Epigenetic Immune Remodeling of Mesothelioma Cells: A New Strategy to Improve the Efficacy of Immunotherapy

Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a severe progno- sis, and with a long-standing need for more effective therapeutic approaches. However, treatment with immune checkpoint inhibitors is becoming an increasingly effective strategy for MPM pa- tients. In this scenario, epigenetic modifications may negatively regulate the interplay between immune and malignant cells within the tumor microenvironment, thus contributing to the highly immunosuppressive contexture of MPM that may limit the efficacy of immunotherapy. Aiming to further improve prospectively the clinical efficacy of immunotherapeutic approaches in MPM, we investigated the immunomodulatory potential of different classes of epigenetic drugs (i.e., DNA hypomethylating agent (DHA) guadecitabine, histone deacetylase inhibitors VPA and SAHA, or EZH2 inhibitors EPZ-6438) in epithelioid, biphasic, and sarcomatoid MPM cell lines, by cytofluo- rimetric and real-time PCR analyses. We also characterized the effects of the DHA, guadecitabine, on the gene expression profiles (GEP) of the investigated MPM cell lines by the nCounter platform. Among investigated drugs, exposure of MPM cells to guadecitabine, either alone or in combination with VPA, SAHA and EPZ-6438 demonstrated to be the main driver of the induction/upregulation of immune molecules functionally crucial in host-tumor interaction (i.e., HLA class I, ICAM-1 and cancer testis antigens) in all three MPM subtypes investigated. Additionally, GEP demonstrated that treatment with guadecitabine led to the activation of genes involved in several immune-related func- tional classes mainly in the sarcomatoid subtype. Furthermore, among investigated MPM subtypes, DHA-induced CDH1 expression that contributes to restoring the epithelial phenotype was highest in sarcomatoid cells. Altogether, our results contribute to providing the rationale to develop new epigenetically-based immunotherapeutic approaches for MPM patients, potentially tailored to the specific histologic subtypes

Critical flow speeds of pipes conveying fluid by the Generalized Differential Quadrature method

The aim of this study is to clarify the discrepancy regarding the critical flow speed of straight pipes conveying fluids that appears to be present in the literature by using the Generalized Differential Quadrature method. It is well known that for a given “mass of the fluid” to the “mass of the pipe” ratio, straight pipes conveying fluid are unstable by a flutter mode via Hopf bifurcation for a certain value of the fluid speed, i.e. the critical flow speed. However, there seems to be lack of consensus if for a given mass ratio the system might lose stability for different values of the critical flow speed or only for a single speed value. In this paper an attempt to answer to this question is given by solving the governing equation following first the practical aspect related to the engineering problem and than by simply considering the mathematics of the problem. The Generalized differential quadrature method is used as a numerical technique to resolve this problem. The differential governing equation is transformed into a discrete system of algebraic equations. The stability of the system is thus reduced to an eigenvalue problem. The relationship between the eigenvalue branches and the corresponding unstable flutter modes are shown via Argand diagram. The transfer of flutter-type instability from one eigenvalue branch to another is thoroughly investigated and discussed. The critical mass ratios, at which the transfer of the eigenvalue branches related to flutter take place, are determined

Critical Flow Speeds of Pipes Conveying Fluid Using the Generalized Differential Quadrature Method

The aim of this study is to clarify the discrepancy regarding the critical flow speed of straight pipes conveying fluids that appears to be present in the literature by using the Generalized Differential Quadrature method. It is well known that for a given “mass of the fluid ” to the “mass of the pipe ” ratio, straight pipes conveying fluid are unstable by a flutter mode via Hopf bifurcation for a certain value of the fluid speed, i.e. the critical flow speed. However, there seems to be lack of consensus if for a given mass ratio the system might lose stability for different values of the critical flow speed or only for a single speed value. In this paper an attempt to answer to this question is given by solving the governing equation following first the practical aspect related to the engineering problem and than by simply considering the mathematics of the problem. The Generalized differential quadrature method is used as a numerical technique to resolve this problem. The differential governing equation is transformed into a discrete system of algebraic equations. The stability of the system is thus reduced to an eigenvalue problem. The relationship between the eigenvalue branches and122 Francesco Tornabene et al the corresponding unstable flutter modes are shown via Argand diagram. The transfer of flutter-type instability from one eigenvalue branch to another is thoroughly investigated and discussed. The critical mass ratios, at which the transfer of the eigenvalue branches related to flutter take place, are determined

Current developments in elastic and acoustic metamaterials science.

