Search Results (60)

This paper aims to systematically investigate the out-of-plane yield performance, structural reliability, and sensitivity boundaries of minor-axis joints under construction overloads. To achieve this objective, a high-fidelity three-dimensional non-linear finite element framework incorporates precise solid continuum elements, contact non-linearities, and multi-linear material models, which is successfully validated against referenced experimental curves. Utilizing efficient Latin Hypercube Sampling integrated with response surface surrogate methodologies, a comprehensive stochastic parametric scanning is conducted to map the multi-dimensional scatter profiles and probabilistic capacity responses at targeted elastic thresholds. Furthermore, based on the upper-bound theorem of plasticity, closed-form analytical formulations defining the competition between independent and global plastic mechanisms are established and rigorously validated against extensive numerical parametric matrices. The core mechanical insights demonstrate that the column web thickness t_w and column section depth b overwhelmingly dictate nearly 60% of the joint’s elastic-limit resistance by directly defining the out-of-plane bending span. While the divergence between the two competitive plastic mechanisms remains minute under severe flange constraints, the research uncovers a critical localized interaction: in connections with a relatively thick t_w, the extended endplate thickness t_ep and endplate flexibility trigger a dynamic migration of the rotation axis between the longitudinal boundaries L₀ and L_a, significantly shortening the effective internal lever arm. For practical design applications, calibrating these formulations with a partial safety factor γ_M = 1.25 successfully establishes a dependable lower-bound design strength, providing a verified safety red-line for temporary cantilevered scaffolding installations. Full article

Accurate measurement of attenuation during acoustic wave propagation in viscoelastic solid media is of theoretical and practical significance. Conventional studies primarily rely on analogies to models of electromagnetic wave attenuation in non-ideal media. Many modern models of acoustic attenuation rely on continuum mechanics and complex material properties. Although there are similarities between acoustic and electromagnetic waves, conventional models overlook their fundamental physical differences and neglect the influence of particle-vibration damping in viscoelastic media. Additionally, in applications with a single-transmitter and dual-receiver configuration, the effects of specific characteristics on the measurement of the acoustic attenuation coefficient are eliminated in both the electric–acoustic conversion of the transmitting transducer and the acoustic–electric conversion of the receiving transducer. The discrepancies in geometric parameters (size and shape) between the two measurement modules lead to inconsistent frequency responses, thereby introducing measurement errors in acoustic attenuation. To address these issues, we investigate the coupling mechanism between particle vibration damping and wave propagation attenuation, derive an analytical expression for the acoustic attenuation coefficient that accounts for this coupling, and propose a new method for accurately measuring acoustic attenuation in viscoelastic solid media. The experimental results validate the theoretical predictions of acoustic attenuation. Full article

Transformative therapeutic innovation should not begin with a molecule—or even a molecular target. It should begin with a clearly defined unmet clinical need. Here, we present a seven-step Translational Therapeutic Development Roadmap that systematically connects an unmet medical need to a developable drug candidate through the disciplined sequence of (i) defining the need, (ii) understanding disease and resistance biology, (iii) building a mechanistic hypothesis, (iv) defining a target product profile (TPP), (v) molecular design and experimental validation, (vi) developability and manufacturability assessment, and (vii) clinical translation. A central conclusion emerging from this review is that resistance biology should be viewed not merely as a cause of therapeutic failure, but as a primary design input for next-generation therapeutic innovation. Our analysis identifies continuous alignment among unmet clinical needs, resistance biology, mechanistic hypothesis, molecular design, developability, and clinical translation as the defining characteristic of successful therapeutic development. We use dual-payload antibody–drug conjugates (ADCs) as a contemporary and highly illustrative case study of this resistance-informed therapeutic development approach. Single-payload ADCs such as trastuzumab deruxtecan and sacituzumab govitecan have transformed treatment across multiple solid tumors, yet most patients ultimately relapse through antigen loss, defective intracellular trafficking, drug efflux, payload-target alterations, and tumor heterogeneity, creating an emerging post-ADC treatment gap. Dual-payload ADCs, which deliver two mechanistically distinct warheads from a single antibody, represent a form of molecular combination therapy designed to increase the barrier to resistance and address multiple escape pathways simultaneously, as well as provide a clinically relevant model for resistance-informed therapeutic design. Using dual-payload ADCs as a worked example, we demonstrate how resistance biology directly informs payload pairing, molecular architecture, conjugation strategy, experimental validation, and developability. Our analysis indicates that successful dual-payload ADC design depends not simply on combining two cytotoxic payloads, but on selecting complementary mechanisms with non-overlapping resistance liabilities while satisfying predefined target product profiles and manufacturability requirements. We further summarize resistance-guided payload pairing strategies, including topoisomerase I plus tubulin inhibitors, topoisomerase I plus DNA-damage-response inhibitors, cytotoxic plus immunomodulatory payloads, and cell-permeable plus non-permeable combinations; the conjugation chemistries that enable defined dual-payload products; the preclinical validation, pharmacological optimization, and developability hurdles that separate promising biology from viable therapeutics; and the rapidly expanding clinical landscape, including the first-in-human program KH815 and emerging bispecific dual-payload constructs. Finally, we demonstrate that the same translational roadmap extends beyond ADCs to radiopharmaceutical conjugates, multispecific antibodies, targeted protein degraders, and cell and gene therapies, indicating that it represents a general framework for therapeutic innovation rather than an ADC-specific strategy. Collectively, this review supports the concept that therapeutic innovation is most successful when unmet clinical needs, resistance biology, molecular design, developability, and clinical translation are considered as an integrated continuum rather than as independent stages of drug discovery. This Translational Therapeutic Development Roadmap provides an organizing framework for guiding the rational development of next-generation targeted therapeutics across diverse therapeutic modalities. Full article

