Search Results (327)

Ovarian cancer is a deadly gynecological malignancy that will affect about 21,000 women and result in almost 153,000 deaths in the United States in 2025. New clinical tools that facilitate early diagnosis and treatment of ovarian malignancies will significantly help reduce mortality and improve current long-term survival rates. We utilized a previously identified single-strand DNA aptamer RLA01 that binds and internalizes into target epithelial ovarian cancer cells to label PLGA-based nanoparticles and determine their ability to selectively target EOC cells and deliver payloads for cellular internalization. Nanoparticles labeled with RLA01 significantly enhanced cellular uptake 20–85% by receptor-mediated endocytosis into target EOC Caov-3 cells and inhibited cellular uptake in non-target HOSE 6-3 cells. Further, labeling of paclitaxel-loaded nanoparticles with RLA01 significantly decreased cell proliferation and induced apoptosis. A preliminary pilot study looking at the in vivo stability of aptamers demonstrated their ability to promote retention and honing of nanoparticles at tumors. These data demonstrate the effective combinatorial use of aptamer RLA01 and nanoparticle technologies for the direct targeting of tumor cell populations both in vitro and in vivo. Full article

Relapsed/refractory diffuse large B-cell lymphoma and other non-Hodgkin lymphomas represent significant clinical challenges, particularly in patients who have exhausted standard immunochemotherapy and cellular therapies. Bispecific antibodies and antibody–drug conjugates have emerged as promising treatments, offering targeted and more effective treatment options compared to current standards. Bispecific antibodies, including epcoritamab and glofitamab, third-line therapies for diffuse large B-cell lymphoma, are recombinant immunoglobulins engineered to recognize two distinct antigens or epitopes simultaneously. This capability enhances therapeutic precision by bridging immune effector cells and tumor cells and modulating multiple signaling pathways involved in the pathogenesis of non-Hodgkin lymphoma. In the context of new therapies, antibody–drug conjugates, such as loncastuximab tesirine, are therapies composed of monoclonal antibodies linked to cytotoxic agents, in which the antibody selectively binds to tumor-associated antigens, delivering the cytotoxic payload directly to cancer cells while minimizing off-target effects. They combine the specificity of antibodies with the potency of chemotherapy, offering enhanced efficacy and safety in hematological malignancies. Ongoing clinical trials are investigating other molecules like odronextamab and the use of bispecific antibodies in combination regimens and earlier lines of therapy. The aim of this review is to explore actual therapies in relapsed/refractory diffuse large B-cell lymphoma, focusing on bispecific antibodies and antibody–drug conjugates. Full article

Advancements in Unmanned Aerial Vehicle (UAV) technologies have increased exponentially in recent years, with UAV swarm being a key area of interest. UAV swarm overcomes the energy reserve, payload, and single-objective limitations of single UAVs, enabling broader mission scopes. Despite these advantages, UAV swarm has yet to see widespread application within global industry. A leading factor hindering swarm application within industry is the divide that currently exists between the functional capacity of modern UAV swarm systems and the functionality required by legislation. This paper investigates this divide through an overview of global legislative practice, contextualized via a case study of Australia’s UAV regulatory environment. The overview highlighted legislative objectives that coincided with open challenges in the UAV swarm literature. These objectives were then formulated into analysis criteria that assessed whether systems presented sufficient functionality to address legislative concern. A systematic review methodology was used to apply analysis criteria to multi-objective UAV swarm mission planning systems. Analysis focused on multi-objective mission planning systems due to their role in defining the functional capacity of UAV swarms within complex real-world operational environments. This, alongside the popularity of these systems within the modern literature, makes them ideal candidates for defining new enabling technologies that could address the identified areas of weakness. The results of this review highlighted several legislative considerations that remain under-addressed by existing technologies. These findings guided the proposal of enabling technologies to bridge the divide between functional capacity and legislative concern. Full article

Background/Objectives: Clofazimine (CFZ) is a versatile antimicrobial active against several bacterial species, although its reduced aqueous solubility and the occurrence of side effects limit its use. Nanostructured lipid carriers (NLCs) constitute an interesting approach to increase drug bioavailability and safety. However, the development of nanoparticle-based formulations is challenging. In the present work, a combination of smart pharmaceutical technology approaches was proposed to develop CFZ-loaded NLCs, taking advantage of previous knowledge on NLCs screening. Methods: A design space previously established using Artificial Intelligence (AI) tools was applied to develop CFZ-loaded NLC formulations. After formulation characterization, Neurofuzzy Logic (NFL) and in silico docking simulations were employed to enhance the understanding of lipid nanocarriers. Then, the performance of formulations designed following NFL guidelines was characterized in terms of biocompatibility, using murine fibroblasts, and antimicrobial activity against several strains of Staphylococcus aureus. Results: The followed approach enabled CFZ-loaded NLC formulations with optimal properties, including small size and high antimicrobial payload. NFL was useful to investigate the existing interactions between NLC components and homogenization conditions, that influence CFZ-loaded NLCs’ final properties. Also, in silico docking simulations were successfully applied to examine interactions and affinity between the drug and the lipid matrix components. Finally, the designed CFZ-loaded formulations demonstrated suitable biocompatibility, together with antimicrobial activity. Conclusions: The implementation of smart strategies during nanoparticle-based therapeutics development, such as those described in this manuscript, would enable the more efficient design of new systems for suitable antimicrobial delivery. Full article