The concept of metamaterial recently emerged as a new frontier of scientific research, encompassing physics, materials science and engineering. In a broad sense, a metamaterial indicates an engineered material with exotic properties not found in nature, obtained by appropriate architecture either at macro-scale or at micro-/nano-scales. The architecture of metamaterials can be tailored to open unforeseen opportunities for mechanical and acoustic applications, as demonstrated by an impressive and increasing number of studies. Building on this knowledge, this theme issue aims to gather cutting-edge theoretical, computational and experimental studies on elastic and acoustic metamaterials, with the purpose of offering a wide perspective on recent achievements and future challenges. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 1)'

Modeling wave propagation in damped waveguides of arbitrary cross-section

In this paper the Semi-Analytical Finite Element (SAFE) method for modeling guided wave propagation is extended to account for linear viscoelastic material damping. Linear viscoelasticity is introduced by allowing for complex stiffness constitutive matrices for the material. Dispersive characteristics of viscoelastic waveguides, such as phase velocity, attenuation, energy velocity and cross-sectional wavestructures are extracted. Knowledge of the above-mentioned dispersive properties is important in any structural health monitoring attempt that uses ultrasonic guided waves for long range inspection. The proposed damped formulation is applied to several waveguides with different mechanical and geometric properties. In particular, a viscoelastic isotropic plate, a railroad track and a pipe are studied

Analysis of the Interaction Between Buried Pipelines and Slope Instability Phenomena

Economic and social integration across Europe requires secure lifelines, such as roads, railways and pipelines. Existing and planned lifelines may come across a large number of different natural and anthropic hazards. For instance, past catastrophic events have dramatically shown that steel pipelines may be highly vulnerable to permanent ground deformation due to earthquakes and landslides. Therefore, their behaviour when exposed to processes that can generate large displacement and strain (co-seismic deformation and faulting, liquefaction, earth and rock slides and flows, rock falls) needs to be assessed. In fact, and in particular if toxic and/or flammable materials are transported, structural damage with eventual leakage might result in a severe risks for both human life and the environment, with associated relevant economic costs. To such purpose, in this work, a methodology for the assessment, prevention and efficient management of geological risks, mainly landslides, in steel buried pipelines will be presented. The proposed procedure aims at reducing the risk of environmental disasters and the subsequent huge financial and environmental losses

Modeling wave propagation in damped waveguides of arbitrary cross-section

In this paper the Semi-Analytical Finite Element (SAFE) method for modeling guided wave propagation is extended to account for linear viscoelastic material damping. Linear viscoelasticity is introduced by allowing for complex stiffness constitutive matrices for the material. Dispersive characteristics of viscoelastic waveguides, such as phase velocity, attenuation, energy velocity and cross-sectional wavestructures are extracted. Knowledge of the above-mentioned dispersive properties is important in any structural health monitoring attempt that uses ultrasonic guided waves for long range inspection. The proposed damped formulation is applied to several waveguides with different mechanical and geometric properties. In particular, a viscoelastic isotropic plate, a railroad track and a pipe are studied

Design of an Adaptive Feedback Based Steering Wheel

This paper aims at describing the architectural model of an adaptiveforce-feedback for a By Wire steering wheel system. This solution uses asteering wheel to replicate the reactive torque law which allows the driver tocomplete a precise driving scenario or a task with the higher performances.Then, the steering wheel adapts the reactive torque to the driving scenario.Since the design of this system considers the driver performances, it is calledErgonomic Steer-By-Wire. Now a prototype version of the ESBW is connectedon a professional driving simulator and several tests are going to be conductedin order to tune the system components. Adapting the force feedback to thedriving scenario could be a solution for improving driver’s safety and vehiclecontrol