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Pulsed laser assisted high-Throughput intracellular delivery in hanging drop based three dimensional cancer spheroids
No full textTargeted intracellular delivery of biomolecules and therapeutic cargo enables the controlled manipulation of cellular processes. Laser-based optoporation has emerged as a versatile, non-invasive technique that employs light-based transient physical disruption of the cell membrane and achieves high transfection efficiency with low cell damage. Testing of the delivery efficiency of optoporation-based techniques has been conducted on single cells in monolayers, but its applicability in three-dimensional (3D) cell clusters/spheroids has not been explored. Cancer cells grown as 3D tumor spheroids are widely used in anti-cancer drug screening and can be potentially employed for testing delivery efficiency. Towards this goal, we demonstrated the optoporation-based high-Throughput intracellular delivery of a model fluorescent cargo (propidium iodide, PI) within 3D SiHa human cervical cancer spheroids. To enable this technique, nano-spiked core-shell gold-coated polystyrene nanoparticles (ns-AuNPs) with a high surface-To-volume ratio were fabricated. ns-AuNPs exhibited high electric field enhancement and highly localized heating at an excitation wavelength of 680 nm. ns-AuNPs were co-incubated with cancer cells within hanging droplets to enable the rapid aggregation and assembly of spheroids. Nanosecond pulsed-laser excitation at the optimized values of laser fluence (45 mJ cm-2), pulse frequency (10 Hz), laser exposure time (30 s), and ns-AuNP concentration (5 × 1010 particles per ml) resulted in the successful delivery of PI dye into cancer cells. This technique ensured high delivery efficiency (89.6 2.8%) while maintaining high cellular viability (97.4 0.4%), thereby validating the applicability of this technique for intracellular delivery. The optoporation-based strategy can enable high-Throughput single cell manipulation, is scalable towards larger 3D tissue constructs, and may provide translational benefits for the delivery of anti-cancer therapeutics to tumors. This journal i
Effect of TiO<inf>2</inf> coating on the surface condition and corona characteristics of positive DC conductors with particle matters
No full textPersistent severe smog and dust weather exists in many regions of China. Particles accumulate on the surface of high-voltage transmission lines, which affects the surface morphology of the transmission line and induces corona discharge. This work mainly studies the influence of electric field and photocatalysis on the corona characteristics of transmission lines. In this work, plasma spraying is used to prepare a dense, smooth and excellent photocatalytic TiO2 coating on the surface of transmission wires. An electron microscope and a white light interference profilometer is used to study the surface condition of the samples. The variation in the surface condition of the samples is observed under different fouling, light time and electric field intensity. The corona characteristics of power transmission lines under different surface conditions are studied. The results show that light and applied electric field promote the photocatalytic effect of TiO2, which helps to decompose the contamination on the surface of power transmission wires and thus reduce the corona discharge of transmission lines. The increase in corona inception voltage reduces the corona current pulse repetition rate and the ion current density during corona discharge
Exploration of Long-Chain Vitamin E Metabolites for the Discovery of a Highly Potent, Orally Effective, and Metabolically Stable 5-LOX Inhibitor that Limits Inflammation.
No full textEndogenous long-chain metabolites of vitamin E (LCMs) mediate immune functions by targeting 5-lipoxygenase (5-LOX) and increasing the systemic concentrations of resolvin E3, a specialized proresolving lipid mediator. SAR studies on semisynthesized analogues highlight α-amplexichromanol (27a), which allosterically inhibits 5-LOX, being considerably more potent than endogenous LCMs in human primary immune cells and blood. Other enzymes within lipid mediator biosynthesis were not substantially inhibited, except for microsomal prostaglandin E2 synthase-1. Compound 27a is metabolized by sulfation and β-oxidation in human liver-on-chips and exhibits superior metabolic stability in mice over LCMs. Pharmacokinetic studies show distribution of 27a from plasma to the inflamed peritoneal cavity and lung. In parallel, 5-LOX-derived leukotriene levels decrease, and the inflammatory reaction is suppressed in reconstructed human epidermis, murine peritonitis, and experimental asthma in mice. Our study highlights 27a as an orally active, LCM-inspired drug candidate that limits inflammation with superior potency and metabolic stability to the endogenous lead
A risk-informed decision support tool for the strategic asset management of railway track infrastructure
No full textThe provision of safe, efficient, reliable and affordable railway transport requires the railway track infrastructure to be maintained to an appropriate condition. Given the constrained budgets under which the infrastructure is managed, maintenance needs to be predicted in advance of track failure, prioritized and identified risks and uncertainties need to be considered within the decision-making process. This paper describes a risk-informed approach that can be used to economically justify railway track infrastructure conditions by comparing on a life-cycle basis infrastructure maintenance costs, train operating costs, travel time costs, safety, social and environmental impacts. The approach represents a step-change for the railway industry as it will enable economic maintenance standards to be derived which considers the needs of the infrastructure operator, but also those of users, train operating companies and the environment. Further, the risk-informed capability of the tool enables asset managers to deal with uncertainties associated with forecasting costs and the effects of track maintenance, and unavailability of data. The Monte Carlo simulation technique and a Fuzzy reasoning approach are used to address safety data uncertainties through probabilistic risk assessment allied to expert opinion. The approach is illustrated using data from three routes on the UK mainline railway network. The results demonstrate that the approach can be used to support strategic and tactical levels of railway asset management to inform plausible design and maintenance strategies that realise the maximum benefit for the available budget
Recursive maximum likelihood estimation with t-distribution noise model