Macrophages are highly plastic innate immune cells that adopt context-dependent phenotypes along a continuum, integrating developmental origin with local microenvironmental cues rather than conforming to discrete M1/M2 states. This review delineates the molecular circuits shaping macrophage identity—TLR/cytokine signaling, microRNA networks, metabolic rewiring, and epigenetic mechanisms including histone lactylation—and traces how circulating monocyte subsets contribute to tissue macrophage diversity. We examine macrophage plasticity across a broad disease spectrum—oncology, autoimmune and rheumatic diseases, inflammatory bowel disease, infectious diseases, metabolic disorders, and neurological conditions—showing that the pathogenic phenotype is strikingly context-dependent: for instance, M2-like tumor-associated macrophages promote immune evasion in solid tumors, whereas M1-skewed programs drive tissue damage in autoimmunity. Soluble markers (sCD163, sCD14, soluble mannose receptor) are emerging biomarkers of disease activity and prognosis. High-dimensional flow cytometry and mass cytometry (CyTOF) bridge molecular biology and clinical phenotyping, enabling integrated readouts of surface phenotype, intracellular signaling, and metabolic state. Therapeutic strategies discussed include selective tumor-associated macrophage (TAM) reprogramming, chimeric antigen receptor (CAR)-M cell therapies, and biomaterial-based platforms. Future priorities encompass spatially resolved multi-omics, epigenetic and metabolic targeting, and macrophage-centered vaccine approaches. Standardized cytometry panels will be essential for biomarker-guided stratification and context-specific interventions. Full article

The structural strength requirements for timber buildings have been significantly tightened in the second generation of Eurocodes (EN 1990:2023, EN 1991-1-7), which poses a particular challenge for solid timber frames with a beam-and-column structure, where the transfer of tensile forces via dowel connections is inherently limited. Existing multiscale frameworks for timber post-and-beam robustness lack operational detail at each scale, and no validated workflow currently bridges joint-level continuum damage mechanics and frame-level progressive failure analysis in compliance with the second-generation Eurocodes. This paper addresses this gap by proposing an effective two-scale finite element method (FEM) modelling framework for assessing the strength of such frames during column removal. Existing multiscale models describing the strength of timber structures with beam-and-column systems lack the operational details necessary to integrate failure mechanics at the joint level and progressive failure modelling at the frame level within a single, validated workflow. In this paper, this gap is addressed through three specific contributions: a physically modified quadratic Hashin-type failure criterion for timber, which eliminates the non-physical increase in shear strength under combined stress states perpendicular to the grain; a two-scale structure based on the finite element method (FEM), in which the results of continuous damage mechanics at the joint level directly parameterise non-linear joint elements with six degrees of freedom at the frame level, taking into account coupled directional wear and erosion of the elements; and quantitative validation of both scales against experimental data and the conversion factors for characteristic values of the second generation of Eurocode 5 (prEN 1995-1-1:2023). At the connection level, the simulated strength and stiffness values agree with the experiments to within an error of no more than 5%. At the frame level, the model correctly reproduces the non-linear ‘load–displacement’ relationship, the sequence of joint failure, and the axial forces in the chain line for vertical displacements up to 390 mm, which corresponds to experimental observations. Full article

