Search Results (15)

The aim of this study was to investigate the molecular interactions of heparin, diclofenac, and their supramolecular complexes with cyclooxygenase enzymes (COX-1 and COX-2) using computational docking techniques. Diclofenac is a widely used nonsteroidal anti-inflammatory drug (NSAID) that inhibits COX isoforms, whereas heparin is a polyanionic glycosaminoglycan with established anticoagulant and emerging anti-inflammatory properties. Supramolecular association between these agents may modulate their physicochemical behavior and target engagement. Molecular modeling, dual-drug docking, and molecular dynamics (MD) simulations were employed to characterize the interactions of heparin, diclofenac, and pre-formed heparin–diclofenac complexes with COX-1 and COX-2. Geometry optimization and lipophilicity (logP) estimates were obtained using HyperChem, while protein–ligand docking was performed in HEX using crystallographic COX structures from the Protein Data Bank. Docking poses were analyzed in Chimera, and selected complexes were refined through short MD simulations. Pre-formed heparin–diclofenac assemblies exhibited markedly enhanced docking scores toward both COX isoforms compared with single ligands. Binding orientation strongly influenced affinity: for COX-1, the heparin–diclofenac configuration yielded the most favorable interaction, whereas for COX-2 the diclofenac–heparin configuration was preferred. Both assemblies adopted binding modes distinct from free diclofenac, suggesting cooperative electrostatic and hydrophobic contacts at the enzyme surface. Supramolecular complexation also altered calculated logP values relative to the individual compounds. MD simulations supported the relative stability of the top-ranked complex–COX assemblies. These findings indicate that heparin–diclofenac assemblies may enhance and reorganize predicted COX interactions in a configuration-dependent manner and illustrate the utility of dual-drug docking for modeling potential synergistic effects. Such insights may inform the design of localized or topical formulations, potentially incorporating non-anticoagulant heparin derivatives, to achieve effective COX inhibition with reduced systemic exposure. However, the results rely on simplified heparin fragments, legacy docking tools, and short MD simulations, and should therefore be interpreted qualitatively. Experimental studies will be essential to confirm whether such supramolecular assemblies form under physiological conditions and whether they influence COX inhibition in vivo. Full article

Wire Arc Additive Manufacturing (WAAM) enables cost-effective fabrication of complex metallic components but faces challenges in achieving consistent tensile strength for cylindrical parts with intricate internal features (e.g., cooling channels, helical grooves), where conventional machining is often infeasible or prohibitively expensive. This study introduces a novel stacked ring substrate strategy with pre-formed low-carbon steel rings defining complex internal geometries, followed by external WAAM deposition using ER70S-6 wire to overcome these limitations. Five process parameters (welding current: 110–130 A; offset distance: 2.5–3.0 mm; Step Length: rotary to straight; torch speed: 400–500 mm/min; weld thickness: 2.0–3.0 mm) were optimized using a Taguchi L25 orthogonal array (25 runs in triplicate). ANOVA identified Step Length as the dominant factor, with straight paths significantly reducing thermal cycling and improving interlayer bonding, alongside a notable current × speed interaction. Optimal settings achieved tensile strengths of 280–290 MPa, significantly below wrought ER70S-6 benchmarks (400–550 MPa) due to interfacial weaknesses at ring fusion zones and thermal accumulation from stacked cylindrical geometry, a limitation acknowledged in the absence of microstructural or thermal history data. A Random Forest Regressor predicted strength with R² = 0.9312, outperforming conventional models. This hybrid approach significantly enhances design freedom and mechanical reliability for high-value cylindrical components in aerospace and tooling, establishing a scalable, data-driven framework for geometry-constrained WAAM optimization. Full article

Accurate preform design in forging processes is critical for improving part quality, conserving material, reducing manufacturing costs, and eliminating secondary operations. This paper presents a finite element (FE) simulation-based methodology for preform design aimed at achieving flashless and near-flashless forging. The approach leverages material point backtracking within FE models to generate physics-informed preform geometries that capture complex material flow, die geometry interactions, and thermal gradients. An iterative scheme combining backtracking, surface reconstruction, and point-cloud solid modeling was developed and applied to several three-dimensional forging case studies, including a cross-joint and a three-lobe drive hub. The methodology demonstrated significant reductions in flash formation, particularly in parts that traditionally exhibit severe flash under conventional forging. Beyond supporting the development of new flashless forging sequences, the method also offers a framework for modifying preforms during production to minimize waste and for diagnosing preform defects linked to variability in frictional conditions, die temperatures, or material properties. Future integration of the proposed method with design of experiments (DOE) and surrogate modeling techniques could further enhance its applicability by optimizing preform designs within a localized design space. The findings suggest that this approach provides a practical and powerful tool for advancing both new and existing forging production lines toward higher efficiency and sustainability. Full article

