Search Results (56)

Background: Human African trypanosomiasis (HAT), caused by Trypanosoma brucei, is a neglected tropical disease with limited treatments, highlighting the pressing need for new drugs. Cell division cycle-2-related kinase 12 (CRK12), a pivotal protein involved in the cell cycle regulation of T. brucei, has emerged as a promising therapeutic target for HAT, yet effective CRK12 inhibitors remain lacking. Methods: An integrated strategy combining computational modeling, virtual screening, molecular dynamics (MD) simulations, and experimental validation was adopted to discover potential inhibitors against CRK12. By using the predicted and refined 3D structure of CRK12 from AlphaFold2 and MD simulation, over 1.5 million compounds were screened based on multiple-scale molecular docking, and 26 compounds were selected for evaluation of biological activity based on anti-T. brucei bioassays. Dose–response curves were generated for the most potent inhibitors, and the interaction mechanism between the top four compounds and CRK12 was explored by MD simulations and MM/GBSA binding free energy analysis. Results: Of the 26 compounds, six compounds demonstrated sub-micromolar to low-micromolar IC₅₀ values (0.85–3.50 µM). The top four hits, F733-0072, F733-0407, L368-0556, and L439-0038, exhibited IC₅₀ values of 1.11, 1.97, 0.85, and 1.66 µM, respectively. Binding free energy and energy decomposition analyses identified ILE335, VAL343, PHE430, ALA433, and LEU482 as hotspot residues for compound binding. Hydrogen bonding analysis demonstrated that these compounds can form stable hydrogen bonds with the hinge residue ALA433, ensuring their stable binding within the active site. Conclusions: This study establishes a robust and cost-effective pipeline for CRK12 inhibitor discovery, identifying several novel inhibitors demonstrating promising anti-HAT activity. The newly discovered scaffolds exhibit structural diversity distinct from known CRK12 inhibitors, providing valuable lead compounds for anti-trypanosomal drug development. Full article

Steel slag aggregate (SSA), as a high-performance and sustainable material, has demonstrated significant potential in enhancing the mechanical properties of concrete and improving the bond behavior between reinforcement and the concrete matrix, thereby contributing to the seismic resilience of steel slag concrete columns (SSCCs). Nevertheless, the underlying mechanism through which SSA influences the seismic performance of SSCCs remains insufficiently understood, and current analytical models fail to accurately capture the effects of bond strength on structural behavior. In this study, a comprehensive experimental program comprising central pull-out tests and quasi-static cyclic loading tests was conducted to investigate the influence of SSA on bond strength and the seismic response of SSCCs. Key seismic performance indicators, including the hysteresis curve, equivalent viscous damping ratio, and ductility coefficient, were evaluated. The role of bond strength in governing energy dissipation and ductility characteristics was elucidated in detail. The results indicate that bond strength significantly affects the seismic performance of SSCC components. At an SSA replacement ratio of 40%, the specimens show optimal performance: energy dissipation capacity increases by 11.3%, bond–slip deformation in the plastic hinge region decreases by 10%, and flexural deformation capacity improves by 9% compared to the control group. However, when the SSA replacement exceeds 60%, the performance metrics are similar to those of ordinary concrete, showing no significant advantages. Based on the experimental findings, a modified bond–slip constitutive model for the steel slag concrete–reinforcement interface is proposed. Furthermore, a finite element model incorporating bond–slip effects is developed, and its numerical predictions exhibit strong agreement with the experimental results, effectively capturing the lateral load-carrying capacity and stiffness degradation behavior of SSCCs. Full article