Hydraulic fracture network initiation and propagation in tight sandstone are strongly controlled by mineral heterogeneity and fluid–solid interaction. However, existing numerical models still have limited capability in simultaneously representing multi-mineral distributions and dynamically coupled fracture-fluid processes. In this study, a two-dimensional polygonal discrete element fluid–solid coupled model was established based on mineralogical images of tight sandstone. Compared with conventional continuum-based approaches, the proposed model is better suited to describing fracture initiation, branching, and network evolution in multi-mineral granular media. Under dimensionless operating conditions calibrated against field data, coupled and uncoupled formulations were systematically compared to evaluate the role of hydro-mechanical interaction during hydraulic fracturing. The coupled simulations generated consistently more fractures than the uncoupled simulations over the investigated injection-rate range, with an average increase of 28.7% and a maximum increase of 67.2%. Compared with the uncoupled model, the coupled model also predicted higher breakdown pressures and stronger fracture-tip pressure concentrations, and the breakdown pressure increased with injection rate. Under low injection rates, the coupled formulation reproduced pressure-buildup-driven fracture-tip advance, whereas the uncoupled formulation failed to sustain fracture propagation. Under higher injection rates, the coupled formulation produced multilayered and highly branched fracture networks, while the uncoupled formulation mainly generated simple first-order branching. These results demonstrate that hydro-mechanical coupling is a controlling mechanism for fluid-energy dissipation, fracture-tip pressure evolution, and complex fracture network formation in tight sandstone. This study provides an image-based polygonal DEM framework for evaluating hydro-mechanical fracture network evolution in multi-mineral tight sandstone. Full article

With the advancement of aerospace equipment toward high-speed and heavy-duty applications, conventional forced lubrication systems are facing significant challenges in terms of reliability and adaptability to complex operating conditions. Porous medium materials, owing to their unique self-lubricating and oil-retention capabilities, are regarded as an ideal lubrication solution. However, their seepage behavior is governed by the strong coupling effects of microscopic pore structures and fluid physicochemical properties, the mechanisms of which remain inadequately understood, thereby severely constraining the design and application of high-performance lubricating materials. To address this, this paper systematically reviews recent research progress on seepage behavior in porous media, with the aim of establishing a correlation between microstructural characteristics and macroscopic performance. Starting from the characterization of porous media, this work comprehensively analyzes the structure–seepage relationships in porous polymers, metal foams, and porous ceramics, and constructs a multi-scale theoretical framework encompassing macroscopic continuum theories, mesoscopic lattice Boltzmann methods (LBM), pore network models, and microscopic molecular dynamics. The advantages and limitations of experimental measurements and numerical simulation approaches are also compared. In particular, this study critically highlights the current neglect of key interfacial parameters such as surface wettability and pore roughness, and proposes an in-depth investigation into the seepage mechanisms of polyimide porous cage materials based on LBM. Furthermore, the potential application of emerging research paradigms such as data-driven approaches and intelligent computing in seepage studies is discussed. Finally, it is emphasized that future efforts should focus on developing deeply integrated cross-scale simulation methodologies, strengthening multi-physics coupling and artificial intelligence-assisted research, and advancing the development of intelligent porous lubricating materials with gradient structures or stimulus-responsive characteristics. This is expected to provide a solid theoretical foundation and technical pathway for the rational design and optimization of high-performance lubrication systems. Full article

Material failure by adiabatic shear is analyzed in viscoplastic metals that can demonstrate up to three distinct softening mechanisms: thermal softening, ductile fracture, and melting. An analytical framework is constructed for studying simple shear deformation with superposed static pressure. A continuum power-law viscoplastic formulation is coupled to a ductile damage model and a solid–liquid phase transition model in a thermodynamically consistent manner. Criteria for localization to a band of infinite shear strain are discussed. An analytical–numerical method for determining the critical average shear strain for localization and commensurate stress decay is devised. Averaged results for a high-strength steel agree reasonably well with experimental dynamic torsion data. Calculations probe possible effects of ductile fracture and melting on shear banding, and vice versa, including influences of cohesive energy, equilibrium melting temperature, and initial defects. A threshold energy density for localization onset is positively correlated to critical strain and inversely correlated to initial defect severity. Tensile pressure accelerates damage softening and increases defect sensitivity, promoting shear failure. In the present steel, melting is precluded by ductile fracture for loading conditions and material properties within realistic protocols. For this steel, if conduction, fracture, and damage softening are artificially suppressed, melting is confined to a narrow region in the core of the band. However, for other metals with vastly different physical properties, or for more diverse loading conditions, melting has not been unequivocally ruled out, even if fracture and conduction are permitted. Full article

