Search Results (156)

Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the maximum tolerated dose (MTD) of IBR in combination with LEN + dexamethasone (DEX) in patients with relapsed/refractory (RR) MM who had at least one prior line of therapy. Three dose levels (DLs) were planned. The cycle length was 28 days. IBR was administered orally daily in doses of 560 mg on DL1-2 and 840 mg on DL3, LEN was administered orally on days 1–21 in doses of 15 mg on DL1 and 25 mg on DL2-3, and DEX was administered orally on days 1, 8, 15, and 22 in a dose of 40 mg if age < 75 years or in a dose of 20 mg if it was ≥75 years for DL1-3. Patients with a glomerular filtration rate (GFR) <60 but ≥30 mL/min were treated in accordance with the manufacturer’s instructions with LEN 10 mg. Dose-limiting toxicities (DLTs) included the following: grade 4 neutropenia lasting more than 5 days, thrombocytopenia, febrile neutropenia, nausea, vomiting or diarrhea; grade 3 thrombocytopenia with bleeding or platelet transfusion; and grade 3–4 hyperglycemia or a thrombotic/embolic event, and other nonhematologic toxicities. The overall response rate (ORR) was defined as the percentage of patients with a partial response (PR), very good partial response (VGPR), or complete response (CR) according to IMWG criteria on two consecutive evaluations at least 4 weeks apart. The clinical benefit rate (CBR) was defined as the percentage of patients with stable disease (SD) or a better outcome on two consecutive evaluations at weeks apart. Results: Fourteen patients (DL1: six patients; DL2: three patients; DL3: five patients) were registered for the study from March 2019 to May 2023, prior to its closure due to limited accrual. Thirteen patients are included in the summary of toxicities and response as one patient on DL3 halted participation prior to the start of the treatment. Two patients on DL3 were excluded from the determination of MTD: one having discontinued cycle 1 treatment due to COVID-19 infection and the another having mistakenly taken 280 mg/day of IBR instead of the assigned 840 mg/day dose during cycle 1. Only one patient developed a DLT, on DL1 with grade 3 non-viral hepatitis. The median number of cycles administered was 4 (range: 1–56). Severe toxicities reported included grade 4 lymphocytopenia (1), grade 4 thrombocytopenia (1), and grade 5 sepsis in the setting of PD (1). Disease responses included a VGPR on DL1 and CR on DL3. Thus, the ORR was 15.4% (90% CI: 2.8–41.0%). One patient on DL1 maintained SD for 4.6 years before discontinuing the treatment to undergo an alternative therapy. Another five patients maintained SD for ≥ 2 consecutive cycles. Thus, the CBR was 61.5% (90% CI: 35.5–83.4%). Conclusions: The combination of LEN with IBR in RR MM proved feasible, with manageable toxicities and the majority of discontinuations being due to disease progression. Full article

This study addresses the urgent demand for high-precision manufacturing of curved components by developing a fully servo-driven multi-axis controlled four-roll bending machine. By integrating a modular symmetric roller system design with a distributed hierarchical motion control architecture, we achieved substantial enhancements in scalability, forming stability, and machining accuracy. The mechanical system underwent static simulation optimization using SolidWorks Simulation, ensuring maximum stress in the guiding mechanism was controlled below $7.118\times {10}^3$ N/m². ABAQUS-based roll-bending dynamic simulations validated the geometric adaptability and process feasibility of the proposed mechanical configuration. A master-slave dual-core control architecture was implemented in the control system, enabling synchronized error ≤ 0.05 mm, dynamic response time ≤ 10 ms, and positioning accuracy of ±0.01 mm through collaborative control of the master controller and servo drives. Experimental validation demonstrated that the machine achieves bending errors within 1%, with an average forming error of 0.798% across various radii profiles. The arc integrity significantly outperforms conventional equipment, while residual straight edge length was reduced by 86.67%. By adopting fully servo-electric cylinder actuation and integrating a C#-developed human–machine interface with real-time feedback control, this research effectively enhances roll-bending precision, minimizes residual straight edges, and exhibits broad industrial applicability. Full article