Ru-based catalysts manifest unparalleled hydrogen evolution reaction (HER) performance, but the hydrolysis of Ru species and the accumulation of corresponding reaction intermediates greatly limit HER activity and stability. Herein, Ru nanoparticle assemblies modified with single Mo atoms and supported on N-incorporated graphene (referred to as MoRu-NG) are compounded via hydrothermal and chemical vapor deposition (CVD) methods. The incorporation of single Mo atoms into Ru lattices modifies the local atomic milieu around Ru centers, significantly improving HER catalytic behavior and stability. More specifically, MoRu-NG achieves overpotentials of 53 mV and 28 mV at 10 mA cm⁻², with exceptional stability in acidic and alkaline seawater solutions, respectively. In MoRu-NG, Ru atoms have a special electronic structure and thus possess optimal hydrogen adsorption energy, which indicates that excellent HER activity mainly hinges upon Ru centers. To be specific, the d-electron orbitals of Ru atoms are close to half full, giving Ru atoms moderate bond energy for the assimilation and release of hydrogen, which is beneficial for the conversion of reaction intermediates. Moreover, the incorporation of single Mo atoms facilitates the formation of O and O’-bidentate ligands, significantly enhancing the structural stability of MoRu-NG in universal-pH seawater electrolysis. This work advances a feasible construction method of hexagonal octahedral configuration (Ru-O-Mo-N-C) and provides a route to synthesize an efficient and stable catalyst for electrocatalytic HER in universal-pH seawater. Full article

In recent years, researchers have focused on the usability of fiber-reinforced polymer (FRP) bars due to their lightweight, corrosion-resistant, and eco-friendly characteristics. Geopolymers, as low-carbon alternatives to traditional binders, aim to reduce CO₂ emissions in concrete production. The bond strength between FRP bars and concrete is critical for the load-bearing capacity and deformation characteristics of reinforced elements. The objectives of this work are to investigate the bond performance of GFRP bars in chopped glass and basalt fiber-added geopolymer concrete using hinged beam tests. Since the hinged beam test accurately represents the behavior of real bending elements, this test method was selected as a main bonding test. Initially, three geopolymer mixtures with Ms modulus values of 1.2, 1.3, and 1.4 were prepared and tested. The mixture with a modulus of 1.2 Ms, achieving a compressive strength of 56.53 MPa, a flexural strength of 3.54 MPa, and a flow diameter of 57 cm, was chosen for beam production due to its optimal workability and strength. After mechanical and workability tests, SEM analysis was performed to evaluate its internal structure. For evaluating the bond performance of GFRP bars, 12 geopolymer beam specimens were prepared, incorporating varying fiber types (chopped glass fiber or basalt fiber) and embedment lengths (5 Ø or 20 Ø). Hinged beam tests revealed that the bond strengths of glass and basalt fiber-added mixtures were up to 49% and 37% higher than that of the control geopolymer concrete, respectively. It was concluded that incorporating fibers positively influenced the bond between geopolymer concrete and GFRP bars, with glass fibers proving more effective than basalt fibers. These findings enhance the understanding of bond mechanisms between GFRP bars and geopolymer concrete, emphasizing their potential for sustainable and durable construction in both industrial and scientific applications. Full article

The frequent occurrence of major earthquakes highlights the structural challenges posed by long-period ground motions (LPGMs). This study investigates the seismic performance and resilience of five reinforced concrete (RC) columns with different high-strength steel bars under LPGM-induced cyclic loading, both experimentally and numerically. The results show that low-bond and debonded high-strength steel bars significantly enhance self-centering capabilities and reduce residual drift, with lateral force reductions of 7.6% for normal cyclic loading and 19.2% for multiple reversed cyclic loading. The concrete damage in the hinge zone of the columns was increased; however, the significant inside damage of the concrete near the steel bars made it easier to restore the columns for the damage accumulation caused by multiple loading. Based on the experiment, a numerical model was developed for the columns, and a simplified model was proposed to predict energy dissipation capacity, providing practical design methods for resilient RC structures that may be attacked by LPGMs. Full article

The selection of an appropriate fabric for technical applications, such as protective masks, hinges on a thorough understanding of the fabric’s physical and mechanical properties. This study addresses the challenge of selecting the optimal material structure for the upper layer of a protective mask, aiming to ensure adequate breathability while providing effective filtration against airborne particles and contaminants. We assessed and compared the physical–mechanical properties of five polymer spun-bond nonwoven fabrics from different suppliers. Our comprehensive evaluation included, as follows: a visual inspection; light permeability analysis; mass and thickness measurements; elongation and tensile strength tests; breathing resistance assessments; and filter penetration tests with paraffin oil. The results revealed significant variations in performance among the samples, with one fabric consistently outperforming the others across multiple parameters. Notably, this top-performing fabric met or exceeded the EN 149:2001+A1:2009 standard for breathing resistance and filtration efficiency and, in combination with additional filter layers, met the requirements or exceeded class FFP2 (filtering face piece). This study underscores the importance of meticulous material selection and quality control in optimizing PPE (personal protective equipment) performance and user safety, providing valuable insights for mask manufacturers and healthcare professionals. Full article

