Search Results (900)

Wheel slipping during trajectory tracking presents significant challenges for wheeled mobile robots (WMRs), degrading accuracy and stability on low-friction or dynamic terrain. Effective control requires addressing unknown slipping parameters while balancing tracking precision and energy efficiency. To address this challenge, a control framework integrating a sliding mode observer (SMO), an improved particle swarm optimization (PSO) algorithm, and a linear quadratic regulator (LQR) is proposed. First, a dynamic model incorporating longitudinal slipping is established. Second, an SMO is designed to estimate the slipping ratio in real-time, with chattering suppressed using a low-pass filter. Finally, an improved PSO algorithm featuring a nonlinear cosine-decreasing inertia weight strategy optimizes the LQR weighting matrices (Q/R) online to both minimize tracking errors and control energy consumption. Simulations including both circular and sine wave trajectories demonstrate that the SMO achieves rapid and accurate slipping ratio estimation, while the PSO-optimized LQR significantly enhances tracking accuracy, achieves smoother control inputs, and maintains stability under varying slipping conditions. Full article

With the widespread adoption of intelligent electronic devices (IEDs) in smart substations, the real-time data transmission and interoperability features of the IEC 61850 communication standard play a crucial role in ensuring seamless automation system integration. This paper presents a hardware-in-the-loop (HIL) platform experiment analysis based on a simulated IED and man-in-the-middle (MITM) attack, leveraging built-in IEC 61850 protocol software to replicate an existing substation communication architecture in cyber physical systems. This study investigates the framework performance and protocol robustness of this approach. First, the physical network infrastructure of smart grids is analyzed in detail, followed by the development of an HIL testing platform tailored for discrete communication network scenarios. Next, virtual models of intelligent electrical equipment and MITM attacks are created, along with their corresponding communication layer architectures, enabling comprehensive simulation analysis. Finally, in the 24-h stability operation test and the test of three typical fault scenarios, the simulated IED can achieve 100% of the protocol consistency passing rate, which is completely consistent with the protection action decision of the physical IED, the end-to-end delay is less than 4 ms, and the measurement accuracy matches the accuracy level of the physical IED, which verifies that the proposed test platform can effectively guide the commissioning of smart substations. Full article

Background/Objectives: The conventional treatment of glioblastoma (GBM) with alkylating agents is not curative. The protein O6-methylguanine DNA methyltransferase (MGMT) is a significant limitation, being able to repair drug-induced DNA damage. Thus, exploring non-alkylating agents already approved by the FDA is imperative. The antidepressant fluoxetine (FL) has been explored due to its anti-cancer properties. However, its first-pass effect and its non-targeted distribution to brain tissue are major limitations of FL’s administration, which is conventionally orally administered. Thus, the primary objective of this work was the development of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) tailored with folic acid (FA) for FL delivery to GBM cells. Methods: A Central Composite Design (CCD) was applied to optimize the NPs. Results: The developed FA-functionalized PLGA NPs exhibited physicochemical properties suitable for brain-targeted delivery. The final formulation presented an average diameter of 167 ± 8 nm, a polydispersity index (PdI) of 0.23 ± 0.07, and a zeta potential of −22.2 ± 0.3 mV. The encapsulation efficiency (EE) and loading capacity (LC) values were 44.4 ± 3.8% and 3.1 ± 0.3%, respectively. In vitro studies demonstrated that the NPs are stable in storage and simulated physiological conditions and can maintain a controlled and slow-release profile of FL for 17 days. In vitro cell uptake experiments demonstrated that conjugation with FA enhances the NPs’ internalization in GBM cells overexpressing folate receptors through endocytosis mediated by this receptor. Furthermore, in vitro cytotoxicity experiments demonstrated that the FL encapsulation in the developed NPs maintains drug efficacy, as well as it was able to increase cell sensitivity to treatment with an alkylating agent. Conclusions: These results suggest that the developed NPs are effective nanocarriers, either as a standalone therapy or as a chemosensitizer in combination with the standard GBM treatment. Full article

