Andrea Arena

Within the theoretical and applied research on nonlinear dynamics of periodic microstructured systems, the amplitude-dependent dispersion properties of mechanical metamaterials are attracting increasing interest. The paper investigates the nonlinear free and forced oscillations of a minimal two degrees-of-freedom (2DoF) model simulating the local interplay between plain woven yarns in pretensioned textile metamaterials. Numerical solutions are obtained by time-integrating the equations of motion, which are characterized by nonlinear forces. Nonlinearities arise from the piecewise constitutive law determined by the superposition of geometric stiffness caused by pretension and unilateral elastic stiffness due to interyarn contact. Frequency-response curves of the harmonically forced system are numerically obtained, and the nonlinear behavior arising from the piecewise and amplitude-dependent stiffness characteristics is discussed. Particular attention is given to the effective possibility of consistently describing the unilateral elastic stiffness governed by smooth Hertzian laws with linear and cubic nonsmooth approximations. It is shown that numerical solutions exhibit time periodicity disturbed by significant distortions of the linear solutions as soon as the cubic nonlinearities are activated or the oscillation amplitude exceeds a certain detachment threshold. Finally, parametric analyses disclose a marked softening trend in the frequency response functions, as well as the birth of superharmonic components in the time-histories.

A parametric lattice model is formulated to describe the dispersion properties of harmonic elastic waves propagating in two-dimensional textile metamaterials. Within a weak nonlinear regime, the free undamped motion of the textile metamaterial, starting from a spatially periodic prestressed configuration, is governed by nonlinear differential difference equations, where nonlinearities arise from the elastic contact between plain woven yarns. Within the linear field, the linear dispersion properties characterizing the regime of small oscillation amplitudes are obtained, by applying the Bloch’s theorem. Parametric analyses are carried out to study the influence of the mechanical parameters on wavefrequencies, waveforms, and group velocities. As major outcome, the dispersion spectrum is found to possess two distinct passbands, covering the low- and the high-frequency ranges, respectively, while a complete midfrequency bandgap exists for large parameter regions. Within the nonlinear field, the nonlinear wavefrequencies and the multiharmonic nonresonant response in the time domain are described, by means of perturbation techniques. As interesting finding, the free wave is shown to propagate with a systematic softening behavior. The wave polarization exalts the nonlinear effects in the high-frequency passband.

An original parametric lattice model is formulated to describe the propagation of harmonic elastic waves in two-dimensional textile metamaterials. Within a weak nonlinear regime, the free undamped motion of the textile metamaterial, starting from a spatially periodic pretensioned configuration, is governed by nonlinear differential difference equations. Quadratic and cubic nonlinearities arise from the elastic contact between plain woven yarns. By applying the asymptotic method of multiple scales, the nonlinear dynamics of the periodic cell are governed by an ordered hierarchy of linear perturbation equations. Therefore, by virtue of the linearity and spatial periodicity, the Floquet-Bloch theory is recursively applied at each order of the perturbation equations to study the linear and nonlinear dispersion properties. Specifically, the lowest order solutions return the linear dispersion diagram characterizing the free undamped propagation of small-amplitude harmonic waves. Within the technical range of the parameters, the dispersion diagram shows the coexistence of two passbands, separated by a large mid-frequency stopband. By virtue of an energy-based classification criterion, the different polarizations of the waves propagating in the low-frequency and high-frequency bands are disclosed. The higher orders allow to determine analytically the combined effects of the nonlinearities on the dispersion properties, in the absence of internal resonances. In particular, the wavefrequencies exhibit a quadratic dependence on the wave oscillation amplitude, characterized by a systematic softening behavior. Moreover, the amplitudes of the damped nonlinear response induced by the external excitation due to a harmonically oscillating pretension are analyzed in the frequency domain and the instability regions of the primary resonance are obtained in the whole range of feasible mechanical parameters. Finally, analytical results are successfully validated by numerical simulations in the time domain.

