Search Results (45,759)

This paper presents a novel hybrid algorithm for determining the optimal Phasor Measurement Units (PMU) configuration in power networks to ensure full topological and numerical observability through a multi-phase process. In the first phase, a graph-theoretic Heuristic Node Selector (HNS) is developed to rapidly establish topological observability via Core-Tree construction and node dominance evaluation. Unlike most existing studies that implicitly assume topological observability implies numerical observability, the second phase applies a Genetic Algorithm to refine and extend the initial solution from HNS, ensuring complete numerical observability while minimizing number of PMUs. This hybrid method significantly reduces the search space and improves convergence. The HNS procedure is further extended in this work to explicitly handle Zero Injection Buses (ZIB) through rule-based topological modifications, enabling a modified version of the algorithm applicable to real networks with complex structures. Real-world implementation practices from European Transmission System Operators are considered through the adoption of a “one PMU per feeder” configuration. The proposed method is validated on standard IEEE test systems and Serbian transmission networks. Results demonstrate high scalability, adaptability to various network topologies (with and without ZIB nodes), and efficient PMU allocation. Notably, the method consistently achieves high values of the System Observability Redundancy Index, indicating strong robustness and redundancy in measurement placement. Full article

Integrating waste materials into road infrastructure is essential for environmental sustainability and resource efficiency. This study addresses the modification of short-term-aged 50/70-penetration-grade bitumen using two sustainable additives: waste toner powder and lignin. Waste toner was added at weight percentages of 4%, 8%, 12%, and 16%, while lignin was added at 15% and 20%. Since these modifiers have individual uses, this study examines how they may strengthen the oxidized binder. It focuses on extending the lifespan of the mixture by combining industrial and bio-based polymers. The main aim was to delineate the impact of these modifiers on the physical consistency, low-temperature flexibility, and microstructural morphology of the binder. The results show that both modifiers increase binder stiffness by reducing penetration at all modification rates. The resins in the waste toner enhance the polymer matrix, and the lignin’s aromatic structure increases the elastic components, improving high-temperature stability. However, ductility tests showed a reduction in elongation capability, suggesting a brittle state at lower temperatures. Also, waste toner additive is identified as the ideal modifier for high-temperature applications. SEM analysis illuminated the mechanisms underlying these performance modifications. Both additives had homogeneous distribution and good bitumen matrix interfacial bonding at lower concentrations. Full article

Peptide nucleic acids (PNAs) are versatile molecules with promising diagnostic and therapeutic applications, including gene expression regulation and miRNA targeting. However, their moderate biological efficacy limits their therapeutic application. This can be addressed by leveraging a key advantage of PNAs over other nucleic acids—the ease of modification, which enhances their functional properties. Notably, γ-modified PNAs have improved binding affinity and cellular uptake properties, underscoring the potential of backbone engineering. In this study, we introduced a novel γ-amino carboxylic acid modification into PNAs targeting miR-221-3p, a key miRNA implicated in various pathological processes. The binding affinity of the modified PNAs to their targets and their ability to inhibit miR-221-3p expression were considerably higher than those of unmodified PNAs in Lung cancer cell lines, leading to effective regulation of downstream gene and protein expression. These findings underscore the potential of γ-modified PNAs as a platform for developing miRNA-targeted therapeutics. Full article

In a sentinel health event investigation of a back disorder claim, the vibration exposure and ergonomic function of a modified suspension seat were assessed. Background: In a forensic occupational injury investigation, an aftermarket-altered operator seat in a railroad rail-track tamper machine was evaluated. Methods: Detailed whole-body vibration (WBV) exposure measurements were conducted according to current applicable technical standards and guidelines (i.e., ISO 2631-1:1997) on a 09-16 DYNACAT Continuous Action Tamper with Stabilizer during routine track repair services. The modified Grammer Mfg. suspension operator seat was evaluated for performance and ergonomic features (i.e., adjustability, posture, and suspension quality). Results: The tested seat appeared to underperform and was overloaded with the aftermarket control devices, attachments and modifications. The suspension system’s end-stopper was damaged. The seat system had excessive play and wobbles; it was not firmly braced and attached. The vector sum (a_v) results ranged from 0.26 m/s² (no tamping) to a maximal 0.55 m/s² (tamping). The seat transfer (SEAT) analysis showed magnification of vibration input and variable performance of the suspension depending on operational tasks. Conclusions: The modified suspension seat underperformed and seemed to magnify and worsen the vibration, jolts and shock exposures of the seated operator. The heavy and bulky seat modifications likely limited the suspension function. The malfunctioning seat was more likely than not a contributing factor in the pathogenesis of the spinal disorders of the injured machine operator. Full article

