The tumor microenvironment of classical Hodgkin lymphoma (cHL) is clearly responsible for the maintenance of the malignant Hodgkin-Reed-Sternberg (HRS) cells, and Epstein-Barr virus (EBV) has been shown to play a role in this immune evasion. EBV can increase the migration of CD4(+)CD25(+)FOXP3(+) lymphocytes, named regulatory T cells (Tregs). In this study, we assessed the distribution and biological significance of Tregs in patients with cHL. Tissue microarrays were constructed using diagnostic biopsies available in 130 cHL patients and stained with CD4, CD8, CD25, and FOXP3 antibodies. For the present study, only cHL patients whose histology could be confirmed and EBV association established were studied. From the 130 cHL patients selected for this study, 56 were classified as EBV-related and 74 EBV non-related cHL. There were no association between clinical characteristics and the expression of Tregs. However, higher levels of Tregs correlated with EBV presence on HRS cells (p = 0.02), although it did not influence event-free survival (EFS) and overall survival (p = 0.98 and p = 0.59, respectively). This study demonstrates that Tregs expression correlates with EBV presence in HRS cells and has no impact on survival of patients with cHL. Further studies investigating the mechanisms in which EBV recruits Tregs to the tumor microenvironment will contribute not only to our understanding on the pathogenesis of cHL but also to the development of new therapeutic strategies.
High-performance locally resonant metamaterials represent the next frontier in materials technology due to their extraordinary properties obtained through materials design, enabling a variety of potential applications. the most exceptional feature of locally resonant metamaterials is the subwavelength size of their unit cells, which allows to overcome the limits in wave focusing, imaging and sound/vibration isolation. To respond to the fast evolution of these artificial materials and the increasing need for advanced and exceptional properties, the emergence of a new mechanism for wave mitigation and control consisting in a nonlinear interaction between propagating and evanescent waves has recently been theoretically demonstrated. Here, we present the experimental proof of this phenomenon: the appearance of a subharmonic transmission attenuation zone due to energy exchange induced by autoparametric resonance. these results pave the path to a new generation of nonlinear locally resonant metamaterials. Metamaterials 1, 2 are artificially engineered materials designed to obtain specific, often exotic, properties. Among the wide variety of possible metamaterial properties, the opening of a band gap, which is defined as the frequency range where elasto-acoustic waves cannot propagate, is attracting increasing interest because of its versatile applications 3-5. In particular, a wide and low frequency band gap offers a number of potential applications, such as sound attenuation, super-resolution acoustic imaging, and vibration mitigation. Typical physical phenomena responsible for the band gap opening are Bragg scattering 6,7 , inherent to periodic structures, and local resonance 8 that also promotes band gaps in materials composed of unit cells with subwavelength dimensions. The latter is the focus of the present work. Locally resonant metamaterials operating in the nonlinear regime 9-11 provide even more opportunities for breakthrough applications. Recently, nonlinearities have been exploited in locally resonant granular crystals 12,13 or to obtain logic gates 14 and acoustic diodes 15. Despite of great interest, the number of investigations carried out on the nonlinear dynamic behavior of locally resonant metamaterials exhibiting attenuation frequency ranges is quite limited in comparison with linear ones, also because of the conceptual and modelling difficulties 16-20. Only few works investigated the energy transfer mechanisms induced by the nonlinear coupling between the resonator and the host medium. In some papers 21-24 , the irreversible energy transfer mechanisms are induced by a single purely nonlinear attachment, the so-called nonlinear energy sinks (NES). Only very few papers have considered cases in which nonlinear resonant attachments are densely or periodically distributed in a host material. In this case, two main energy transfer mechanisms can arise. The first one is called inter/intra-modal tunneling and is a well-studied phenomenon in nonlinear wave dynamics. It consists of an energy exchange between t...
In this paper, the transient computational homogenization scheme is extended to allow for nonlinear elastodynamic phenomena. The framework is used to analyze wave propagation in a locally resonant metamaterial containing hyperelastic rubber-coated inclusions. The ability to properly simulate realistic nonlinearities in elasto-acoustic metamaterials constitutes a step forward in metamaterial design as, so far, the literature has focused only on academic nonlinear material models and simple lattice structures. The accuracy and efficiency of the framework are assessed by comparing the results with direct numerical simulations for transient dynamic analysis. It is found that the band gap features are adequately captured. The ability of the framework to perform accurate nonlinear transient dynamic analyses of finite-size structures is also demonstrated, along with the significant computational time savings achieved.
the use of the wave finite element method for passive vibration control of periodic structures.Abstract. In this work, a strategy for passive vibration control of periodic structures is proposed which involves adding a periodic array of simple resonant devices for creating band gaps. It is shown that such band gaps can be generated at low frequencies as opposed to the well known Bragg scattering effects when the wavelengths have to meet the length of the elementary cell of a periodic structure. For computational purposes, the wave finite element (WFE) method is investigated, which provides a straightforward and fast numerical means for identifying band gaps through the analysis of dispersion curves. Also, the WFE method constitutes an efficient and fast numerical means for analyzing the impact of band gaps in the attenuation of the frequency response functions of periodic structures. In order to highlight the relevance of the proposed approach, numerical experiments are carried out on a 1D academic rod and a 3D aircraft fuselage-like structure.
The Tissue Engineering appears with a modern proposal for the treatment of damages or diseases. The study of materials and methods for tissues and organs regeneration by the patient cells culture had been developed on the last years but still couldn’t be used for all different tissues. In this multidisciplinary research field, the present work joins the biodegradability of poly(ε-caprolactone) (PCL) with the osteoconductive properties of β-tricalcium phosphate (β-TCP) in order to create a composite which acts as a temporary support for cell culture without a second surgery to remove the biomaterial. This work evaluates three membranes types, obtained by casting in chloroform, on the biocompatibility and differentiation on mesenquimal stem cells (hMSC). These analyses showed cell viability with the rezasurin method and the alkaline phosphatase activity (ALP). DMA analyses, MEV and OPM were performed.
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