytical (i.e., zig-zag theory), computational (i.e., finite element) and experimental tests. We also analyzed the effects of different geometrical parameters (e.g., angle, thicknesses, and length to the height ratio of unit cells) of re-entrant lattice structures on the overall mechanical behavior of sandwich structures. We found that the core structures with auxetic behavior (i.e., negative Poisson's ratio) resulted in a higher bending strength and a minimum out-of-plane shear stress as compared to those with conventional lattices. Our results can pave way in designing advanced engineered sandwich structures with architected core lattices for aerospace and biomedical applications. [ABSTRACT FROM AUTHOR]

ABSTRACT Many biological materials are generally considered composites, made of relatively weak constituents and with a hierarchical arrangement, resulting in outstanding mechanical properties, difficult to be reached in man-made materials. An example is human bone, whose hierarchical structure strongly affects its mechanical performance, toughness in particular, by activating different toughening mechanisms occurring at different length scales. At microscale, the principal toughening mechanism occurring in bone is crack deflection. Here, we study the structure of bone and we focus on the role of the microstructure on its fracture behaviour, with the goal of mimicking it in a new composite. We select the main structural features, the osteons, which play a crucial role in leading to crack deflection, and we reproduce them in a synthetic composite. The paper describes the design, manufacturing and characterization of a newly designed composite, whose structure is inspired to the Haversian structure of cortical bone, and that of a classic laminate developed for comparative reasons. We conclude with a critical discussion on the results of the mechanical tests carried out on the new composite and on the comparative laminate, highlighting strengths and shortcomings of the new biomimetic material. [ABSTRACT FROM AUTHOR]

Dealing with composites in polymeric matrix, the pultruded ones are among the more suitable for large production rates and volumes. For this reason, their use is increasing also in structural applications in civil and mechanical engineering. However, their use is still limited by the partial knowledge of their fatigue behaviour; in many applications it is, indeed, required a duration of many millions of cycles, while most of the data that can be found in literature refer to a maximum number of cycles equal to 3 millions. In this paper a pultruded composite used for manufacturing structural beams is considered and its mechanical behaviour characterized by means of static and high-cycle fatigue tests. The results allowed to determine the S-N curve of the material and to assess the existence of a fatigue limit. Observations at the scanning electronic microscope (SEM) allowed to evaluate the damage mechanisms involved in the static and fatigue failure of the material. [ABSTRACT FROM AUTHOR]

Abstract: The wheel–rail interface is fundamental for the comfort and the safety of the train. For this reason the wheel and the rail surface condition are checked with periodic non-destructive controls. The presence of a crack can be tolerated if we are able to predict its evolution by using fracture mechanics concepts. The problem is complicated by the fact that surface cracks propagate in mixed mode conditions. In this paper a photoelastic technique is presented to experimentally determine the stress intensity factors in a model of cracked rail under contact loads. The first results are critically discussed. [Copyright &y& Elsevier]

Abstract: A numerical/analytical approach is proposed to determine the stress intensity factors K I, K II, and K III of a 3D internal crack. The main point of this approach is the meshing technique that can model very sharp crack fronts. The meshing technique is based on an elliptical coordinate transformation that starts from a circular crack. It allows the obtainment of a curved crack front with elements normal to the crack front. Remarkable accuracy can be obtained for elliptical crack fronts with axes ratio smaller that 0.01. Accuracy demonstration is provided for cylindrical element with an inclined internal crack subjected to uni-axial tension. This case corresponds to crack propagation for all three modes of loading, the solution of which can checked with references’ results. [Copyright &y& Elsevier]

Abstract: The ever increasing research of performances and lightness leads engineers and manufactures toward the development of heavily loaded components, subjected to multiaxial fatigue loads, made of materials with improved surface mechanical properties. In these cases it is not rare the development of internal cracks, whose propagation involves mixed-mode conditions; where an accurate prediction of the growth rate and of the crack path requires the knowledge of the stress intensity factors concerning modes I, II and III. In this paper, an original method for the experimental determination of these quantities is described. It is based on the photoelastic technique and allows to obtain internal cracks with regular shape without using any cutting device. [Copyright &y& Elsevier]