Applying state-of-the-art RGB object detectors (e.g., YOLOv8) to underwater scenes often yields unstable performance due to scattering, absorption, illumination deficiency, and bandwidth-limited transmission that severely corrupt image contrast and details. Forward-looking sonar (FLS) remains informative in turbid or low-visibility water, yet its low resolution and weak semantics make conventional fusion architectures costly and difficult to deploy on resource-constrained robots. This paper proposes a paired-sample-free RGB–FLS joint training paradigm based on parameter sharing, where RGB and FLS images from different datasets are jointly used during training without any frame-level pairing or architectural modification. The resulting model preserves the original detector parameter scale and inference cost, and requires only RGB input at test time. Experiments on the SeaClear and Marine Debris FLS datasets under six representative underwater degradation factors (contrast loss, blur, resolution reduction, color cast, and JPEG compression) show consistent robustness gains over RGB-only training. In particular, under severe low-contrast corruption, the proposed training strategy improves mAP50 by more than 14 percentage points compared with the RGB-only baseline. These results indicate that sonar-domain supervision functions as an auxiliary structural constraint during optimization, rather than a conventional multi-source data enlargement. By forcing a shared-parameter detector to fit a texture-poor, geometry-dominant sonar domain, the learned representation is biased away from color/texture shortcuts and becomes more stable under adverse underwater degradations, without increasing deployment complexity. Full article

(1) Introduction. To improve access times and provide effective treatment to the growing patient population with acute stroke due to large vessel occlusion (LVO), thrombectomy-capable stroke centers (TCSCs) should be made an integral part of hospital infrastructure in Poland. The geographical proximity of thrombectomy-capable centers and recently extended treatment time windows will considerably increase patient numbers, decrease patient disability, and reduce the costs of long-term care. (2) Aim of the study. This study investigates the clinical outcomes, time metrics, and angiographic data of a cohort containing 250 thrombectomy patients at a single TCSC in Poland. We measured performance against data from the national database during two crucial time intervals: at the very beginning of the center’s service and after the involvement of a new operator. This study considers concurrent modifications in qualification guidelines, the TCSC’s transition from a ‘direct-admission-only’ to a ‘drip-and-ship’ model, and the learning curve of the interventional stroke team. (3) Methods. A retrospective analysis was conducted on 250 patients treated from August 2020 to May 2025 at a newly established TCSC. The cohort was dived into 2 subgroups: an initial group of 100 patients, whose treatment corresponded to the involvement of a new, previously trained on-site operator and the establishment of 24/7 service, and a group of 150 patients who received later treatment. Additional comparisons were made between a cohort of directly admitted patients and those treated under the drip-and-ship model. The results compared between patients treated with early and expanded time windows. (4) Results. Significant differences were observed between the first 100 and subsequent 150 patients in terms of admission scheme (97% vs. 70%, p < 0.0001), extended time window treatment (8% vs. 17.3%, p < 0.05), and intravenous thrombolysis treatment (81% vs. 65.3%, p < 0.01). Improvements in time intervals and procedural factors were noted in the second group, reflecting the operator’s increased experience (groin-to-first pass time: 27 vs. 23 min, p < 0.05). A comparative analysis between the direct admission and drip-and-ship models revealed extended time intervals in the latter (door-to-groin: 110 vs. 159 min, p < 0.001; door-to-recanalization: 158 vs. 200 min, p < 0.001; door-to-CT: 9 vs. 16.5 min, p < 0.001; and door-to-IVT: 21 vs. 43 min, p < 0.001). Patients in the extended time window exhibited lower intravenous thrombolysis rates (78.2% vs. 29.4%, p < 0.0001) and prolonged door-to-groin (117.5 vs. 150 min, p < 0.005), door-to-CT (10 vs. 19.5 min, p < 0.01), and door-to-IVT (25 vs. 77.5 min, p < 0.001) times. No significant differences were found in complication rates, clinical outcomes, or mortality between the analyzed subgroups. (5) Conclusions. The present data demonstrate favorable clinical and angiographic results among acute LVO stroke patients at the newly established TCSC, both at the onset of the mechanical thrombectomy service and after the involvement of a newly trained operator. Even when treating patients with prolonged times due to transportation and late window qualification, we observed favorable clinical outcomes and low rates of complications. The results achieved in our TCSC compared with the national data suggest that TCSCs could potentially play an important role within the overall endovascular treatment system for acute ischemic stroke patients in Poland. Full article

