Search Results (627)

Previous studies have suggested a role for selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac^®) in the treatment of dizziness and inner ear vestibular dysfunction. The potential mechanism of action within the vestibular system remains unclear; however, fluoxetine has been reported to block certain types of K⁺ channel in other systems. Here, we investigated the direct actions of fluoxetine on membrane currents in presynaptic hair cells and postsynaptic calyx afferents of the gerbil peripheral vestibular system using whole cell patch clamp recordings in crista slices. We explored differences in K⁺ currents in peripheral zone (PZ) and central zone (CZ) calyces of the crista and their response to fluoxetine application. Outward K⁺ currents in PZ calyces showed greater inactivation at depolarized membrane potentials compared to CZ calyces. The application of 100 μM fluoxetine notably reduced K⁺ currents in calyx terminals within both zones of the crista, and the remaining currents exhibited distinct traits. In PZ cells, fluoxetine inhibited a non-inactivating K⁺ current and revealed a rapidly activating and inactivating K⁺ current, which was sensitive to blocking by 4-aminopyridine. This was in contrast to CZ calyces, where low-voltage-activated and non-inactivating K⁺ currents persisted following application of 100 μM fluoxetine. Additionally, marked inhibition of transient inward Na⁺ currents by fluoxetine was observed in calyces from both crista zones. Different concentrations of fluoxetine were tested, and the EC₅₀ values were found to be 40 µM and 32 µM for K⁺ and Na⁺ currents, respectively. In contrast, 100 μM fluoxetine had no impact on voltage-dependent K⁺ currents in mechanosensory type I and type II vestibular hair cells. In summary, micromolar concentrations of fluoxetine are expected to strongly reduce both Na⁺ and K⁺ conductance in afferent neurons of the peripheral vestibular system in vivo. This would lead to inhibition of action potential firing in vestibular sensory neurons and has therapeutic implications for disorders of balance. Full article

Many years ago, asbestos fibers were banned and replaced by synthetic vitreous fibers because of their carcinogenicity. However, the toxicity of the latter fibers is still under debate, especially when it concerns the early fiber interactions with biological cell membranes. Here, we aimed to investigate the effects of a synthetic vitreous fiber named FAV173 on the Xenopus laevis oocyte membrane, the cell model we have already used to characterize the effect of crocidolite asbestos fiber exposure. Using an electrophysiological approach, we found that, similarly to crocidolite asbestos, FAV173 was able to stimulate a chloride outward current evoked by step membrane depolarizations, that was blocked by the potent and specific TMEM16A channel antagonist Ani9. Exposure to FAV173 fibers also altered the oocyte cell membrane microvilli morphology similarly to crocidolite fibers, most likely as a consequence of the TMEM16A protein interaction with actin. However, FAV173 only partially mimicked the crocidolite fibers effects, even at higher fiber suspension concentrations. As expected, the crocidolite fibers’ effect was more similar to that induced by the co-treatment with (Fe³⁺ + H₂O₂), since the iron content of asbestos fibers is known to trigger reactive oxygen species (ROS) production. Taken together, our findings suggest that FAV173 may be less harmful that crocidolite but not ineffective in altering cell membrane properties. Full article

During the modulation process of the VSI motor drive system, the nonlinear errors caused by the dead-time and conduction voltage drop will increase the phase current harmonic distortion and the torque ripple. To solve this problem, a novel dead-time free modulation scheme is proposed in this paper. In the non-zero crossing region of the phase current, the switching tube, whose body diode can provide a continuation path, is set as off-state, the driving signal is only implemented on another switching tube with the same bridge arm, and the errors caused by the conduction voltage drop and switching delay are compensated to the pulse duration. At the same time, to suppress the zero current clamp effect that exists near the zero crossing point of the phase current, another modulation scheme for the phase current crossing zero in advance is proposed, which avoids the complicated determination and calculation of the current polarity near the zero crossing point of the current. Both of the above modulation schemes eliminate the dead-time, and the switching principle is presented. In addition, to suppress the impact of the current ripple and high-frequency noise on the accuracy of the phase current detection, a second-order resonance digital filter without phase shift is introduced. Finally, compared to two deadtime compensation methods, the effectiveness and superiority of the proposed dead-time free modulation scheme are verified by the experimental results. Full article

