Search Results (34)

Basonuclin 2 (BNC2) is a highly conserved cysteine–histidine (C2H2)-type zinc-finger nuclear regulatory protein characterized by three pairs of zinc-finger domains, a putative nuclear localization signal, a serine-rich region, broad tissue distribution, and remarkable transcript diversity generated through alternative promoter usage, alternative splicing, and polyadenylation. Increasing evidence from human genetics, animal models, functional genomics, and transcriptomic studies indicates that BNC2 links nuclear regulatory mechanisms to tissue-specific developmental and disease phenotypes. In the nervous system, BNC2-positive neuronal populations and BNC2-derived circular RNAs have been implicated in energy-balance circuits and neuroinflammatory regulation. In the skeletal system, BNC2 contributes to osteochondral development, periosteal stem-cell activation, chromatin remodeling, fracture repair, and genetic susceptibility to adolescent idiopathic scoliosis. BNC2 variants have also been associated with congenital lower urinary tract obstruction, whereas its expression and regulatory landscape are closely related to germ-cell development, epithelial ovarian cancer susceptibility, pigmentation traits, fibrosis, and several tumor contexts. Mechanistically, BNC2-associated phenotypes appear to involve cysteine–histidine zinc-finger-mediated transcriptional regulation, non-coding enhancer activity, epigenetic alterations, RNA-processing-associated nuclear functions, and chromatin-remodeling-dependent control of cell proliferation, differentiation, and stromal activation. This review integrates current evidence on the molecular architecture and regulatory functions of BNC2, critically discusses its context-dependent roles across development and disease, and highlights unresolved questions regarding isoform-specific activity, cell-type-specific regulation, downstream target networks, and clinical translation. A clearer understanding of these mechanisms may support the future evaluation of BNC2 as a biomarker, genetic susceptibility locus, molecular stratification factor, and potential therapeutic regulatory node. Full article

Silver films are key building blocks for plasmonic and nanophotonic devices, whose optical performance and device reliability are highly sensitive to particulate contamination introduced during fabrication and operation. Herein, a non-destructive surface cleaning strategy specifically applicable to silver film systems is proposed, based on the synergistic regulation of the mechanical properties of a polymer layer and its interfacial adhesion to the silver film. Such regulation is achieved by tuning hydrogen-bond-mediated interactions within a modified poly(vinyl alcohol) (PVA) layer, enabling effective control over the locus of fracture during peeling, such that fracture preferentially occurs at the polymer/silver interface. Unlike conventional polymer-assisted cleaning methods that suffer from an inherent trade-off between bulk cohesion and interfacial adhesion, this approach decouples the two properties through molecular-level hydrogen-bond redistribution. As a result, particulate contaminants can be efficiently removed from the silver surface while preserving the structural integrity of the silver film. The proposed method achieves a particle removal efficiency of up to 98% for contaminants larger than 30 nm and can be stably applied to silver films with lateral dimensions ranging from 1 inch to 12 inches, demonstrating excellent scalability. By further adjusting the processing parameters and compositional ratios of the polymer layer, this strategy is expected to be adaptable to silver films with different thicknesses and structural configurations, providing a reliable surface cleaning solution for improving the performance and reliability of plasmonic and optoelectronic thin-film devices. Full article

McCune–Albright Syndrome (MAS) is a rare mosaic disorder caused by somatic activating mutations of the GNAS gene, resulting in constitutive Gsα signaling and a broad spectrum of clinical phenotypes. The syndrome typically presents with fibrous dysplasia (FD) of bone, café-au-lait macules, and endocrinopathies such as gonadotropin-independent precocious puberty, hyperthyroidism, and/or growth hormone excess. FD, which characterizes the skeletal phenotype, results in the replacement of normal bone with disorganized fibro-osseous tissue, often leading to pain, deformities, and increased risk of fractures. This review discusses the following: 1. The molecular biology of the GNAS locus and its relation to the pathophysiology of FD/MAS; 2. The skeletal manifestations of FD/MAS; 3. Bone biomechanics and organizational skeletal aberrations observed in FD/MAS; and 4. Current and future therapeutic strategies for patients with FD/MAS. While there is much current literature available regarding FD/MAS, this review specifically aims to outline core understandings and summarize some of the latest investigations into the genotypic and phenotypic foundations of the disorders, while shedding new light on the biomechanical aberrations observed in skeletal structure within them and comparing them to those observed in related disease processes such as osteoporosis and Paget’s disease. Full article

