Search Results (105)

The inchworm piezoelectric motor, with the advantages of long stroke and high resolution, is ideally suited for precise positioning in wafer-level electron beam inspection systems. However, the large number of piezoelectric actuators and the complex excitation signal sequences significantly increase the complexity of system assembly and temporal control. A flexure-based actuation stator structure, along with simplified excitation signal sequences of a high-precision inchworm piezoelectric motor, is proposed. The alternating actuation of upper/lower clamping mechanisms and the driving mechanism fundamentally mitigates backstep effects while generating stepping linear displacement. The inchworm piezoelectric motor achieves precision linear motion operation using only two piezoelectric actuators. The actuation stator is analyzed via the compliance matrix method to derive its output compliance, input stiffness, and displacement amplification ratio. Furthermore, a kinematic model and natural frequency expression incorporating the pseudo-rigid-body method and Lagrange’s equations are established. The actuation stator and inchworm piezoelectric motor are analyzed through both simulations and experiments. The results show that the maximum step displacement of the motor is 16.3 μm, and the maximum speed is 9.78 mm/s, at a 600 Hz operation frequency with a combined alternating piezoelectric voltage of 135 V and 65 V. These findings validate the designed piezoelectric motor’s superior motion resolution, operational stability, and acceptable load capacity. Full article

Voltage-gated Na⁺ channels (Nav) are the molecular determinants of action potential initiation and propagation. Among the nine voltage-gated Na⁺ channel isoforms (Nav1.1–Nav1.9), Nav1.2 and Nav1.6 are of particular interest because of their developmental expression profile throughout the central nervous system (CNS) and their association with channelopathies. Although the α-subunit coded by each of the nine isoforms can sufficiently confer transient Na⁺ currents (I_Na), in vivo these channels are modulated by auxiliary proteins like intracellular fibroblast growth factor (iFGFs) through protein–protein interaction (PPI), and probes developed from iFGF/Nav PPI complexes have been shown to precisely modulate Nav channels. Previous studies identified ZL0177, a peptidomimetic derived from a short peptide sequence at the FGF14/Nav1.6 PPI interface, as a functional modulator of Nav1.6-mediated I_Na⁺. However, the isoform specificity, binding sites, and putative physiological impact of ZL0177 on neuronal excitability remain unexplored. Here, we used automated planar patch-clamp electrophysiology to assess ZL0177’s functional activity in cells stably expressing Nav1.2 or Nav1.6. While ZL0177 was found to suppress I_Na in both Nav1.2- and Nav1.6-expressing cells, ZL0177 elicited functionally divergent effects on channel kinetics that were isoform-specific and supported by differential docking of the compound to AlphaFold structures of the two channel isoforms. Computational modeling predicts that ZL0177 modulates Nav1.2 and Nav1.6 in an isoform-specific manner, eliciting phenotypically divergent effects on action potential discharge. Taken together, these results highlight the potential of PPI derivatives for isoform-specific regulation of Nav channels and the development of therapeutics for channelopathies. Full article

L-type Ca²⁺ channels, particularly Ca_V1.2, play a crucial role in cardiac excitation-contraction coupling and are known to exhibit mechanosensitivity. However, the mechanisms regulating their response to mechanical stress remain poorly understood. To investigate the mechanosensitivity and nitric oxide (NO)-dependent regulation of L-type Ca²⁺ channels in rat ventricular cardiomyocytes, we used RNA sequencing to assess isoform expression and whole-cell patch-clamp recordings to measure L-type Ca²⁺ current (I_Ca,L) under controlled mechanical and pharmacological conditions. RNA sequencing revealed predominant expression of Ca_V1.2 (TPM: 0.1170 ± 0.0075) compared to Ca_V1.3 (0.0021 ± 0.0002) and Ca_V1.1 (0.0002 ± 0.0002). Local axial stretch (6–10 μm) consistently reduced I_Ca,L in proportion to stretch magnitude. The NO donor SNAP (200 μM) had variable effects on basal I_Ca,L in unstretched cells (stimulatory, inhibitory, or biphasic) but consistently restored stretch-reduced I_Ca,L to control levels. Ascorbic acid (10 μM), which reduces S-nitrosylation, increased basal I_Ca,L and partially restored the reduction caused by stretch, implicating S-nitrosylation in channel regulation. The sGC inhibitor ODQ (5 μM) decreased I_Ca,L in both stretched and unstretched cells, indicating involvement of the NO–cGMP pathway. Mechanical stress modulates L-type Ca²⁺ channels through a complex interplay between S-nitrosylation and NO–cGMP signaling, with S-nitrosylation playing a predominant role in stretch-induced effects. This mechanism may represent a key component of cardiac mechanotransduction and could be relevant for therapeutic targeting in cardiac pathologies involving mechanically induced dysfunction. Full article

