Search Results (735)

This paper presents a high-performance and resource-efficient Field Programmable Gate Array (FPGA)-based architecture for satellite telemetry transmission systems. The proposed design implements a flexible channel coding chain, including Reed–Solomon (R-S) encoding, convolutional encoding, symbol interleaving, pseudo-randomization, and Attached Synchronization Marker (ASM) insertion, in accordance with CCSDS recommendations. The architecture is fully integrated and configurable, allowing dynamic selection of coding schemes without requiring structural modifications. The system is implemented on a modern FPGA platform with a 32-bit AXI4-Stream interface at 110 MHz, reaching an effective throughput of up to 1.76 Gbps. Experimental results demonstrate reliable timing with positive setup and hold margins, allowing the system to operate at approximately 130 MHz. Power consumption is measured using Switching Activity Interchange Format (SAIF)-based switching activity, providing a realistic estimate of programmable logic power consumption. The total on-chip power is about 1.77 W for individual coding modes. It rises to 1.91 W in the concatenated setup, which is the worst-case scenario. The results show that the proposed architecture efficiently uses resources, runs reliably at high speeds, and exhibits predictable power consumption. This makes it well suited for high-reliability and energy-constrained satellite communication systems. resources are used. Full article

Rotational turning is a hybrid machining process that combines features of milling and conventional turning, resulting in altered chip formation and force generation mechanisms. Despite its technological relevance, the predictive modeling of cutting forces and surface roughness in rotational turning has received little attention. This study applies and evaluates a hybrid regression and machine learning modeling for the multi-output prediction of three cutting force components and two surface roughness parameters during rotational turning of normalized C45 steel. The input variables are tool inclination angle, depth of cut, feed, and cutting speed. Three modeling approaches are compared: stepwise polynomial regression, Gaussian Process Regression, and Random Forest regression, using repeated five-fold cross-validation with ten repetitions. The results show that Gaussian Process Regression provides the highest predictive accuracy for most outputs, particularly for axial and radial forces and roughness parameters, while stepwise regression achieves comparable performance for tangential force with greater interpretability. Random Forest regression exhibits lower accuracy under the structured experimental design. The study demonstrates that combining interpretable regression with probabilistic machine learning enables the accurate prediction of process responses in rotational turning. The proposed methodology represents a novel, statistically validated approach for multi-output modeling of this machining process and supports future applications in process optimization and adaptive manufacturing systems. Full article

Background/Objectives: Antibodies are a rapidly expanding field in drug discovery, but their monospecificity limits therapeutic applications, particularly in complex inflammatory diseases. Multispecific therapeutics, which combine variable regions targeting two or more antigens, offer potential advantages such as enhanced efficacy, broader target modulation, and reduced side effects. This study aimed to identify and characterize bispecific, VHH-based antibodies simultaneously targeting IL-6 and IL-17A—two key cytokines involved in autoimmune and chronic inflammatory conditions. Methods: A phage display screening was conducted using llama-derived VHH libraries to select binders against human IL-6 and IL-17A. Binding affinities of individual VHHs and assembled bispecific constructs were assessed using Bio-Layer Interferometry (BLI). Functional activity was evaluated using reporter cell lines responsive to IL-6 and IL-17A signaling. Biophysical and quality assessments of selected VHHs and bispecific antibodies were performed using the Uncle screening platform and LabChip capillary electrophoresis. Results: Several high-affinity VHH binders were identified for both IL-6 and IL-17A, and incorporated into bispecific antibody formats. The bispecific candidates exhibited simultaneous inhibition of both cytokine pathways in functional reporter assays. Biophysical characterization confirmed good stability and purity profiles for selected molecules. Conclusions: This study demonstrates the feasibility of generating stable, functional bispecific VHH-based antibodies targeting IL-6 and IL-17A. These constructs show potential as therapeutic agents for treating autoimmune and chronic inflammatory diseases by modulating multiple signaling pathways simultaneously. Full article