This paper discusses the iteration of a seismic retrofit solution for shear-deficient end regions of 19 reinforced concrete (RC) moment-resisting frame (MRF) T-beams located in a 12-story RC MRF building in downtown Los Angeles, California. Local strengthening with externally bonded (EB) fiber-reinforced polymer (FRP) fabric was chosen as the preferred retrofit strategy due to its cost-effectiveness and proven performance. The FRP-shear-strengthening scheme for the deficient end-hinging regions of the MRF beams was designed and evaluated through large-scale cyclic testing of three replica specimens. The specimens were constructed at 4/5 scale and cantilever T-beam configurations with lengths of 3.40 m or 3.17 m. The cross-sectional geometry was 0.98 × 0.61 m with a top slab of 1.59 m in width and 0.12 m in thickness. Applied to these specimens were three different retrofit configurations, tested sequentially, namely: (a) unanchored continuous U-wrap; (b) anchored continuous U-wrap with conventional FRP-embedded anchors at the ends; and (c) fully closed external FRP hoops made of discrete FRP U-wrap strips and FRP through-anchors that penetrate the top slab and connect both ends of the FRP strips, combined with intermediate crack-control joints. The strengthening concept with FRP hoops precluded the premature debonding and anchor pullout issues of the two more conventional retrofit solutions and, despite a more challenging and labor-intensive installation, was selected for the in-situ implementation. The proposed hooplike EB-FRP shear-strengthening scheme enabled the deficient MRF beams to overcome a 30% shear overstress at the end-yielding region and to develop high-end rotations (e.g., 0.034 rad [3.4% drift] at peak and 0.038 rad [3.8% drift]) at strength loss for a beam that, otherwise, would have prematurely failed in shear. These values are about 30% larger than the ASCE 41 prescriptive value for the Life Safety (LS) performance objective. Energy dissipation achieved with the fully closed scheme was 108% higher than that of the unanchored FRP U-wrap and 45% higher than that of the FRP U-wrap with traditional embedded anchors. The intermediate saw-cut grooves successfully attracted crack formation between the strips and away from the FRP reinforcement, which contributed to not having any discernable debonding of the strips up to 3% drift. This paper presents the experimental evaluation of the three large-scale laboratory specimens that were used as the design basis for the final retrofit solution. Full article

The application of machine learning (ML) in structural engineering is receiving increasing attention recently. This paper experimentally studies three self-restoring reinforced concrete (SRRC) columns reinforced with low-bond ultra-high strength rebars, to first discuss the reliability and evaluation of the SRRC columns under multiple reversed cyclic (MRC) loads induced by strong earthquakes, and to also first introduce the Transformer method into the analysis and discussion of structural tests. The tests confirmed the superior seismic behavior and high self-centering performance of the columns and presented how MRC loads affect the seismic performance of SRRC columns in terms of the lateral load-carrying capacity and energy dissipation capacity. Superior to conventional methods, a high-accuracy Transformer-based model is proposed to evaluate the plastic hinge height (PHL) of the tested SRRC columns compared with the other three algorithms (MLP, KNN, and XGBoost). Furthermore, the Shapley Additive exPlanations (SHAP) approach is adopted to explain the insight relationship between the structural parameters and PHL of the columns. Full article

