Fabry Disease and the Heart: A Comprehensive Review

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat.     

A novel ceramic matrix composite based on YNbO4–TiO2 for microwave applications

This work presents the dielectric properties of YNbO₄ (YNO)–TiO₂ composites in the microwave range. X-ray diffraction analysis demonstrates that the addition of TiO₂ to YNO results in the formation of a Y(Nb_0.5Ti_0.5)₂O₆ phase. In the microwave range, the values of permittivity and dielectric loss did not present major changes with the increment of TiO₂. Moreover, the addition of TiO₂ results in an improvement in the thermal stability of YNO, with YNO63 demonstrating a resonant frequency of ?8.96 ppm.°C^?1. We utilised numerical simulations to evaluate the behaviour of these materials as dielectric resonator antennae and it is found that they exhibit a reflection coefficient below ?10 dB at the resonant frequency, with a realised gain of 4.94 – 5.76 dBi, a bandwidth of 665–1050 MHz and a radiation efficiency above 84%. Our results indicate that YNO–TiO₂ composites are interesting candidates for microwave operating devices.     

Low-cost and high-performance 3D printed YBCO superconductors

High-performance YBCO 123 (YBa₂Cu₃O_7-x) bulk superconductor samples were produced using the 3D printing paste-extrusion technique. The YBCO powder obtained after sintering a pre-mixture of Y₂O₃, BaCO₃ and CuO powders at 950 °C was used in the formulation of pastes for extrusion in a 3D freeform printer. The 3D samples printed from pastes containing the pre-mixture powders were sintered, while those produced using the YBCO powder were not. X-ray diffraction (XRD), energy dispersive spectroscopy (EDS) and Raman analysis all confirmed the YBCO phase after sintering, both in the powder and in the samples made with the pre-mixture. Scanning electron microscopy (SEM) images revealed powder grains of heterogeneous size and geometry, as well as grain aggregation, in the sintered samples. Superconducting quantum interference device (SQUID) measurements taken within a fixed magnetic range revealed that the printed pieces have a typical magnetization temperature of 92 K, reaching ?1.43 emu/g and ?1.59 emu/g respectively a zero-field-cooled magnetization (ZFC) for sintered and non-sintered printed samples.     

District Metered Areas Design Under Different Decision Makers’ Options: Cost Analysis

Water loss is a big challenge for water supply companies worldwide, and the Water Network Partitioning (WNP) is an excellent tool for water loss management–particularly in the current difficult economic and financial conditions. WNP is a recent research line and consists in dividing the water distribution network into smaller zones called District Metered Areas (DMAs) with one (or more, in exceptional cases) supply point, to reduce the network complexity and/or allow pressure management. Since there are several possible future scenarios, such as the water demand and/or the infrastructure degradation forecasts, which may have different impacts on the hydraulic behaviour, in this paper a computational application, based on an optimization model, is proposed to achieve a compromise between robustness required for the DMAs design (using a baseline scenario) and different decision makers’ options (using other scenarios with a lower “probability” of occurrence), to reduce the total cost. The objective function reflects the minimization of the squared deviations between the total cost of the DMAs design and the minimum cost for each scenario forecasted for the project plan, multiplied by the weight or “probability” of occurrence for each of the scenarios. The performance of the computational application is illustrated with a case study, and the results are encouraging.     

Physicochemical,mineral and sensory properties of set‐type yoghurts produced by addition of grape,mulberry and carob molasses (Pekmez) at different ratios

This study investigated the effects of adding grape, mulberry and carob molasses (Pekmez) at 6%, 10% or 14% on titratable acidity, pH, viscosity, whey separation, water holding capacity (WHC), gel firmness, acetaldehyde, volatile fatty acids, colour values, mineral profile and sensory properties of set‐type yoghurts. Increasing concentration of the molasses decreased whiteness value, viscosity and WHC, but increased redness/greenness and yellowness/blueness values, whey separation and mineral contents of the samples significantly (P < 0.05). Nevertheless, the yoghurts produced by adding grape molasses had the highest points in the sensory evaluation, followed by mulberry and carob molasses.     