The initiation of ductile fractures in medium-strength AW5754 and high-strength AW6082 aluminum alloys at different quasi-static strain rates and under multiaxial stress states was investigated through a series of tensile tests using various specimen geometries. The sensitivity of the stress triaxiality locus to variations in the loading rate was examined for these two aluminum alloy families. Fractographic and elemental analyses were also conducted via SEM and EDS. Numerical simulations based on the finite element method (FEM) were performed using ABAQUS/Standard to determine the actual stress triaxialities and the equivalent plastic strains at fracture. The numerical approach was validated by comparing the simulation results with the experimental findings. These simulations facilitated the generation of a stress triaxiality locus through a curve-fitting process. Among the considered fitting functions, an exponential function was selected as it provided the most accurate relation between the equivalent plastic strain at fracture and the corresponding stress state across different strain rates. The results reveal different strain rate dependencies for the two alloys within a very low strain rate range. The resulting stress triaxiality loci provide a valuable tool for predicting fracture strains and for more accurately evaluating stress states. Overall, the findings of this study significantly advance the understanding of the fracture initiation behavior of aluminum alloys under multiaxial loading conditions and their sensitivity to various quasi-static loading rates. Full article

When two axisymmetric stress waves of the same strength propagate radially at the same velocity, the stress wave wavefronts collide and interact along a specific locus, which is the perpendicular bisector between the two sources. The maximum principal stress occurs along this perpendicular bisector, and the tensile stresses result in crack bridging between the two source points. This symmetric wave propagation behavior allows us to use the Voronoi tessellation diagram and its symmetric dual graph, the Delaunay triangulation, to gain first-order insight into complex wave propagation phenomena for an arbitrary distribution of wave propagation sources. The inherent symmetry of these simultaneous wave propagation mechanics allows us to rapidly visualize and predict the stress wave propagation and interactions, and the resultant crack bridging patterns that arise from random blast sources. The current work is focused on rock blast fracture mechanics, but the visualization scheme can be implemented for any application where waves propagate axisymmetrically and interact. Full article

Cor-Ten steels, also known as weathering steels, are construction materials of growing importance in the field of architecture and crash barriers, not only due to their good mechanical and corrosion resistance properties but also for the appealing color of their oxides. However, a complete description of the fracture locus of Cor-Ten steels in both low and high triaxiality ranges is still lacking. The present study aims at integrating and extending the data available in the literature for this peculiar material by evaluating four different planar specimens with a mixed numerical–experimental methodology. A non-notched specimen was tested in terms of tension to calibrate the true stress–strain curve of the material after necking by means of an iterative process involving the FEM. Once the model had been calibrated, a tensile test of each specimen was simulated, and the corresponding results were validated using the experimental test data. From the FEM results, the quantities of interests, namely, the stress triaxiality, the equivalent plastic strain, and the normalized Lode angle, were extrapolated. Subsequently, the fracture locus of the Cor-Ten steel was determined through the interpolation of the experimental data collected in the present study as well as data available in the literature for low triaxiality ranges. The results confirmed the parabolic trend characterizing the fracture locus at low triaxiality suggested in the literature, and an exponential decreasing trend was found at higher triaxiality values after reaching a local maximum. The results thus confirm that the fracture locus of Cor-Ten steels, as generally found for metallic materials, cannot be completely described by a monotonic function. Moreover, it was found that the highly ductile behavior of the material induces a significant topology change in the specimens before failure, thus making it more complex to forecast the location of crack nucleation and, as a consequence, the stress state. Full article

TC4 ELI alloy is widely used in the marine, medicine, and aviation fields. The failure performance of TC4 ELI alloy is significantly different from that of other metal materials, such as steels. In this paper, a modified Mohr–Coulomb criterion is calibrated based on several kinds of specimens under different stress states and a 3D geometric representation of a modified Mohr–Coulomb fracture locus for TC4 ELI is obtained based on these parameters. The effectiveness of the modified M-C criterion is studied by a ring-stiffened cylinder made of TC4 ELI. The ultimate strength of the cylinder obtained in the simulation with the modified M-C criterion is close to that obtained in an external pressure experiment, which shows that the modified M-C criterion is suitable for predicting failure in pressure hulls made of titanium alloy used in the deep-sea field. Full article

