An in plane flexible ring model for the analysis of the free and forced response of a rolling tyre

The increased demand for vibroacoustic comfort as well as regulations on noise and vibration levels made the NVH performances of a vehicle one of the fundamental design criteria. Therefore, predictive models for the analysis of noise and vibration transmission mechanisms represent interesting tools to support the R&D department of the automotive companies. Focusing the attention on passenger’s comfort, the vibrations induced by the tyre/road interaction propagate from the contact area to the hub and finally inside the cockpit through structure-borne transmission paths. This can be regarded as one of the major contributors to car cabin interior noise at low frequencies (20-500 Hz). Simplified models able to interpret the waves propagating inside the tyre structure and influenced by the angular speed may support the studies in this research field. To this end, an analytical model based on the theory of the flexible ring on elastic foundation was developed. It allows analysing the tyre dynamics in both static and rotating conditions. Model parameters were calibrated based on an Experimental Modal Analysis of the static tyre. The free response of the tyre shows the bifurcation effect at different rotating speeds, while a cleat test simulation allows investigating the forced response of the tyre

Clinical characteristics and risk of arrhythmic events in patients younger than 12 years diagnosed with Brugada syndrome

Background Brugada syndrome (BrS) is an inheritable disease with an increased risk of sudden cardiac death. Although several score systems have been proposed, the management of children with BrS has been inconsistently described. Objective The purpose of this study was to identify the characteristics, outcome, and risk factors associated with cardiovascular and arrhythmic events (AEs) in children younger than 12 years with BrS. Methods In this single-center case series, all children with spontaneous or drug/fever-induced type 1 Brugada electrocardiographic (ECG) pattern and younger than 12 years at the time of diagnosis were enrolled. Results Forty-three patients younger than 12 years at the time of diagnosis were included. The median follow-up was 3.97 years (interquartile range 2–12 years). In terms of first-degree atrioventricular block, premature beats, nonmalignant AEs, malignant AEs, and episodes of syncope, no significant differences were observed either between patients with spontaneous and drug/fever-induced type 1 Brugada ECG pattern or between female and male patients (except a significant difference between female and male patients for first-degree atrioventricular block). A higher incidence of malignant AEs was observed in patients with syncope (3 of 8 [37.5%] vs 0 of 35 [0%]; P = .005) than in patients without syncope. SCN5A mutations were associated with a higher occurrence of malignant AEs (3 of 14 [21.4%] vs 0 of 25 [0%]; P = .04) compared with no SCN5A mutations. Conclusion A spontaneous type 1 Brugada ECG pattern is not associated with a higher incidence of syncope, first-degree atrioventricular block, premature beats, nonmalignant AEs, and malignant AEs than the drug/fever-induced type 1 Brugada ECG pattern. Syncope events are correlated with an increased incidence of malignant AEs. Moreover, SCN5A mutations are associated with a higher occurrence of malignant AEs

High MYC Levels Favour Multifocal Carcinogenesis

The term “field cancerisation” describes the formation of tissue sub-areas highly susceptible to multifocal tumourigenesis. In the earlier stages of cancer, cells may indeed display a series of molecular alterations that allow them to proliferate faster, eventually occupying discrete tissue regions with irrelevant morphological anomalies. This behaviour recalls cell competition, a process based on a reciprocal fitness comparison: when cells with a growth advantage arise in a tissue, they are able to commit wild-type neighbours to death and to proliferate at their expense. It is known that cells expressing high MYC levels behave as super-competitors, able to kill and replace less performant adjacent cells; given MYC upregulation in most human cancers, MYC-mediated cell competition is likely to pioneer field cancerisation. Here we show that MYC overexpression in a sub-territory of the larval wing epithelium of Drosophila is sufficient to trigger a number of cellular responses specific to mammalian pre-malignant tissues. Moreover, following induction of different second mutations, high MYC-expressing epithelia were found to be susceptible to multifocal growth, a hallmark of mammalian pre-cancerous fields. In summary, our study identified an early molecular alteration implicated in field cancerisation and established a genetically amenable model which may help study the molecular basis of early carcinogenesis

The beam and detector of the NA62 experiment at CERN

NA62 is a fixed-target experiment at the CERN SPS dedicated to measurements of rare kaon decays. Such measurements, like the branching fraction of the K+ → π+ ν bar nu decay, have the potential to bring significant insights into new physics processes when comparison is made with precise theoretical predictions. For this purpose, innovative techniques have been developed, in particular, in the domain of low-mass tracking devices. Detector construction spanned several years from 2009 to 2014. The collaboration started detector commissioning in 2014 and will collect data until the end of 2018. The beam line and detector components are described together with their early performance obtained from 2014 and 2015 data