Secretory IgA (SIgA) presents a promising avenue for mucosal immunotherapy yet faces challenges in expression, purification, and stability. IgA exists in two primary isotypes, IgA1 and IgA2, with IgA2 further subdivided into two common allotypes: IgA2m(1) and IgA2m(2). The major differences between IgA1 and IgA2 are located in the hinge region, with IgA1 featuring a 13-amino acid elongation that includes up to six O-glycosylation sites. Furthermore, the IgA2m(1) allotype lacks a covalent disulfide bond between heavy and light chains, which is present in IgA1 and IgA2m(2). While IgA1 demonstrates superior epitope binding and pathogen neutralization, IgA2 exhibits enhanced effector functions and stability against mucosal bacterial degradation. However, the noncovalent linkage in the IgA2m(1) allotype raises production and stability challenges. The introduction of distinct single mutations aims to facilitate an alternate disulfide bond formation to mitigate these challenges. We compare four different IgA2 versions with IgA1 to further develop secretory IgA antibodies against SARS-CoV-2 for topical delivery to mucosal surfaces. Our results indicate significantly improved expression levels and assembly efficacy of SIgA2 (P221R) in Nicotiana benthamiana. Moreover, engineered SIgA2 displays heightened thermal stability under physiological as well as acidic conditions and can be aerosolized using a mesh nebulizer. In summary, our study elucidates the benefits of stability-enhancing mutations in overcoming hurdles associated with SIgA expression and stability. Full article

In medium- to high-rise buildings, single shear walls (SSWs) are often used to resist lateral force due to wind and earthquakes. They are designed to dissipate seismic energy mainly through plastic hinge zones at the base. However, they often display large post-earthquake deformations that can give rise to many economic and safety concerns within buildings. Hence, the primary objective of this research study is to minimize residual deformations in existing SSWs located in the Western and Eastern seismic zones of Canada, thereby enhancing their resilience and self-centering capacity. To that end, four SSWs of 20 and 15 stories, located in Vancouver and Montreal, were meticulously designed and detailed per the latest Canadian standards and codes. The study assessed the impact of three innovative strengthening schemes on the seismic response of these SSWs through 2D nonlinear time history (NLTH) analysis. All three strengthening schemes involved the application of Externally Bonded Fiber Reinforced Polymer (EB-FRP) to the shear walls. Accordingly, a total of 208 NLTH analyses were conducted to assess the effectiveness of all strengthening configurations. The findings unveiled that the most efficient technique for reducing residual drift in SSWs involved applying three layers of vertical FRP sheets to the extreme edges of the wall, full FRP wrapping the walls, and full FRP wrapping of the plastic hinge zone. Nevertheless, it is noteworthy that implementing these strengthening schemes may lead to an increase in bending moment and base shear force demands within the walls. Full article

This paper investigates the seismic performance of prefabricated segmental bridge columns (PSBCs) with hybrid post-tensioned tendons and energy dissipation (ED) bars under cyclic loading. PSBCs with unbonded and hybrid bonded prestressed tendons and columns incorporating ED bars are designed to improve the lateral strength, energy dissipation, and limit the residual drift. The PSBCs under cyclic loading were investigated using the three-dimensional finite element (FE) modeling platform ABAQUS. The FE model was calibrated against experimental results, with an overall error of less than 10%. The seismic performance of the proposed PSBCs was evaluated based on critical parameters, including lateral strength, residual plastic displacement, and the energy dissipation capacity. The results show that bonding the tendons in the plastic hinge region as opposed to the overall bonding along the column leads to a better cyclic performance. The lateral strength, and recentering abilities are further improved by bonding tendons up to 2/3 of the length in the plastic hinge region, along with 100–300 mm in the footing. It was also found that selecting a longitudinal length of ED bars crossing multiple precast segmental joints and having a circumferential spread of 70–90% of core concrete results in a higher bearing capacity and energy dissipation compared to ED bars crossing the single joint. Full article

Among the techniques utilized for strengthening masonry structures with advanced materials, the adoption of near-surface mounted (NSM) titanium rods stands out as a promising method for increasing the flexural and shear strength of masonry structures. This method is also known as Bed Joint Reinforcement. Ensuring an effective performance of this technique hinges on establishing a strong bond between the NSM reinforcement and the substrate masonry material. The primary objective of this project was to study the mechanics of this bond using NSM threaded and smooth titanium rods while scrutinizing the impact of key parameters on bond performance. Variables under investigation encompassed the rod type (smooth and threaded), bond length, and the material used to fill the groove (type of mortars). It was found that threaded rods outperformed all other types investigated, and pull-out strengths can be significantly improved through careful selection and optimization of the mortar type and bond length. Full article