Modern electric motors developed for the automotive industry have an ever higher power density with a relatively compact size. Among the various existing solutions to improve torque and power density, a reduction in the dimensions of the end-windings has been explored, aiming to decrease volume, weight, and losses. However, more compact end-windings often lead to complex shapes of the conductors, especially when preformed hairpin windings are considered. The rectangular cross-section of hairpin conductors makes them prone to deviating out of the bending plane during the forming process. This phenomenon, known as torsional–flexural instability, is influenced by the specific aspect ratio of the cross-section dimensions and the bending direction. This study focuses on understanding this instability phenomenon, aiming to identify a potential threshold of the cross-section aspect ratio. The instability makes it difficult to predict the final geometry, potentially compromising the compliance with the geometric tolerances. A finite element model is developed to analyse a single planar bend in a hairpin conductor. Various cross-section dimensions with different aspect ratios are simulated identifying those that experience instability. Moreover, an experimental campaign is conducted to confirm the occurrence of instability by testing the same single planar bending. The experimental data obtained are used to validate the finite element model for the tested dimensions. The aim is to provide designers with a useful tool to select hairpin geometries that are more suitable for the folding process, contributing to successful assembly and improving the overall design process of preformed hairpin conductors. Full article

The study refers to the application of numerical modeling for the improvement of the currently realized precision forging technology performed on a hammer to produce connecting rod forgings in a triple system through the development of an additional rolling pass to be used before the roughing operation as well as preparation of the charge to be held by the robot’s grippers in order to implement future process robotization. The studies included an analysis of the present forging technology together with the dimension–shape requirements for the forgings, which constituted the basis for the construction and development of a thermo-mechanical numerical model as well as the design of the tool construction with the consideration of the additional rolling pass with the use of the calculation package Forge 3.0 NxT. The following stage of research was the realization of multi-variant numerical simulations of the newly developed forging process with the consideration of robotization, as a result of which the following were obtained: proper filling of the tool impressions (including the roller’s impression) by the deformed material, the temperature distributions for the forging and the tools as well as plastic deformations (considering the thermally activated phenomena), changes in the grain size as well as the forging force and energy courses. The obtained results were verified under industrial conditions and correlated with respect to the forgings obtained in the technology applied so far. The achieved results of technological tests confirmed that the changes introduced into the tool construction and the preform geometry reduced the diameter, and thus also the volume, of the charge as well as provided a possibility of implementing robotization and automatization of the forging process in the future. The obtained results showed that the introduction of an additional rolling blank resulted in a reduction in forging forces and energy by 30% while reducing the hammer blow by one. Attempts to implement robotization into the process were successful and did not adversely affect the geometry or quality of forgings, increasing production efficiency. Full article

The rolling process of rings is a commonly used method for producing annular forgings. There are two primary types of this process: radial-axial rolling and radial rolling. This article presents the research results regarding the latter, in which obtaining a product with the assumed dimensions constitutes a major problem. In industrial practice, the process parameters are based on the experience of technologists and/or by trial and error. This is why the authors considered it justified to undertake the research aimed at determining the influence of the main process parameters, that is, preform temperature and tool speed, on the shape and dimensions of the cross-section, which determine the internal and external diameters of the rolled ring. The research was based on numerical simulations and experimental studies. The results obtained proved that the higher the feed speed of the main roll, the greater the change in the cross-sectional height during rolling, and the smaller the cross-sectional deformation (the so-called fishtail). Nevertheless, a higher preform temperature reduces the final height of the ring and reduces cross-section deformation. On the basis of the obtained test results, guidelines for the process design were postulated, considering the influence of temperature and speed parameters on the final dimensions of the forging and the dimensions of the preform. Full article

Acrylonitrile Butadiene Styrene (ABS) is a common thermoplastic polymer that has been widely employed in the manufacturing industry due to its impact resistance, tensile strength, and rigidity. Additive manufacturing (AM) is a promising manufacturing technique being used to manufacture products with complex geometries, but it is a slow process producing mechanically inferior products when compared to traditional production processes like injection molding (IM). Thus, our hybrid manufacturing (HM) process combining materials extrusion AM and IM to create a single article was investigated in this study, in which eleven batches of specimens were made and extensively tested. These include the AM, IM, and hybrid manufactured (HYM) samples, in which the HYM samples were made by inserting AM substrates into the IM tool and were varied in infill density of AM preforms and geometries. The HYM samples outperformed AM parts in terms of mechanical performance while retaining customizability dependent on the HYM processing parameters, and the best mechanical performance for HYM samples was found to be comparable to that of IM samples, implying that the overmolding process in HM had primarily improved the mechanical performance of AM products. This work leads to a deeper knowledge of applications to confirm the optimal component fabrication in high design flexibility and mass production. Full article