Up until recently, the rational design of mechanical metamaterials has usually involved devising geometrical arrangements of micro-architectures that deliver unusual properties on the macro-scale. A less explored route to rational design is spatially distributing materials with different properties within lattice structures to achieve the desired mechanical properties. Here, we used computational models and advanced multi-material 3D printing techniques to rationally design and additively manufacture multi-material cellular solids for which the elastic modulus and Poisson's ratio could be independently tailored in different (anisotropic) directions. The random assignment of a hard phase to originally soft cellular structures with an auxetic, zero Poisson's ratio, and conventional designs allowed us to cover broad regions of the elastic modulus-Poisson's ratio plane. Patterned designs of the hard phase were also used and were found to be effective in the independent tuning of the elastic properties. Close inspection of the strain distributions associated with the different types of material distributions suggests that locally deflected patterns of deformation flow and strain localizations are the main underlying mechanisms driving the above-mentioned adjustments in the mechanical properties. [ABSTRACT FROM AUTHOR]

Abstract: Finite element method is used to analyze a rail with a vertical bottom up crack at its foot, under the axle load and surface traction of a wheel. The possibility of crack formation at the foot of the rail in the neighborhood of a welding connection is discussed. A brief review on the importance of T‐stress in brittle fracture is presented. Seven cases with different locations of the crack relative to rail's sleeper contact region are considered. Numerous positions of the wheel are considered, and in each case, 3 crack parameters KI, KII, and T‐stress are calculated. Then, the biaxiality ratio and the mixity parameter for each loading and crack condition are calculated. It is shown that the location of crack and wheel can create mixed mode loading in the cracked rail and that the magnitude of crack tip parameters are strongly dependent on these geometric variables. In particular, the magnitudes of T‐stress and biaxiality ratio are significant in some cases. The effect of friction between the crack faces in the presence of compressive mode I loading on the mode II stress intensity factor is studied. Under mixed mode loading, due to the axle load and surface traction, the most critical condition is the formation of vertical cracks near the sleeper contact region. [ABSTRACT FROM AUTHOR]

The elastic properties of mechanical metamaterials are direct functions of their topological designs. Rational design approaches based on computational models could, therefore, be used to devise topological designs that result in the desired properties. It is of particular importance to independently tailor the elastic modulus and Poisson's ratio of metamaterials. Here, we present patterned randomness as a strategy for independent tailoring of both properties. Soft mechanical metamaterials incorporating various types of patterned randomness were fabricated using an indirect additive manufacturing technique and mechanically tested. Computational models were also developed to predict the topology-property relationship in a wide range of proposed topologies. The results of this study show that patterned randomness allows for independent tailoring of the elastic properties and covering a broad area of the elastic modulus-Poisson's ratio plane. The uniform and homogenous topologies constitute the boundaries of the covered area, while topological designs with patterned randomness fill the enclosed area. [ABSTRACT FROM AUTHOR]

Tetrabromobisphenol A (2,2-bis(3,5-dibromo-4-hydroxyphenyl propane-TBBPA) is the most produced brominated flame retardant, detected in the environment and in biological samples. TBBPA shares structural similarities with thyroid hormones (THs), and it has been shown to interfere with different aspects of TH physiology, this raising concern on its possible effects as an endocrine disruptor in humans and wildlife. THs play a major role in lipid metabolism, with the liver representing one of their main target tissues. At the cellular level, THs act through interactions with TH receptors (TRs), as well as through TR-independent mechanisms. Rat hepatoma FaO cells (a liver cell line defective for functional TRs) overloaded with lipids have been utilized as a model to investigate the anti-steatotic effects of THs in the hepatocyte. In this work, the possible effects of TBBPA in steatotic FaO cells were investigated. Exposure to TBBPA for 24h reduced triglyceride (TAG) content and the size of lipid droplets (LDs); similar effects were obtained with equimolar doses (10−6M) of T3 (3,3′,5-1L 1-triiodothyronine). TBBPA and T3 showed common effects on transcription of genes involved in lipid homeostasis. In particular, TBBPA mainly up-regulated mRNA levels for LD-associated oxidative tissue-enriched PAT protein (OXPAT), peroxisome proliferator-activated receptor (PPAR) isoform β/δ, and the mitochondrial uncoupling protein 2 (UCP2). The results demonstrate that TBBPA can decrease lipid accumulation in steatotic cells through stimulation of oxidative pathways. These data identify novel thyromimetic actions of TBBPA at the cellular level. [ABSTRACT FROM AUTHOR]