PDMS SlipChips are vital for precision medicine, but their performance often degrades when solutions leak or air pockets become trapped between layers. These failures stem from the inherent stickiness of PDMS and uneven surface contact, as the sliding nature of the device prevents permanent sealing. This work addresses these technical hurdles by integrating magnetic clamping with oil-infused lubrication and refined microwell geometries. A 3D-printed magnetic fixture maintains steady contact pressure during operation, while custom-made microstages provide the precise control needed to align microwells across the x–y plane. By allowing the porous PDMS to absorb silicone oil, we created a stable lubricating interface that prevents leakage and reduces friction without sacrificing mobility. We found that a microwell-to-channel width ratio of five substantially suppresses bubble formation compared with narrower designs. These enhancements ensure the generation of consistent, discrete concentration gradients and establish a reliable platform for high-throughput assays using minute sample volumes. Full article

Bone is a dynamic and multifunctional tissue that provides mechanical support, regulates mineral homeostasis, supports hematopoiesis, and relies on complex interactions among multiple cell types. The increasing incidence of bone-related diseases, such as osteoporosis, osteoarthritis, fracture non-union, and bone cancer, highlights the need for in vitro models that better reflect human bone physiology. Bone-on-a-chip technology, developed through advances in microfluidics, biomaterials, and tissue engineering, offers a promising approach to recreate key features of the bone microenvironment in vitro. By incorporating bone-mimicking materials, relevant bone cells, vascular components, fluid perfusion, and mechanical stimulation, these platforms allow more realistic investigation of bone remodeling, regeneration, disease mechanisms, and drug responses. In parallel, bone organoids and their integration with microfluidic chips have further expanded the capabilities of in vitro bone models by enabling the formation of self-organized, human-relevant bone tissues with increased cellular complexity. This review summarizes recent progress in bone-on-a-chip systems, including models for osteogenesis and bone regeneration, vascularized bone, bone marrow and hematopoietic niches, cancer bone metastasis, and mechanobiological studies. Key design principles, materials, cellular components, and applications in disease modeling, drug screening, toxicity assessment, and personalized medicine are discussed. Current challenges and future directions are also discussed to support the continued development of more physiologically relevant in vitro bone models. Full article

Hepatocellular carcinoma (HCC) is a highly malignant tumour with a poor prognosis and few effective treatment options. Development of resistance to conventional therapies and occurrence of severe side effects highlight the urgent need for novel, low-toxicity interventions. Natural products are promising candidates for HCC drug development thanks to their multi-target activity and favourable safety profiles. Previous studies reported that Lingonberry extract, a bioactive natural product, inhibits proliferation of HepG₂ cells. However, the key molecular targets and underlying anticancer mechanisms remain unclear. In this study, we analysed gene chip data from Lingonberry extract-treated HepG₂ tumour-bearing mice using bioinformatics tools, employing a cross-species, multi-level screening strategy to identify PSMB8 as the core regulatory gene. In vitro functional validations (Western blotting, RT-PCR, CCK-8 assay, colony formation assay, flow cytometry and TUNEL staining) confirmed these findings. Downregulating PSMB8 was found to effectively induce late apoptosis in HepG₂ cells, and Lingonberry extract was found to significantly reduce PSMB8 protein expression. This study identifies PSMB8 as a key mediator of the anticancer effect of Lingonberry extract in HepG₂ cells. It provides a reliable methodological reference for screening anticancer targets of natural products and supports further exploration of Lingonberry extract as a potential adjuvant/lead compound for HCC. Full article

Pulmonary embolism (PE) is biologically heterogeneous. Despite guideline-directed anticoagulation, a subset of patients develops recurrent venous thromboembolism, persistent exertional limitation, residual perfusion defects, and progression to chronic thromboembolic pulmonary disease (CTEPD) or chronic thromboembolic pulmonary hypertension (CTEPH). Conventional risk factors explain much of the index event but incompletely account for thrombus non-resolution and chronic sequelae. Clonal hematopoiesis of indeterminate potential (CHIP)—the age-associated expansion of hematopoietic clones carrying somatic mutations—defines a measurable thrombo-inflammatory endophenotype that is strongly genotype- and clone-size (variant allele frequency; VAF)-dependent. Across human studies, JAK2-CHIP and TET2-CHIP show the most consistent associations with VTE/PE, whereas isolated DNMT3A-CHIP is frequently neutral, and larger clones tend to confer stronger effects. Mechanistically, CHIP can bias myeloid cells toward inflammasome/IL-1β signaling and endothelial activation, increase monocyte tissue factor activity, and promote immunothrombosis with neutrophil extracellular trap (NET) formation. NET-rich thrombi may adopt a dense fibrin–DNA–histone architecture that resists endogenous fibrinolysis, favoring organization and persistence. CTEPH offers a translational window to interrogate this model because thrombotic material and deep phenotyping are accessible. We synthesize genotype- and VAF-resolved clinical and mechanistic evidence using a structured strength-of-evidence framework and propose a pragmatic phenotyping roadmap with testable predictions for prospective post-PE validation. CHIP testing in PE/CTEPH remains investigational and should not currently change standard care. Full article