The diagnosis of open-circuit (OC) faults in power switches is the premise for implementing fault-tolerant control, a critical aspect in ensuring the reliable operation of three-level hybrid active neutral-point-clamped (HANPC) converters in flexible distribution networks. However, existing fault diagnosis methods do not clearly reveal the relationship between the switching-state sequence state and the modulation voltage before and after the fault, which limits their applicability in grid-tied HANPC converters. In this article, a generalized voltage residuals model, taken as the primary diagnostic variable, is proposed for switch OC fault diagnosis in HANPC converters, and the physical meaning is established by introducing the metric of “the variation of the pulse equivalent area”. To distinguish between faulty switches with similar fault characteristics, the neutral current path is reconfigured with a set of rearranged gate sequences. Meanwhile, the auxiliary diagnostic variable, named the current polarity state variable, is developed by means of a sliding window counting algorithm. Additionally, as a case study, a diagnostic criterion for the single-switch fault of HANPC converters is designed by using proposed diagnostic variables. Experimental results are presented to verify the effectiveness of the proposed fault diagnosis method, which achieves accurate faulty switch identification in all tested scenarios within 25 ms. Full article

Cardiomyocytes, similarly to cells in various tissues, are responsive to mechanical stress of all types, which is reflected in the significant alterations to their electrophysiological characteristics. This phenomenon, known as mechanoelectric feedback, is based on the work of mechanically gated channels (MGCs) and mechano-sensitive channels (MSCs). Since microgravity (MG) in space, as well as simulated microgravity (SMG), changes the morphological and physiological properties of the heart, it was assumed that this result would be associated with a change in the expression of genes encoding MGCs and MSCs, leading to a change in the synthesis of channel proteins and, ultimately, a change in channel currents during cell stretching. In isolated ventricular cardiomyocytes of rats exposed to SMG for 14 days, the amount of MGCs and MSCs gene transcripts was studied using the RNA sequencing method by normalizing the amount of “raw” reads using the Transcripts Per Kilobase Million (TPM) method. Changes in the level of channel protein, using the example of the MGCs TRPM7, were assessed by the Western blot method, and changes in membrane ion currents in the control and during cardiomyocyte stretching were assessed by the patch-clamp method in the whole-cell configuration. The data obtained demonstrate that SMG results in a multidirectional change in the expression of genes encoding various MGCs and MSCs. At the same time, a decrease in the TPM of the MGCs TRPM7 gene leads to a decrease in the amount of TRPM7 protein. The resulting redistribution in the synthesis of most channel proteins leads to a marked decrease in the sensitivity of the current through MGCs to cell stretching and, ultimately, to a change in the functioning of the heart. Full article

The main purpose of this research is to develop an improved space vector pulse-width modulation (SVPWM) algorithm for three-level (3L) neutral point clamped (NPC) voltage source inverters (VSIs). The results of experiments conducted on the three-level power converter laboratory setup showed that the proposed SVPWM algorithm with a seven-stage switching sequence (SS) can reduce a VSI’s switching frequency by 43.48% compared to the SVPWM algorithm with the base SS. It also improves the neutral point (NP) voltage balance in the VSI DC link by 4.2% by controlling the duty factor of distributed base vectors in each SVPWM period based on phase load currents. It reduced the values of the 5th- and 7th-order harmonics of the VSI output voltage by 19% and 15.7%, respectively. The results show that the usage of the improved SVPWM algorithm helps increase the efficiency of a 3L NPC VSI by 0.6% and reduce the higher harmonics. The obtained results confirm the efficiency of the suggested algorithm and its great potential for power converters in industry. Full article

