The approach of conformational chimeras to model the role of proline-containing helices on GPCR mobility: the fertile case of Cys-LTR1

The homology modeling of GPCRs has benefitted vastly from the availability of some resolved structures, which allow the generation of many reliable GPCR models. However, the dynamic behavior of such receptors has been only minimally examined in silico, although several pieces of evidence have highlighted some conformational switches that can orchestrate the activation mechanism. Among such switches, Pro-containing helices play a key role in determining bending in TM helices and thereby the width of the TM bundle. The approach proposed herein involves the generation of a set of possible models (conformational chimeras) by exhaustively combining the two main conformations (straight and bent) that a Pro-containing helix can assume. This approach was validated by generating conformational chimeras for the Cys-LTR1 receptor, which is involved in contractile and inflammatory processes. The generated chimeras were then used for docking a small set of representative ligands. The results revealed the flexibility mechanisms of Cys-LTR1, showing how the docked agonists vary their stabilizing interactions, shifting from the open to closed state, and how the examined antagonists are able to block the receptor in an open and inactive conformation, thus behaving as inverse agonists. This study emphasizes the promising potential of chimera modeling, confirms the key role of proline residues in receptor activation, and suggests that docking results can be improved by considering the often-overlooked flexibility of receptors.     

Prestressing wire breakage monitoring using sound event detection

Detecting prestressed wire breakage in concrete bridges is essential for ensuring safety and longevity and preventing catastrophic failures. This study proposes a novel approach for wire breakage detection using Mel-frequency cepstral coefficients (MFCCs) and back-propagation neural network (BPNN). Experimental data from two bridges in Italy were acquired to train and test the models. To overcome the limited availability of real-world training data, data augmentation techniques were employed to increase the data set size, enhancing the capability of the models and preventing over-fitting problems. The proposed method uses MFCCs to extract features from acoustic emission signals produced by wire breakage, which are then classified by the BPNN. The results show that the proposed method can detect and classify sound events effectively, demonstrating the promising potential of BPNN for real-time monitoring and diagnosis of bridges. The significance of this work lies in its contribution to improving bridge safety and preventing catastrophic failures. The combination of MFCCs and BPNN offers a new approach to wire breakage detection, while the use of real-world data and data augmentation techniques are significant contributions to overcoming the limited availability of training data. The proposed method has the potential to be a generalized and robust model for real-time monitoring of bridges, ultimately leading to safer and longer-lasting infrastructure.     

Minimum reinforcement in concrete structures and material/structural instability

The problem of the assessment of minimum reinforcement in concrete members has been examined both theoretically and experimentally by the bridged crack model. The model has been demonstrated to be an efficient numerical tool for investigating the behavior of structural elements in bending, and allowed to show the minimum reinforcement percentage depends on the structural element size, and decreases with increasing beam depths. In the model, Linear Elastic Fracture Mechanics concepts are used to determine the equilibrium and the compatibility equations of a beam segment subjected to bending in presence of a mode I crack. Recently, the model has been extended to include the presence of closing stresses as a function of the crack opening in addition to steel reinforcement closing traction. This allows to characterize the mechanical behavior of fiber reinforced structural elements. A criterion for accounting for crushing in compression has been introduced as well, to bound from below (minimum reinforcement) and from above (maximum reinforcement) a region of stable and ductile mechanical behavior as a function of the mechanical properties as well as of the size of the structural element. Some experimental results are commented under this light.     

Synthesis of hydroxyapatite on titanium coated with organic self-assembled monolayers

The work focuses the formation of hydroxyapatite (HA) layers from simulated body fluids (SBF) onto titanium coated with NH₂-, SH-, and SO₃H-SAMs, respectively, at room temperature and 37 °C as well as pH values of SBF of 7.4, 8, and 8.4. At an upside up arrangement of the samples in the SBF, the formation of sufficient thick HA layers with a pillow like structure onto all SAMs were observed, which is believed to be caused by combined homogeneous and heterogeneous precipitation of HA from the SBF. These layers do not show sufficient adhesive strength. An upside down arrangement of the samples result in the formation of up to 5–10 μm thick flat HA layers with a much higher adhesive strength, which is believed to be due to formation of HA from the SBF only by heterogeneous precipitation. Also HA layers were obtained onto all studied SAMs, SH-SAM appears to favour the formation of HA resulting in a layer with a thickness of about 10 μm and an almost stoichiometric Ca/P-ratio of the layer of 1.72. All other layers exhibit much lower ratios.     

Solid–Liquid Equilibria for the CO<Subscript>2</Subscript> + R143a and N<Subscript>2</Subscript>O + R143a Systems

A recently built experimental setup for determination of solid–liquid equilibria was slightly modified. The action taken on the existing system focused on correcting the drawbacks of the cooling system. In this version of the setup, a direct liquid nitrogen supply was preferred. By means of the modified apparatus, solid–liquid equilibria of the CO₂ + R143a and N₂O + R143a binary systems were studied. The triple point of R143a was measured to check the reliability of the modified apparatus, revealing good consistency with the literature. The system’s behavior was measured down to temperatures of 148 K. The results obtained for the mixtures were interpreted by means of the Schröder equation.     

Strengthening of Brick Masonry Arches with Externally Bonded Steel Reinforced Composites

The objective of this study is to investigate the efficiency of an innovative technique for strengthening masonry arches, based on the use of high strength steel cords embedded in either an epoxy (steel reinforced polymer) or mortar matrix (steel reinforced grout). Ten prototypes of brickwork arches strengthened by composite laminates were tested under a monotonic vertical load applied at the quarter-span. Load tests were performed to compare the behavior up to collapse of strengthened masonry arches; the influence of the types of reinforcement (steel and carbon fibers) and matrices (epoxy and cementitious), as well as location of the strengthening layer (intrados, extrados, and both) and the presence of anchorage systems has been investigated. The experimental results highlight the enhanced strength of the arches reinforced with steel cords, as well as the role of the mechanical anchoring with regard to the resulting final strength.     

Use of neural networks for quick and accurate auto-tuning of PID controller

With reference to a real industrial application of process control, some considerations are discussed concerning the accuracy of methods for auto-tuning of proportional, integral and derivative factor (PID). In particular, a theoretical–experimental approach is described, that allows to evaluate the adequateness of new methods for auto-tuning of PID, able to significantly reduce the time duration for auto-tuning with respect to traditional ones. This result has been achieved by using suitable techniques of experimental data processing, based on neural-networks algorithms, set for this specific application. The effect on described methodology of environmental and operating disturbances is also described.     

A new cacospongionolide inhibitor of human secretory phospholipase A2 from the Tyrrhenian sponge Fasciospongia cavernosa and absolute configuration of cacospongionolides

A new inhibitor of human secretory phospholipase A2 (PLA2), cacospongionolide E (4a), has been isolated from the Tyrrhenian sponge Fasciospongia cavernosa. The structure was proposed on the basis of spectroscopic data and by chemical transformations. The absolute configuration of cacospongionolides 2a-4a was established using the modified Mosher's method. Cacospongionolide E was the most potent inhibitor toward human synovial PLA2, showing higher potency than the reference compound manoalide and exerting no signs of toxicity on human neutrophils. It showed high activity in the Artemia salina bioassay and moderate toxicity in the fish (Gambusia affinis) lethality assay.