Field-Programmable Gate Arrays (FPGAs) have become an important platform for accelerating real-time communication systems, and System-on-Chip (SoC) devices provide the flexibility to design and optimize architectures that support high data rates, different modulation formats, and channel equalization schemes. Selecting the appropriate architecture can be guided through Design Space Exploration (DSE) using high-level synthesis tools, which enables the identification of numerical representations that balance performance with reduced hardware resource consumption. Despite their relevance, recent developments in communication systems often overlook the impact of numerical precision in Digital Signal Processing algorithms, particularly the trade-offs between floating- and fixed-point arithmetic when targeting hardware implementations. In this work, two widely used blind equalization algorithms, the Constant Modulus Algorithm (CMA) and the Multi-Modulus Algorithm (MMA), were implemented on a low-cost Ultra96 SoC-FPGA to analyze the effect of a fixed-point representation. A multi-objective Design Space Exploration methodology was applied to minimize hardware utilization while maintaining reliable transmission performance. Resource consumption, latency, and throughput were measured across different binary formats using the Minimum Mean Square Error (MMSE) criterion. Parallelization techniques were incorporated to improve throughput. The DSE generated comprehensive performance surfaces quantifying latency, MMSE convergence, and FPGA resource utilization (DSP48E/FF/LUT/BRAM) across fixed-point formats, achieving optimal 4 MS/s throughput configurations. Although this throughput is naturally lower than the Gigabit speeds required in backbone optical networks, the results demonstrate the effectiveness of numerical representation optimization in resource-constrained SoC-FPGA devices, offering a practical approach for real-time Edge and IoT implementations where cost and hardware limitations are critical. Full article

Notch wear in austenitic stainless steel turning develops rapidly and remains a key productivity limitation with carbide tools. This work identifies the initiation mechanism of notch wear when turning EN 1.4307 stainless steel using CVD-coated cemented carbide inserts with an Al₂O₃ top layer. Turning tests were performed under dry conditions, followed by optical wear measurements and chip surface analysis. The tool–chip interface chemistry and material transfer were characterized using SEM/EDS, while high-frequency acoustic emissions were recorded to resolve the dynamics of adhesive events. Thermo-mechanical FEM simulations were conducted to map contact pressure and temperature along the cutting edge. The results show that adhesive wear initiates immediately at engagement and governs notch formation: polluted SiO₂ deposits act as an active bonding medium, and repeated bond formation/rupture removes extremely thin flakes of tool and coating material, evidenced by Al₂O₃ and Ti(C,N) fragments on the chip and by characteristic acoustic cluster waves. A new tool–chip contact model is presented, indicating that high pressure and high temperature within the polluted SiO₂ near the chip’s outmost side promote larger, stronger adhesive bonds together with the absence of ceramic particles near the rake in the notch area. Oxidation and diffusion are assumed to be secondary processes that become relevant after local coating loss, while adhesion remains the primary removal mechanism during early and intermediate stages. Full article

Dynamic phase transition of natural gas hydrates confined within complex pore–throat structures is a key factor impacting the safe and efficient development of hydrate-bearing deposits. In this work, hydrate-bearing samples with varying saturation were first reconstructed with the proposed ice-seeding method using actual marine soil in hydrate-bearing sediments from the South China Sea. Dynamic evolution characteristics of hydrate formation in evolving porous media under different temperature and pressure conditions were analyzed in detail. Combined with high-resolution CT scanning, image processing, pore network extraction, and statistical analysis, the typical microscopic pore–throat structures of hydrate-bearing sediments were revealed, and the presence of nanopores was identified. Furthermore, highly controllable heterogeneous pore–throat structures were constructed for microfluidic chips by integrating stochastic modeling, equivalent modeling, and machine learning approaches. On this basis, a novel microfluidic testing method was developed for investigating the dynamic formation, dissociation, and phase transition characteristics of natural gas hydrates in complex pore structures by controlling the temperature. This study provides reliable data support and theoretical guidance for the productivity prediction of marine hydrate-bearing deposits. Full article