The aim of this study was to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of two insulin glargine preparations in healthy Chinese male subjects. Methods: Forty healthy Chinese male subjects were enrolled in this randomized, open, two-sequence, four-period, single-dose, crossover study and were randomly divided into RTRT or TRTR (first-period injection of test preparation, second-period injection of reference preparation, third-period injection of test preparation, fourth-period injection of reference preparation) groups. A 24 h euglycemic clamp test measured GIR. Plasma insulin glargine concentration and C-peptide were collected during the trial and analyzed by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) and enzyme-linked immunosorbent assay (ELISA). WinNonLin calculated PD/PK parameters and the equivalence of the two preparations was testified by SAS9.2. Results: The average concentration of C-peptide was lower than the baseline and the blood glucose was close to the targeted value in each sequence. PK parameters c_max of the test and the reference preparation insulin glargine were 0.580 and 0.614 ng·mL⁻¹, and the AUC_0–24h were 9.782 and 10.436 h·ng·mL⁻¹, respectively. PD parameters GIR_max were 42.748 and 45.279 mg·kg⁻¹·min⁻¹, and AUC_GIR,0–24h were 2.924 and 3.096 h·mg·kg⁻¹·min⁻¹, respectively. There was no clinically significant adverse reaction observed during the experiment. Conclusions: The glucose clamp has been established and bioequivalence between test preparation and reference preparation has been demonstrated. Full article

This study established a real-time measurement system to monitor the melt quality in an injection molding process using a pressure sensor installed on the nozzle and a strain gauge installed on the tie bar. Based on the sensing curves from these two external sensors, the characteristic values of nozzle pressure and clamping force were used to optimize parameters. This study defined product weight as a quality indicator and developed a scientific molding parameter setup process. The optimization sequence of parameters is injection speed, V/P switchover point, packing pressure, packing time, and clamping force. Finally, an adaptive process control system was established based on the online quality characteristic values to maintain product quality consistency. Continuous production experiments were conducted at two sites to verify the system’s effectiveness. The results revealed that the optimized process parameters can ensure product weight stability during long-term production. Furthermore, using the adaptive process control system further enhanced product weight stability at both sites, reducing the standard deviation of product weight to 0.0289 g and 0.0148 g, and the coefficient of variation to 0.065% and 0.035%, respectively. Full article

Xylella fastidiosa (Xf) is a quarantine pathogen heavily affecting economically important crops worldwide. Different sequence types (STs) belonging to Xf subspecies are present in various areas of Spain, including the Balearic Islands, and cause the almond leaf scorch disease (ALSD) in Prunus spp. The increased demand for rapid tests for early detection of the pathogen should enforce strict containment measures. Molecular detection through isothermal amplification reactions enables simplified instrumentation and the use of raw nucleic acid extracts. Colorimetric loop-mediated isothermal amplification (cLAMP) was applied to rapidly detect Xf in naturally infected almonds on Mallorca Island (Spain), using a quick crude sap extraction without DNA purification. Following tissue homogenization, an alkaline treatment for target DNA extraction was conducted before the cLAMP test. The cLAMP assay was able to detect up to 100 CFU/mL of the Xf bacterial suspension diluted in healthy almond sap. The same crude extracts used in the cLAMP test were also tested by qPCR. An overall positive agreement of about 47% was observed between the results of the two techniques, while a decrease in cLAMP sensitivity was evident as the bacterial titer declined in infected plants over Cq > 26–27. This study shows the potential of the cLAMP application as a rapid and low-cost point-of-care diagnostic method for the timely monitoring of Xf directly in the field. Full article