No full textIn this paper, a recursive t-distribution noise model based maximum likelihood estimation algorithm for discrete-time dynamic state estimation is proposed. The proposed estimator is robust to outliers because the “thick tail” of the t-distribution reduces the effect of large errors in the likelihood function. A computationally efficient recursive algorithm is derived using the influence function. As the t-distribution reduces to the Gaussian distribution when its degree of freedom tends to infinity, the proposed estimator reduces to the Kalman filter. The mean squared error is used to evaluate the performance of the proposed estimator. Compared with the Kalman filter, the proposed estimator is more robust to outliers in the process and measurement noise. Simulations show that for the particle filter to give a better mean squared error, its computational time is two orders of magnitude slower than the proposed estimator
Numerical Study on AC Loss Characteristics of Conductor on Round Core Cables under Transport Current and Magnetic Field
No full textConductor on round core (CORC) cables wound by higherature superconducting (HTS) tapes have received much attention due to the advantages in power capacity and mechanical flexibility. This paper first developed a 3D model for a CORC cable through the finite-element method (FEM). Next, the total AC loss caused by transported current only was investigated, revealing the eddy current loss in the tube former contributes to the cable loss. The numerical CORC model was validated by published measurements. Moreover, the AC loss that resulted from a simultaneous presence of transport current and magnetic field was explored. With the induced current, the magnetisation loss generated in superconductors can increase the total loss. It is concluded that the addition of a magnetic field can result in a surge in the total loss of a current-carrying cable
A Novel All-Superconducting Propulsion and Protection System for the HTS Maglev: Concept, Experimental Verification and Planning
No full textThis article presents a novel all-superconducting propulsion and protection system for the higherature superconducting (HTS) Maglev. The HTS magnet is the key component in the HTS Maglev, as it is in charge of the most crucial works, the propulsion and levitation of the train, to realize the zero-friction and ultra-high-speed just above the ground. The HTS magnet can conduct massive electric current and generate extremely high magnetic field, but the HTS magnet is also relatively venerable compared to the conventional copper magnet, regarding the strict operating conditions of temperature, magnetic field and electric current. Therefore, we proposed a new all-superconducting propulsion and protection system, introducing the superconducting fault current limiter (SFCL) and superconducting magnetic energy storage (SMES) to be equipped into the HTS Maglev, which can protect the HTS magnet, but also ensure the safety and reliability of Maglev operation. The real size HTS magnet was modeled to check the magnetic requirements of HTS Maglev and determine the specifications of other superconducting devices. Then a scaled all-superconducting protection and energy compensation system with the scaled HTS magnet, SFCL and SMES was analyzed, and some components were verified by experiments. Future plans were proposed to merge the full size all-superconducting protection and protection system into an HTS Maglev prototype
Optimal Remanufacturing Service Resource Allocation for Generalized Growth of Retired Mechanical Products: Maximizing Matching Efficiency
No full textMaximizing the residual value of retired products and reducing process consumption and resource waste are vital for Generalized Growth-oriented Remanufacturing Services (GGRMS). Under the GGRMS, the traditional product-oriented remanufacturing methods to be changed: the products in GGRMS should be divided into multiple parts for maximizing residual value of different parts. However, this increases the difficulty of resource matching for service activities. To improve the efficiency of resource matching, we first used rough-fuzzy number and structural entropy weighting method to perform a coupling analysis on all service activities in the generalized growth scheme set, and to merge redundant service activities. We then considered the interests of both the service providers and integrators and added flexible impact factors to establish a service resource optimization configuration model, and solved it with the Non-Dominated Sorting Genetic Algorithm (NSGA-II). Finally, we, using a retired manual gearbox an experiment, optimized the service resource allocation for its generalized growth scheme set. The experimental results shown that the overall matching efficiency was increased by 74.56% after merging redundant service activities, showing that the proposed method is suitable for the resource allocation of the generalized growth for complex single mechanical products, and can offer guidelines to the development of RMS
Giant All-Optical Modulation of Second-Harmonic Generation Mediated by Dark Excitons
No full textAll-optical control of nonlinear photonic processes in nanomaterials is of significant interest from a fundamental viewpoint and with regard to applications ranging from ultrafast data processing to spectroscopy and quantum technology. However, these applications rely on a high degree of control over the nonlinear response, which still remains elusive. Here, we demonstrate giant and broadband all-optical ultrafast modulation of second-harmonic generation (SHG) in monolayer transition-metal dichalcogenides mediated by the modified excitonic oscillation strength produced upon optical pumping. We reveal a dominant role of dark excitons to enhance SHG by up to a factor of ∼386 at room temperature, 2 orders of magnitude larger than the current state-of-the-art all-optical modulation results. The amplitude and sign of the observed SHG modulation can be adjusted over a broad spectral range spanning a few electronvolts with ultrafast response down to the sub-picosecond scale via different carrier dynamics. Our results not only introduce an efficient method to study intriguing exciton dynamics, but also reveal a new mechanism involving dark excitons to regulate all-optical nonlinear photonics
Self-healing circuits for space technology
No full textElectronic systems used in space technology applications experience harsh environments, resulting in several failures among which open circuit faults are one. In this work, we investigate self-healing circuits to automatically respond to and repair open circuit failures in electronic systems. The active material is a dispersion of metallic particles in an insulating fluid, and the mechanism of healing is triggered by the electric field appearing in the fault. Specifically, this work discusses the physics of self-healing and investigates the compatibility of the mechanism to high vibration (1-16 g) as well as thermovacuum conditions (5 × 10-5 Torr and −40-125 °C). In conclusion, we demonstrate that the electric field assisted self-healing mechanism is feasible for space technology applications