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The work shows correct procedures needed in order to gather reliable data from measurement of displacements versus axial load in a laboratory mounting of the Ilizarov external fixator. The mechanism of settling after load cycling is investigated. Detension under load is a major problem of wires. By means of vibration frequency measurements, tests on single wire allow determination of reduction in wire tension due to transverse loading: it is found that, almost independently from the amount of clamp tightening, the tension reaches a lower limit related only to the transverse load and not related to pretension. It is shown that, for higher clamp tightening torques, wire detension must be attributed to permanent plastic deformation of the wires; moreover, it is shown that the unavoidable errors in the spacing of the tensioned wires lead to marked decrease of their stiffness under transverse load., The mechanical stability of the wire fixator when subjected to loads was determined through an experiment relating displacements and axial loads. Vibration frequency measurements allowed the determination of reduction in wire tension due to transverse loading. The outcome of the tests showed that the tension reaches a lower limit related only to the transverse load and not to pretentsion or amount of clamp tightening.

Using matrix algebra, a mathematical model is formulated for a particular type of external fixator with wires (system developed by Ilizarov) for the treatment of bone fractures. The mathematical model is used to give a linear estimate of the stiffness under lateral and axial loads in a representative number of practical conditions. Relative displacements of the bone ends at the fracture site are calculated not only in the common case of a gap, but also for various angles of inclined sliding contact; in this case, a realistic load is applied and nonlinear stiffening of the wires under transversal loads is iteratively taken into account., The biomecanical stability of a fixator is analyzed and a set of coefficients and formulae is formulated to evaluate the stiffness of certain wire fixators. A mathematical model is developed and applied to provide a linear estimate of the stiffness of the fixator under lateral and axial stress. The formulae developed permits the simulation of any fixation geometry with the least computational efforts and shows the correlation between some variables and mechaniical properties of the fixator.

The virtual design of components undergoing thermo mechanical fatigue (TMF) and plastic strains is usually run in many phases. The numerical finite element method gives a useful instrument which becomes increasingly effective as the geometrical and numerical modelling gets more accurate. The constitutive model definition plays an important role in the effectiveness of the numerical simulation [1, 2] as, for example, shown in Figure 1. In this picture it is shown how a good cyclic plasticity constitutive model can simulate a cyclic load experiment. The component life estimation is the subsequent phase and it needs complex damage and life estimation models [3-5] which take into account of several parameters and phenomena contributing to damage and life duration. The calibration of these constitutive and damage models requires an accurate testing activity. In the present paper the main topic of the research activity is to investigate whether the parameters, which result to be influent in the experimental activity, influence the numerical simulations, thus defining the effectiveness of the models in taking into account of all the phenomena actually influencing the life of the component. To obtain this aim a procedure to tune the parameters needed to estimate the life of mechanical components undergoing TMF and plastic strains is presented for commercial steel. This procedure aims to be easy and to allow calibrating both material constitutive model (for the numerical structural simulation) and the damage and life model (for life assessment). The procedure has been applied to specimens. The experimental activity has been developed on three sets of tests run at several temperatures: static tests, high cycle fatigue (HCF) tests, low cycle fatigue (LCF) tests. The numerical structural FEM simulations have been run on a commercial non linear solver, ABAQUS®6.8. The simulations replied the experimental tests. The stress, strain, thermal results from the thermo structural FEM simulations have been used to assess specimens life by means of several damage models implemented in two dedicated softwares. One of them is commercial life estimation software and the second one has been developed by the present research group. The life estimations results obtained from the two softwares and from the damage models have been compared with experimental duration in different test conditions. A statistical analysis of life estimation results allowed evaluating the effectiveness of the procedure.

ABSTRACT The micro-mechanical model for fatigue crack initiation proposed by K. Tanaka and A. Mura in 1981 is analysed and rewritten in a different form, which allows highlighting its formal analogy with an empirical model previously introduced by W. Weibull in 1934. The result is a unified phenomenological model that can be used for both fatigue data fitting and life predictions. Strengths and limitations of the model are discussed and a case study of experimental data fitting is presented. In the example application, the model parameters of 18NiCrMo5 carburized steel are obtained through the likelihood maximization over fatigue test data. A comparison between the estimated parameters for the material in two different conditions (untreated and deep cryogenically treated) is then given to confirm the micro-mechanical changes that should be induced by the cold processing and to point out the direction for further investigations. [ABSTRACT FROM AUTHOR]

A simple demonstrator for a magnetic levitation vehicle (MagLev) based on repulsive suspension forces generated by permanent magnets is presented. The lateral and yaw motions are stabilized using controlled electromagnets. A mathematical model, aimed mainly at defining the control strategy, has been developed and then experimentally validated using the demonstrator. Two different control strategies have been tested, namely a zero position error and a zero average current control strategy. Both proved to grant a stable behaviour and to effectively counteract external force disturbances. This demonstrator will be used in future research on MagLev vehicles but also on magnetic suspensions in general. [ABSTRACT FROM AUTHOR]

