Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity

Background: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. Methods: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. Results: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0) patients. Two patients (7.7) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7) developed one type of autoimmunity, and 16 patients (59.3) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6). In 13 patients (61.9), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7), gastrointestinal (48.1), rheumatologic (25.9), and dermatologic (22.2) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. Conclusion: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity. © 2020 Georg Thieme Verlag. All rights reserved

Numerical analysis of the hydrodynamic characteristics of the accelerating and decelerating ducted propeller

This paper investigates the open-water characteristics of the 5-blade propeller with accelerating and decelerating ducts using the Reynolds-Averaged Navier-Stokes (RANS) equation code. In the first step, numerical open-water hydrodynamic characteristics of the propeller in the absence of a duct were validated using the available experimental data. The shear stress transport (SST) turbulence model was chosen, which shows less error in thrust and torque coefficients than others. In the second step, two accelerating and decelerating ducts, namely ducts 19A and N32, were modeled. In these simulations, the clearance value was selected at 3 percent of the propeller’s diameter and uniform-flow conditions were assumed. After analysis of the mesh sensitivity for the propeller thrust, the results were compared to the corresponding open-water condition values. In this regard, results of the hydrodynamic coefficients, pressure distribution, and coefficients on the propeller-blade surface and ducts were also analyzed and discussed

Microstructure and tribological properties of as-cast and multi-pass friction stir processed Mg-0.5Zn-0.5Zr/SiC composite fabricated by stir casting technique

In this investigation, the Mg-0.5Zn-0.5Zr/4%SiC composite fabricated by the stir casting method was subjected to multi-pass friction stir processing (MFSP) to evaluate its microstructure, hardness, dry-sliding wear, and friction properties in comparison to those of the as-cast composite (ACC). Microstructural observations revealed the formation of a Mg matrix with average grain size (AGS) of 107 ± 12 μm, uneven dispersion (agglomeration) of SiC particles in the structure, and the formation of Zr-rich phase with the chemical composition of Zr:78.42, C:19.46, Mg:1.86, and Zn:0.26 wt%, ZrC, as well as some new formed carbide-based phases mostly propagated along the grain boundaries. On the other hand, the MFSP implementation led to a significant microstructural modification, i.e., in the optimum circumstance, the AGS and SiC particle size in the stir zone was reduced by 97.28 % (107–2.9 μm) and 67.69 % (21.33–6.89 μm), respectively, and the density of the composite increased from 1.669 to 1.774 gr/cm3. According to dry-sliding wear test results, applying FSP and increasing the pass number to three reduced the wear rate and coefficient of friction (COF) of the composites by about 45 % and 24 %, respectively, compared to those of ACC. The wear resistance enhancement was ascribed to wear mechanisms changing from delamination/adhesion/severe abrasion to mild abrasion wear, which stemmed from the formation of a stable O-rich tribolayer on the worn surface of FSPed samples

Enhancing the elevated temperatures tribological properties of Al–Mg2Si composites by in-situ addition of Ti-based intermetallics and hot working

Dry-sliding wear and friction behaviors of Al–15Mg2Si–5TiB2–4TiAl3 in-situ hybrid composites were evaluated at different temperatures (100–300 °C) and loads (10–60 N). The addition of TiB2 and TiAl3 particles enhanced the wear resistance. Moreover, the severe wear transition condition was changed from 300 °C to 10 N for the as-received Al–15Mg2Si composite to 300 °C - 60 N for the as-cast Al–15Mg2Si–5TiB2–4TiAl3 hybrid composite. This change was ascribed to the presence of thermostable particles and refined/modified Mg2Si particles via nucleation mechanism. Applying thermomechanical processing and hot deformation by the extrusion process necessitated higher loads and temperatures for this transition. Indeed, fragmentation and more homogeneous dispersion of reinforcements, higher hardness and toughness of composite due to grain refinement by dynamic recrystallization (DRX), reduction and closure of casting defects, and stability of tribolayer were recognized as leading reasons for replacing severe adhesive/plastic deformation wear with the abrasive mechanism. Accordingly, this study introduced an Al matrix hybrid composite with excellent performance at elevated temperatures

Process-induced microstructural variations in laser powder bed fusion of novel titanium alloys: A comprehensive study on volumetric energy density and alloying effects

This study explores the effect of in-situ alloying and volumetric energy density (VED) on the microstructure of Laser Powder Bed Fusion (L-PBF) fabricated Ti alloys. Pure Ti, Ti–5Cu, and Ti–5Cu–1Si (wt%) samples were printed using elemental powders with varying VEDs. This study investigates the influence of VED and Cu/Si additions on the growth restriction factor (Q) and columnar-to-equiaxed transition of the β phase. Pure Ti samples exhibited coarse, prior columnar β grains with an average diameter of 106 μm, and a grain shape factor greater than 3.0. In contrast, both Ti–Cu and Ti–Cu–Si samples displayed a significant fraction of equiaxed prior β grains with a near-spherical morphology. Additionally, Cu/Si addition refined the prior β columnar grains, reducing their average diameter to 37 μm and 25 μm in Ti–Cu and Ti–Cu–Si, respectively. Furthermore, the study reveals a strong dependence of microstructure on VED in the Ti–5Cu–1Si alloy. Higher VED promotes a more uniform distribution of solute elements and a lower thermal gradient, resulting in finer equiaxed β grains with an average diameter of 4.9 μm, compared to samples printed at lower VEDs. The addition of Cu and Si also significantly refined the lath-like α phase and decreased the c/a ratio of the Ti HCP lattice, introducing lattice microstrains in the Ti–Cu and Ti–Cu–Si alloys. These findings demonstrate the potential of in-situ alloying and VED optimization for tailoring microstructures in novel Ti alloys fabricated via L-PBF, paving the way for achieving superior mechanical properties