Reservoir stimulation is a critical technique for the efficient development of coalbed methane (CBM), playing a significant role in improving permeability. Controlled shock wave fracturing, as an emerging stimulation method, offers advantages such as safety and high energy utilization, making it a promising candidate for CBM reservoir enhancement. Due to the substantial potential of deep CBM reservoirs, conventional physical simulations and field experiments are limited in accurately analyzing the fracturing effects. Research on the fracture propagation and damage evolution of coal rock under the influence of different geological and engineering parameters is limited, hindering the determination of key operational parameters. In this study, a coupled mathematical model of solid mechanics and damage continuum mechanics is established using the finite element method, alongside a geometric model, to investigate fracture propagation characteristics under the influence of geological and engineering factors. The core contribution of this work is a systematic numerical analysis that clarifies the controlling effects of key parameters. The main conclusions are as follows: (1) a high stress contrast (≥6 MPa) favors fracture extension along the direction of the maximum principal stress while inhibiting the expansion of the damage area; (2) the increase in the orientation of natural fissures and the angle of horizontal stress inhibits the propagation of fractures and the growth of damage area; (3) engineering parameters exert a considerable effect on fracture propagation and multiple shock cycles (≥2 times) and high peak pressure (≥250 MPa) are conducive to fracture formation; and (4) a key distinguishing feature is the formation of radioactive fractures induced by high-energy shock waves, which are beneficial for enhancing communication between rock layers and natural fractures. Compared to hydraulic fracturing, the shock wave method achieves distinctly faster fracture extension in a shorter time, highlighting its unique advantage for improving coalbed permeability and porosity. This study extends the numerical simulation research on controlled shock waves in deep coal seams, elucidates the dynamic response of fracture propagation and damage evolution under the control of geological and engineering parameters, reveals the sensitivity of key parameters to fracture extension, and provides a critical basis for the selection and optimization of operational parameters in field applications of shock wave fracturing. Full article

Accurate conjugate heat transfer (CHT) analysis is critical to the thermal management of hypersonic vehicles operating in rarefied environments, where non-equilibrium gas dynamics dominate. While numerous sophisticated CHT solvers exist for continuum flows, they are physically invalidated by rarefaction effects. This paper presents a novel partitioned coupling framework that bridges this methodological gap by utilizing the preCICE library to non-intrusively integrate the Direct Simulation Monte Carlo (DSMC) method, implemented in SPARTA, with the finite element method (FEM) via FEniCS for high-fidelity simulations of rarefied hypersonic CHT. The robustness and accuracy of this approach are validated through three test cases: a quasi-1D flat plate benchmark confirms the fundamental coupling mechanism against a reference finite difference solution; a 2D flat-nosed cylinder demonstrates the capability of the framework to handle highly non-uniform heat flux distributions and resolve the ensuing transient thermal response within the solid; finally, a standard cylinder case confirms the compatibility with curved geometries and its stability and accuracy in long-duration simulations. This work establishes a validated and accessible pathway for high-fidelity aerothermal analysis in rarefied gas dynamics, effectively decoupling the complexities of multi-physics implementation from the focus on fundamental physics. Full article

Modeling the pre-extraction of coalbed methane presents a significant mathematical challenge due to the complex interplay of multiple physical fields. This paper presents a robust mathematical model based on a thermo-hydro-mechanical damage (THMD) framework to describe this process. The model is formulated as a system of coupled, non-linear partial differential equations (PDEs) that integrate governing equations for heat transfer, fluid seepage, and solid mechanics with a damage evolution law derived from continuum damage mechanics. A key contribution of this work is the integration of this multi-physics model, solved numerically using the Finite Element Method (FEM), with a statistical modeling approach using Response Surface Methodology (RSM) and Analysis of Variance (ANOVA). This integrated framework allows for a systematic analysis of the model’s parameter space and a rigorous quantification of sensitivities. The ANOVA results reveal that the model’s damage output is most sensitive to the borehole diameter (F = 2531.51), while the effective extraction radius is predominantly governed by the initial permeability (F = 4219.59). This work demonstrates the power of combining a PDE-based multi-physics model with statistical metamodeling to provide deep, quantitative insights for optimizing gas extraction strategies in deep, low-permeability coal seams. Full article