Abstract: In the presence of gaseous hydrogen or of H2S, metallic materials, such as carbon and low alloy steels, may suffer hydrogen damage and hydrogen embrittlement. In this paper the influence of hydrogen and low temperature on fatigue crack growth properties of two pipeline materials, X65 micro-alloyed and F22 low alloy steels, is studied. An electrochemical charging method has been adopted and fatigue propagation tests were carried out on hydrogen charged and uncharged specimens, by varying the test temperature and the frequency of the load application cycle. The experimental results show an evident effect of the hydrogen presence on the fatigue crack growth. The diffusion rate of hydrogen in the steels seems to be the most important parameter in order to explain the influence of temperature and frequency on the fatigue crack propagation rate. Fracture surface examination has been correlated with the results of mechanical testing. [Copyright &y& Elsevier]

Abstract: In the presence of H2S, metallic materials, such as carbon and low alloy steels, may suffer hydrogen damage and hydrogen embrittlement. Sour service materials must be used in compliance with international standards when fluids are classified as sour. Gas transporting pipes in low temperature environment, during the shutdown and the subsequent re-starting operations, are exposed to very low temperatures (T =−40°C). In presence of high H2S content in the gas the risk of brittle failure can be increased due to the effect of hydrogen on steel toughness. In this paper the influence of hydrogen and low temperature on mechanical properties of two pipeline materials, X65 micro-alloyed and F22 low alloy steels, is studied. An electrochemical hydrogen charging method has been setup, avoiding any critical condition from the point of view of preparation, safety and disposal. Diffusible hydrogen content of steels is in the range 0.6 to 2ppm. Charpy and J–R curve tests were carried out in the range from room temperature to T =−120°C. Hydrogen affects mechanical properties of the tested materials, mainly reducing fracture toughness in J integral tests, while little influence has been observed in Charpy tests. Fracture surface examination confirms the results of mechanical testing. [Copyright &y& Elsevier]

Abstract: Myotonic dystrophy type 1 (DM1) is a complex multisystemic disorder caused by an expansion of a CTG repeat located at the 3′ untranslated region (UTR) of DMPK on chromosome 19q13.3. Aberrant messenger RNA (mRNA) splicing of several genes has been reported to explain some of the symptoms of DM1 including insulin resistance, muscle wasting and myotonia. In this paper we analyzed the expression of the MYH14 mRNA and protein in the muscle of DM1 patients (n=12) with different expansion lengths and normal subjects (n=7). The MYH14 gene is located on chromosome 19q13.3 and encodes for one of the heavy chains of the so called class II “nonmuscle” myosins (NMHCII). MYH14 has two alternative spliced isoforms: the inserted isoform (NMHCII-C1) which includes 8 amino acids located in the globular head of the protein, not encoded by the non inserted isoform (NMHCII-C0). Results showed a splicing unbalance of the MYH14 gene in DM1 muscle, with a prevalent expression of the NMHCII-C0 isoform more marked in DM1 patients harboring large CTG expansions. Minigene assay indicated that levels of the MBNL1 protein positively regulates the inclusion of the MYH14 exon 6. Quantitative analysis of the MYH14 expression revealed a significant reduction in the DM1 muscle samples, both at mRNA and protein level. No differences were found between DM1 and controls in the skeletal muscle localization of MYH14, obtained through immunofluorescence analysis. In line with the thesis of an “RNA gain of function” hypothesis described for the CTG mutation, we conclude that the alterations of the MYH14 gene may contribute to the DM1 molecular pathogenesis. [Copyright &y& Elsevier]

The mechanisms underlying the plasticity-induced shielding of a crack tip during fatigue are investigated at both constant amplitude loading and in a case with a substantial single-cycle overload. A recently developed mathematical model of the stress field around the crack was fitted to maps of isochromatic fringe data obtained from phase-stepped photoelastic images captured during crack opening and closing in a polycarbonate compact tension specimen. The model is derived using Muskhelishvili's approach and contains additional terms to describe the interfacial shear at the elastic-plastic boundary around the crack and the normal stresses retarding crack growth. These stress fields are characterized by stress intensity factors, K and K, respectively, which during and after the overload exhibited substantial changes in behaviour that can be explained in terms of the development of an enlarged plastic zone. [ABSTRACT FROM AUTHOR]