The endocannabinoid system (ECS) has emerged as a potential therapeutic target in veterinary medicine due to its involvement in a wide range of physiological processes including pain, inflammation, immune function, and neurological function. Modulation of the ECS receptors has been shown to have anti-inflammatory, analgesic, and immunomodulatory effects in various animal models of disease, including dogs with osteoarthritis. The goal of this study was to identify and compare the cellular expression and distribution of cannabinoid receptor type 1 (CB1R) and type 2 (CB2R) and the cannabinoid-related G protein-coupled receptor 55 (GPR55) on the synovial cells of hip and stifle joints of seven dogs of different breeds without overt signs of osteoarthritis (OA). The synovial membranes of seven hips and seven stifle joints were harvested post mortem. The expression of the CB1R, CB2R, and GPR55 present in the synovial tissues was investigated using qualitative and quantitative immunofluorescence and Western blot (Wb) analysis. Synoviocytes of the stifle and hip joints expressed CB1R, CB2R, and GPR55 immunoreactivity (IR); no significant differences were observed for each different joint. Cannabinoid receptor 2- and GPR55-IR were also expressed by macrophages, neutrophils, and vascular cells. The ECS receptors were widely expressed by the synovial elements of dogs without overt signs of OA. It suggests that the ECS could be a target for the therapeutic use of Cannabis sativa extract in canine arthropathies.

The complex pathobiology of lung cancer, and its spread worldwide, has prompted research studies that combine radiomic and genomic approaches. Indeed, the early identification of genetic alterations and driver mutations affecting the tumor is fundamental for correctly formulating the prognosis and therapeutic response. In this work, we propose a radiogenomic workflow to detect the presence of KRAS and EGFR mutations using radiomic features extracted from computed tomography images of patients affected by lung adenocarcinoma. To this aim, we investigated several feature selection algorithms to identify the most significant and uncorrelated sets of radiomic features and different classification models to reveal the mutational status. Then, we employed the SHAP (SHapley Additive exPlanations) technique to increase the understanding of the contribution given by specific radiomic features to the identification of the investigated mutations. Two cohorts of patients with lung adenocarcinoma were used for the study. The first one, obtained from the Cancer Imaging Archive (TCIA), consisted of 60 cases (25% EGFR, 23% KRAS); the second one, provided by the Azienda Ospedaliero-Universitaria 'Ospedali Riuniti' of Foggia, was composed of 55 cases (16% EGFR, 28% KRAS). The best-performing models proposed in our study achieved an AUC of 0.69 and 0.82 on the validation set for predicting the mutational status of EGFR and KRAS, respectively. The Multi-layer Perceptron model emerged as the top-performing model for both oncogenes, in some cases outperforming the state of the art. This study showed that radiomic features can be associated with EGFR and KRAS mutational status in patients with lung adenocarcinoma.

Maintenance scheduling is a fundamental element in industry, where excessive downtime can lead to considerable economic losses. Active monitoring systems of various components are ever more used, and rolling bearings can be identified as one of the primary causes of failure on production lines. Vibration signals extracted from bearings are affected by noise, which can make their nature unclear and the extraction and classification of features difficult. In recent years, the use of the discrete wavelet transform for denoising has been increasing, but studies in the literature that optimise all the parameters used in this process are lacking. In the current article, the authors present an algorithm to optimise the parameters required for denoising based on the discrete wavelet transform and thresholding. One-hundred sixty different configurations of the mother wavelet, threshold evaluation method, and threshold function are compared on the Case Western Reserve University database to obtain the best combination for bearing damage identification with an iterative method and are evaluated with tradeoff and kurtosis. The analysis results show that the best combination of parameters for denoising is dmey, rigrSURE, and the hard threshold. The signals were then distributed in a 2D plane for classification through an algorithm based on principal component analysis, which uses a preselection of features extracted in the time domain.

Fabry disease (FD) is a X-linked lysosomal storage disorder caused by deficient function of the alpha-galactosidase A (α-GalA) enzyme. α-GalA deficiency leads to multisystemic clinical manifestations caused by the preferential accumulation of globotriaosylceramide (Gb3). A hallmark symptom of FD patients is neuropathic pain that appears in the early stage of the disease as a result of peripheral small fiber damage. Previous studies have shown that Acetyl-L-carnitine (ALC) has neuroprotective, neurotrophic, and analgesic activity in animal models of neuropathic pain. To study the action of ALC on neuropathic pain associated with FD, we treated α-GalA gene null mice (α-GalA(-/0)) with ALC for 30 days. In α-Gal KO mice, ALC treatment induced acute and long-lasting analgesia, which persisted 1 month after drug withdrawal. This effect was antagonized by single administration of LY341495, an orthosteric antagonist of mGlu2/3 metabotropic glutamate receptors. We also found an up-regulation of mGlu2 receptors in cultured DRG neurons isolated from 30-day ALC-treated α-GalA KO mice. However, the up-regulation of mGlu2 receptors was no longer present in DRG neurons isolated 30 days after the end of treatment. Taken together, these findings suggest that ALC induces analgesia in an animal model of FD by up-regulating mGlu2 receptors, and that analgesia is maintained by additional mechanisms after ALC withdrawal. ALC might represent a valuable pharmacological strategy to reduce pain in FD patients.