This study revisits the taxonomy of Anthocotyle merluccii, originally described from the European hake Merluccius merluccius in the northeast Atlantic, addressing discrepancies in clamp morphology across populations. The original description from Belgium noted near-equal anterior clamp sizes, contrasting with populations from Plymouth (Atlantic) and the Mediterranean, which show marked size differences, questioning their conspecificity. We describe A. radkeaminorum n. sp. from M. merluccius in the western Mediterranean (off Algeria), distinguished from A. merluccii (Belgium) by differing anterior clamp size, genital atrium spine number, and overall anterior clamp dimensions. Populations from Plymouth, previously attributed to A. merluccii, are herein assigned to A. aff. merluccii based on differences in morphometrical traits pending further investigations. Additionally, A. radkeaminorum n. sp. differs from A. americanus in body and clamp size, atrial spine count, and hosts. Based on analysis of morphological and molecular data, we refute the synonymy of A. merluccii and A. americanus, and we reinstate the latter as a valid species. The distinction between A. merluccii and A. americanus was further supported by divergence in cox1 gene sequences analyzed from GenBank (10–11%). Finally, inconsistencies in terminal lappet hook morphology are discussed, cautioning against its use in species delineation. This work highlights the need for continued research to resolve species relationships within this genus. Full article

This paper conducts a numerical simulation of the laser welding process for 6056 aluminum alloy stringers and skin T-joints using Simufact Welding. Initially, the accuracy of the finite element simulation is validated, followed by an exploration of the impact of bilateral asynchronous and bilateral synchronous laser welding on molten pool stability. Process parameters, including laser power, welding speed, fixture clamping force, and preheat temperature, are optimized through orthogonal testing. Furthermore, the influence of welding sequences on post-weld equivalent stress and deformation in three stringers’ T-joints is analyzed. The numerical simulation results indicate that the stability of the molten pool is superior in bilateral synchronous welding compared to asynchronous welding. Optimized process parameters were obtained through orthogonal testing, and subsequent experiments demonstrated that the welding sequence of welding both sides first, followed by the middle, produced lower post-weld equivalent stress and reduced overall joint deformation. Full article

Trajectory planning is a key task in unmanned aerial vehicle navigation systems. Although trajectory planning in the presence of obstacles is a well-understood problem, unknown and dynamic environments still present significant challenges. In this paper, we present a trajectory planning method for unknown and dynamic environments that explicitly incorporates the uncertainty about the environment. Assuming that the position of obstacles and their instantaneous movement are available, our method represents the environment uncertainty as a dynamic map that indicates the probability that a region might be occupied by an obstacle in the future. The proposed method first divides the free space into non-overlapping tetrahedral partitions using Delaunay triangulation. Then, a topo-graph that describes the topology of the free space and incorporates the uncertainty of the environment is created. Using this topo-graph, an initial path and a safe flight corridor are obtained. The initial safe flight corridor provides a sequence of control points that we use to optimize clamped B-spline trajectories by formulating a quadratic programming problem with safety and smoothness constraints. Using computer simulations, we show that our algorithm can successfully find a collision-free and uncertainty-aware trajectory in an unknown and dynamic environment. Furthermore, our method can reduce the computational burden caused by moving obstacles during trajectory replanning. Full article

Background: Chronic hypoperfusion is a risk factor for neurodegenerative diseases. However, the sequence of events driving ischemia-induced functional changes in a cell-specific manner is unclear. Methods: To address this gap in knowledge, we used the bilateral common carotid artery stenosis (BCAS) mouse model, and evaluated progressive functional changes to neurons, arterioles, astrocytes, and microglial cells at 14 and 28 days post-BCAS surgery. To assess the neuro-glio-vascular response to an acute ischemic insult, brain slices were superfused with low O₂ conditions. Using whole-cell patch-clamp electrophysiology, we measured basic membrane properties (e.g., resting membrane potential, capacitance, input resistance) in cortical pyramidal neurons. The activity of astrocytes was evaluated by monitoring Ca²⁺ from Aldh1l1-CreERT2; R26-lsl-GCaMP6f mice. Vascular reactivity to low O₂ from the BCAS mice was also assessed ex vivo. Results: Our data showed no changes to the basic membrane properties of cortical pyramidal neurons. On the other hand, astrocyte activity was characterized by a progressive increase in the resting Ca²⁺. Notably, at 14 and 28 days post-BCAS, there was an increased expression of anti-inflammatory-related markers (IL-10, S100A10, TRPA1, and Nrf2). These data suggest that, in young mice, BCAS-induced increases in resting Ca²⁺ were associated with the expression of neuroprotective signals. Contrary to observations in glial cells, vascular function was impaired post-BCAS surgery, as shown by a blunted vasodilatory response to low O₂ and the vasodilatory signal, adenosine. Conclusions: Together, these data suggest that, in young mice, BCAS leads to vascular dysfunction (e.g., impaired vasodilation in parenchymal arterioles), and in the absence of neuronal dysfunction, mild ischemia is associated with the activation of glial-derived neuroprotective signals. Full article

