Lanthionine,a Novel Uremic Toxin,in the Vascular Calcification of Chronic Kidney Disease: The Role of Proinflammatory Cytokines

Vascular calcification (VC) is a risk factor for cardiovascular events and mortality in chronic kidney disease (CKD). Several components influence the occurrence of VC, among which inflammation. A novel uremic toxin, lanthionine, was shown to increase intracellular calcium in endothelial cells and may have a role in VC. A group of CKD patients was selected and divided into patients with a glomerular filtration rate (GFR) of <45 mL/min/1.73 m² and ≥45 mL/min/1.73 m². Total Calcium Score (TCS), based on the Agatston score, was assessed as circulating lanthionine and a panel of different cytokines. A hemodialysis patient group was also considered. Lanthionine was elevated in CKD patients, and levels increased significantly in hemodialysis patients with respect to the two CKD groups; in addition, lanthionine increased along with the increase in TCS, starting from one up to three. Interleukin IL-6, IL-8, and Eotaxin were significantly increased in patients with GFR < 45 mL/min/1.73 m² with respect to those with GFR ≥ 45 mL/min/1.73 m². IL-1b, IL-7, IL-8, IL-12, Eotaxin, and VEGF increased in calcified patients with respect to the non-calcified. IL-8 and Eotaxin were elevated both in the low GFR group and in the calcified group. We propose that lanthionine, but also IL-8 and Eotaxin, in particular, are a key feature of VC of CKD, with possible marker significance.     

Effect of comonomer partitioning on the kinetics of mesophase formation in random copolymers of propene and higher α-olefins

The effect of counit type on the kinetics of mesophase formation has been investigated by means of chip-calorimetry in propene/α-olefin random copolymers, containing counits which show large differences in their co-crystallization behavior with propene, i.e. 1-butene and 1-hexene. Non-isothermal crystallization experiments indicated that the minimum cooling rate at which mesophase formation is observed is directly related to the kinetic of α-phase crystallization, which is lower for the copolymer with the bulkier 1-hexene counit. Isothermal structuring was probed in a wide temperature range, revealing that a double bell-shaped curve is required to describe the temperature dependence of crystallization times of the two polymorphs. The ordering kinetics of the mesophase is the fastest in i-PP homopolymer and decreases with increasing comonomer bulkiness, analogous to what happens for the monoclinic phase. The results are discussed by considering the effect of comonomer on the driving force for mesophase formation, also at the light of new WAXD and density evidences, which prove different extents of inclusion of 1-butene and 1-hexene in the ordered phases.     

Accuracy analysis of the amplitude estimation of a sine-wave by the energy-based method using the direct and indirect procedures

The energy-based method (EBM) can be used to estimate the amplitude of a sine-wave either directly from Discrete Fourier Transform (DFT) samples or indirectly. In this paper the accuracies achieved with both these approaches are compared when some of the most commonly used cosine class windows are adopted. The effect on the estimation accuracy of the algorithm error, the spectral interference from the image component, and wideband noise superimposed to the sine-wave signal are separately evaluated and compared. The statistical efficiencies of both procedures with respect to the unbiased single-tone Cramér-Rao lower bound are determined and compared. Moreover, the overall root mean square of the amplitude estimation error achieved when taking into account all the three contributions above is derived for both direct and indirect estimation procedures. The accuracy of the obtained expressions is verified by means of computer simulations. Besides, experimental data validate the theoretical results.     

Patterning photo-curable light-emitting organic composites by vertical and horizontal capillarity: a general route to photonic nanostructures

We demonstrate the patterning of organic light-emitting composites made by conjugated polymers and photo-curable matrices. Using blends that exhibit both the structural properties of a low-viscosity photo-curable polymer, and the emission features of conjugated light-emitting materials, we study the operational principle of the pattern transfer and the modifications induced by the imprinting and microfluidic procedures on the optical properties of the compounds investigated. The combination of high-resolution silicone and perfluoropolyether elastomeric templates and low-viscosity, light-emitting polymeric blends offers the possibility to easily produce active organic structures with 100?nm scale resolution, thus extending current nanopatterning routes to this important class of composite material.     

Creep behavior of INCOLOY alloy 617

The microstructural features of INCOLOY alloy 617 in the solution annealed condition and after long-term creep tests at 700 and 800 °C were characterized and correlated with hardness and creep strength. Major precipitates included (Cr,Mo,Fe)₂₃C₆ carbides and the δ-Ni₃Mo phase. M₆C and MC carbides were also detected within the austenitic grains. However, minor precipitates particularly γ′-Ni₃(Al,Ti) was found to play an important role. At different exposure temperatures, the microstructural features of the Ni–22Cr–12Co–9Mo alloy changed compared with the as-received condition. The presence of discontinuously precipitated (Cr,Mo,Fe)₂₃C₆ carbides and their coarsening until the formation of an intergranular film morphology could be responsible both for a reduction in rupture strength and for enhanced intergranular embrittlement. The fraction and morphology of the γ′-phase, precipitated during exposure to high temperature, also changed after 700 or 800 °C exposure. At the latter test temperature, a lower volume fraction of coarsened and more cubic γ′ precipitates were observed. These microstructural modifications, together with the presence of the δ-phase, detected only in specimens exposed to 700 °C, were clearly responsible for the substantially good creep response observed at 700 °C, compared with that found at 800 °C.     