Vandammella animalimorsus is a Gram-negative and non-motile bacterium typically transmitted to humans through direct contact with the saliva of infected animals, primarily through biting, scratches, or licks on fractured skin. The absence of a confirmed post-exposure treatment of V. animalimorsus bacterium highlights the imperative for developing an effective vaccine. We intended to determine potential vaccine candidates and paradigm a chimeric vaccine against V. animalimorsus by accessible public data analysis of the strain by utilizing reverse vaccinology. By subtractive genomics, five outer membranes were prioritized as potential vaccine candidates out of 2590 proteins. Based on the instability index and transmembrane helices, a multidrug transporter protein with locus ID A0A2A2AHJ4 was designated as a potential candidate for vaccine construct. Sixteen immunodominant epitopes were retrieved by utilizing the Immune Epitope Database. The epitope encodes the strong binding affinity, nonallergenic properties, non-toxicity, high antigenicity scores, and high solubility revealing the more appropriate vaccine construct. By utilizing appropriate linkers and adjuvants alongside a suitable adjuvant molecule, the epitopes were integrated into a chimeric vaccine to enhance immunogenicity, successfully eliciting both adaptive and innate immune responses. Moreover, the promising physicochemical features, the binding confirmation of the vaccine to the major innate immune receptor TLR-4, and molecular dynamics simulations of the designed vaccine have revealed the promising potential of the selected candidate. The integration of computational methods and omics data has demonstrated significant advantages in discovering novel vaccine targets and mitigating vaccine failure rates during clinical trials in recent years. Full article

This study investigates multiple cyclic loading scenarios of non-oriented electrical steel sheets through both experimental and numerical approaches. The numerical simulations were conducted using Representative Volume Elements generated with DRAGen. DRAGen allowed for the generation of Representative Volume Elements with a non-cubic shape to cover the complete sheet thickness and enough grains to represent the material’s texture. The experimental results, on the other hand, are utilized to calibrate and validate a prediction model, highlighting the significance of accumulated plastic slip as a suitable parameter correlated with fatigue life. Using the accumulated plastic slip from the simulations, a fatigue fracture locus is introduced, which describes a 3D surface dependent on the maximum stress, fatigue life, and the fatigue stress ratio. The study shows reliable results for the fatigue life prediction using the calibrated fatigue fracture locus. While substantial progress has been made in predicting the fatigue life at multiple fatigue stress ratios, notable disparities between experimental and simulation results suggest the need for further investigations regarding the influence of the surface quality. This observation motivates ongoing research efforts aimed at refining simulation methodologies to better incorporate surface roughness effects. In summary, this study presents a validated model for predicting fatigue life in non-oriented electrical steel sheets, offering valuable insights into material behavior at different loading scenarios and informing future research directions for enhanced structural performance and durability. Full article

Before a new type of engine is introduced into civil aviation, it must comply with various safety regulations. These regulations include the analysis of secondary damage caused by the re-ingestion of a tooth fragment. The purpose is to prevent crack propagation through the gear rim, which would lead to catastrophic failure. In this context, identification of the initial crack location is crucial to determine the crack propagation path. Therefore, this paper presents a technique to determine and validate a constitutive material model and fracture locus for case-hardened spur gears. As the modelling of the surface-hardened layer is computationally intensive, it is necessary to homogenise the model. This paper comprehensively reviews and discusses the associated effects and errors. To determine the plastic behaviour of the case-hardened external gear (30CrNiMo8) and the nitrided internal gear (35CrAlNi7-10), the widely acknowledged Johnson–Cook material model is implemented using compression and Vickers indenter tests to define the necessary parameters. The fracture locus implementation is also based on the Johnson–Cook method and an axial shift of the fracture locus based on the hardness profile of the spur gears is determined by quasi-static pulsator tests. For validation, a project-specific gearbox test rig is used, enabling consistent ingestion of defined fragments. In addition, to check the likelihood of a tooth flank crack and to validate the results, a simplified ingestion experiment is performed. Full article

Increasing evidence highlights a robust correlation between the gut microbiota and bone diseases; however, the existence of a causal relationship between them remains unclear. In this study, we thoroughly examined the correlation between gut microbiota and skeletal diseases using genome-wide association studies. Linkage disequilibrium score regression and Mendelian randomization were used to probe genetic causality. Furthermore, the potential mediating role of neuropsychological states (i.e., cognition, depression, and insomnia) between the gut microbiota and bone diseases was evaluated using mediation analysis, with genetic colocalization analysis revealing potential targets. These findings suggest a direct causal relationship between Ruminococcaceae and knee osteoarthritis (OA), which appears to be mediated by cognitive performance and insomnia. Similarly, a causal association was observed between Burkholderiales and lumbar pelvic fractures, mediated by cognitive performance. Colocalization analysis identified a shared causal variant (rs2352974) at the TRAF-interacting protein locus for cognitive ability and knee OA. This study provides compelling evidence that alterations in the gut microbiota can enhance cognitive ability, ameliorate insomnia, and potentially reduce the risk of site-specific fractures and OA. Therefore, strategies targeting gut microbiota optimization could serve as novel and effective preventive measures against fractures and OA. Full article