The glycosylation of pregnancy-associated glycoproteins and prolactin-related protein-I in bovine binucleate trophoblast giant cells changes before parturition

Binucleate trophoblast giant cells (BNC) in the bovine placenta produce glycoproteins, which are delivered into the mother after fusion of BNC with uterine epithelial cells. During most time of pregnancy, BNC produce pregnancy-associated glycoproteins (PAGs) and prolactin-related protein-I (PRP-I) with asparagine-linked lactosamine-type glycans terminating with N-acetyl-galactosamine. We show by lectin histochemistry that terminal N-acetyl-galactosamine (detected by Dolichos biflorus agglutinin, DBA) in placentomal BNC is greatly reduced prior to parturition, while lactosamine-type N-glycans (detected by Phaseolus vulgaris leucoagglutinin, PHA-L) remain unaltered. The change in DBA-staining showed no statistically significant differences between placentomes of cows with and without retention of fetal membranes. Western blots revealed that, at parturition the apparent molecular mass of PAGs and PRP-I is 1-2 kDa lower than in late pregnancy. These changes are due to alterations of asparagine-linked glycans, since the molecular weight of the peptide backbones after enzymatical release of asparagine-linked glycans is identical at late pregnancy and parturition. Lectin western blots showed a reduction of terminal N-acetyl-galactosamine on PAGs at parturition. A lectin sandwich-ELISAwas used to differentiate DBA- and PHA-L-binding PAGs in sera of pregnant and non-pregnant cows. The values for DBA-binding PAGs at parturition were not significantly different from non-pregnancy, while the values for PHA-L-binding PAGs were significantly higher at parturition. The peripartal changes of PAG- and PRP-I-glycosylation could alter functional properties of these proteins and might therefore be considered for functional studies. The differentiation of PAG glycoforms in maternal serum could be valuable for a further optimization of PAG-based pregnancy diagnosis in cattle.     

A Feature Selection Algorithm for the Regularization of Neuron Models

This paper presents a novel training method for estimating the parameters of retina models, such as integrate-and-fire (IF) or Poisson based. The presented models are constructed using a set of linear and nonlinear filters, which are described by basis functions and Taylor polynomials, respectively. This approach allows for the identification of a set of features that can be used for reproducing retina responses. By using the Bayesian-Laplace feature selection algorithm herein proposed, an efficient model with a reduced set of parameters is achieved. Experimental results show that the proposed algorithm is able to remove unimportant features while still accurately reproducing retina responses. These results also show that the IF model is able to mimic the retina visual processing system using less parameters than the Poisson-based model.     

Evaluation of different advanced finite element concepts for detailed stress analysis of laminated composite structures

Despite their high specific stiffness and strength, laminated composite materials, e.g. fibre-reinforced plastic plies stacked at different fibre orientations, are susceptible to damage. Damage can be divided into interalaminar damage and interlaminar damage. Delamination is a typical kind of interlaminar damage which occurs in laminated composite materials, often accompanied with intralaminar damage, and may lead to a catastrophic structural collapse. The first and most crucial step in the prediction of failure of Laminated Composite Structures (LCS) is to accurately determine the stresses, particularly the three transverse stress components, also called the interlaminar stresses. It is proposed in the present paper that the integration of a displacement based solid-shell formulation and partial-hybrid stress formulation will lead to an accurate and robust solid-shell element, suitable for the efficient and detailed interlaminar stress calculation.     

Numerical modeling of the impact of the Ancão Inlet relocation (Ria Formosa,Portugal)

This work describes the application of hydrodynamic (ELCIRC) and transport (VELA and VELApart) models to the Ria Formosa lagoon (Portugal) to study the impact of the relocation of the Ancão Inlet. Located in the south of Portugal, this lagoon is a mesotidal barrier island system that communicates with the sea through 6 inlets. The Old Ancão Inlet was artificially closed and the New Ancão Inlet was relocated into a westward position. This work investigates the hydrodynamic patterns and the potential pathways of tracers in Ria Formosa in two distinct configurations: before and after the Ancão Inlet relocation. The hydrodynamic model was successfully calibrated and validated against elevation, velocity and inlet discharges data, accurately reproducing the tidal propagation. The inlet relocation increases the magnitude of tidal currents, residual velocities and the tidal prism across the bar, suggesting a better stability. The tracers transport simulations suggest enhanced water exchanges through the Ancão Inlet and smaller residence times in the western part of Ria Formosa with the present configuration. Overall, it is concluded that the Ancão Inlet relocation had a positive contribution towards increasing the water renewal of the western part of the lagoon, thus decreasing its vulnerability to pollution.     

Influence of the calcium concentration in the presence of organic phosphorus on the physicochemical compatibility and stability of all-in-one admixtures for neonatal use

Background  

Preterm infants need high amounts of calcium and phosphorus for bone mineralization, which is difficult to obtain with parenteral feeding due to the low solubility of these salts. The objective of this study was to evaluate the physicochemical compatibility of high concentrations of calcium associated with organic phosphate and its influence on the stability of AIO admixtures for neonatal use.