Micro- and nanoplastics represent ubiquitous environmental contaminants with emerging concerns regarding their impact on human health. The gastrointestinal tract is the primary site of contact, where micro- and nanoplastics may interact with the intestinal epithelium, potentially disrupting barrier integrity, altering microbiota composition, and triggering inflammatory or oxidative stress responses. Moreover, variability in particle size, shape, chemical composition, and surface modifications adds complexity to assessing their health impact. Findings remain inconsistent, and the mechanisms of toxicity are not yet fully elucidated. This study developed a tri-culture in vitro intestinal barrier model incorporating Caco-2 enterocytes, HT29-MTX mucus-secreting cells, and Raji B-induced M-like cells to mimic the structural and functional features of the human gut epithelium. Polystyrene beads of different sizes (40 nm and 200 nm) and surface functionalization (carboxylated and aminated) were characterized and exposed to the model to examine their effects on barrier integrity, cellular uptake, and cytotoxicity. The results showed that size and surface chemistry play key roles in particle interaction dynamics with the intestinal barrier, affecting cellular internalization and toxicological outcomes. This validated in vitro model provides a valuable tool for investigating micro- and nanoplastic behavior upon oral exposure, contributing to more accurate health risk assessments associated with plastic pollution. Full article

Direct borohydride fuel cells (DBFCs) are emerging as a promising source of clean energy; however, their performance depends heavily on efficient anode catalysts for the oxidation reaction of sodium borohydride (BOR). In this study, we developed and tested the Au–NiZn/Ti electrocatalyst designed to improve the performance of DBFCs. Electrodeposition and alkaline leaching were utilized to transform a zinc-rich nickel coating into a porous dendritic structure on a titanium substrate. By adding a small amount of gold crystallites through galvanic displacement, the surface roughness and the number of active sites available for the reaction were significantly increased. Electrochemical tests confirmed that this modification enhances BOR and effectively suppresses unwanted side reactions like hydrogen evolution. The resulting catalyst demonstrated high stability, maintaining over 88% of its current density during extended operation. Ultimately, the study positions this gold-modified material as a cost-effective and durable solution for clean energy conversion technologies. Full article

Background/Objectives: Testicular germ cell tumors (TGCTs) are uniquely curable with cisplatin-based therapies even when widely metastatic; however, cisplatin resistance does occur, resulting in very poor prognosis. The mechanisms to explain TGCT hypersensitivity to cisplatin and mechanisms of resistance are not well-understood. Methods: The global transcriptional response to acute cisplatin treatment (24 h after a 6 h pulse of cisplatin) was assessed in three parental embryonal carcinoma TGCT cells lines compared to multiple isogenic, stable, cisplatin-resistant clonal lines from these parental cells. Results: Cisplatin treatment of parental cells consistently showed a more robust overall transcriptional response to cisplatin compared to their cisplatin-resistant cellular counterparts for a common set of genes and pathways including the upregulation of genes associated with histone modifications and p53, EMT, and KRAS signaling and the downregulation of genes normally upregulated by MYC. Focusing on genes exclusively altered in parental cells revealed upregulated genes known to be induced by p53 and downregulated by MYC and the transferrin receptor, TFRC1. Several of these p53/MYC/TFRC1 targets were associated with a higher instance of disease-free survival in a cohort of TGCT patients. Conclusions: Cisplatin resistance in TGCT cells is associated with a diminished alteration in cisplatin-responsive genes, especially genes known to be regulated by p53, MYC and TFRC1, that may be linked to cisplatin hypersensitivity and survival in TGCTs. Full article

β-Carotene has extensive applications in the food, pharmaceutical, and cosmetics industries. Traditional chemical synthesis methods face challenges such as byproduct residues and high costs, whereas natural extraction is constrained by low yields and complex processes. Recent advancements in synthetic biology and metabolic engineering have paved the way for the heterologous biosynthesis of β-carotene in microorganisms. Owing to its rapid growth, convenience of genetic manipulation, and suitability for producing apocarotenoids, Escherichia coli is an ideal host for the production of β-carotene and its derivatives, as exemplified by the record production of multiple apocarotenoids in engineered E. coli strains. Here, we summarize the metabolic engineering strategies employed to produce β-carotene in E. coli, including manipulation of the endogenous MEP pathway, introduction of the hybrid MVA pathway, modulation of central carbon metabolism, modification of the cell membrane, and fermentation process optimization. As β-carotene acts as a biosynthetic hub for many carotenoids and apocarotenoids, we also highlighted the importance of efficient β-carotene production for the sustainable preparation of these compounds. This review aims to provide theoretical insights for designing talented β-carotene producers and laying the foundation for the sustainable manufacturing of valuable carotenoids and apocarotenoids. Full article