Laser propulsion is a new conceptual technology that drives spacecraft and possesses advantages such as high specific impulse, large payload ratio, and low launch cost. It has potential applications in diverse areas, such as space debris mitigation and removal, microsatellite attitude control, and orbital maneuvering. Liquid pulse laser propulsion has notable advantages among the various laser propulsion systems. We review the concept and the theory of liquid laser propulsion. Then, we categorize the current state of research based on three types of propellants—non-energetic liquids, energetic liquids, and liquid metals—and provide an analysis of the propulsion characteristics arising from the laser ablation of liquids such as water, glycidyl azide polymer (GAP), hydroxylammonium nitrate (HAN), and ammonium dinitramide (ADN). We also discuss future research directions and challenges of pulsed liquid laser propulsion. Although experiments have yielded encouraging outcomes due to the distinctive properties of liquid propellants, continued investigation is essential to ensure that this technology performs reliably in actual aerospace applications. Consistent results under both spatial and ground conditions remain a key research content for fully realizing its potential. Full article

In this study, the cooling performance of fuel cell electric vehicles (FCEVs) with regard to thermal derating is investigated. Particularly in hot climate conditions, low operating temperature of the fuel cell stack and hence low temperature difference to the environment can result in thermal derating of the fuel cell stack. Experimental investigations on a production vehicle with a fuel cell drive (Hyundai Nexo) are conducted to analyze the influence of climatic boundary conditions and a dynamic driving scenario on the thermal management system of the vehicle. Therefore, a new method based on energy balances is introduced to indirectly measure the average cooling air velocity at the cooling module. The results indicate that the two high-power radiator fans effectively maintain a high cooling airflow between a vehicle speed of approximately 30 and 100 $\mathrm{k}\mathrm{m}/\mathrm{h}$, leading to efficient heat rejection at the cooling module largely independent of vehicle speed. Furthermore, this study reveals that the efficiency of the fuel cell system is notably affected by ambient air temperature, attributed to the load on the electric air compressor (EAC) as well as on cooling system components like cooling pump and radiator fans. However, at the stack level, balance of plant (BoP) components demonstrate the ability to ensure ambient temperature-independent performance, likely due to reliable humidification control up to 45 °C. Additionally, a new method for determining thermal derating of FCEVs on roller dynamometer tests is presented. A real-world uphill drive under ambient temperatures exceeding 40 °C demonstrates derating occurring in 6.3% of the time, although a worst case with an aged stack and high payload is not investigated in this study. Finally, a time constant of 50 $\mathrm{s}$ is found to be suitable to correlate the average fuel cell stack power with a coolant temperature at the stack inlet, which gives information on the thermal inertia of the system observed and can be used for future simulation studies. Full article

The context of this study is the geolocation of signal emitters on the Earth’s surface through satellite platforms able to perform Angle of Arrival (AOA) measurements. This paper provides the theoretical framework to solve the optimization problem for the orbital deployment of the satellites minimizing the variance on the position error estimation with constraints on the line of sight (LOS). The problem is theoretically formulated for an arbitrary number of satellites in Low Earth Orbit (LEO) and target pointing attitude, focusing on minimizing the Position Dilution of Precision (PDOP) metric, providing a methodology for translating mission design requirements into problem formulation. An exemplary numerical application is presented for the operative case of the placement of a second satellite after a first one is launched. Simulation results are on angles of true anomaly, right ascension of the ascending node, and spacing angle, while accounting for orbital radius and emitter latitude. New insights on trends, parameter dependencies, and properties of symmetry and anti-symmetry are presented. The topic is of interest for new technological demonstrators based on CubeSats with AOA payload. Civil applications of interest are on interceptions of non-cooperative signals in activities of spectrum monitoring or search and rescue. Full article

