Toll-like receptor-mediated signaling cascade as a regulator of the inflammation network during alcoholic liver disease

Chronic abuse of alcohol leads to various histological abnormalities in the liver. These are conditions collectively known as alcoholic liver disease (ALD). Currently, ALD is considered to be one of the major causes of death worldwide. An impaired intestinal barrier with related endotoxemia is among the various pathogenetic factors. This is mainly characterized by circulating levels of lipopolysaccharide (LPS), considered critical for the onset of intra-hepatic inflammation. This in turn promotes hepatocellular damage and fibrosis in ALD. Elevated levels of LPS exert their effects by binding to Toll-like receptors (TLRs) which are expressed by all liver-resident cells. The activation of TLR signaling triggers an overproduction and release of some cytokines, which promote an autocatalytic cascade of other proinflammatory signals. In this review, we provide an overview of the mechanisms that sustain LPS-mediated activation of TLR signaling, reporting current experimental and clinical evidence of its role during inflammation in ALD

Asymptotically consistent size-dependent plate models based on the couple-stress theory with micro-inertia

Several beam and plate models have been recently developed in the literature to accommodate for size-dependence. These are usually obtained starting from a generalized continuum theory (such as the couple-stress, strain-gradient or non-local theory or their modifications) and then deducing the governing equations through Hamilton's principle and ingenuous kinematical assumptions. This approach, originated by Kirchhoff, usually fails to reproduce the dispersion features of the equivalent 3D theory. Besides, it produces a variety of models, in dependence of the different assumptions, such as Kirchhoff's or Mindlin's. In contrast, in this paper we adopt asymptotic reduction: moving from the couple-stress linear theory of elasticity with micro-inertia, we deduce new models for elongation and flexural deformation of microstructured plates. The resulting models are consistent, in the sense that they reproduce the dispersion features of the corresponding 3D body. Also, models are unique, for they may only differ by the order of the approximation. We find that microstructure especially affects inertia terms, which can be hardly captured by a-priori kinematical assumptions. For static flexural deformations, our results match those already obtained assuming plane cross-sections within the modified couple-stress theory. In fact, we show that couple-stress, reduced couple-stress and strain gradient theories all lead to equivalent results. Higher order models are also given, that describe the near first-cut-off behaviour and account for thickness deformations in the spirit of Timoshenko

Stoneley Waves in Media with Microstructure

The role of microstructure in affecting propagation of antiplane Stoneley waves, that are waves localized at the discontinuity surface between two perfectly-bonded half-spaces, is considered. Microstructure is described within the linear theory of isotropic couple stress elastic materials with micro-inertia. The dispersion relation is a symmetric tri-term combination of the Rayleigh functions in the relevant half-space with a coupling term. In contrast to classical elasticity, where antiplane Stoneley waves are never supported and in-plane waves exist only inasmuch as shear velocities for the half-spaces are close enough, it is found that propagation is largely possible, although it occurs beyond a cuton frequency. For the latter, an explicit expression is given alongside dispersion curves. These results may adopted in next-generation non-destructive testing (NDT) appliances to account for the material microstructure

The use of ultrasound in clinical setting for children affected by NAFLD. is it safe and accurate?

Non-alcoholic fatty liver disease (NAFLD) has become over the last decade the most common form of chronic liver disease in children and adults. Thus, establishing the diagnosis of NAFLD is of utmost importance and represents a major challenge as the disease is generally silent and the current gold standard for diagnosis is an invasive liver biopsy, a procedure that is not suitable for screening purposes. Many non-invasive diagnostic tools have been evaluated so far. Recently the utility of ultrasonography for non-invasive diagnosis and estimation of hepatic steatosis has been demonstrated in a large prospective pediatric study

ADAR enzyme and miRNA story: A nucleotide that can make the difference

Adenosine deaminase acting on RNA (ADAR) enzymes convert adenosine (A) to inosine (I) in double-stranded (ds) RNAs. Since Inosine is read as Guanosine, the biological consequence of ADAR enzyme activity is an A/G conversion within RNA molecules. A-to-I editing events can occur on both coding and non-coding RNAs, including microRNAs (miRNAs), which are small regulatory RNAs of ~20-23 nucleotides that regulate several cell processes by annealing to target mRNAs and inhibiting their translation. Both miRNA precursors and mature miRNAs undergo A-to-I RNA editing, affecting the miRNA maturation process and activity. ADARs can also edit 3' UTR of mRNAs, further increasing the interplay between mRNA targets and miRNAs. In this review, we provide a general overview of the ADAR enzymes and their mechanisms of action as well as miRNA processing and function. We then review the more recent findings about the impact of ADAR-mediated activity on the miRNA pathway in terms of biogenesis, target recognition, and gene expression regulation

A robust approach for analysing dispersion of elastic waves in an orthotropic cylindrical shell

