Search Results (172)

Tau proteins are microtubule-associated proteins that regulate axonal structure, dynamics, and transport, and their dysregulation underlies several neurodegenerative diseases. The MAPT gene produces multiple tau isoforms through alternative splicing, including the high-molecular-weight isoform known as Big tau, which contains an insert of the large 4a exon of approximately 250 amino acids. Big tau is predominantly expressed in neurons of the peripheral nervous system (PNS), cranial motor nuclei, and select neurons of the central nervous system (CNS) such as the cerebellum and brainstem. Developmental expression studies indicate a switch from low-molecular-weight isoforms of tau to Big tau during axonal maturation, suggesting that Big tau optimizes cytoskeletal dynamics to accommodate long axonal projections. Comparative sequence and biophysical analyses show that the exon-4a insert is highly acidic, intrinsically disordered, and evolutionarily conserved in its length but not its primary sequence, implying a structural role. Emerging modeling and in vitro assays suggest that the extended projection domain provided by the exon-4a insert spatially and electrostatically shields the aggregation-prone PHF6 and PHF6* motifs in tau’s microtubule-binding domain, thereby reducing β-sheet driven aggregation. This mechanism may explain why tauopathies that involve aggregation of tau have little effect on the PNS and specific regions of the CNS such as the cerebellum, where Big tau predominates. Transcriptomic and proteomic data further suggest that alternative Big tau variants, including 4a-L, are expressed in certain cancerous tissues, indicating broader roles in cytoskeletal remodeling beyond neurons. Despite its putative anti-aggregation properties, the physiological regulation, interaction partners, and in vivo mechanisms of Big tau remain poorly defined. This review summarizes what is known about Big tau and what is missing toward a better understanding of how expansion via inclusion of exon 4a modifies tau’s structural and functional properties. Our purpose is to inspire future studies that could lead to novel therapeutic strategies to mitigate tau aggregation in neurodegenerative diseases. Full article

Reliable posture and loading characteristics detection of hydraulic supports is one of the indispensable factors to realizing the intelligentization of fully mechanized coal mining faces. Due to the complexity and dynamic nature of mining process, achieving real-time and accurate detection of the hydraulic support posture and load presents an exceptionally challenging task. Therefore, an interactive algorithm for evaluating the load-carrying characteristic of hydraulic support by considering the three-dimensional space driving theory and dynamic theory was developed and experimentally verified based on a self-designed experimental platform. The paper aimed to establish a three-dimensional spatial dynamic and kinematics model for shield support, evaluating its loading performance in challenging working conditions. Initially, a three-dimensional kinematics model was developed to describe the bearing capacity of powered support in various postures based on the three-dimensional drive space theory. A dynamic model was suggested to investigate the effects of multiple factors on the position of hydraulic support drive units on their load-carrying capability in various demanding working situations. The results indicate that increasing the length of the drive units can significantly improve the bearing performance of shield support. The proposed mathematical technique offers a novel method for modifying the coupling of surrounding rock with hydraulic supports and supplying coal mining with real-time assistance. Full article

In this study, the changes in the DNA native conformation induced by pH changes in the alkaline and acidic regions were examined. It was shown by the methods of low gradient viscometry and flow birefringence that protonation and deprotonation of nitrogen bases inside the double helix cause a change in the persistent length of DNA. The pK values shift with the change in the ionic strength of the solution (NaCl concentration). The additional charges appearing on the DNA bases are not shielded by counterions from the solution. The increase and decrease in the volume of the DNA coil in solution resulting from protonation and deprotonation of base pairs, respectively, are mainly determined by changes in the persistent length of the macromolecule. The stability of the double-helical conformation of DNA ensures the steadiness of the equilibrium rigidity of this macromolecule. The emergence of charges on the bases, resulting from DNA protonation or deprotonation, weakens and even disrupts the hydrogen bonds between complementary bases. However, at the first stage, this occurs without altering the stacking interactions of base pairs, as reflected in the absorption spectra of DNA and in the stability of the DNA persistent length at different pH levels. Full article

In spatially constrained water domains, surface sensing agents(SSAs) must achieve safe path planning, uncertain currents, and sensor noise. We present a decentralized motion planning and collision-avoidance framework based on distributional reinforcement learning (DRL) that models the full return distribution to enable risk-aware decision making. Each surface sensing agent autonomously proceeds to its designated coordinates without rigid spatial constraints, coordinating implicitly through learned policies and a lightweight safety shield that enforces separation and kinematic limits. The method integrates (i) distributional value estimation for controllable risk sensitivity near hazards, (ii) domain randomization of sea states and disturbances for robustness, and (iii) a shielded action layer compatible with standard reactive rules (e.g., velocity obstacle-style constraints) to guarantee feasible maneuvers. In simulations across cluttered maps and stochastic current fields, the proposed approach improves success rates and reduces near-miss events compared to non-distributional RL and classical planners, while maintaining competitive path length and computation time. The results indicate that DRL-based surface sensing agent navigation is a practical path toward safe, efficient environmental monitoring and surveying. Full article

