93 research outputs found

    Prediction of Fretting-fatigue Crack Nucleation Using a Surface Shear - Sliding Size Crack Analog Parameter

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    AbstractFretting fatigue is a critical load that appears on many structures, such as the blade/disk contact of aircraft engines, train wheel assemblies, etc. Predicting crack nucleation risk is essential for safety, but is particularly complex. Fretting contact stress is multiaxial, with severe stress gradients. To palliate this difficulty, a common approach consists in computing multiaxial fatigue at a critical distance, thus correcting the stress gradient effect and achieving stable pertinent predictions. However, this strategy is very costly in FEM computation due to very fine FEM mesh size, which may be <10μm, and application needs to be limited in large 3D industrial contacts. Investigating the partial slip fretting crack nucleation boundaries of 35NCD16 steel (plane) fretted against 52100 steel cylinders, a new semi-empirical contact loading parameter was introduced, defined as the maximum shear stress generated in the interface (qmax) multiplied by the square-root of the sliding size (s) of the partial slip interface (i.e., ϕ = qmax ×√s). Using this very simple parameter inspired by “crack analog strategy”, it was found that all the crack nucleation data obtained for a wide spectrum of contact pressures and cylinder radii were aligned along a single master curve. Scatter was very low, even less than for the costly “fatigue-critical distance method”. The approach was extended to various fretting-fatigue loading conditions, confirming stability of prediction

    Alteration of ribosome function upon 5-fluorouracil treatment favors cancer cell drug-tolerance.

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    Mechanisms of drug-tolerance remain poorly understood and have been linked to genomic but also to non-genomic processes. 5-fluorouracil (5-FU), the most widely used chemotherapy in oncology is associated with resistance. While prescribed as an inhibitor of DNA replication, 5-FU alters all RNA pathways. Here, we show that 5-FU treatment leads to the production of fluorinated ribosomes exhibiting altered translational activities. 5-FU is incorporated into ribosomal RNAs of mature ribosomes in cancer cell lines, colorectal xenografts, and human tumors. Fluorinated ribosomes appear to be functional, yet, they display a selective translational activity towards mRNAs depending on the nature of their 5'-untranslated region. As a result, we find that sustained translation of IGF-1R mRNA, which encodes one of the most potent cell survival effectors, promotes the survival of 5-FU-treated colorectal cancer cells. Altogether, our results demonstrate that "man-made" fluorinated ribosomes favor the drug-tolerant cellular phenotype by promoting translation of survival genes

    Near-Field Scanning Optical Microscope Combined with Digital Holography for Three-Dimensional Electromagnetic Field Reconstruction

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    International audienceNear-field scanning optical microscopy (NSOM) has proven to be a very powerful imaging technique that allows overcoming the diffraction limit and obtaining information on a scale much smaller than what can be achieved by classical optical imaging techniques. This is achieved using nanosized probes that are placed in close proximity to the sample surface, and thus allow the detection of evanescent waves that contain important information about the properties of the sample on a subwavelength scale. In particular, some aperture-based probes use a nanometer-sized hole to locally illuminate the sample. The far-field radiation of such probes is essential to their imaging properties, but cannot be easily estimated since it highly depends on the environment with which it interacts. In this chapter, we tackle this problem by introducing a microscopy method based on full-field off-axis digital holography that allows us to study in details the three-dimensional electromagnetic field scattered by a NSOM probe in different environments. We start by describing the NSOM and holography techniques independently, and continue by highlighting the advantage of combining both methods. We present a comparative study of the reconstructed light from a NSOM tip located in free space or coupled to transparent and plasmonic media. While far-field methods, such as back focal plane imaging, can be used to infer the directionality of angular radiation patterns, the advantage of our technique is that a single hologram contains information on both the amplitude and phase of the scattered light, allowing to reverse numerically the propagation of the electromagnetic field towards the source. We also present Finite Difference Time Domain (FDTD) simulations to model the radiation of the NSOM tip as a superposition of a magnetic and an electric dipole. We finally propose some promising applications that could be performed with this combined NSOM-holography technique

    Identification of β-Lactams Active against Mycobacterium tuberculosis by a Consortium of Pharmaceutical Companies and Academic Institutions