Background/Objectives: Recently, a novel magnetic attachment system was introduced to improve performance. Using the same technology, a new ultra-thin magnetic attachment (UTMA) was possible to produce. This study aimed to evaluate the feasibility of a magnet-retained telescopic partial denture (MTPD) utilizing the new UTMA. Methods: This in vitro study was performed using a titanium master model representing prepared lower first-premolar and second-molar abutment teeth. The inner crowns (ICs) (h: 4 mm, 4° taper) and four-unit MTPDs were fabricated via computer-aided design/computer-aided manufacturing (CAD/CAM) using zirconia. A Ø4 mm UTMA system (magnet assembly and keeper thickness: 0.6 mm and 0.4 mm, respectively) was cemented into the MTPD and the ICs using dual-cure resin cement. A load of 100 N was applied along with 10,000 insertion–removal cycles. The MTPD retentive force was measured before and after every set of 1000 cycles. Stability tests and surface morphology evaluations were conducted before and after cycling. A paired t-test (α = 0.05) was used to observe statistical differences. Results: The average retentive force of the MTPD was 6.86 ± 0.63 N and did not change significantly (p > 0.05) following the load cycles (6.66 ± 0.79 N). The MTPD demonstrated adequate stability under the occlusal load. Minimal deformations were observed on the magnet assemblies, keepers, ICs, and MTPD surfaces after the load tests. Conclusions: Considering the limitations of this study, an MTPD utilizing novel UTMAs fabricated through a digital workflow demonstrated adequate retentive force, stability, and durability for clinical use. Full article

For several years now, fruit-growers have increasingly often used pre-tensioned, pre-stressed concrete posts for supporting branches of fruit trees and suspending protective nets in order to limit damage to fruits caused by hail, wind, snow, heavy rainfall, insects and birds. Pre-tensioned, pre-stressed concrete posts most often have a trapezoidal cross-section, which is ideally suitable for mass production in a self-supporting non-dismantlable steel mould on a pre-stressing bed. Posts with 70 mm × 75 mm, 80 mm × 85 mm and 90 mm × 95 mm cross-sections are typically produced, whereas 100 mm × 120 mm and 130 mm × 140 mm posts are manufactured to order. Furthermore, it is proposed to produce hollow posts. Such posts are lighter than solid posts, but they require a more complicated production technology. This paper presents selected parts of a comparative computational–experimental analysis of solid and hollow posts. In the Building Structures Laboratory in the Building Structures Department at the Civil Engineering Faculty of the Wrocław University of Science and Technology, experimental tests of pre-stressed concrete orchard posts of 70 mm × 75 mm and 90 mm × 95 mm with solid and hollow cross-sections were carried out on a full scale. The theoretical analysis and research has shown that the resistance to bending, cracking resistance and rigidity of hollow posts (with their cross-sectional outline unchanged) will not significantly differ from those of the currently produced solid posts. At same time, material savings will be achieved. Therefore, the main task is to master the continuous moulding of hollow posts from dense plastic concrete with the simultaneous pulling out of the cores, producing longitudinal hollows in the posts. Full article

In recent years, as an important alternative to traditional gasoline-powered vehicles, new electric vehicles (NEVs) have gained widespread attention and rapid development globally. In the traditional automotive industry chain, downstream vehicle manufacturers need to master core technologies, such as engines, chassis, and transmissions. In contrast to the traditional automotive industry chain, where downstream vehicle manufacturers must master core technologies, like engines, chassis, and transmissions, the electric vehicle industry chain has evolved in a way that the development of core components is gradually separated from the vehicle manufacturers. Downstream vehicle manufacturers can now outsource key components, such as batteries, electric controls, and motors. Additionally, in terms of sales models, the electric vehicle industry chain can adopt either the traditional 4S dealership model or a direct-sales model. As the research and development of core components are increasingly separated from vehicle manufacturers, the downstream vehicle manufacturers can source components, like batteries, electric controls, and motors, externally. At the same time, they can choose to use either the traditional 4S dealership model or the direct-sales model. The underlying mechanisms and channel selection in this context require further exploration. Based on this, a mathematical model is established by incorporating terminal marketing input, product competitiveness, and after-sales service levels from the literature to solve for the optimal pricing under centralized and decentralized pricing strategies. Using numerical examples, the pricing and profit performance under different market structures are analyzed to systematically examine the impact of the electric vehicle supply chain on business operations, as well as the changes in various elements across different channels. We will focus on how after-sales services (including the spare part supply) influence the pricing strategy and profit distribution in the supply chain, aiming to provide insights into advanced manufacturing system management for manufacturing enterprises and improve the efficiency of intelligent logistics management. The research indicates that (1) The direct-sales model helps to improve the terminal marketing input, after-sales service quality, and product competitiveness for supply chain stakeholders; (2) It is noteworthy that the manufacturer’s direct-sales model also significantly contributes to lowering prices, highlighting that the direct-sales model has substantial impacts on both supply chain stakeholders and, importantly, consumers. Full article