A Theoretical Model for Investigating the Structural Dynamics of a Rolling Tyre

The noise generated by the rolling tyre contributes significantly to the car's interior noise. This is caused by the tyre-road contact, and at low frequencies (0-500 Hz) is mostly transmitted inside the cockpit through the structure-borne transmission path. In support of the studies in this research field, an interpretative model of the tyre-wheel system accounting for the effects induced by the angular speed represents a useful tool. To this aim, we implemented an analytical model based on a flexible ring on an elastic foundation to analyze the dynamics of the tyre-wheel system, in both static and rotating configurations. We fine-tuned the parameters of the tyre based on data coming from experimental modal analysis of the static tyre. Particular attention has been paid to the system's free and forced responses, commonly analyzed with the so-called cleat test. The results are discussed interpreting the behavior in different reference systems

MYC, Cell Competition, and Cell Death in Cancer: The Inseparable Triad

Deregulation of MYC family proteins in cancer is associated with a global reprogramming of gene expression, ultimately promoting glycolytic pathways, cell growth, and proliferation. It is well known that MYC upregulation triggers cell-autonomous apoptosis in normal tissues, while frankly malignant cells develop resistance to apoptotic stimuli, partly resulting from MYC addiction. As well as inducing cell-autonomous apoptosis, MYC upregulation is able to trigger non cell-autonomous apoptotic death through an evolutionarily conserved mechanism known as "cell competition". With regard to this intimate and dual relationship between MYC and cell death, recent evidence obtained in Drosophila models of cancer has revealed that, in early tumourigenesis, MYC upregulation guides the clonal expansion of mutant cells, while the surrounding tissue undergoes non-cell autonomous death. Apoptosis inhibition in this context was shown to restrain tumour growth and to restore a wild-type phenotype. This suggests that cell-autonomous and non cell-autonomous apoptosis dependent on MYC upregulation may shape tumour growth in different ways, soliciting the need to reconsider the role of cell death in cancer in the light of this new level of complexity. Here we review recent literature about MYC and cell competition obtained in Drosophila, with a particular emphasis on the relevance of cell death to cell competition and, more generally, to cancer. Possible implications of these findings for the understanding of mammalian cancers are also discussed

A neurogenic model of adult brain cancer in the fly

Inactivation of the tumour suppressor gene PTEN is prevalent in primary Glioblastoma. In mammals, PTEN loss has been associated with the failure of a specific molecular axis, including aPKC and Lgl, responsible for the maintenance of the Glioblastoma Stem Cells (GSCs), a reservoir of self-sustaining cells with characteristics similar to neural progenitors. Here we developed a neurogenic model of Drosophila brain cancer based on the dysfunction of the PTEN-aPKC-Lgl axis in type II neuroblasts (NB), whose differentiation proceeds through transit-amplifying intermediate precursors, as it is for mammalian neural progenitors. We obtained neurogenic tumours that express high levels of MYC, keep growing in the adult and lead the animal to premature death, summarising several traits typical of human brain cancers. Recently, our laboratory has demostrated that the physiological phenomenon called MYC-Mediated Cell Competition (MMCC) is conserved in human cancers, where malignant cells are likely to use MYC activity to colonise the organ. Preliminary data will be presented about a possible correlation between MMCC and cell division in brain cancer development

Exploring MYC relevance to cancer biology from the perspective of cell competition

Cancer has long been regarded and treated as a foreign body appearing by mistake inside a living organism. However, now we know that cancer cells communicate with neighbours, thereby creating modified environments able to support their unusual need for nutrients and space. Understanding the molecular basis of these bi-directional interactions is thus mandatory to approach the complex nature of cancer. Since their discovery, MYC proteins have been showing to regulate a steadily increasing number of processes impacting cell fitness, and are consistently found upregulated in almost all human tumours. Of interest, MYC takes part in cell competition, an evolutionarily conserved fitness comparison strategy aimed at detecting weakened cells, which are then committed to death, removed from the tissue and replaced by fitter neighbours. During physiological development, MYC-mediated cell competition is engaged to eliminate cells with suboptimal MYC levels, so as to guarantee selective growth of the fittest and proper homeostasis, while transformed cells expressing high levels of MYC coopt cell competition to subvert tissue constraints, ultimately disrupting homeostasis. Therefore, the interplay between cells with different MYC levels may result in opposite functional outcomes, depending on the nature of the players. In the present review, we describe the most recent findings on the role of MYC-mediated cell competition in different contexts, with a special emphasis on its impact on cancer initiation and progression. We also discuss the relevance of competition-associated cell death to cancer disease

A numerical simulation of fluid-structure interaction in internal flows

The present article is a summary of the activities done by a research group of the University of Rome “La Sapienza” on the subject of fluid–structure interaction (FSI). Implementation and numerical simulations have been conducted by means of a technique known in the literature as the partition treatment technique. A procedure to transfer the interaction effects between the individual components (fluid and structure) has been developed. As example of the methodology implemented, a numerical study of a hot flow through a pipe with a flexible structure inside, is presented. Results show that the heat flux distribution along the structure is highly influenced by the structure deformation