Low-cost MEMS sensors are widely utilized in UAV platforms to address attitude estimation problems due to their compact size, low power consumption, and cost-effectiveness. Diverse UAV payloads pose new challenges for attitude estimation, such as magnetic interference environments and high dynamic environments. In this paper, we propose a hierarchical decoupled attitude estimation algorithm, termed HDAEA. Initially, a novel hierarchical decoupling approach is introduced for the attitude and angle representation of the direction cosine matrix, enabling the representation of angles in a new manner. This method reduces the data dimensionality and nonlinearity of observation equations. Furthermore, a magnetic interference identification algorithm is proposed to compute the magnetic interference intensity accurately and quantitatively. Combining the quantified errors of estimated state variables, an error model for magnetic interference and attitude angles in high-dynamic environments is constructed. Subsequently, the proposed error model is employed to calibrate the hierarchical decoupled angles using accelerometer and magnetometer measurements, effectively mitigating the impact of magnetic interference on the calculation of pitch angles and roll angles. Moreover, the integration of the proposed hierarchical decoupled attitude estimation algorithm with the error-state extended Kalman filter reduces system nonlinearity and minimizes linearization errors. Experimental results demonstrate that HDAEA exhibits significantly improved attitude estimation accuracy of UAV payloads. Full article

Sea surface height (SSH) serves as a fundamental geophysical parameter in oceanographic research. In 2023, China successfully launched the world’s first spaceborne interferometric GNSS-R (iGNSS-R) altimeter, which features dual-frequency multi-beam scanning, interferometric processing, and compatibility with three major satellite navigation systems: the BeiDou Navigation Satellite System (BDS), the Global Positioning System (GPS), and the Galileo Satellite Navigation System (GAL). This launch marked the first in-orbit validation of the iGNSS-R altimetry technology. This study provides a detailed overview of the iGNSS-R payload design and analyzes its dual-frequency delay mapping (DM) measurements. We developed a refined DM waveform-matching algorithm that precisely extracts the propagation delays between reflected and direct GNSS signals, enabling the retrieval of global sea surface height (SSH) through the interferometric altimetry model. For validation, we employed an inter-satellite crossover approach using Jason-3 and Sentinel-6 radar altimetry as references, achieving an unprecedented SSH accuracy of 17.2 cm at a 40 km resolution. This represents a breakthrough improvement over previous GNSS-R altimetry efforts. The successful demonstration of iGNSS-R technology opens up new possibilities for cost-effective, wide-swath sea level monitoring. It showcases the potential of GNSS-R technology to complement existing ocean observation systems and enhance our understanding of global sea surface dynamics. Full article

Primary and secondary brain tumors have always been a challenge due to their high morbidity and poor prognosis. The incidence of brain metastasis is also increasing with the advent of effective new treatments. Traditional systemic treatments have historically had limited success, partly due to poor central nervous system (CNS) penetration. However, the advent in recent decades of new therapies that have shown high encephalic response rates are challenging this paradigm. ADCs represent a new class of compounds revolutionizing cancer treatment with high systemic response rates and lower toxicities. The continuing evolution of ADCs has shown that certain structural features such as payload, linker, and drug-to-antibody ratio (DAR) are essential in determining their efficacy at the encephalic level, and some ADCs have started to exhibit promising efficacy in treating primary and secondary brain tumors. Unfortunately, most patients with untreated encephalic metastases are excluded from clinical trials, with data primarily from retrospective studies or post hoc analyses. This review describes the early signs of ADC efficacy in brain tumors, the role of complementary treatments like radiation therapy, and critical points to improve ADC efficacy in brain malignancies. Full article

The present work aims to develop the current CubeSats architecture. Starting from the framework of project ARAMIS (an Italian acronym for a highly modular architecture for satellite infrastructures), a new concept of smart tiles has been developed, employing multifunctional structures and lightweight, composite materials. This enables increased CubeSat mass efficiency and payload volume. An embedded battery tile has been designed, built, and tested from a vibration point of view. In the present work, the LiPo batteries selected for the prototype have been tested with the HPPC testing procedure, to extract their equivalent Randles circuit parameters. Thus, the thermal power dissipation from the batteries can be estimated. With these data, Thermal Desktop simulations of a representative ARAMIS CubeSat are performed, considering LEO orbit and hot/cold cases. Firstly, a parametric analysis was conducted to evaluate the thermal behaviors of various design alternatives. A suitable configuration for the CubeSat was then found, enabling the validation of the embedded battery tile from a thermal point of view. The final configuration includes heaters for the LiPo batteries, a commercial CubeSat skeleton made in aluminum alloy, and a top coating for smart tiles with proper solar absorptivity. Full article