A simple Lagrangian travelling slice model has been successfully used to predict the relations between the process parameters and the strand temperatures in the continuous casting of steel. The present paper aims to include a simple macrosegregation, grain structure and mechanical stress and deformation model on top of the thermal slice framework. The basis of all the mentioned models is the slice heat-conduction model that considers the complex heat extraction mechanisms in the mould, with the sprays, rolls, and through radiation. Its main advantage is the fast calculation time, which is suitable for the online control of the caster. The macroscopic thermal and species transfer models are based on the continuum mixture theory. The macrosegregation model is based on the lever rule microsegregation model. The thermal conductivity and species diffusivity of the liquid phase are artificially enhanced to consider the convection of the melt. The grain structure model is based on cellular automata and phase-field concepts. The calculated thermal field is used to estimate the thermal contraction of the solid shell, which, in combination with the metallostatic pressure, drives the elastic-viscoplastic solid-mechanics models. The solution procedure of all the models is based on the meshless radial basis function generated finite difference method on the macroscopic scale and the meshless point automata concept on the grain structure scale. Simulation results point out the areas susceptible to hot tearing. Full article

Fluid flow in microporous and nanoporous media exhibits unique behaviors that deviate from classical continuum predictions due to dominant surface forces at small scales. Understanding these microscale flow mechanisms is critical for optimizing unconventional reservoir recovery and other energy applications. This review provides a comparative analysis of the existing literature, highlighting key advances in experimental techniques, theoretical models, and numerical simulations. We discuss how innovative micro/nanofluidic devices and high-resolution imaging methods now enable direct observation of confined flow phenomena, such as slip flow, phase transitions, and non-Darcy behavior. Recent theoretical models have clarified scale-dependent flow regimes by distinguishing microscale effects from macroscopic Darcy flow. Likewise, advanced numerical simulations—including molecular dynamics (MD), lattice Boltzmann methods (LBM), and hybrid multiscale frameworks—capture complex fluid–solid interactions and multiphase dynamics under realistic pressure and wettability conditions. Moreover, the integration of artificial intelligence (e.g., data-driven modeling and physics-informed neural networks) is accelerating data interpretation and multiscale modeling, offering improved predictive capabilities. Through this critical review, key phenomena, such as adsorption layers, fluid–solid interactions, and pore surface heterogeneity, are examined across studies, and persistent challenges are identified. Despite notable progress, challenges remain in replicating true reservoir conditions, bridging microscale and continuum models, and fully characterizing multiphase interface dynamics. By consolidating recent progress and perspectives, this review not only summarizes the state-of-the-art but underscores remaining knowledge gaps and future directions in micro/nanopore flow research. Full article

As a generalization of the symmetry of the stress tensor of continuum mechanics, the paper investigates symmetry properties arising in models of magneto- and electro-mechanical interaction. First, the balance of angular momentum is considered, thus obtaining a symmetry condition that is applied as a mathematical constraint on admissible constitutive equations. Next, thermodynamic restrictions are also investigated and, among others, a further symmetry condition is determined. The joint validity of the two symmetry conditions implies that the dependence on electromagnetic fields has to be through variables involving deformation gradients. These variables constitute two classes that prove to be Euclidean invariants. The simplest selection of the variables is just that of Lagrangian fields in the literature. Furthermore, the variables of one class allow a positive magnetostriction and of the other one allow a negative magnetostriction. Some applications to (NO) Fe-Si are outlined. The use of entropy production as a constitutive function allows generalization to dissipative and heat-conducting electromagnetic solids. Full article

This study addresses an existing gap in the literature by providing a comparative analysis of various adhesive model representation approaches, using cohesive zone models—both local and continuum models. Through a systematic investigation of stress distribution and force–displacement characteristics across different modeling techniques, we reveal the advantages and limitations of each method. This study provides a comparison of various adhesive modeling approaches, including single-row cohesive elements, interfacial elements, middle cohesive elements, and single-row continuum solid elements, highlighting their effects on stress distribution and failure modes in single lap joints across a range of adherend thicknesses and overlap lengths. The findings demonstrate that the choice of modeling techniques yields a similar prediction of failure modes in single lap joints under tensile loading. Consequently, choosing among these methods can be guided by the level of detail in capturing localized damage mechanisms. The results offer a foundation for informed decision making in adhesive modeling, with implications for improving joint design and reliability in real-world applications. Full article