Myotonic dystrophy (DM) is caused by a (CTG)n expansion in the 3′-untranslated region of DMPK gene. Mutant transcripts are retained in nuclear RNA foci, which sequester RNA binding proteins thereby misregulating the alternative splicing. Controversy still surrounds the pathogenesis of the DM1 muscle distress, characterized by myotonia, weakness and wasting with distal muscle atrophy. Eight primary human cell lines from adult-onset (DM1) and congenital (cDM1) patients, (CTG)n range 90–1800, were successfully differentiated into aneural-immature and contracting-innervated-mature myotubes. Morphological, immunohistochemical, RT-PCR and western blotting analyses of several markers of myogenesis indicated that in vitro differentiation–maturation of DM1 myotubes was comparable to age-matched controls. In all pathological muscle cells, (CTG)n expansions were confirmed by long PCR and RNA fluorescence in situ hybridization. Moreover, the DM1 myotubes showed the splicing alteration of insulin receptor and muscleblind-like 1 (MBNL1) genes associated with the DM1 phenotype. Considerable myotube loss and atrophy of 15-day-differentiated DM1 myotubes indicated activated catabolic pathways, as confirmed by the presence of apoptotic (caspase-3 activation, cytochrome c release, chromatin fragmentation) and autophagic (P62/LC3) markers. Z-VAD treatment significantly reduced the decrease in myonuclei number and in average width in 15-day-differentiated DM1 myotubes. We thus propose that the muscle wasting typical in DM1 is due to impairment of muscle mass maintenance–regeneration, through premature apoptotic–autophagic activation, rather than altered myogenesis. [ABSTRACT FROM AUTHOR]

Abstract: This paper describes the failure analysis carried out on a 12″-non-integral pipeline collet connector, joining a 12″-pipeline with an offshore platform riser. This kind of joint allows to seal the two extremity of the pipe, by using a locking ring that slides pushed by a hydraulic jack; this movement causes the sliding of 12 fingers that allows the pipes to contact. During service, the failure of 10 fingers occurred. In order to figure out the reasons of this failure, 3-D finite element stress analysis and experimental investigation have been carried out. This latter regarded the chemical composition and the microstructure of the finger material, the analysis of the fracture surfaces and the measurement of material fracture toughness, while the FE stress analysis was executed in order to find the most stressed zones of the fingers under the service condition. All these studies allow to conclude that the stress value in the critical section together with the experimentally determined toughness can justify the finger failure. [Copyright &y& Elsevier]

• Experimental fatigue tests on ex-vivo porcine trabecular bone samples are performed. • Fatigue-induced damage on bone microarchitecture is studied by means of μCT imaging. • A new fatigue model based on specimen-specific effective area is proposed. Bone quantity and quality are considered the main predictors of bone mechanical properties (i.e., strength and fracture resistance). These factors deal with the morphology and chemical composition of bone and can be assessed by non-invasive techniques such as dual-energy x-ray absorptiometry (DXA), providing the bone mineral density (BMD) and the trabecular bone score (TBS). These parameters, and in particular BMD, are currently used as clinical predictors of fracture risk but do not provide information regarding the fatigue life. Bone is continuously subjected to fatigue loading and fatigue-induced damage can be crucial in fragility fractures. To probe the effect of fatigue-induced damage on bone microarchitecture and elucidate the effect of such damage on the bone clinical parameters, we combined fatigue testing on ex-vivo porcine trabecular bone samples with DXA measurements and μCT imaging. In addition, we performed interrupted cyclic tests at different load levels and measured fatigue-induced damage accumulation in the form of stiffness degradation. We also highlighted the change of clinical and microstructural parameters during the accumulation of fatigue-induced damage in interrupted fatigue tests. Our results suggest that the parameters obtained from the current non-invasive diagnostic protocols (i.e. μCT and DXA) are not able to assess the amount of fatigue-induced damage. This can be due to the fact that such techniques provide global parameters, whereas fatigue-induced damage is a local phenomenon, closely connected to the microarchitecture. [ABSTRACT FROM AUTHOR]