Background/Objectives: In the past two decades, the primary therapeutic use of sildenafil has shifted significantly, from the treatment of angina to managing erectile dysfunction, and since the early 2000s it has been used in the treatment of pulmonary hypertension, particularly pulmonary arterial hypertension. Sildenafil is used as a citrate salt; after oral administration, it presents an absorption of ~90% and an absolute bioavailability of 38%, due to the first-pass effect, such that it belongs to class II of the Biopharmaceutics Classification System. Currently, studies are seeking to obtain new pharmaceutical formulations with an optimized biopharmaceutical profile. In this study, an inclusion complex of sildenafil citrate and 2-hydroxypropyl-beta-cyclodextrin in a molar ratio of 1:1 was obtained and its pharmaceutical compatibility with six pharmaceutical excipients was assessed. For three of these excipients, the presence of chemical interactions with sildenafil citrate has been presented in the literature, and for the other three, compatibility has not been evaluated. Methods: To certify the stoichiometry of the obtained inclusion complex molecular modeling, Job’s method and the Benesi–Hildebrand method were employed. Furthermore, we have described the inclusion complex and the obtained binary mixtures via ATR-FTIR and thermal (TG/DTG and DSC) analysis. Results: The results indicated a lack of chemical interactions between the inclusion complex and the six pharmaceutical excipients at ambient temperature (confirmed by ATR–FTIR investigations) and the presence of chemical interactions between the inclusion complex and three of the excipients when the mixture was heated under non-isothermal conditions (TG/DTG and DSC investigations). Conclusions: This study describes the inclusion complex between sildenafil citrate and 2-hydroxypropyl-beta-cyclodextrin in a molar ratio of 1:1 and its compatibility with several pharmaceutical excipients, results with further applications in the preformulation stage of novel delivery systems. Full article

One hundred and eighteen years have passed since Alzheimer’s disease (AD) was first diagnosed by Alois Alzheimer as a multifactorial and complex neurodegenerative disorder with psychiatric components. It is inaugurated by a cascade of events initiating from amnesic-type memory impairment leading to the gradual loss of cognitive and executive capacities. Pathologically, there is overwhelming evidence that clumps of misfolded amyloid-β (Aβ) and hyperphosphorylated tau protein aggregate in the brain. These pathological processes lead to neuronal loss, brain atrophy, and gliosis culminating in neurodegeneration and fueling AD. Thus, at a basic level, abnormality in the brain’s protein function is observed, causing disruption in the brain network and loss of neural connectivity. Nevertheless, AD is an aging disorder caused by a combination of age-related changes and genetic and environmental factors that affect the brain over time. Its mysterious pathology seems not to be limited to senile plaques (Aβ) and neurofibrillary tangles (tau), but to a plethora of substantial and biological processes, which have also emerged in its pathogenesis, such as a breakdown of the blood–brain barrier (BBB), patients carrying the gene variant APOE4, and the immuno-senescence of the immune system. Furthermore, type 2 diabetes (T2DM) and metabolic syndrome (MS) have also been observed to be early markers that may provoke pathogenic pathways that lead to or aggravate AD progression and pathology. There are numerous substantial AD features that require more understanding, such as chronic neuroinflammation, decreased glucose utilization and energy metabolism, as well as brain insulin resistance (IR). Herein, we aim to broaden our understanding and to connect the dots of the multiple comorbidities and their cumulative synergistic effects on BBB dysfunction and AD pathology. We shed light on the path-physiological modifications in the cerebral vasculature that may contribute to AD pathology and cognitive decline prior to clinically detectable changes in amyloid-beta (Aβ) and tau pathology, diagnostic biomarkers of AD, neuroimmune involvement, and the role of APOE4 allele and AD–IR pathogenic link—the shared genetics and metabolomic biomarkers between AD and IR disorders. Investment in future research brings us closer to knowing the pathogenesis of AD and paves the way to building prevention and treatment strategies. Full article

Geothermal power generation offers a high availability factor and independence from weather conditions, yet steam production in geothermal wells often declines over time due to factors such as pressure depletion and scale deposition. To enable early detection of production anomalies and optimize maintenance, this paper proposes an anomaly detection framework based on Singular Spectrum Analysis (SSA). First, a Butterworth low-pass filter reduces high-frequency noise; then, SSA decomposes the time series, focusing on the largest singular value’s corresponding vectors. An anomaly score measures the deviation between current and historical singular vectors, and Non-Maximum Suppression (NMS) aggregates consecutive peaks to reduce false positives. We apply this method to 14 years of data from nine geothermal wells, comparing two threshold strategies: a unified threshold and well-specific thresholds. Results show that while a unified threshold simplifies deployment, individual thresholds can improve detection in certain wells, underscoring the impact of well characteristics and class imbalance. Our findings demonstrate that SSA-based anomaly detection, combined with NMS and threshold optimization, can effectively support maintenance decisions in geothermal power plants. Full article