Welding-based manufacturing and joining processes are extensively used in various areas of industrial production. While welding has been used as a primary method of joining in many applications, its capability to fabricate metal components such as the Wire Arc Additive Manufacturing (WAAM) method should not be undermined. WAAM is a promising method for producing large metal parts, but it is still prone to defects such as porosity that can reduce structural reliability. To ensure these defects are found and measured in a consistent way, inspection methods must be tied directly to code-based acceptance limits. In this work, a three-pass WAAM joint specimen was made in a welded-joint configuration using robotic GMAW-based deposition. This setup provided a stable surface for Phased Array Ultrasonic Testing (PAUT) while still preserving WAAM process conditions. The specimen, which was intentionally seeded with porosity, was divided into five zones and inspected using the 6 dB drop method for defect length and amplitude-based classification, with AWS D1.5 serving as the reference code. The results showed that porosity was not uniform across the bead. Zones 1 and 3 contained the longest clusters (15 mm and 16.5 mm in length) and exceeded AWS length thresholds, while amplitude-based classification suggested they were less critical than other regions. This difference shows the risk of relying on only one criterion. By embedding these results in a DMAIC (Define–Measure–Analyze–Improve–Control) workflow, the inspection outcomes were linked to likely causes such as unstable shielding and cooling effects. Overall, the study demonstrates a code-referenced, dual-criteria approach that can strengthen quality control for WAAM. Full article

Therapeutics involving small interfering RNA (siRNA) have enormous potential for treating a number of diseases, but their effective delivery to target cells remains a major challenge. We studied the influence of the structure and combination of targeted (folate conjugated, F13) and shield lipoconjugates (P1500, diP1500) on the ability of cationic liposomal formulations based on the 2X3-DOPE system to deliver siRNA into cells in vitro and in vivo. The loop-structured PEG lipoconjugate equipped with two hydrophobic anchor groups (diP1500) demonstrated superior performance across multiple evaluation criteria. The F13/diP1500 composition maintained a compact particle size (126.0 ± 23.0 nm), while F13/P1500 with the same PEG chain equipped with one anchor group maintained an increased particle size of 241.8 ± 65.7 nm. Most critically, F13/diP1500 preserved substantial positive surface charges (21.6–30.5 mV) across all N/P ratios, demonstrating superior ability in avoid the “PEG dilemma”, whereas F13/P1500 suffered substantial charge neutralization (3.9–9.1 mV). Competitive inhibition with free folate confirmed receptor-mediated cellular accumulation of siRNA mediated by F13 containing liposomal compositions. In vivo biodistribution revealed statistically significant circulation advantages: DSPE-PEG2000/diP1500 achieved the highest plasma concentration at 15 min (1.84 ± 0.01 pmol/mL), representing the first direct in vivo comparison of compositions with PEG lipoconjugates of the same length, but formed different structures in the liposomes due to the presence of one or two anchor groups. Our findings provide critical insights for the rational design of targeted liposomal delivery systems, highlighting the importance of balanced optimization between folate targeting functionality and PEG shielding for effective siRNA delivery both in vitro and in vivo. Full article

Multi-channel optical systems can provide more feature information compared to single-channel systems, making them valuable for optical remote sensing, target identification, and other applications. The division of aperture polarization imaging modality allows for the simultaneous imaging of targets in the same field of view with a single detector. To overcome the limitations of conventional refractive aperture-divided systems for miniaturization, this work proposes an off-axis catadioptric aperture-divided technique for polarization imaging. First, the design method of the off-axis reflective telescope structure is discussed. The relationship between optical parameters such as magnification, surface coefficient, and primary aberration is studied. Second, by establishing the division of the aperture optical model, the method of maximizing the field of view and aperture is determined. Finally, an off-axis catadioptric cooled aperture-divided infrared optical system with a single aperture focal length of 60 mm is shown as a specific design example. Each channel can achieve 100% cold shield efficiency, and the overall length of the telescope module can be decreased significantly. The image quality of each imaging channel is close to the diffraction limit, verifying the effectiveness and feasibility of the method. The proposed off-axis catadioptric aperture-divided design method holds potential applications in simultaneous infrared polarization imaging. Full article