This article addresses the current issue of energy consumption in the hydraulic drive systems of working machines, with particular emphasis on elevators. This paper describes the results of experimental comparative research and estimation of energy and time consumption for two drive systems of a hydraulic indirect elevator. The purpose of this article is to compare the energy consumption of a typical multi-valve system (MV) system with that of an innovative new electro-hydraulic drive (EHD) system with a variable speed pump. The EHD system uses a frequency converter with an energy recovery module to control the speed of the car in both directions and the return of potential energy during the lowering cycle. The comparison of these drive systems was performed under the same conditions, realizing the same elevator work cycles. This paper proposes methods for estimating the energy consumption of an MV system based on measurement data collected during an experiment. The results indicate that the EHD system was less energy-intensive, even at below 60%. The smaller the load mass, the shorter the operating time of the EHD system compared to the MV system. The introduced coefficients defining the energy consumption per unit of mass and payload displacement showed more than twice the decrease in energy demand during lifting and energy recovery possibility during lowering. The EHD system provides the same coefficient values regardless of the distance traveled, which makes it a predictable system, in contrast to the MV system, especially during lowering cycles. The benefits of the EHD also include a less complex hydraulic system (elimination of most valves). Full article

This paper presents a new decentralized adaptive control scheme for motion control of robot manipulators built based on a closed-kinematic chain mechanism (CKCM). By employing the synchronization technique and model reference adaptive control (MRAC) based on the Lyapunov direct method, the Decentralized Adaptive Synchronized Control scheme (DASCS) is developed. The DASCS can ensure global asymptotic convergence of tracking errors while forcing all active joints to move in a predefined synchronous manner in the presence of uncertainties and sudden changes in payload. Furthermore, the control scheme has a simple structure, independent of the manipulator’s dynamic model, ensuring computational efficiency. Results of computer simulations conducted to evaluate the performance of the control scheme applied to controlling the motion of a CKCM manipulator with six degrees of freedom are reported and discussed. Full article

In recent years, balloon-borne threats carrying hazardous or explosive materials have emerged as a novel form of asymmetric terrorism, posing serious challenges to public safety. In response to this evolving threat, this study presents an AI-driven autonomous drone defense system capable of real-time detection, tracking, and neutralization of airborne hazards. The proposed framework integrates state-of-the-art deep learning models, including YOLO (You Only Look Once) for fast and accurate object detection, and convolutional neural networks (CNNs) for X-ray image analysis, enabling precise identification of hazardous payloads. This multi-stage system ensures safe interception and retrieval while minimizing the risk of secondary damage from debris dispersion. Moreover, a robust data collection and storage architecture supports continuous model improvement, ensuring scalability and adaptability for future counter-terrorism operations. As balloon-based threats represent a new and unconventional security risk, this research offers a practical and deployable solution. Beyond immediate applicability, the system also provides a foundational platform for the development of next-generation autonomous security infrastructures in both civilian and defense contexts. Full article

Reconstituted high-density lipoprotein nanoparticles (NPs), which mimic the structure and function of endogenous human plasma HDL, hold promise as a robust drug delivery system. These nanoparticles, when loaded with appropriate agents, serve as powerful tools for targeted drug delivery. The fundamental challenge lies in controlling and estimating the actual drug load and the efficiency of drug release at the target. In this report, we present a novel approach based on enhanced Förster Resonance Energy Transfer (FRET) to assess particle load and monitor payload release. The NPs are labeled with donor molecules embedded in the lipid phase, while the spherical core volume is filled with acceptor molecules. Highly enhanced FRET efficiency to multiple acceptors in the NP core has been observed at distances significantly larger than the characteristic Förster distance (R₀). To confirm that the observed changes in donor and acceptor emissions are a result of FRET, we developed a theoretical model for nonradiative energy transfer from a single donor to multiple acceptors enclosed in a spherical core volume. The load-dependent shortening of the fluorescence lifetime of the donor correlated with the presence of a negative component in the intensity decay of the acceptor clearly demonstrates that FRET can occur at a large distance comparable to the nanoparticle size (over 100 Å). Comparison of theoretical simulations with the measured intensity decays of the donor and acceptor fluorophores constitute a new method for evaluating particle load. The observed FRET efficiency depends on the number of acceptors in the core, providing a simple way to estimate the nanoparticle load efficiency. Particle disintegration and load release result in a distinct change in donor and acceptor emissions. This approach constitutes a novel strategy for assessing NP core load, monitoring NP integrity, and evaluating payload release efficiency to target cells. Significants: In the last decade, nanoparticles have emerged as a promising strategy for targeted drug delivery, with applications ranging from cancer therapy to ocular neurodegenerative disease treatments. Despite their potential, a significant issue has been the real-time monitoring of these drug delivery vehicles within biological systems. Effective strategies for monitoring NP payload loading, NP integrity, and payload release are needed to assess the quality of new drug delivery systems. In our study, we have found that FRET-enabled NPs function as an improved method for monitoring these aspects currently missing from current drug delivery efforts. Full article