This study aimed to investigate the production of nanoemulgels structured with flaxseed fiber, designed to simulate salad dressings. For this purpose, the influence of microfluidizer passes (from one to four) on physicochemical and rheological properties was determined, followed by an assessment of thermal behavior. Rotor–stator homogenization followed by microfluidization were employed to produce nanoemulgels, which were characterized using laser diffraction, multiple light scattering, and rheological measurements. The resulting systems exhibited monomodal particle size distributions with mean diameters below 220 nm. Increasing the number of microfluidizer passes from one to four led to slight reductions in particle size, although they were not statistically significant. The formulation with two passes demonstrated superior physical stability during aging studies. Rheological evaluation indicated enhanced gel-like behavior with up to three passes, whereas excessive energy input (four passes) slightly compromised structural integrity. The linear viscoelastic region decreased notably after the first pass but remained relatively stable thereafter. The two-pass nanoemulgel, identified as the optimal formulation, was further tested for thermal stability. Temperature increases (5–20 °C) led to minor decreases in viscosity and firmness, yet the structure remained thermally stable. These findings support microfluidization as an effective strategy for developing stable flaxseed fiber-based nanoemulgels, with potential applications in functional food systems. Full article

In inertial confinement fusion (ICF) laser drivers, large-aperture high-intensity third-harmonic (3ω, central wavelength 351 nm) laser pulses passing through KDP crystals (potassium dihydrogen phosphate) can produce strong transverse stimulated Raman scattering (TSRS). TSRS not only depletes the energy of the 3ω laser beam but also damages the KDP crystal, thus significantly limiting the enhancement of ICF laser driver capabilities. Therefore, effectively suppressing TSRS in KDP crystals is a critical issue in the design and construction of ICF laser driver systems. This paper first proposes that SSD has the ability to suppress TSRS through theoretical analysis of the characteristics of SSD beams. Secondly, through numerical simulations, it presents the influence of variations in three key parameters—modulation amplitude, modulation frequency, and grating dispersion coefficient—on the TSRS gain. The results show that the Stokes gain decreases with increasing modulation amplitude and modulation frequency; specifically, the suppression capability of SSD for TSRS gradually strengthens as modulation bandwidth increases. In addition, previous reports have demonstrated that SSD can significantly suppress stimulated rotational Raman scattering (SRRS) in air, which highlights the potential value of applying SSD in large laser facilities such as ICF driver systems. Full article

Lung cancer is the leading cause of cancer mortality worldwide, with a poor prognosis driven by late diagnosis, systemic toxicity of existing therapies, and rapid development of multidrug resistance (MDR) to agents such as paclitaxel and cisplatin. MDR arises through multiple mechanisms, including overexpression of efflux transporters, alterations in apoptotic pathways, and tumour microenvironment-mediated resistance. The application of nanotechnology offers a potential solution to the aforementioned challenges by facilitating the enhancement of drug solubility, stability, bioavailability, and tumour-specific delivery. Additionally, it facilitates the co-loading of agents, thereby enabling the attainment of synergistic effects. Halloysite nanotubes (HNTs) are naturally occurring aluminosilicate nanocarriers with unique dual-surface chemistry, allowing hydrophobic drug encapsulation in the positively charged lumen and functionalisation of the negatively charged outer surface with targeting ligands or MDR modulators. This architecture supports dual-delivery strategies, enabling simultaneous administration of phytocannabinoids and chemotherapeutics or efflux pump inhibitors to enhance intracellular retention and cytotoxicity in resistant tumour cells. HNTs offer additional advantages over conventional nanocarriers, including mechanical and chemical stability and low production cost. Phytocannabinoids such as cannabidiol (CBD) and cannabigerol (CBG) show multitarget anticancer activity in lung cancer models, including apoptosis induction, proliferation inhibition, and oxidative stress modulation. However, poor solubility, instability, and extensive first-pass metabolism have limited their clinical use. Encapsulation in HNTs can overcome these barriers, protect against degradation, and enable controlled, tumour-targeted release. This review examined the therapeutic potential of HNT-based phytocannabinoid delivery systems in the treatment of lung cancer, with an emphasis on improving therapeutic selectivity, which represents a promising direction for more effective and patient-friendly treatments for lung cancer. Full article