In urban redevelopment, adding basements beneath existing buildings often requires specialized retaining structures, such as existing and newly added double-row piles, yet their complex load-sharing mechanism is not yet fully understood. This study addresses this gap through a series of physical model tests, systematically investigating the influence of two key variables: the row spacing and the newly added/existing pile length ratio. The results reveal that row spacing is a critical factor governing the system’s stability and cooperative behavior. The newly added piles bear the majority of the earth pressure, effectively shielding the existing piles. A distinct, layered pressure distribution was observed in the inter-row soil, a phenomenon that classical earth pressure theories cannot adequately predict. Based on a comprehensive evaluation of structural performance, deformation control, and stability, this study proposes an optimized configuration with a row spacing of 4D and a newly added/existing pile length ratio of 9/6. This configuration achieves an effective balance between structural performance and economic efficiency, offering valuable practical guidance for the design of supplementary retaining systems in basement addition projects. Full article

Cable shields may develop holes when the sheath is damaged. Time–frequency domain reflectometry (TFDR) is an effective method for detecting cable defects, but it cannot directly evaluate hole sizes. To address this issue, we analyze the impact of shield hole sizes on TFDR signals. Building on this analysis, we propose an improved dual-frequency TFDR method to measure shield holes and evaluate their sizes. This method directly measures the characteristic impedances and damage ratios using dual-frequency TFDR, followed by a two-step evaluation process to determine the hole center angles and lengths based on these measurements. Simulations and experiments validate the proposed method. In laboratory-scale experiments using a scaled cable model, and considering measurement noise, the maximum relative errors for shield hole length and center angle are 11% and 5%, respectively. Full article

This study employs CST simulations to analyze the electromagnetic response and cable coupling characteristics of electric vertical takeoff and landing (eVTOL) aircraft under lightning conditions. Based on the SAE ARP5414B standard, lightning zoning was carried out, and three typical strike scenarios—the nose, wing, and vertical tail—were established. Referring to representative lightning current waveforms in SAE ARP5412B, Component A was selected as the primary excitation source. On this basis, the L9(3³) orthogonal design method was applied to evaluate the influence of cable structure, length, and routing method on the induced current. The results show that nose attachment produces the strongest coupling to the airframe. Shielded cables effectively reduce the induced current in the conductor core by diverting most of the coupled current through the shielding layer, while unshielded single-core cables demonstrate the weakest resistance to interference. The induced current increases with cable length, and Z-shaped wall-mounted routing produces stronger coupling than straight or suspended routing. This research provides a systematic approach for evaluating indirect lightning effects in eVTOL and offers engineering guidance for electromagnetic protection and cable design. Full article

In recent years, the increasing complexity of shield tunneling environments has made it critical to control the deformation of adjacent excavation structures and surrounding soils. This study employs numerical simulation using MIDAS GTS/NX to comprehensively analyze the spatial interaction factors between shield tunnels and wall-pile-anchor-supported foundation pits. Structural parameters of the retaining system and tunneling conditions are also evaluated to identify the key factors influencing construction-induced deformation. The results show that the maximum settlement of the adjacent retaining wall occurs when the tunnel burial depth reaches 1.4L, where L is the height of the diaphragm wall. In addition, when the horizontal distance between the tunnel and the excavation is less than 0.75D (D being the tunnel diameter), significant settlement deformation is observed in the nearby support structures. A linear correlation is also identified between the variation in tunnel crown settlement and the excavation depth of the overlying pit during tunnel undercrossing. Furthermore, sensitivity analysis indicates that increasing the embedment depth of the diaphragm wall effectively reduces horizontal displacement at the wall base. Increasing the wall thickness decreases displacement in the upper section of the wall. Similarly, increasing pile diameter and anchor length and diameter, while reducing the inclination angle of anchors, are all effective in minimizing the lateral displacement of the support structure. Full article

Accidental ground surcharge loads can induce adverse effects such as segment cracking in underlying shield tunnel structures, with particularly pronounced impacts on pre-damaged tunnel segments. Cracks represent one of the most common initial damage forms in shield tunnel structures. To investigate through-crack failure mechanisms in shield tunnel segments with initial cracks under surcharge loading, this study conducted 1:8 scaled indoor model tests, considering factors including initial crack length, quantity, morphology, and surcharge position. Research findings demonstrate that increased initial crack length and quantity significantly reduce the critical load required for through-crack formation. Specifically, segments with 9 cm longitudinal initial cracks required 50.9% less load to develop through-cracks compared to intact segments. Similarly, segments containing two 9 cm circumferential initial cracks exhibited a 22.1% reduction in critical load relative to those with single circumferential cracks. Initial cracks in pre-damaged segments substantially influence the propagation path of new cracks during subsequent loading failures. The detrimental effects of staggered longitudinal-circumferential initial cracks exceed those of purely longitudinal cracks, which themselves pose greater risks than circumferential cracks alone. Bilateral surcharge loading significantly increases the critical load threshold for through-crack formation compared to unilateral loading. This highlights the severe structural risks associated with uneven load distribution. Full article