Achieving right-first-time-manufacture (RFTM) of co-infused textile assemblies is challenging, without improving the accessibility to design knowledge of trade-offs between different tooling and infusion strategies. As demonstrated in previous work, the choice between a flexible or rigid mould material can result in trade-offs between dimensional accuracy and geometrical precision. Similarly, the choice of an infusion strategy can result in trade-offs in infusion quality and time. Building on past work, an investigation into forming variability across the length of six co-infused multi-textile components, with three different tooling inserts and two infusions set-ups, was conducted. To quantitatively assess variation, a method adapting principles of statistical process control was employed to analyse the yarn crimp measured from high-resolution cross-sectional scans of the components. The results were compared to a geometrical and dimensional analysis of the manufactured parts presented in a previous work. The analysis represents a method for capturing forming differences in textile preforms, which can be used to inform designs for the manufacture of textile CFRPs. The results were used to improve a hybrid rigid-flexible tooling design for an infused multi-textile component. Full article

This study aimed to design a hybrid oral liposomal delivery system for selenium nanoparticles (Lip-SeNPs) to improve the bioavailability of selenium. Thiolated chitosan, a multifunctional polymer with mucoadhesive properties, was used for surface functionalization of Lip-SeNPs. Selenium nanoparticle (SeNP)-loaded liposomes were manufactured by a single step microfluidics-assisted chemical reduction and assembling process. Subsequently, chitosan-N-acetylcysteine was covalently conjugated to the preformed Lip-SeNPs. The Lip-SeNPs were characterized in terms of composition, morphology, size, zeta potential, lipid organization, loading efficiency and radical scavenging activity. A co-culture system (Caco-2:HT29-MTX) that integrates mucus secreting and enterocyte-like cell types was used as a model of the human intestinal epithelium to determine adsorption, mucus penetration, release and transport properties of Lip-SeNPs in vitro. Thiolated Lip-SeNPs were positively charged with an average size of about 250 nm. Thiolated Lip-SeNPs tightly adhered to the mucus layer without penetrating the enterocytes. This finding was consistent with ex vivo adsorption studies using freshly excised porcine small intestinal tissues. Due to the improved mucoadhesion and retention in a simulated microenvironment of the small intestine, thiolated Lip-SeNPs might be a promising tool for oral selenium delivery. Full article

Purpose: The known preformed osteosynthesis plates for the midface are helpful tools for a precise and fast fixation of repositioned fractures. The purpose of the current study is to analyze the precision of newly developed prototypes of preformed osteosynthesis plates for the mandible. Methods: Four newly designed preformed osteosynthesis plates, generated by a statistical shape model based on 115 CT scans, were virtually analyzed. The used plates were designed for symphyseal, parasymphyseal, angle, and condyle fractures. Each type of plate has three different sizes. For analysis, the shortest distance between the plate and the bone surface was measured, and the sum of the plate-to-bone distances over the whole surface was calculated. Results: A distance between plate and bone of less than 1.5 mm was defined as sufficient fitting. The plate for symphyseal fractures showed good fitting in 90% of the cases for size M, and in 84% for size L. For parasymphyseal fractures, size S fits in 80%, size M in 68%, and size L in 65% of the cases. Angle fractures with their specific plate show good fitting for size S in 53%, size M in 60%, and size L in 47%. The preformed plate for the condyle part fits for size S in 75%, for size M in 85%, and for size L in 74% of the cases. Conclusion: The newly developed mandible plates show sufficient clinical fitting to ensure adequate fracture reduction and fixation. Full article

Edge race-tracking is a frequently reported issue during resin transfer molding. It is caused by highly permeable channels and areas between the preform edge and cavity, which can significantly change the preform impregnation pattern. To date, information is scarce on the effect of edge race-tracking in compression resin transfer molding (CRTM). To close this gap, laboratory equipment was developed to study the CRTM preform impregnation via flow visualization experiments. The preform was thereby encapsulated in thin thermoplastic films sealing its impregnation. Film-sealed compression resin transfer molding (FS-CRTM) experiments of preforms with a small geometrical aspect ratio showed fast filling of the injection gap and a subsequent through-thickness preform impregnation. Creating an edge race-tracking channel, an additional lateral in-plane flow from the channel towards the preform center was observed, initiating soon after the injection started and caused by the spatial connection between the injection gap and the race-tracking channel. To diminish edge race-tracking, a passive flow control strategy was implemented via a split design of the upper tool to spatially isolate the injection gap from the channel and to pre-compact the preform edge. A delayed and reduced lateral race-tracking flow was observed, showing that the passive flow control strategy increases the process robustness of FS-CRTM regarding edge race-tracking effects. Full article