Enzymes capable of processing a variety of compounds enable plants to adapt to diverse environmental conditions. PRISEs (progesterone-5β-reductase/iridoid synthase-like enzymes), examples of such substrate-promiscuous enzymes, are involved in iridoid and cardenolide pathways and demonstrate notable substrate promiscuity by reducing the activated C=C double bonds of plant-borne and exogenous 1,4-enones. In this study, we identified PRISE genes in Plantago media (PmdP5βR1) and Plantago lanceolata (PlP5βR1), and the corresponding enzymes were determined to share a sequence identity of 95%. Despite the high sequence identity, recombinant expressed PmdP5βR1 was 70 times more efficient than PlP5βR1 for converting progesterone. In order to investigate the underlying reasons for this significant discrepancy, we focused on specific residues located near the substrate-binding pocket and adjacent to the conserved phenylalanine “clamp”. This clamp describes two phenylalanines influencing substrate preferences by facilitating the binding of smaller substrates, such as 2-cyclohexen-1-one, while hindering larger ones, such as progesterone. Using structural analysis based on templates PDB ID: 5MLH and 6GSD from PRISE of Plantago major, along with in silico docking, we identified positions 156 and 346 as hot spots. In PlP5βR1 amino acid residues, A156 and F346 seem to be responsible for the diminished ability to reduce progesterone. Moreover, the double mutant PlP5βR_F156L_A346L, which contains the corresponding amino acids from PmdP5βR1, showed a 15-fold increase in progesterone 5β-reduction. Notably, this modification did not significantly alter the enzyme’s ability to convert other substrates, such as 8-oxogeranial, 2-cyclohexen-1-one, and methyl vinyl ketone. Hence, a rational enzyme design by reducing the number of hotspots selectively, specifically improved the substrate preference of PlP5βR1 for progesterone. Full article

Background/Objectives: Recent studies, typically using patient cerebrospinal fluid (CSF), have suggested that different autoantibodies (Aabs) acting on their respective receptors, may underlie neuropsychiatric disorders. The GluN1 (NR1) subunit of the N-methyl-D-aspartate receptor (NMDAR) has been identified as a target of anti-NMDAR Aabs in a number of central nervous system (CNS) diseases, including encephalitis and autoimmune epilepsy. However, the role or the nature of Aabs responsible for effects on neuronal excitability and synaptic plasticity is yet to be established fully. Methods: Peptide immunisation was used to generate Aabs against selected specific GluN1 extracellular sequences based on patient-derived anti-NMDAR Aabs that have been shown to bind to specific regions within the GluN1 subunit. ‘Protein A’ purification was used to obtain the total IgG, and further peptide purification was used to obtain a greater percentage of NMDAR-target specific IgG Aabs. The binding and specificity of these anti-NMDAR Aabs were determined using a range of methodologies including enzyme-linked immunosorbent assays, immunocytochemistry and immunoblotting. Functional effects were determined using different in vitro electrophysiology techniques: two-electrode voltage-clamps in Xenopus oocytes and measures of long-term potentiation (LTP) in ex vivo hippocampal brain slices using multi-electrode arrays (MEAs). Results: We show that anti-NMDAR Aabs generated from peptide immunisation had specificity for GluN1 immunisation peptides as well as target-specific binding to the native protein. Anti-NMDAR Aabs had no clear effect on isolated NMDARs in an oocyte expression system. However, peptide-purified anti-NMDAR Aabs prevented the induction of LTP at Schaffer collateral-CA1 synapses in ex vivo brain slices, consistent with causing synaptic NMDAR hypofunction at a network level. Conclusions: This work provides a solid basis to address outstanding questions regarding anti-NMDAR Aab mechanisms of action and, potentially, the development of therapies against CNS diseases. Full article