Shape memory and self-healing polymer nanocomposites have attracted considerable attention due to their modifiable properties and promising applications. The incorporation of nanomaterials (polypyrrole, carboxyl methyl cellulose, carbon nanotubes, titania nanotubes, graphene, graphene oxide, mesoporous silica) into these polymers has significantly enhanced their performance, opening up new avenues for diverse applications. The self-healing capability in polymer nanocomposites depends on several factors, including heat, quadruple hydrogen bonding, π–π stacking, Diels–Alder reactions, and metal–ligand coordination, which collectively govern the interactions within the composite materials. Among possible interactions, only quadruple hydrogen bonding between composite constituents has been shown to be effective in facilitating self-healing at approximately room temperature. Conversely, thermo-responsive self-healing and shape memory polymer nanocomposites require elevated temperatures to initiate the healing and recovery processes. Thermo-responsive (TRSMPs), light-actuated, magnetically actuated, and Electrically actuated Shape Memory Polymer Nanocomposite are discussed. This paper provides a comprehensive overview of the different types of interactions involved in SMP and SHP nanocomposites and examines their behavior at both room temperature and elevated temperature conditions, along with their biomedical applications. Among many applications of SMPs, special attention has been given to biomedical (drug delivery, orthodontics, tissue engineering, orthopedics, endovascular surgery), aerospace (hinges, space deployable structures, morphing aircrafts), textile (breathable fabrics, reinforced fabrics, self-healing electromagnetic interference shielding fabrics), sensor, electrical (triboelectric nanogenerators, information energy storage devices), electronic, paint and self-healing coating, and construction material (polymer cement composites) applications. Full article

Reinforced concrete buildings are prone to collapse during seismic events due to the brittle shear failure of non-seismic beam-column joints (BCJ). In this study, two one-third scale reinforced concrete (RC) frames incorporating various non-seismic details were tested under lateral cyclic loading. One of the RC frames was used as control, while the other was strengthened using externally bonded carbon-fiber-reinforced polymer (CFRP) sheets in a L-Shaped configuration with particular attention to anchorage to evade debonding. For the strengthening process, L-shaped CFRP sheets were bonded to the inner face of columns, extended on beams both above and below the joint up to a hinge length. To avert debonding, the L-shaped CFRP sheets were fully wrapped with CFRP sheets around the column, both near the joint and at the end of the sheet. The sheets were also wrapped around the beam, through two slots in the slab that were adjacent to the beam-column interface and at the far end of the sheet. Test results confirmed that the installation of CFRP sheets in an L-shaped configuration altered the brittle-shear failure mechanism of the beam-column joints to a ductile failure by repositioning the hinges away from the columns. Additionally, the proposed anchorage method successfully eradicated the debonding and peel-off of the CFRP sheets. Moreover, strengthening with the CFRP sheets in the L-shaped configuration enhanced the strength and ductility of the RC frame by 45% and 43%, respectively. According to the findings of this study, the application of L-shaped CFRP sheets proved effective in strengthening RC frame structures. Full article

Multi-degree-of-freedom piezoelectric motors have the advantages of high torque and resolution, simple structure, and direct drive, which are widely used in robot wrist joints, deep-sea mechanisms, medical equipment, and space mechanisms. To solve the problems of high force/torque coupling degree and ball low stator and rotor bonding strength of the traditional traveling wave type three-degree-of-freedom piezoelectric spherical motor, a new structure of ball-hinged piezoelectric spherical motor is proposed. Through coordinate transformation and force analysis, the driven mathematical model of the spherical motor is given. The model shows that the three degrees of freedom of the motor are coupled with each other. According to the mathematical model of the spherical motor, the mechanical properties of the motor are analyzed by the computer simulation. The results show that the stalling torque coefficient k_t has a linear relationship with the friction coefficient ε and the stator preload F_c, has a nonlinear relationship with the stator radius R and the rotor radius r, and increases with the increase of R and decreases with the increase of r. The no-load speed of motor ω_n is not related to the friction coefficient ε and the stator preload F_c, and increases with the increase of R and decreases with the increase of r. The anisotropic characteristics of torque and speed of a spherical motor are further analyzed, which lays a theoretical foundation for the drive control of a spherical motor. Full article