Objective: Mesenchymal stem cells (MSCs) display a remarkable ability to modulate the immune response and protect the central nervous system (CNS) mainly through the release of soluble factors in a paracrine fashion, affecting the functional behavior of cells in the tissues. Here we investigated the effect of the interaction between MSC and microglia in vitro and we dissected the molecular and cellular mechanisms of this cross talk. Materials and Methods: In this study, we addressed the in vitro effect of MSC on microglia and we dissected the molecular and cellular mechanisms of these interactions demonstrating that MSC can switch microglia from a detrimental behavior dominated by the release of proinflammatory molecules to a neuroprotective phenotype associated with the production of anti-inflammatory and trophic factors. Moreover we showed that MSC induce functional changes on microglia as depicted by modifications in intracellular calcium concentration and phagocytic activity. Finally we provided compelling evidence that CX3CL1 released by MSC plays a major role in inducing these beneficial effects on microglia. Results: We demonstrated that MSC impair microglia activation by inflammatory cues through the inhibition of the expression and release of inflammatory molecules and stress associated proteins. We showed that MSC significantly increase microglial expression and release of molecules associated with a neuroprotective phenotype such as CX3CR1, NURR1, CD200R and IGF1. Interestingly MSC can enhance functional changes on microglia as depicted by the increase of intracellular calcium concentration and phagocytic activity. This last event is associated with an increased expression of TREM2, an innate immune receptor involved in phagocytosis in the absence of inflammation. The observed effects on CX3CR1-expressing microglia are due to the release of CX3CL1 by MSC, driven by inflammatory signals, as demonstrated by the reversal of the observed results when CX3CL1 expression was silenced in MSC or its release was blocked. Last, we showed that exogenous CX3CL1 induce phenotypic and functional changes of microglia similar to those induced by MSC. Conclusion: These findings demonstrate that MSC instruct, through the release of CX3CL1, microglia responsiveness to pro-inflammatory signals by modulating constitutive "calming" receptors, typically expressed by "steady-state microglia" thus switching microglia from a detrimental phenotype to a neuroprotective one. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs are highly conserved, noncoding RNAs involved in post-transcriptional gene silencing. They have been shown to participate in a wide range of biological processes, including myogenesis and muscle regeneration. The goal of this study is to test the hypothesis that myo-miRs (myo = muscle + miR = miRNA) expression is altered in muscle from patients affected by myotonic dystrophy type 1 (DM1), the most frequently inherited neuromuscular disease in adults. In order to gain better insights about the role of miRNAs in the DM1 pathogenesis, we have also analyzed the muscular expression of miR-103 and miR-107, which have been identified in silico as attractive candidates for binding to the DMPK mRNA.Methods: To this aim, we have profiled the expression of miR-133 (miR-133a, miR-133b), miR-1, miR-181 (miR-181a, miR-181b, miR-181c) and miR-206, that are specifically induced during myogenesis in cardiac and skeletal muscle tissues. miR-103 and miR-107, highly expressed in brain, heart and muscle have also been included in this study. QRT-PCR experiments have been performed on RNA from vastus lateralis biopsies of DM1 patients (n = 7) and control subjects (n = 4). Results of miRNAs expression have been confirmed by Northern blot, whereas in situ hybridization technique have been performed to localize misexpressed miRNAs on muscle sections from DM1 and control individuals.Results: Only miR-206 showed an over-expression in 5 of 7 DM1 patients (threshold = 2, fold change between 1.20 and 13.22, average = 5.37) compared to the control group. This result has been further confirmed by Northern blot analysis (3.37-fold overexpression, R2 = 0.89). In situ hybridization localized miR-206 to nuclear site both in normal and DM1 tissues. Cellular distribution in DM1 tissues includes also the nuclear regions of centralized nuclei, with a strong signal corresponding to nuclear clumps.Conclusions: This work provides, for the first time, evidences about miRNAs misexpression in DM1 muscle tissues, adding a new element in the pathogenesis of this complex genetic disease. [ABSTRACT FROM AUTHOR]