Dry machining of medium-carbon steels plays an important role in sustainable manufacturing; however, high tool wear and thermal instability pose challenges. The study aims to evaluate the kinematic–tribological performance of EN8 steel during dry milling and compare up-milling and down-milling to trade-off tool life and surface finish. The experiments were conducted using a central composite design (CCD) as part of response surface methodology (RSM), with 36 runs to evaluate interactions among spindle speed, feed rate, and depth of cut. Down-milling outperformed up-milling, achieving 12.4% less tool wear, 45.9% better surface finish, and a 47 °C lower peak temperature from cutting. The above benefits are attributed to the unique kinematics of chip formation during down-milling, which offers lower friction at entry and better heat dissipation, contrasting with the high-friction ploughing phase of up-milling. Grey relational analysis (GRA) found that down-milling with a mid-range cutting speed (22.31 m/min) and a low feed rate (25 mm/min) provided a multi-objective optimum. The findings support the existence of a kinematic–tribological coupling, providing a solid single approach to optimising the dry machining of harder materials. Full article

Macrophages and other phagocytic cells are central regulators of tendon immunobiology, orchestrating inflammation, tissue repair, and extracellular matrix (ECM) remodeling in the tendons. They derive from circulating monocytes and resident tendon-specific populations, including tenophages. Macrophage polarization along the M1/M2 axis exerts a decisive influence on tendon healing trajectories. Activated M1 macrophages promote the early healing phase for debris clearance initiating the reparative cascade. However, their sustained activity leads to inflammation, ECM degradation, impaired healing, tendinopathy, and heterotopic ossification (HO). Conversely, a timed shift toward activated M2 macrophages promotes resolution of inflammation, angiogenesis, ECM deposition, and fibrocartilage formation, whereas excessive or prolonged M2 activity facilitates adhesion formation, fibrosis, scarring and HO. Recent single-cell and spatial profiling studies showed macrophage heterogeneity across tendon compartments, thereby extending the classical M1/M2 paradigm and underscoring the relevance of macrophages/resident tendon cell’s interaction in tendon-specific local niches. Mechanobiological stimuli (depending on magnitude, frequency and duration) further modulate macrophage phenotypes and tendon healing. Emerging coculture models and human tendon-on-chip systems provide high-resolution platforms for dissecting these spatiotemporal interactions. Promising therapeutic approaches comprise the application of extracellular vesicles, controlled mechanoloading regimens, and immunomodulatory biomaterials demonstrating potential to induce regenerative macrophage signatures for improved healing outcomes. Notably, platelet-rich plasma (PRP) formulations shape macrophage responses: leukocyte-rich PRP preferentially promotes M1 activity whereas leukocyte-poor PRP supports M2 polarization. Thus, mechano- and immunomodulatory strategies can offer precise control over macrophage dynamics. Regarding the Achilles tendon pathologies, such approaches are helpful by directing macrophage-mediated inflammation towards effective tendon healing outcomes. Full article