Genome-wide association studies (GWAS) are one of the most common approaches to identify genetic loci that are associated with bone mineral density (BMD). Such novel genetic loci represent new potential targets for the prevention and treatment of fragility fractures. GWAS have identified hundreds of associations with BMD; however, only a few have been functionally evaluated. A locus significantly associated with femoral neck BMD at the genome-wide level is intronic SNP rs17040773 located in the intronic region of the anaphase-promoting complex subunit 1 (ANAPC1) gene (p = 1.5 × 10⁻⁹). Here, we functionally evaluate the role of ANAPC1 in bone remodelling by examining the expression of ANAPC1 in human bone and muscle tissues and during the osteogenic differentiation of human primary mesenchymal stem cells (MSCs). The expression of ANAPC1 was significantly decreased 2.3-fold in bone tissues and 6.2-fold in muscle tissue from osteoporotic patients as compared to the osteoarthritic and control tissues. Next, we show that the expression of ANAPC1 changes during the osteogenic differentiation process of human MSCs. Moreover, the silencing of ANAPC1 in human osteosarcoma (HOS) cells reduced RUNX2 expression, suggesting that ANAPC1 affects osteogenic differentiation through RUNX2. Altogether, our results indicate that ANAPC1 plays a role in bone physiology and in the development of osteoporosis. Full article

Current tests for plane stress characterization of fracture in automotive sheet metals include simple shear, uniaxial, plane strain, and biaxial tension, but there is a significant gap between shear and uniaxial tension. Presently, it remains uncertain whether the fracture strain experiences a reduction between simple shear and uniaxial tension or undergoes an exponential increase as the triaxiality decreases. Fracture in combined simple shear and tension is complicated by premature edge cracking in tension along with a strong sensitivity of fracture strain to the measurement lengthscale. To address these issues, several existing simple shear geometries were modified and evaluated, with a focus on obtaining approximately linear strain paths corresponding to combined uniaxial tension and simple shear suitable for experimental fracture characterization using digital image correlation (DIC). An experimental and numerical investigation was conducted using two planar geometries that do not require through-thickness machining and can be easily tested on a universal test frame. Finite-element analysis was used to investigate the influence of the notch eccentricity on the stress state and predicted fracture location. The most promising geometry in each coupon type was then selected and tested for a dual-phase advanced high-strength steel, DP1180. The performance of the two planar geometries was evaluated based on the linearity of strain and stress state, along with the location of fracture initiation. The best geometry was then used to evaluate and recalibrate the modified Mohr-Coulomb (MMC) fracture locus with data in combined shear and tension. The initial MMC calibration using four fracture tests that suppressed necking provided an accurate estimate for the fracture strain in combined uniaxial tension and simple shear. The MMC model correctly predicted a valley in the fracture strain between these two loading conditions. Full article

Hydrogen can degrade the mechanical properties of steel components, which is commonly referred to as “hydrogen embrittlement” (HE). Quantifying the effect of HE on the structural integrity of components and structures remains challenging. The authors investigated an X70 pipeline steel through uncharged and hydrogen-charged (notched) tensile tests. This paper presents a combination of experimental results and numerical simulations using a micro-mechanics-inspired damage model. Four specimen geometries and three hydrogen concentrations (including uncharged) were targeted, which allowed for the construction of a fracture locus that depended on the stress triaxiality and hydrogen concentration. The multi-physical finite element model includes hydrogen diffusion and damage on the basis of the complete Gurson model. Hydrogen-Assisted degradation was implemented through an acceleration of the void nucleation process, as supported by experimental observations. The damage parameters were determined through inverse analysis, and the numerical results were in good agreement with the experimental data. The presented model couples micro-mechanical with macro-mechanical results and makes it possible to evaluate the damage evolution during hydrogen-charged mechanical tests. In particular, the well-known ductility loss due to hydrogen was captured well in the form of embrittlement indices for the different geometries and hydrogen concentrations. The limitations of the damage model regarding the stress state are discussed in this paper. Full article

In this paper, a validation study of a recently proposed rate-dependent shell element fracture model using quasi-static and dynamic impact tests on square hollow sections (SHS) made from offshore high-tensile strength steel was presented. A rate-dependent forming limit curve was used to predict the membrane loading-dominated failure, while a rate-dependent ductile fracture locus was applied for predicting failure governed by bend loading. The predicted peak force and fracture initiation using the adopted material and fracture model agreed well with the experimental results. The fracture mode was also captured accurately. Further simulations were performed to discuss the importance of the inclusion of dynamic effects and the separate treatment of failure modes. Finally, the shortcomings of the common practice of treatment of rate-effects in low-velocity impact simulations involving fracture were highlighted. Full article