Peroxiredoxins (Prdxs) are a family of thiol-specific peroxidases that play a central role in maintaining intracellular redox homeostasis. In addition to their classical antioxidant activities, Prdxs function as peroxide sensors, modulators of redox signaling, and molecular chaperones. In this review, we summarize the peroxide-reducing activity, their redox-switch mechanism driven by reversible hyperoxidation, and the chaperone function that arises through oligomerization and accompanying structural changes. We also highlight that the Prdx1–Prdx6 isoforms exhibit distinct subcellular localizations and perform isoform-specific functions, thereby contributing to a wide range of physiological and pathological processes. Furthermore, we compile recent findings showing that diverse post-translational modifications (PTMs), including phosphorylation, acetylation, ubiquitination, glutathionylation, sumoylation, and S-nitrosylation, not only regulate Prdx activity but also contribute to cellular signaling processes. Overall, this review emphasizes that Prdxs are more than simple antioxidant enzymes: they serve as guardians of cellular redox balance and dynamic regulators of signaling networks, underscoring their potential as disease biomarkers and therapeutic targets. Full article

Epilepsy is a heterogeneous neurological disorder with a strong genetic basis, yet recent evidence underscores the critical role of epigenetic mechanisms in its pathogenesis. This review synthesizes current knowledge on how chromatin remodeling, histone modifications, DNA methylation, and transcriptional regulation intersect with classical channelopathies and signaling pathways. We emphasize how epigenetic dysregulation contributes to neuronal excitability and network plasticity, particularly through interactions with mTOR, PI3K-AKT, and GABAergic signaling cascades. The convergence of genetic mutations and epigenetic modifications creates a dynamic landscape in which environmental factors can modify gene expression and contribute to the development of epilepsy. Emerging therapeutic strategies—including epigenetic drugs (HDAC inhibitors, DNMT inhibitors), CRISPR/dCas9-based epigenome editing, and multi-omics approaches—offer promising avenues for precision medicine. This review provides a comprehensive synthesis of genetic and epigenetic mechanisms in epilepsy, examining how these layers interact to produce disease phenotypes and discussing the therapeutic implications of this multilayered regulation. Full article

Amorphous metal alloys (AMAs) are characterized by good mechanical and electrochemical properties. However, due to crystallization processes occurring at higher temperatures (Ta ˃ 600 K), these properties may deteriorate. The aim of this work was to investigate the effects of short-term annealing at T₃ = 611 ± 1 K and to determine the risks of such thermal modifications for the electrochemical properties of the material. A comprehensive analysis shows that short-term isothermal annealing (5 min) of the amorphous metal alloy Al₈₇Y₄Gd₁Ni₈ at a temperature of 611 ± 1 K improves the tribological properties of the material. However, it has been established that heat treatment for 5 min is optimal and leads to temporary thickening of the film and the formation of an almost ideal double layer, but annealing for 15–60 min negatively affects the electrochemical properties of this material, indicating a decrease in the protective properties of the passivating layers. Full article

Lung cancer ranks among the most commonly diagnosed malignancies worldwide, with dismal prognosis largely due to its intrinsic drug resistance and high recurrence rate. Herein, we synthesized 30 glycyrrhetinic acid derivatives and evaluated their anti-lung cancer potential both in vitro and in vivo. The biological effects of compound 17 on A549 cells were determined using MTT, colony formation, and Transwell assays. Flow cytometry, transcriptomic profiling, and RT-qPCR were performed to identify differentially expressed genes, followed by GO and KEGG enrichment analyses and molecular docking validation. A mouse xenograft tumor model was employed to assess therapeutic efficacy and systemic toxicity. Compound 17 exhibited dose-dependent inhibition of A549 cell proliferation, migration, and invasion, achieving an IC₅₀ value of 0.6011 ± 0.05 μM. It induced G1-phase cell cycle arrest and apoptosis by inhibiting the TNF signaling pathway and modulating apoptosis-related proteins. In vivo experiments demonstrated that compound 17 exerted a tumor inhibition rate of 80.61% without observable toxic side effects. This study is the first to demonstrate that compound 17 exerts potent anti-lung cancer activity by targeting the TNF signaling pathway and activating the mitochondrial apoptosis pathway, providing a critical experimental foundation for its development as a novel therapeutic agent against lung cancer. Full article

In recent decades, lignocellulosic biomass has attracted increasing attention as a sustainable alternative to fossil-fuel-based resources. However, the compact and highly crystalline structure of cellulose remains a major limitation to its effective utilization. In this study, the allomorphic transformation of cellulose was induced through chemical treatments using sodium hydroxide (NaOH) and ethylenediamine (EDA), enabling the conversion of native cellulose I into cellulose II and cellulose III, respectively. The resulting changes in the crystalline structure were systematically investigated using X-ray diffraction and Raman spectroscopy. Both NaOH- and EDA-treated celluloses exhibited enhanced enzymatic digestibility compared to untreated cellulose, consistent with the observed modifications in the crystal structure. Nevertheless, some results indicate that crystalline structure is not an absolute determining factor, but rather one of several parameters, including specific surface area, particle size, and degree of polymerization. Full article