Objective: We developed a targeted integration-based CHO cell platform for simultaneous antibody display and secretion, enabling a streamlined transition from antibody library screening to production without requiring the re-cloning of antibody genes. Methods: The platform consists of a CHO master cell line with a single-copy landing pad, a helper vector expressing FLPe recombinase, and bi-functional targeting vectors. Recombinase-mediated cassette exchange was utilized to integrate targeting vectors into the landing pad. Bi-functional vectors were designed by incorporating a minimal furin cleavage sequence (mFCS), RRKR, and various 2A peptides between the heavy chain (HC) and a membrane anchor. Results: Incomplete cleavage at the mFCS and 2A sites facilitated the expression of both membrane-bound and secreted antibodies, while mutations in the 2A peptide produced a range of display-to-secretion ratios. However, a fraction of secreted antibodies retained 2A residues attached to the HC polypeptides. Further analysis demonstrated that modifying the first five amino acids of the 2A peptide significantly influenced furin cleavage efficiency, resulting in different display-to-secretion ratios for targeting vectors containing mFCS-2A variant combinations. To overcome this, we designed nine-amino-acid FCS variants that, when placed between the HC and membrane anchor, provided a range of display-to-secretion ratios and eliminated the issue of attached 2A residues in the secreted antibodies. Vectors with lower display levels proved more effective at distinguishing cells expressing high-affinity antibodies with closely matched binding affinities. The platform also demonstrated high sensitivity in isolating high-affinity antibody-expressing cells and supported robust antibody production. Conclusion: This targeted integration-based CHO platform enables efficient, in-format screening and production of antibodies with tunable display-to-secretion profiles. It provides a powerful and scalable tool for accelerating the development of functional, manufacturable therapeutic antibodies. Full article

Background: Mucostatic impressions have been always indicated in thin, sharp, or flabby ridges, and have been addressed for their beneficial effect on long-term residual ridge stability. Nonetheless, a purely mucostatic impression was not possible until intraoral scans became available. This provides an option for digital removable denture which is biologically sensible but might reduce retention in comparison with a mucocompressive impression with border molding. On the other hand, pressure applied to the mucosa may have harmful effects on the long-term residual ridge stability, causing higher resorption and ultimately reduced denture retention. Hence, the possibility to merge mucostatics and mucocompressive philosophies would be a clinically and biologically sensible option for oral rehabilitation in aging populations where patients will potentially wear dentures for longer periods. This possibility is demonstrated in this technical report with a cast-free digital workflow. Technique: Baseplates for occlusion rims, closely adapted to the mucosa, were designed on intraoral scans of edentulous arches and, once 3D-printed, used to register maxillomandibular relations and information for tooth arrangement, as well as to perform border molding. Occlusion rims were then scanned and, within the 3Shape Dental System 2024 software program, the intaglio surfaces of their baseplates were segmented and inverted to obtain the digital master casts which incorporated the precise reproduction of the molded borders. Then, denture design was performed and manufactured; no limitations regarding manufacturing options are applicable to the presented technique. Conclusions: The potential benefits (i.e., improved retention in the initial period after denture delivery and the preservation of tissues) of the presented digital cast-free workflow, based on merging mucostatic and mucocompressive philosophies to obtain dentures with a mucostatic intaglio surface and functional borders, are sensible clinical outcomes which recommend the clinical application of the technique, although further validation, especially in the long term, is required. Full article

To address the challenges of confined workspaces and high-precision requirements in thyroid surgery, this paper proposes a modular cable-driven robotic system with a hybrid rigid–continuum structure. By integrating rigid mechanisms and continuum joints within a closed-loop cable-driven framework, the system achieves a balance between flexibility in narrow spaces and operational stiffness. To tackle kinematic model inaccuracies caused by manufacturing errors, an innovative joint decoupling strategy combined with the Particle Swarm Optimization (PSO) algorithm is developed to dynamically identify and correct 19 critical parameters. Experimental results demonstrate a 37.74% average improvement in repetitive positioning accuracy and a 52% reduction in maximum absolute error. However, residual positioning errors (up to 4.53 mm) at motion boundaries highlight the need for integrating nonlinear friction compensation. The feasibility of a safety-zone-based force feedback master–slave control strategy is validated through Gazebo simulations, and a ring-grasping experiment on a surgical training platform confirms its clinical applicability. Full article