Adopting mobile robots for high voltage (HV) live-line operations can mitigate personnel casualties and enhance operational efficiency. However, conventional mechanical arms cannot inspect concealed spaces in the power cable tunnel because their joint integrates metallic motors or hydraulic serial-drive mechanisms, which limit the arm’s length and insulation performance. Therefore, this study proposes a 7-degree-of-freedom (7-DOF) bionic mechanical arm with rigid-flexible coupling, mimicking human arm joints (shoulder, elbow, and wrist) designed for HV live-line operations in concealed cable tunnels. The arm employs a tendon-driven mechanism to remotely actuate joints, analogous to human musculoskeletal dynamics, thereby physically isolating conductive components (e.g., motors) from the mechanical arm. The arm’s structure utilizes dielectric materials and insulation-optimized geometries to reduce peak electric field intensity and increase creepage distance, achieving intrinsic self-insulation. Furthermore, the mechanical design addresses challenges posed by concealed spaces (e.g., shield tunnels and multi-circuit cable layouts) through the analysis of joint kinematics, drive mechanisms, and dielectric performance. The workspace of the proposed arm is an oblate ellipsoid with minor and major axes measuring 1.25 m and 1.65 m, respectively, covering the concealed space in the cable tunnel, while the arm’s quality is 4.7 kg. The maximum electric field intensity is 74.3 kV/m under 220 kV operating voltage. The field value is less than the air breakdown threshold. The proposed mechanical arm design significantly improves spatial adaptability, operational efficiency, and reliability in HV live-line inspection, offering theoretical and practical advancements for intelligent maintenance in cable tunnel environments. Full article

This study analyzed the compression isotherms of 7β-alkyl cholic acid derivatives and compared them to those of cholic and deoxycholic acids to elucidate their orientation and molecular interactions (acidic aqueous substrate—pH 2; NaCl concentration—3 M; temperature—T = 298.15 K). It was found that the compression isotherm of the 7β-octyl derivative of cholic acid in the monomolecular layer is most similar to the compression isotherm of deoxycholic acid. In 7β-alkyl derivatives of cholic acid, the hydrophobic interaction energy in their aggregates from a monomolecular film increased with the length of the alkyl chain. However, this energy did not increase linearly with C atoms, suggesting the existence of a conformational equilibrium. In binary mixtures of the tested bile acids and lecithin, only the 7β-octyl derivatives of cholic acid and deoxycholic acid had orientations in which the steroid skeleton had a “vertical” position, i.e., only the C3 OH group was immersed in the aqueous substrate, which resulted in the maximum hydrophobic interaction with lecithin. In 7β-octyl derivatives, part of the octyl chain probably also participated in the interaction with lecithin. In 7β-propyl and 7β-butyl derivatives, C7 alkyl groups sterically shielded the C7 α-axial OH group. However, in the 7β-ethyl derivative the C7 OH group was not additionally sterically shielded, so this derivative, similarly to cholic acid, partially dissolved in the aqueous substrate after the collapse point. Full article

Dust accumulation on Photovoltaic (PV) panels represents a major challenge for the operation of panels. There are several passive dust mitigation techniques, such as using a dust shield whose performance has been enhanced by integrating it with an air nozzle. The air exiting the nozzle acts as an air barrier that obstructs the approach of dust particles to the panel’s surface. The objective of this study is to minimize dust accumulation over PV panels by adding slits within the dust shield. The function of the slit is to induce air drafts that can sweep dust away from the surface of the PV panel. Numerical simulations are performed to determine the influence of the slit size and position on dust mitigation. It has been found that there is a critical slit size, such that the deposition of particles for slits of sizes smaller or larger than that size decreases. Increasing the slit size increases dust deposition until a certain limit, i.e., the critical size, and that is due to the Coanda effect that keeps the flow intact with the shield until it reaches the panels’ surface, which increases the dust accumulation rate. On the other hand, increasing the slit size above the critical size decreases the dust deposition due to the change from a non-inertial flow to an inertial flow, which diverts the incoming particles from reaching the panels’ surface. Also, it has been found that keeping the slit location away from the panel’s surface decreases the accumulation of dust over the panels’ surface. Therefore, based on the performed simulations, the slit size should always be either greater or smaller than the critical size and as far as possible from the panel’s surface to minimize dust accumulation over PV panels. Full article