Reversal of the Inflammatory Responses in Fabry Patient iPSC-Derived Cardiovascular Endothelial Cells by CRISPR/Cas9-Corrected Mutation

The late-onset type of Fabry disease (FD) with GLA IVS4 + 919G > A mutation has been shown to lead to cardiovascular dysfunctions. In order to eliminate variations in other aspects of the genetic background, we established the isogenic control of induced pluripotent stem cells (iPSCs) for the identification of the pathogenetic factors for FD phenotypes through CRISPR/Cas9 genomic editing. We adopted droplet digital PCR (ddPCR) to efficiently capture mutational events, thus enabling isolation of the corrected FD from FD-iPSCs. Both of these exhibited the characteristics of pluripotency and phenotypic plasticity, and they can be differentiated into endothelial cells (ECs). We demonstrated the phenotypic abnormalities in FD iPSC-derived ECs (FD-ECs), including intracellular Gb3 accumulation, autophagic flux impairment, and reactive oxygen species (ROS) production, and these abnormalities were rescued in isogenic control iPSC-derived ECs (corrected FD-ECs). Microarray profiling revealed that corrected FD-derived endothelial cells reversed the enrichment of genes in the pro-inflammatory pathway and validated the downregulation of NF-κB and the MAPK signaling pathway. Our findings highlighted the critical role of ECs in FD-associated vascular dysfunctions by establishing a reliable isogenic control and providing information on potential cellular targets to reduce the morbidity and mortality of FD patients with vascular complications.     

Characterization of zirconia specimens fabricated by ceramic on-demand extrusion

The Ceramic On-Demand Extrusion (CODE) process is a novel additive manufacturing method for fabricating dense (~99% of theoretical density) ceramic components from aqueous, high solids loading pastes (>50?vol%). In this study, 3?mol% Y₂O₃ stabilized zirconia (3YSZ) specimens were fabricated using the CODE process. The specimens were then dried in a humidity-controlled environmental chamber and afterwards sintered under atmospheric conditions. Mechanical properties of the sintered specimens were examined using ASTM standard test techniques, including density, Young’s modulus, flexural strength, Weibull modulus, fracture toughness, and Vickers hardness. The microstructure was analyzed and grain size measured using scanning electron microscopy. The results were compared with those from Direct Inkjet Printing, Selective Laser Sintering, Lithography-based Ceramic Manufacturing (LCM), and other extrusion-based processes, and indicated that zirconia specimens produced by CODE exhibit superior mechanical properties among the additive manufacturing processes. Several sample components were produced to demonstrate CODE’s capability for fabricating geometrically complex ceramic components. The surface roughness of these components was also examined.     

Poly(ethylene terephthalate)/poly(ethylene glycol‐co‐1,3/1,4‐cyclohexanedimethanol terephthalate)/clay nanocomposites: Mechanical properties,optical transparency,and barrier properties

Poly(ethylene terephthalate) (PET)/clay, PET/poly(ethylene glycol‐co‐1,3/1,4‐cyclohexanedimethanol terephthalate) (PETG), and PET/PETG/clay nanocomposites were fabricated using the twin‐screw extrusion technique. The spherulitic morphologies, thermomechanical, mechanical, and gas‐barrier properties, as well as the effect of clay on the transparency of the resulting nanocomposites were identified. The clay induced the heterogeneous nucleation of the nanocomposites during the cold crystallization process, thereby increasing the crystallinities and melting temperatures of the resulting nanocomposites. The incorporation of clay increased the storage moduli, Young's moduli, impact strengths, and barrier properties of the PET, PETG, and PET/PETG blend. Regarding the optical transparency, the inclusion of clay can make the crystallizable PET matrix crystalline opaque. However, the amorphous PETG maintained its transparency. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39869.     