To improve pathogenetic studies in cancer development and reliable preclinical testing of anti-cancer treatments, three-dimensional (3D) cultures, including spheroids, have been widely recognized as more physiologically relevant in vitro models of in vivo tumor behavior. Currently, the generation of uniformly sized spheroids is still challenging: different 3D cell culture methods produce heterogeneous populations in dimensions and morphology, that may strongly influence readouts reliability correlated to tumor growth rate or antitumor natural killer (NK) cell-mediated cytotoxicity. In this context, an increasing consensus claims the integration of microfluidic technologies within 3D cell culture, as the physical characterization of tumor spheroids is unavoidably demanded to standardize protocols and assays for in vitro testing. In this paper, we employed a flow-based method specifically conceived to measure weight, size and focused onto mass density values of tumor spheroids. These measurements are combined with confocal and digital imaging of such samples. We tested the spheroids of four colorectal cancer (CRC) cell lines that exhibit statistically relevant differences in their physical characteristics, even though starting from the same cell seeding density. These variations are seemingly cell line-dependent and associated with the number of growing cells and the degree of spheroid compaction as well, supported by different adenosine-triphosphate contents. We also showed that this technology can estimate the NK cell killing efficacy by measuring the weight loss and diameter shrinkage of tumor spheroids, alongside with the commonly used cell viability in vitro test. As the activity of NK cells relies on their infiltration rate, the in vitro sensitivity of CRC spheroids proved to be exposure time- and cell line-dependent with direct correlation to the cell viability reduction. All these functional aspects can be measured by the system and are documented by digital image analysis. In conclusion, this flow-based method potentially paves the way towards standardization of 3D cell cultures and its early adoption in cancer research to test antitumor immune response and set up new immunotherapy strategies., Competing Interests: The authors of Affiliation 1 (AS, FM, FB, DC, FC, SB, SP, and DG) are employed by Cell Dynamics isrl company. The authors declare that a Patent Application (No. 102020000006031) incorporating parts of this work has been filed. DG, SB, DC, AS, and FM are the inventors of patent No. 102020000006031. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Sargenti, Musmeci, Bacchi, Delprete, Cristaldi, Cannas, Bonetti, Pasqua, Gazzola, Costa, Villa, Zocchi and Poggi.)

Additive Manufacturing (AM) processes enable their deployment in broad applications from aerospace to art, design, and architecture. Part quality and performance are the main concerns during AM processes execution that the achievement of adequate characteristics can be guaranteed, considering a wide range of influencing factors, such as process parameters, material, environment, measurement, and operators training. Investigating the effects of not only the influential AM processes variables but also their interactions and coupled impacts are essential to process optimization which requires huge efforts to be made. Therefore, numerical simulation can be an effective tool that facilities the evaluation of the AM processes principles. Selective Laser Melting (SLM) is a widespread Powder Bed Fusion (PBF) AM process that due to its superior advantages, such as capability to print complex and highly customized components, which leads to an increasing attention paid by industries and academia. Temperature distribution and melt pool dynamics have paramount importance to be well simulated and correlated by part quality in terms of surface finish, induced residual stress and microstructure evolution during SLM. Summarizing numerical simulations of SLM in this survey is pointed out as one important research perspective as well as exploring the contribution of adopted approaches and practices. This review survey has been organized to give an overview of AM processes such as extrusion, photopolymerization, material jetting, laminated object manufacturing, and powder bed fusion. And in particular is targeted to discuss the conducted numerical simulation of SLM to illustrate a uniform picture of existing nonproprietary approaches to predict the heat transfer, melt pool behavior, microstructure and residual stresses analysis.

Gathering precise information on mass density, size and weight of cells or cell aggregates, is crucial for applications in many biomedical fields with a specific focus on cancer research. Although few technical solutions have been presented for single-cell analysis, literature does not cover this aspect for 3D models such as spheroids. Since the research interest on such samples is notably rising, here we describe a flow-apparatus, and the associated physical method and operative protocol for the accurate measurements of mass density, size and weight. The technique is based on the detection of the terminal velocity of a free-falling sample into a specifically conceived analysis flow-channel. Moreover, in order to demonstrate the accuracy and precision of the presented flow-device, analyses were initially carried out on standardized polystyrene beads. Finally, to display the application of the proposed system for biological samples, mass density, size and weight of live SW620 tumor spheroids were analyzed. The combined measurements of such parameters can represent a step toward a deeper understanding of 3D culture models., Competing Interests: Authors of Affiliation 1 are employees by CellDynamics isrl. The authors declare no conflict of interest. Daniele Gazzola, Simone Bonetti, Domenico Andrea Cristaldi, Azzurra Sargenti and Francesco Musmeci are the inventors of Patent No. 102020000006031.