Obesity is a major risk factor for both venous and arterial thrombosis, largely mediated by chronic oxidative stress and hemostatic dysregulation. Excess adipose tissue enhances the production of reactive oxygen species (ROS) from adipocytes and infiltrating macrophages, leading to lipid, protein, and DNA oxidation, reduced antioxidant capacity, and a pro-inflammatory milieu. These molecular alterations promote endothelial dysfunction, platelet hyperreactivity, hypercoagulability, and impaired fibrinolysis, creating a systemic prothrombotic state. Traditional coagulation assays provide limited insight into the dynamic process of thrombus formation under physiological flow. The Total Thrombus-Formation Analysis System (T-TAS) offers a microfluidic, flow-based platform that evaluates thrombus formation in whole blood under controlled shear conditions using collagen- or tissue factor-coated chips. T-TAS parameters, such as time to occlusion, area under the curve (AUC), and pressure kinetics, integrate platelet function, coagulation, and thrombus stability, providing a sensitive assessment of prothrombotic phenotypes. Combining oxidative stress biomarkers (e.g., malondialdehyde, 8-hydroxy-2′-deoxyguanosine, and total antioxidant capacity) with T-TAS-derived functional readouts enables a multidimensional evaluation of thrombosis risk in obese individuals. This review highlights current evidence linking obesity-induced oxidative stress to hemostatic disturbances and illustrates the translational potential of the T-TAS for mechanistic studies and clinical risk stratification. Understanding the interplay between redox imbalance and thrombus formation under flow conditions may inform novel therapeutic strategies to prevent obesity-related thromboembolic events. Full article

Microfluidics provides precise control of microscale fluid transport and has become central to biomedical, pharmaceutical, and industrial technologies. However, conventional fabrication methods such as photolithography and soft lithography require cleanroom facilities, use costly materials, and offer limited capability for constructing complex or multi-material architectures. This review highlights emerging manufacturing strategies, focusing on polymer-based micro-milling as an accessible and cost-effective alternative for microfluidic device production. Advances in micro-milling now enable the fabrication of microchannels and functional features with improved dimensional accuracy and surface quality, while additive manufacturing offers complementary rapid prototyping and design flexibility. Micro-milling is particularly promising for rapid prototyping of polymeric biosensor chips designed for point-of-care diagnostics. The technique supports diverse materials and eliminates reliance on cleanroom processing. Critical parameters, including tool geometry, spindle speed, and feeding rate, strongly influence fidelity and surface roughness, which directly affect biosensor sensitivity. Despite its advantages, challenges such as tool wear, burr formation, and limits on minimum feature size continue to hinder reproducibility. Recent progress in toolpath optimization, hybrid additive–subtractive methods, and real-time process monitoring shows the potential to overcome these barriers. Overall, micro-milling offers a scalable and economical route for fabricating accessible microfluidic and biosensing platforms, with future work needed to standardize processes and improve integration with surface functionalization methods. Full article

Purpose: The aim of this in vitro study was to evaluate the degree of surface wear in implant drills from four commercial systems subjected to standardized osteotomy cycles. Materials: Four implant systems (Osstem, Megagen, Straumann, and Bego) were evaluated using sets of three drills of increasing diameters. A total of 120 osteotomies were performed in standardized porcine rib specimens under controlled drilling conditions (1200 rpm, continuous 4 °C saline irrigation, 32:1 reduction handpiece). After each drilling series, drills were cleaned, sterilized, and analyzed using SEM in three orientations. Wear was assessed using a seven-parameter scoring system. Multifactorial ANOVA, Pearson correlation, and hierarchical clustering were employed to evaluate the effects of drill brand, diameter, and wear patterns. Results: Both drill brand and diameter significantly influenced total wear scores (p < 0.001). Small-diameter pilot drills exhibited the highest wear, while large-diameter drills showed minimal degradation. Among the systems tested, Bego drills demonstrated the greatest overall wear, whereas Osstem drills—particularly the 2.0 mm drill—displayed unusually low wear for their size. A strong negative correlation between drill diameter and wear score was observed. Cluster analysis identified distinct wear patterns associated with specific drill sizes, with small drills showing prominent guide-face nicks and accumulation formation, medium drills exhibiting chipping and rake angle cleavage, and large drills presenting minimal wear. SEM imaging confirmed progressive surface deterioration, including edge rounding, microchipping, and irregular surface defects. Conclusions: Implant drill wear is strongly dependent on drill diameter, and cutting geometry. Small-diameter drills are most susceptible to surface degradation, which may increase friction and thermal load during osteotomy. Systems with enhanced material properties or optimized geometries demonstrated superior wear resistance. These findings highlight the importance of monitoring drill condition, adhering to recommended reuse limits, and considering advanced drill coatings or materials to ensure safe and predictable implant site preparation. Further research incorporating real-time thermal measurements and extended drilling cycles is needed to establish evidence-based guidelines for drill longevity and clinical performance. Full article