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    Rising antimicrobial resistance challenges our ability to combat bacterial infections. The problem is acute for tuberculosis (TB), the leading cause of death from infection before COVID-19. Here, we developed a framework for multiple pharmaceutical companies to share proprietary information and compounds with multiple laboratories in the academic and government sectors for a broad examination of the ability of β-lactams to kill Mycobacterium tuberculosis (Mtb). In the TB Drug Accelerator (TBDA), a consortium organized by the Bill & Melinda Gates Foundation, individual pharmaceutical companies collaborate with academic screening laboratories. We developed a higher order consortium within the TBDA in which four pharmaceutical companies (GlaxoSmithKline, Sanofi, MSD, and Lilly) collectively collaborated with screeners at Weill Cornell Medicine, the Infectious Disease Research Institute (IDRI), and the National Institute of Allergy and Infectious Diseases (NIAID), pharmacologists at Rutgers University, and medicinal chemists at the University of North Carolina to screen ∼8900 β-lactams, predominantly cephalosporins, and characterize active compounds. In a striking contrast to historical expectation, 18% of β-lactams screened were active against Mtb, many without a β-lactamase inhibitor. One potent cephaloporin was active in Mtb-infected mice. The steps outlined here can serve as a blueprint for multiparty, intra- and intersector collaboration in the development of anti-infective agents

    TEMPERATURE DEPENDENCE OF THE ELECTRICAL RESISTIVITY OF (V1-xCrx)3Si SINGLE CRYSTALS

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    Nous avons mesuré la résistivité de la phase (VI-xCrx)3Si monocristalline (x = 0...1) entre 4,2 K et 400 K. Lorsque la concentration de Cr augmente, la resistance à basse temperature évolue continuement de ρ ∼T2(x=0) à ρ ∼T5 (x=1). Les résultats sont discutés dans le cadre d'un modèle à 2 bandes (s-d) avec un pic logarithmique pour la densité d'état de la bande d. Le modèle décrit la discontinuité observée dans la pente de la résistivité à la transition de la phase cubique à la phase tétragonale dans V3Si, ainsi que les déviations à la linéarité observées à hautes températures.The electrical resistivity of single phase (V1-xCrx)3Si single crystals (x = 0...1) has been measured between 4.2 K and 400 K. With increasing Cr-content the resistance at low temperature changes continuously from ρ ∼T2 (x=0) to ρ ∼T5 (x=1). The experimental results are discussed on the basis of a two-band (s-d) model with a logarithmic peak in the d-band density of states. The model describes the observed discontinuity in the slope of the resistivity at the cubic-tetragonal phase transition in V3Si as well as the deviation from linearity at higher temperatures

    Analyse thermographique du comportement en fatigue de l'acier DP600

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    La cause la plus fréquente de rupture de pièces ou de structures en fonctionnement normal est due au phénomène de fatigue. Cette rupture qui arrive de façon brutale est en fait le résultat de phénomènes microstructuraux irréversibles cinétiquement lents. Ces irréversibilités s'accompagnent de dissipations de chaleur qui ont pour effet d'échauffer la matière. C'est pourquoi depuis plusieurs années de nombreuses équipes de recherche ont misé sur les mesures d'autoéchauffement pour développer des méthodes de détermination rapide de la limite de fatigue. Même si parfois ces méthodes donnent de bons résultats, elles restent toutefois encore très empiriques. Ceci est dû au fait que l'évolution de la température n'est pas intrinsèque au matériau, elle dépend de l'intensité et de la distribution de sources de chaleur, des conditions aux limites et de la conduction dans le matériau. De plus, du fait de cette conduction, les champs de température restent très réguliers même dans le cas de sources de chaleur très hétérogènes. C'est pour cela que nous avons choisi de travailler en terme de sources de chaleur plutôt qu'en terme de température. Nous avons donc développé une méthode de détermination des sources de chaleur accompagnant le mécanisme de fatigue. Cette méthode s'appuie sur la mesure de champs de températures en surface d'une éprouvette obtenus à l'aide d'une caméra infrarouge à plan focal. Ces sources de chaleur peuvent avoir, au moins, deux origines. Les premières sont induites par la thermodilatabilité du matériau et correspondent au couplage thermoélastique. Les secondes entraînent des échauffements de nature dissipative associés aux transformations microstructurales irréversibles (la fatigue) qui, cycle après cycle, conduisent à la ruine de la structure. La difficulté majeure pour estimer séparément ces deux types de sources vient du fait que l'amplitude des sources thermoélastiques est le plus souvent très grande devant la puissance moyenne dissipée durant un cycle (rapport souvent entre 100 et 1000)

    Thermographic analysis of fatigue dissipation properties of DP60 steel

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    This paper presents an infrared image processing developed to analyse the calorimetric manifestation associated with a fatigue test. Heat sources accompanying the fatigue mechanisms were derived from thermal data provided by an IR camera. Our experiments underlined the precocious, heterogeneous development of the dissipation sources due to fatigue. They also pointed out a linear evolution of the dissipation intensity as a function of the loading frequency
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