Dispersion of elastic waves in a thin orthotropic cylindrical shell is considered, within the framework of classical 2D Kirchhoff-Love theory. In contrast to direct multi-parametric analysis of the lowest propagating modes, an alternative robust approach is proposed that simply requires evaluation of the evanescent modes (quasi-static edge effect), which, at leading order, do not depend on vibration frequency. A shortened dispersion relation for the propagating modes is then derived by polynomial division and its accuracy is numerically tested against the full Kirchhoff-Love dispersion relation. It is shown that the same shortened relation may be also obtained from a refined dynamic version of the semi-membrane theory for cylindrical shells. The presented results may be relevant for modelling various types of nanotubes which, according to the latest experimental findings, possess strong material anisotropy

On the solution of the purely nonlocal theory of beam elasticity as a limiting case of the two-phase theory

In the recent literature stance, purely nonlocal theory of elasticity is recognized to lead to ill-posed problems. Yet, we show that, for a beam, a meaningful energy bounded solution of the purely nonlocal theory may still be defined as the limit solution of the two-phase nonlocal theory. For this, we consider the problem of free vibrations of a flexural beam under the two-phase theory of nonlocal elasticity with an exponential kernel, in the presence of rotational inertia. After recasting the integro-differential governing equation and the boundary conditions into purely differential form, a singularly perturbed problem is met that is associated with a pair of end boundary layers. A multi-parametric asymptotic solution in terms of size-effect and local fraction is presented for the eigenfrequencies as well as for the eigenforms for a variety of boundary conditions. It is found that, for simply supported end, the weakest boundary layer is formed and, surprisingly, rotational inertia affects the eigenfrequencies only in the classical sense. Conversely, clamped and free end conditions bring a strong boundary layer and eigenfrequencies are heavily affected by rotational inertia, even for the lowest mode, in a manner opposite to that brought by nonlocality. Remarkably, all asymptotic solutions admit a well defined and energy bounded limit as the local fraction vanishes and the purely nonlocal model is retrieved. Therefore, we may define this limiting case as the proper solution of the purely nonlocal model for a beam. Finally, numerical results support the accuracy of the proposed asymptotic approach

Targeting functionalised carbon nanotubes at the interphase of Textile Reinforced Mortar (TRM) composites

Tensile performance of textile reinforced inorganic matrix composites strongly depends on the matrix-to-fabric bond strength, that is the weak chain in the system. In this work, we investigate the role of multi-walled carbon nanotubes (MWCNT) dispersion in an amorphous silica nano-coating for AR-glass and carbon fabric Textile Reinforced Mortar (TRM) composites. Two lime mortars are considered at 56-day curing. Comparative mechanical testing in uni-axial tension show remarkable enhancements in terms of mean ductility, strength and energy dissipation capabilities. Besides, coating successfully hinders telescopic failure and delamination, which significantly narrows data scattering and benefits design limits. Crack pattern analysis reveals that coating promotes diffuse cracking in the specimen, with gradual and progressive damage buildup. Indeed, mean crack width and mean crack spacing are consistently reduced. BET, optical and E-SEM microscopy supports the action mechanism of the coating, that promotes wettability, surface roughening and imparts a remarkable increase in the specific surface area of the reinforcement

An unified timing and spectral model for the Anomalous X-ray Pulsars XTE J1810-197 and CXOU J164710.2-455216

Anomalous X-ray pulsars (AXPs) and soft gamma repeaters (SGRs) are two small classes of X-ray sources strongly suspected to host a magnetar, i.e. an ultra-magnetized neutron star with $B\approx 10^14-10^15 G. Many SGRs/AXPs are known to be variable, and recently the existence of genuinely "transient" magnetars was discovered. Here we present a comprehensive study of the pulse profile and spectral evolution of the two transient AXPs (TAXPs) XTE J1810-197 and CXOU J164710.2-455216. Our analysis was carried out in the framework of the twisted magnetosphere model for magnetar emission. Starting from 3D Monte Carlo simulations of the emerging spectrum, we produced a large database of synthetic pulse profiles which was fitted to observed lightcurves in different spectral bands and at different epochs. This allowed us to derive the physical parameters of the model and their evolution with time, together with the geometry of the two sources, i.e. the inclination of the line-of-sight and of the magnetic axis with respect to the rotation axis. We then fitted the (phase-averaged) spectra of the two TAXPs at different epochs using a model similar to that used to calculate the pulse profiles ntzang in XSPEC) freezing all parameters to the values obtained from the timing analysis, and leaving only the normalization free to vary. This provided acceptable fits to XMM-Newton data in all the observations we analyzed. Our results support a picture in which a limited portion of the star surface close to one of the magnetic poles is heated at the outburst onset. The subsequent evolution is driven both by the cooling/varying size of the heated cap and by a progressive untwisting of the magnetosphere.Comment: 15 pages, 12 figures, accepted for publication in Ap