Improved additive manufacturing of silicon carbide parts via pressureless electric field-assisted sintering

High solids loading silicon carbide (SiC)-based aqueous slurries containing only .5 wt. % organic additives were utilized to create specimens of various geometries via an extrusion-based additive manufacturing (AM) technique. Pressureless electric field-assisted sintering was performed to densify each specimen without deformation. The combination of these techniques produced parts with >98% relative density despite containing only 5 wt.% oxide sintering additives. After sintering, specimens contained only the α-SiC and yttrium aluminum perovskite phases. This suggests the evolution of a nonequilibrium yttrium aluminate phase, as well as transformation from β-SiC to α-SiC. The fabrication method presented in this work has advantages over other AM techniques commonly used with SiC, because it does not require significant organic additives nor additional postprocessing steps such as chemical vapor infiltration or polymer impregnation and pyrolysis.     

Null-field BIEM for solving a scattering problem from a point source to a two-layer prolate spheroid

In this paper, the acoustic scattering problem from a point source to a two-layer prolate spheroid is solved by using the null-field boundary integral equation method (BIEM) in conjunction with degenerate kernels. To fully utilize the spheroidal geometry, the fundamental solutions and the boundary densities are expanded by using the addition theorem and spheroidal harmonics in the prolate spheroidal coordinates, respectively. Based on this approach, the collocation point can be located on the real boundary, and all boundary integrals can be determined analytically. In real applications of a two-layer prolate spheroidal structure, it can be applied to simulate the kidney-stone biomechanical system. Here, we consider the confocal structure to simulate the kidney-stone system since its analytical solution can be analytically derived. The parameter study for providing some references in the clinical medical treatment is also considered. To check the validity of the null-field BIEM, a special case of the acoustic scattering problem of a point source by a rigid scatterer is also done by setting the density of the inner prolate spheroid to infinity. Results of the present method are compared with those obtained using the commercial finite element software ABAQUS.     

Growth characteristics of hierarchical ZnO structures prepared by one-step aqueous chemical growth

By varying the initial precursor concentrations of (KOH/Zn(NO₃)₂ 6H₂O) without addition of surfactants, the branched nanostructures with different growth characteristics can be obtained. In this study, the growth behavior of the three-dimensional hierarchical structure arrays varied from randomly oriented to well-defined sixfold symmetry by altering pH value of the solution and the related effect of erosion phenomenon have been illustrated. In summary, the hierarchical structures with different morphologies can be obtained on preformed Zn microtips through a simple one-step solution method.     

Evaluation of friction coefficient using indentation model of Brinell hardness test for sheet metal forming

This work presents an indentation model of the Brinell hardness test, which is a rigid ball-deformable plane contact model (RB-DP model), to elucidate the sliding friction mechanism of sheet metal forming. In the proposed model, the friction force can be defined as a combination of shear (shearing effect) and plough (ploughing effect) forces. The real contact area ratio α is determined from the RBDP model under sliding condition. Moreover, the lateral contact area ratio A _c /A _r can be specified as a function of the real contact area ratio α. Based on Meyer’s law and Hertz contact problem, the maximum contact area ratio α _u , a limiting condition of the real contact area ratio α, can be described as a function of the strain hardening exponent n. Additionally, a limiting condition applies: the strain hardening exponent n must be less than 0.64 in the present model. The present friction model reveals that the friction coefficient μ _d is a function of strain hardening exponent n, the real contact area ratio α and the maximum contact area ratio α _u . The calculated friction coefficient μ _d agrees with the published experimental results.     

Thermoelastic Analysis of Functionally Graded Rotating Disks with Variable Thickness Involving Non-Uniform Heat Source

The research aims to investigate thermoelastic behavior of functionally graded rotating disks with variable thickness involving a non-uniform heat source. We assume material properties and thickness of rotating disks to vary in the radial direction. Axisymmetric thermal loads including non-uniform heat source, heat flux, and temperature boundary conditions are considered. To conduct corresponding simulations, two user subroutines are edited and incorporated into the commercial finite-element code ABAQUS. For verification, analytical formulations are derived and solved uniquely by symbolic calculations using the computing software Mathematica. The developed finite-element technique is then verified with very good agreement between results by ABAQUS and Mathematica.