Patterning of light-emitting conjugated polymer nanofibres

Organic materials have revolutionized optoelectronics by their processability, flexibility and low cost, with application to light-emitting devices for full-colour screens, solar cells and lasers. Some low-dimensional organic semiconductor structures exhibit properties resembling those of inorganics, such as polarized emission and enhanced electroluminescence. One-dimensional metallic, III-V and II-VI nanostructures have also been the subject of intense investigation as building blocks for nanoelectronics and photonics. Given that one-dimensional polymer nanostructures, such as polymer nanofibres, are compatible with sub-micrometre patterning capability and electromagnetic confinement within subwavelength volumes, they can offer the benefits of organic light sources to nanoscale optics. Here we report on the optical properties of fully conjugated, electrospun polymer nanofibres. We assess their waveguiding performance and emission tuneability in the whole visible range. We demonstrate the enhancement of the fibre forward emission through imprinting periodic nanostructures using room-temperature nanoimprint lithography, and investigate the angular dispersion of differently polarized emitted light.     

Small-molecule inhibitors of PDK1

Signal transduction of many growth factors and oncogenes is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1), a master regulator of a number of downstream signal protein kinase cascades. Hence, PDK1 represents a convergence point for receptor tyrosine kinase and cytokine-mediated pathways for the regulation of vital cell processes such as cell survival and proliferation. Pathological upregulation of PDK1 signalling due to constitutive growth factor receptor activation and/or PTEN (phosphatase and tensin homologue) mutations significantly triggers downstream signalling, e.g. PKB/Akt, which subsequently promote proliferative events such as tumour invasiveness, angiogenesis, and progression. Consistent with this, a mouse model expressing low levels of PDK1 is protected from tumourigenesis resulting from loss of PTEN. Because more than 50 % of all human cancers possess significant overstimulation of the PDK1 signalling pathway, inhibition of this protein kinase by small molecules is predicted to result in effective inhibition of cancer cell proliferation and thus be therapeutically beneficial. Various classes of small-molecule PDK1 inhibitors have been published in patents and papers. Herein we present for the first time a comprehensive collection of small molecules reported to interact with PDK1, and we refer to their biological characterisation in terms of activity and selectivity for PDK1.     

Rapid depletion of marbofloxacin residues in rabbit after therapeutic treatment

Although rabbit meat production represents a very small percentage of the world meat market, this percentage has been growing continuously during the last 30 years. Rabbit is considered a minor food species, and therefore no drugs are specifically registered for this animal. This situation encourages rabbit farmers to make off-label use of antibacterial drugs authorized for food-producing animal species other than rabbits. In the present study, the distribution and elimination of the fluoroquinolone antibacterial agent marbofloxacin in rabbit muscle, liver, and kidney was investigated. Marbofloxacin was chosen as a representative of a new generation of antibacterial drugs active against most gram-positive and gram-negative bacteria and mycoplasms; it is well tolerated and has short elimination times in bovine and swine species. Rabbits were treated with marbofloxacin at 2 mg kg of body weight(-1) for 5 days. Residual concentrations in liver, kidney, and muscle tissues were determined posttreatment with high-performance liquid chromatography and fluorescence detection. Marbofloxacin was rapidly distributed and eliminated from rabbit tissues. Concentrations were higher in the liver and kidney than in muscle. However, 48 h after the end of treatment, marbofloxacin concentrations dropped below the maximum residue level fixed for this antibacterial drug in cattle and pigs. Considering the efficacy of marbofloxacin for the treatment of the most common rabbit diseases, its tolerability, and its short elimination time as verified in the present study, use of this antibacterial drug could be extended to therapeutic treatment of rabbits.     

Optimal design and seismic performance of Multi‐Tuned Mass Damper Inerter (MTMDI) applied to adjacent high‐rise buildings

The tuned mass damper inerter (TMDI) is an enhanced variant of the tuned mass damper (TMD) that benefits from the mass‐amplification effect of the inerter. Here, a multi‐TMDI (MTMDI) system (comprising more than one TMDI) linking two adjacent high‐rise buildings is presented as an unconventional seismic protection strategy. The relative acceleration response of the adjacent structures triggers large reaction forces of the inerter devices in the MTMDI, which in turn efficiently improve the seismic performance of the two buildings. By addressing a real project of two adjacent high‐rise buildings connected by two corridors equipped with the proposed MTMDI system, the displacement‐, interstory drift‐, and acceleration‐based parametric optimizations are separately performed by employing Nondominated Sorting Genetic Algorithm II (NSGA‐II) under 44 ground motions from the FEMA P695 far‐field record set. It is found that the frequency content of the seismic input has strong impact on the MTMDI mitigation performance. Adopting realistic mass ratio constraints, the optimally designed MTMDI outperforms both conventional MTMD and single TMDI in acceleration control, while it is not much effective in mitigating the displacement response due to the highly flexible nature of the high‐rise buildings, in contrast to other literature studies generally focused on low‐to‐medium rise buildings.