Neurological disorders are a substantial global health burden, affecting millions of people worldwide. A key challenge in developing effective treatments and preventive measures is the realization of low-power wearable systems with early detection capabilities. Traditional strategies rely on machine learning algorithms, but their computational demands often exceed what miniaturized systems can provide. Neuromorphic computing, inspired by the human brain, demonstrated capabilities of on-chip computing with low power consumption. In this context, bidimensional (2D) semiconductors hold notable promise, thanks to their unique electronic properties, atomic-scale thickness, and scalability, making them ideal for low-power applications. This work presents a neuromorphic reservoir computing system exploiting MoS ₂ -based charge trap memories (CTMs) for processing of electrophysiological signals. Real-time seizures detection is achieved, thanks to the nonlinear integration of local-field potential (LFP) recorded from in vitro rodent models of ictogenesis. The results support MoS ₂ -based CTMs for low-power biomedical devices in clinical diagnosis and treatment of epilepsy.

This paper deals with the free propagation problem of resonant and close-to-resonance waves in one-dimensional lattice metamaterials endowed with nonlinearly viscoelastic resonators. The resonators' constitutive and geometric nonlinearities imply a cubic coupling with the lattice. The analytical treatment of the nonlinear wave propagation equations is carried out via a perturbation approach. In particular, after a suitable reformulation of the problem in the Hamiltonian setting, the approach relies on the well-known resonant normal form techniques from Hamiltonian perturbation theory. It is shown how the constructive features of the Lie Series formalism can be exploited in the explicit computation of the approximations of the invariant manifolds. A discussion of the metamaterial dynamic stability, either in the general or in the weak dissipation case, is presented.

Epigenetic modifications, including aberrant DNA methylation occurring at the promoters of oncogenes and oncosuppressor genes and histone modifications, can contribute to carcinogenesis. Aberrant methylation mediated by histone methylatransferases, alongside histones, can affect methylation of proteins involved in the regulation of pro-survival pathways such as JAK/STAT and contribute to their activation. In this study, we used DNA or histone demethylating agents, 5-Azacytidine (5-AZA) or DS-3201 (valemetostat), respectively, to treat primary effusion lymphoma (PEL) cells, alone or in combination with AG490, a Signal transducer and activator of transcription 3 (STAT3) inhibitor. Cell viability was investigated by trypan blue assay and FACS analysis. The molecular changes induced by 5-AZA and/or AG490 treatments were investigated by Western blot analysis, while cytokine release by PEL cells treated by these drugs was evaluated by Luminex. Statistical analyses were performed with Graphpad Prism^® software (version 9) and analyzed by Student’s t test or a nonparametric one-way ANOVA test. The results obtained in this study suggest that 5-AZA upregulated molecules that inhibit STAT3 tyrosine phosphorylation, namely Suppressor of Cytokine Signaling 3 (SOCS3) and tyrosine–protein phosphatase non-receptor type (PTPN) 6/Src homology region 2 domain-containing phosphatase-1 (SHP-1), reducing STAT3 activation and downregulating several STAT3 pro-survival targets in PEL cells. As this lymphoma is highly dependent on the constitutive activation of STAT3, 5-AZA impaired PEL cell survival, and when used in combination with AG490 JAK2/STAT3 inhibitor, it potentiated its cytotoxic effect. Differently from 5-AZA, the inhibition of the EZH1/2 histone methyltransferase by DS-3201, reported to contribute to STAT3 activation in other cancers, slightly affected STAT3 phosphorylation or survival in PEL cells, either alone or in combination with AG490. This study suggests that 5-AZA, by upregulating the expression level of SOCS3 and PTPN6/SHP1, reduced STAT3 activation and improved the outcome of treatment targeting this transcription factor in PEL cells.

Heat shock proteins (HSPs) are highly expressed in cancer cells and represent a promising target in anti-cancer therapy. In this study, we investigated for the first time the expression of high-molecular-weight HSP110, belonging to the HSP70 family of proteins, in Primary Effusion Lymphoma (PEL) and explored its role in their survival. This is a rare lymphoma associated with KSHV, for which an effective therapy remains to be discovered. The results obtained from this study suggest that targeting HSP110 could be a very promising strategy against PEL, as its silencing induced lysosomal membrane permeabilization, the cleavage of BID, caspase 8 activation, downregulated c-Myc, and strongly impaired the HR and NHEJ DNA repair pathways, leading to apoptotic cell death. Since chemical inhibitors of this HSP are not commercially available yet, this study encourages a more intense search in this direction in order to discover a new potential treatment that is effective against this and likely other B cell lymphomas that are known to overexpress HSP110.