To cost-effectively meet 6G latency requirements, concurrent upstream and direct inter-optical network unit (ONU) communication passive optical networks (PONs) based on flexible point-to-multipoint (P2MP) optical transceivers and intensity modulation and direct detection (IMDD) have been reported to enable direct communications among different ONUs within the same PON without passing data to the optical line terminal (OLT). However, the previously reported P2MP transceivers suffer from high DSP complexity for establishing ultra-dense connections. For such application scenarios, the PON’s remote nodes also have high inter-ONU signal power losses. To effectively solve these technical challenges, this paper experimentally showcases (a) new P2MP transceivers by utilizing parallel multi-channel aggregation/de-aggregation and advanced extended Gaussian function (EGF)-based orthogonal digital filter banks, along with (b) low inter-ONU signal power loss-remote nodes. By introducing these two techniques into a 27 km, >54.31 Gbit/s concurrent upstream and direct inter-ONU communication IMDD PON, comprehensive experimental explorations of the PON’s performances were undertaken for the first time. The remote node is capable of supporting 128 ONUs. The results show that the new P2MP transceivers lead to >75% (>40%) reductions in overall transmitter (receiver multi-channel de-aggregation) DSP complexity, and they can also equip the PONs with an enhanced capability of providing ultra-dense connections. The experimental results also show that the PON allows each ONU to flexibly change its upstream and inter-ONU communication channel count without considerably compromising its performance. Therefore, the PON outperforms those of previously reported works in terms of ensuring low DSP complexity, highly robust transmission performance, and enhanced capabilities of flexibly accommodating numerous applications with diverse requirements regarding traffic characteristics, thus making it suitable for ultra-dense connection application scenarios. Full article

Adequate initial training should ensure that future physical activity and sports sciences (PASS) professionals acquire skills that include not only in-depth knowledge of the content to be taught but also an understanding of the most effective teaching strategies for its transmission. The objective of this descriptive, exploratory, and quantitative study was to analyze the degree of acquisition of gymnastics teaching competencies of 107 future Portuguese PASS professionals, according to gender and training course. The research instrument was the Physical Education Teaching Competence Perception Scale, adapted to the gymnastics context. The main results showed that Portuguese students perceived themselves as having acquired medium levels of teaching competencies for gymnastics across all the dimensions analyzed, and feeling less competent in adapting curricular specifications. Regarding gender and training year, female students perceived themselves as more competent in the dimension related to the ability to use gymnastics content as teaching tools, with a significant difference. First-year students perceived a higher level of competence compared to their second- and third-year peers. Therefore, there is a need for more contextualized and reflective initial training, incorporating experiential learning modules that simulate real scenarios for adapting the gymnastics classroom. Full article

This paper reports the first case in which a hyperlipidemic retriever (due to hypothyroidism) with a nasal tumor was successfully treated—achieving partial remission—and managed using a metronomic combination of chlorambucil (3.74 mg/m², SID) and prednisolone (0.28 mg/kg, SID) orally for 9 months at a general practice. A 35 kg spayed female golden retriever aged 8 years and 8 months with nosebleeds visited the Bundang New York Animal Hospital in July 2023 after being diagnosed with nasal carcinoma. A protocol of 4 weeks of chemotherapy followed by 1 week of rest was repeated in two cycles and continued metronomically for 9 months without pause after the two cycles. The nasal exudate was significantly reduced. The size of the nasal tumor was monitored using computed tomography (CT) imaging at a referral hospital. Since the first occurrence of epistaxis, 18 months have passed (as of January 2025) and the nasal exudate is barely visible, and the vital signs and weight of the dog remain stable. The size of the nasal tumor significantly decreased after 9 months of chemotherapy completion without moderate side effects, and all the blood work was normalized, including hypercholesteremia. This study demonstrates that, in hyperlipidemic cancer patients, a prednisolone/chlorambucil metronomic combination which is cost-effective can be an alternative to tyrosine kinase inhibitors such as sorafenib, even when excluding the price. Through a literature review, the author also investigates the effect of the hyperlipidemic state on cancer, focusing on carcinoma and vascular endothelial growth factor (VEGF), as well as the RAS-RAF-MEK pathway, which is a target for tyrosine kinase inhibitors, in order to reveal the molecular mechanism of chlorambucil metronomic chemotherapy. Also, the author investigates the molecular pathway of carcinoma development in human hyperlipidemia patients through single-cell RNA sequence analysis using open public data, and discusses the molecular action of chlorambucil. Full article