In the design of parts consisting of long-fibre-reinforced Sheet Moulding Compounds (SMC), the potential for the optimisation of processing parameters and geometrical design is limited due to the high number of interdependent variables. One of the influences on fibre orientations and therefore mechanical part performance is the initial filling state of the compression moulding tool, which is defined by the geometry and positioning of the SMC preform. In the past, response surface methodology and linear regression analysis were successfully used for a simulation-based optimisation of rectangular preform size and position in regard to a part performance parameter. However, the computational demand of these increase exponentially with an increase in the number of design variables, such as in the case of more complex preform geometries. In this paper, these restrictions are addressed with a novel approach for metamodelling the correlation of preform and the resulting mechanical part performance. The approach is applied to predicting the maximum absolute deflection of a plate geometry under bending load. For metamodelling, multiple neural networks (NN) are trained on a dataset obtained by process and structural simulation. Based on the discretisation of the plate geometry used in these simulation procedures, the binary initial filling states (completely filled/empty) of each element are used as inputs of the NNs. Outputs of the NNs are combined by ensemble modelling to form the metamodel. The metamodel allows an accurate prediction of maximum deflection; subsequent validation of the metamodel shows differences in predicted and simulated maximum deflection ranging from 0.26% to 2.67%. Subsequently, the metamodel is evaluated using a mutation algorithm for finding a preform that reduces the maximum deflection. Full article

Supramolecular nanostructures formed through peptide self-assembly can have a wide range of applications in the biomedical landscape. However, they often lose biomechanical properties at low mechanical stress due to the non-covalent interactions working in the self-assembling process. Herein, we report the design of cross-linked self-assembling peptide hydrogels using a one-pot in situ gelation system, based on 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide/N-hydroxysulfosuccinimide (EDC/sulfo–NHS) coupling, to tune its biomechanics. EDC/sulfo–NHS coupling led to limited changes in storage modulus (from 0.9 to 2 kPa), but it significantly increased both the strain (from 6% to 60%) and failure stress (from 19 to 35 Pa) of peptide hydrogel without impairing the spontaneous formation of β-sheet-containing nano-filaments. Furthermore, EDC/sulfo–NHS cross-linking bestowed self-healing and thixotropic properties to the peptide hydrogel. Lastly, we demonstrated that this strategy can be used to incorporate bioactive functional motifs after self-assembly on pre-formed nanostructures by functionalizing an Ac-LDLKLDLKLDLK-CONH₂ (LDLK12) self-assembling peptide with the phage display-derived KLPGWSG peptide involved in the modulation of neural stem cell proliferation and differentiation. The incorporation of a functional motif did not alter the peptide’s secondary structure and its mechanical properties. The work reported here offers new tools to both fine tune the mechanical properties of and tailor the biomimetic properties of self-assembling peptide hydrogels while retaining their nanostructures, which is useful for tissue engineering and regenerative medicine applications. Full article

In the process of complex engineering designs or optimizations, a large number of physical experiments or numerical simulations are required to evaluate certain performance qualities before a satisfactory result can be obtained. In both cases, constructing an approximate model is often necessary to provide a reliable response as an alternative to experiments or simulations. In this paper, three types of approximation models were developed and applied in a shape design of an aerofoil forging preform tool. Their modeling techniques are presented in detail. An optimal Latin hypercube technique was employed for the design of the experiment and sampling with the expected coverage of parameter space. Finite element (FE) simulations of multistep forging processes were implemented to acquire the objective function values for evaluating the forging performance. By a parametric study, the effects of design variables on objective responses and correlations were investigated for a clear insight into their functional nature. Comprehensive analyses and comparisons between different approximate models have been carried out. Finally, an optimization design of a preform tool was successfully achieved based on a particle swarm (PSO) algorithm combined with the proposed approximate model. Full article

A two-stage cold forging process was proposed to manufacture a drive shaft with an internal spline and spur gear geometries, and this process was mainly composed of a forward extrusion for preform and a forward-backward extrusion for the drive shaft. In the process design, the preform was designed using a volume apportioning scheme from the required target shape, thereafter, the initial round billet was outlined. AISI 1035 carbon steel was selected as the raw material, and a spheroidizing heat treatment was adopted. Using the raw and spheroidizing annealed workpieces, uni-axial tensile and compression tests were carried out to evaluate the effect of the heat treatment and to measure the mechanical properties. Finite element simulations were sequentially performed to assure the suitability of the proposed process design. Considering the results from the process design and the numerical simulations, the related tool components were prepared and applied to a series of experimental investigations. The preform and the drive shaft fabricated by the two-stage cold forging experiments were compared with the required target and the numerically predicted configurations. The results indicated that the two-stage cold forging process proposed in this study could be well applied to the production of the drive shaft with an internal spline and spur gear structures. Full article