With the advancement of lead–bismuth fast reactors, there has been increasing attention directed towards the design of and manufacturing technology for electromagnetic pumps employed to drive liquid lead–bismuth eutectic (LBE). These electromagnetic pumps are characterized by a simple structure, effective sealing, and ease of flow control. They exploit the excellent electrical conductivity of liquid metals, allowing the liquid metal to be propelled by Lorentz forces generated by the traveling magnetic field within the pump. To better understand the performance characteristics of electromagnetic pumps and master the techniques for integrated manufacturing and performance optimization, this study conducted fundamental research, development of key components, and the assembly of the complete pump. Consequently, an annular linear induction pump (ALIP) suitable for liquid lead–bismuth eutectic was developed. Additionally, within the lead–bismuth thermal experimental loop, startup and preheating experiments, performance tests, and flow-head experiments were conducted on this electromagnetic pump. The experimental results demonstrated that the output flow of the electromagnetic pump increased linearly with the input current. When the input current reached 99 A, the loop achieved a maximum flow rate of 8 m³/h. The efficiency of the electromagnetic pump also increased with the input current, with a maximum efficiency of 5.96% during the experiments. Finally, by analyzing the relationship between the flow rate and the pressure difference of the electromagnetic pump, a flow-head model specifically applicable to lead–bismuth electromagnetic pumps was established. Full article

The use of waste, recycled, and modified materials is increasingly popular in roadway construction for sustainability and pavement longevity. This research examines the combination of steel slag (SS) and low-density polyethylene (LDPE), commonly used in plastic bags and steel manufacturing by-products, to mitigate environmental pollution. LDPE was tested as a binder modifier in two bitumen grades, 60–70 and 80–100, at concentrations of 3%, 5%, and 7% by weight. SS was used as a replacement for coarse aggregate. The physical properties of both modified and unmodified bitumen grades and SS were analyzed before creating and testing hot-mix asphalt (HMA) samples. The dynamic modulus of these samples was measured at temperatures of 4.4 °C, 21.1 °C, 37.8 °C, and 54.4 °C with frequencies of 0.1 Hz, 0.5 Hz, 1 Hz, 5 Hz, 10 Hz, and 25 Hz. Master curves were developed, and the dynamic modulus data underwent design of experiment (DOE) and computational intelligence (CI) analyses. Using KENPAVE, a mechanistic–empirical tool, the analysis assessed the design life and enhancements in damage ratio for each modifier and grade. The results showed that adding LDPE increases the softening point and penetration grade but decreases ductility due to increased bitumen stiffness, leading to premature fatigue failure at higher LDPE levels. Both 3% LDPE and 3% SS-modified LDPE improved Marshall Stability and dynamic modulus across all temperature and frequency ranges. Specifically, 3% LDPE enhanced stability by 13–16% and 3% SS-LDPE by 30–32%. The KENPAVE results for 3% LDPE showed a design life improvement of 19–25% and a damage ratio reduction of 15–18%. In comparison, 3% SS-LDPE demonstrated a design life improvement of 50–60% and a damage ratio reduction of 25–35%. Overall, this study concludes that 3% LDPE- and 3% SS-LDPE-modified HMA in both bitumen grades 60–70 and 80–100 provide optimal results for improving pavement performance. Full article

This paper explores the role of business process optimization in achieving manufacturing excellence in railway manufacturing through Lean principles and Quality Function Deployment (QFD). It identifies key inefficiencies, such as waiting times, overproduction, and document errors, using the DMAIC method, along with Root Cause Analysis (RCA) and Failure Mode and Effect Analysis (FMEA), to prioritize waste reduction. A significant 42.86% of activities were classified as non-value added, pointing to substantial opportunities for improvement. This study proposes key solutions, including the development of a shared database, streamlined procedures, and the alignment of targets with the Master Production Schedule to reduce waste and improve operational efficiency. These recommendations aim to foster manufacturing excellence by enhancing communication, process integration, and employee training. Full article