Icariin (ICA) is a bioactive flavonoid compound extracted from Epimedium plants. In recent years, it has attracted significant research interest in the field of bone tissue repair due to its pharmacological effects via multiple targets and pathways. Studies have shown that ICA promotes the osteogenic differentiation of mesenchymal stem cells (MSCs) and enhances bone matrix formation by regulating signaling pathways such as Akt and Wnt/β-catenin. It concurrently inhibits osteoclast activity to maintain the balance of bone remodeling, thereby simultaneously stimulating new bone regeneration and suppressing bone resorption. At the same time, ICA exerts potent anti-inflammatory and antioxidant effects and promotes angiogenesis, improving the local microenvironment of bone injury and significantly facilitating the regeneration of bone and cartilage tissues. Additionally, ICA exhibits notable protective effects in multiple organ systems including the cardiovascular, hepatic, renal, and nervous systems. Specifically, ICA reduces cardiomyocyte apoptosis and fibrosis to preserve cardiac function, improves hepatic metabolic function and alleviates oxidative stress, attenuates renal inflammation and fibrosis, and—through neuroprotective actions—reduces neuroinflammation and promotes neuronal survival. These multi-organ effects help optimize the systemic environment for bone healing. However, ICA faces significant pharmacokinetic challenges. It has low oral bioavailability (due to poor absorption and extensive first-pass metabolism) as well as a short half-life. Consequently, maintaining effective drug concentrations in vivo is difficult, which limits its therapeutic efficacy and impedes clinical translation. To fully realize its regenerative potential, advanced drug delivery strategies (e.g., nanocarrier-based delivery systems) are being explored to enhance ICA’s bioavailability and prolong its duration of action. Overall, ICA’s multi-modal actions on bone cells, the immune microenvironment, and systemic factors make it a promising multi-target agent for bone regeneration. Addressing its pharmacokinetic limitations through optimized delivery and conducting further clinical studies will be crucial to realize its full therapeutic potential. This review provides a comprehensive overview of recent advances and challenges in translating ICA’s benefits into orthopedic therapy. Full article

To reduce welding deformation during the automated welding of intersection seams on thick plate curved penetrations and thereby improve welding quality and efficiency, an optimized method for segmented and multi-layer multi-pass welding sequences, along with welding process improvement strategies, is proposed. First, based on the welding model of the curved penetrations, a multi-layer multi-pass welding trajectory equation is designed. Next, a Gaussian heat source model is selected, and numerical simulation theories for welding temperature and stress fields are established using finite-element theory. Then, for the intersection seams of curved components with three different thicknesses, four numerical tests of segmented welding sequence optimization are carried out using welding finite-element simulation theory. Finally, the optimal welding process for the welding sequence is improved using orthogonal experimental methods, and the optimal welding process parameters for curved components with different thicknesses are determined. The optimization of welding sequences for intersection seams on three types of thick plates shows that the optimal sequence for segmented welding is first to perform upper–lower diagonal symmetry, followed by left–right symmetry. Compared to other welding sequences, the proposed method reduces welding deformation by an average of 9.24% and welding stress by an average of 7.40%, which verifies the effectiveness of the welding sequence optimization presented in the paper. Full article

Autonomous vehicles and intelligent traffic transportation are widely investigated for road networks. Context-aware traffic light scheduling algorithms determine signal phases by analyzing the real-time characteristics and contextual information of competing traffic flows. The context of traffic flows mainly considers the existence of regular, emergency, or heavy vehicles. This is an important factor in setting the phases of the traffic light schedule and assigning a high priority for emergency vehicles to pass through the signalized intersection first. VANET technology, through its communication capabilities and the exchange of data packets among moving vehicles, is utilized to collect real-time traffic information for the analyzed road scenarios. This introduces an attractive environment for hackers, intruders, and criminals to deceive drivers and intelligent infrastructure by manipulating the transmitted packets. This consequently leads to the deployment of less efficient traffic light scheduling algorithms. Therefore, ensuring secure communications between traveling vehicles and verifying the integrity of transmitted data are crucial. In this work, we investigate the possible attacks on the integrity of transferred messages and vehicles’ identities and their effects on the traffic light schedules. Then, a new secure context-aware traffic light scheduling system is proposed that guarantees the integrity of transmitted messages and verifies the vehicles’ identities. Finally, a comprehensive series of experiments were performed to assess the proposed secure system in comparison to the absence of security mechanisms within a simulated road intersection. We can infer from the experimental study that attacks on the integrity of vehicles have different effects on the efficiency of the scheduling algorithm. The throughput of the signalized intersection and the waiting delay time of traveling vehicles are highly affected parameters. Full article