This study aims to enhance the electrical conductivity of commercially pure aluminium by minimizing impurities and grain boundaries in its microstructure, ultimately improving the efficiency of electric motors constructed from rotors with squirrel cages made from this material. For this purpose, an aluminium–boron (AlB8) master alloy was added to aluminium with a purity of 99.7%, followed by the application of a grain-coarsening heat treatment to the rotors. To obtain commercially pure aluminium with boron additions of 0.05% and 0.1% by weight, specific amounts of the AlB8 master alloy were added into aluminium with a purity of 99.7%. Using these materials, squirrel cage components of rotors were produced via the high-pressure die-casting method. Subsequently, a grain-coarsening heat treatment of the rotors was performed at temperatures of 450 °C, 500 °C, and 550 °C, with holding times of 2, 6, and 10 h. The Box–Behnken design, which is based on statistical experimental design and response surface methodology, was employed to investigate the effects of adding boron and varying the heat treatment temperature and holding time on the electrical conductivity of commercially pure aluminium. The results showed that the synergistic effect of adding boron at 0.05 wt.% and applying the grain-coarsening heat treatment at a temperature of 550 °C for a holding time of 10 h significantly enhanced the electrical conductivity of commercially pure aluminium, increasing it from 60.62% IACS to 63.1% IACS. Correspondingly, the efficiency of the electric motor increased from 90.35% to 91.53%. These findings suggest that this hybrid method not only enhances the electrical conductivity of commercially pure aluminium but also has strong potential to improve its other properties, such as thermal conductivity. This will lead to products composed of components manufactured from the materials exhibiting better performance characteristics, such as increased efficiency and extended service life. Consequently, this innovative method will contribute economically and environmentally by facilitating the manufacture of high-performance products. Full article

Effective high-aspect-ratio molds that minimize vacuum processes are becoming increasingly important for producing metalenses and other devices. To fabricate a high-aspect-ratio structure, a metal film must be used as a mask for dry etching, typically achieved via vacuum deposition. To avoid this vacuum process, we devised a method to develop an etching mask in the air using silver ink. The manufacturing method involved filling the mold with silver ink, baking it, removing silver from the convex parts of the mold with a polyethylene terephthalate film, and placing silver from the concave parts of the mold on top of the ultraviolet (UV)-cured resin using ultraviolet-nanoimprint lithography. The transferred pattern had silver on the convex parts, which was used as a mask for the oxygen dry etching of the UV-curable resin. Consequently, high-aspect-ratio resin shapes were obtained from three types of nano- and micromolds. Additionally, a high-aspect-ratio resin with silver was used as a replica mold to form a silver pattern. This process is effective and allows high-aspect-ratio patterns to be obtained from master molds. Full article

Background/Objectives: Occlusion plays a crucial role in the long-term success and functionality of dental restorations. The purpose of this study was to investigate the changes in occlusal contacts upon the cementation of zirconia crowns with different cement spacer settings in computer-aided design and computer-aided manufacturing (CAD-CAM) software (3Shape Dental System version 2.102.1.0). Methods: A master model of a prepared abutment for a crown on the right maxillary first molar was scanned, and 30 sets of sample casts and zirconia crowns were fabricated with varying cement spaces (70 μm and 120 μm). These casts were mounted in maximal intercuspation (MIP) on a semi-adjustable articulator. Pre-cementation adjustments were made to fit the crowns and maintain the existing occlusion. Occlusal records were taken before and after cementation using polyvinyl siloxane impression material. These records were analyzed using a DC light box and image analyzer to measure changes in contact area, intensity, and patterns. Paired sample t-tests were used to compare pre- and post-cementation occlusal contact areas of each sample (α = 0.05). Results: Significant differences in occlusal contact areas were found between pre- and post-cementation in both groups (p < 0.001). The mean post-cementation contact surface area for the 70 μm group was 6281 ± 3310 μm², compared to 2339 ± 1206 μm² before cementation. For the 120 μm group, the post-cementation area was 5545 ± 3491 μm², compared to 2071 ± 909 μm² before cementation. An increase in contact intensity was also observed after cementation. Conclusions: This study demonstrates that cementation increases occlusal contact surface area and intensity in both cement space groups. Full article

The assembly job shop is a prevalent production organization mode in manufacturing enterprises. During the processing and assembly of products, operation processing times are influenced by numerous factors, leading to significant uncertainty. This paper investigates the flexible assembly job shop scheduling problem (FAJSP) with uncertain processing times, where processing times are represented as variable interval numbers. We develop a robust optimization model for the FAJSP, utilizing confidence level estimation to determine the ranges of processing times and reformulating the model based on the chance-constrained method. A two-individual-based master–apprentice evolutionary (MAE) algorithm is proposed. Two effective encoding schemes are designed to prevent the generation of infeasible solutions under assembly sequence constraints. Additionally, a decoding method based on interval scheduling theory is devised to accurately represent interval processing times. Case studies are conducted to validate the effectiveness of the proposed robust optimization model and demonstrate the superiority of the MAE algorithm. Full article