The primary objective of this paper focuses on developing a control approach to improve the operational performance of a three-level neutral point clamped (3LNPC) shunt active power filter (SAPF) within a grid-tied PV system configuration. Indeed, this developed control approach, based on the used 3LNPC-SAPF topology, aims to ensure the seamless integration of a photovoltaic system into the three-phase four-wire grid while effectively mitigating grid harmonics, grid current unbalance, ensuring grid unit power factor by compensating the load reactive power, and allowing power sharing with the grid in case of an excess of generated power from the PV system, leading to overall high power quality at the grid side. This developed approach is based initially on the application of the four-wire instantaneous p-q theory for the identification of the reference currents that have to be injected by the 3LNPC-SAPF in the grid point of common coupling (PCC). Whereas, the 3LNPC is controlled based on using the finite control set model predictive control (FCS-MPC), which can be accomplished by determining the convenient set of switch states leading to the voltage vector, which is the most suitable to ensure the minimization of the selected cost function. Furthermore, the used topology requires a constant DC-link voltage and balanced split-capacitor voltages at the input side of the 3LNPN. Hence, the cost function is adjusted by the addition of another term with a selected weighting factor related to these voltages to ensure their precise control following the required reference values. However, due to the random changes in solar irradiance and, furthermore, to ensure efficient operation of the proposed topology, the PV system is connected to the 3LNPN-SAPF via a DC/DC boost converter to ensure the stability of the 3LNPN input voltage within the reference value, which is achieved in this paper based on the use of the maximum power point tracking (MPPT) technique. For the validation of the proposed control technique and the functionality of the used topology, a set of simulations has been presented and investigated in this paper following different irradiance profile scenarios such as a constant irradiance profile and a variables irradiance profile where the main aim is to prove the effectiveness and flexibility of the proposed approach under variable irradiance conditions. The obtained results based on the simulations carried out in this study demonstrate that the proposed control approach with the used topology under different loads such as linear, non-linear, and unbalanced can effectively reduce the harmonics, eliminating the unbalance in the currents and compensating for the reactive component contained in the grid side. The obtained results prove also that the proposed control ensures a consistent flow of power based on the sharing principle between the grid and the PV system as well as enabling the efficient satisfaction of the load demand. It can be said that the proposal presented in this paper has been proven to have many dominant features such as the ability to accurately estimate the power sharing between the grid and the PV system for ensuring the harmonics elimination, the reactive power compensation, and the elimination of the neutral current based on the zero-sequence component compensation, even under variable irradiance conditions. This feature makes the used topology and the developed control a valuable tool for power quality improvement and grid stability enhancement with low cost and under clean energy. Full article

Loss-, gain-of-function and mixed variants in SCN1A (Nav1.1 voltage-gated sodium channel) have been associated with a spectrum of neurologic disorders with different severity and drug-responsiveness. Most SCN1A variants are heterozygous changes occurring de novo or dominantly inherited; recessive inheritance has been reported in a few cases. Here, we report a family in which the biallelic inheritance of two novel SCN1A variants, N935Y and H1393Q, occurs in two siblings presenting with drug-responsive developmental and epileptic encephalopathy and born to heterozygous asymptomatic parents. To assess the genotype–phenotype correlation and support the treatment choice, HEK 293 cells were transfected with different combinations of the SCN1A WT and mutant cDNAs, and the resulting sodium currents were recorded through whole-cell patch-clamp. Functional studies showed that the N935Y and H1393Q channels and their combinations with the WT (WT + N935Y and WT + H1393Q) had current densities and biophysical properties comparable with those of their respective control conditions. This explains the asymptomatic condition of the probands’ parents. The co-expression of the N935Y + H1393Q channels, mimicking the recessive inheritance of the two variants in siblings, showed ~20% reduced current amplitude compared with WT and with parental channels. This mild loss of Nav1.1 function may contribute in part to the disease pathogenesis, although other mechanisms may be involved. Full article

A novel ac/dc LED driver with power factor correction and soft-switching functions is proposed. The circuit topology mainly consists of two modified single-ended primary inductance converters (SEPIC) with interleaved operation. The first half stage of SEPIC operates like a boost converter and the second half stage operates like a buck–boost converter. Each boost converter is designed to operate in discontinuous current mode (DCM) to function as a power factor corrector (PFC). The two buck–boost converters that share a commonly coupled inductor are designed to operate at near boundary conduction mode (BCM). Without using any active clamping circuit, auxiliary switch or snubber circuit, the active switches can achieve zero-voltage switching on, and all diodes achieve zero-current switching off. First, operation modes in steady state are analyzed, and the mathematical equations for design component parameters are derived. Finally, a prototype circuit of 180 W rated power was built and tested. Experimental results show satisfactory performance of the proposed circuit. Full article

The three-level neutral-point-clamped (NPC) active power filter (APF) is suitable for harmonic compensation in high voltage and large capacity applications. And, the harmonic compensation effect of APF depends on its dynamic performance and control. This paper propose a repeat proportional integral (PI) decoupling control strategy with linear active disturbance rejection (LADRC) to address the issues of detection in complex harmonic current and power supply current distortion when the nonlinear load varies. To simplify the design of LADRC, this paper adopts inverter current feedback control. Firstly, repeat control is introduced to optimize the traditional PI controller, which improves the compensation accuracy while ensuring the dynamic response capability of the control system. Then, to address the serious coupling of the system model in the d-q coordinate system, a reduced order linear active disturbance rejection (LADRC) control is introduced. The PI and linear extended state observer (LESO) control method is adopted in the outer voltage loop to maintain stable DC voltage and improve the ability to suppress voltage overshoot during grid connection. The effectiveness of this control method has been verified through MATLAB/Simlink. The results show that, compared with the repeat PI method, the control method based on repeat PI–LADRC can achieve better decoupling control, improve robustness and anti-interference ability, enhance the performance of the original system, and can significantly improve the harmonic suppression capability of the APF. Full article

High fat diets have been used as complementary treatments for seizure disorders for more than a century. Moreover, many fatty acids and derivatives, including the broad-spectrum antiseizure medication valproic acid, have been explored and used as pharmacological agents to treat epilepsy. In this work, we have explored the anticonvulsant potential of a large library of fatty acids and fatty acid derivatives, the LIPID MAPS Structure Database, using structure-based virtual screening to assess their ability to block the voltage-gated sodium channel 1.2 (NaV1.2), a validated target for antiseizure medications. Four of the resulting in silico hits were submitted for experimental confirmation using in vitro patch clamp experiments, and their protective role was evaluated in an acute mice seizure model, the Maximal Electroshock seizure model. These four compounds were found to protect mice against seizures. Two of them exhibited blocking effects on NaV1.2, CaV2.2, and CaV3.1. Full article

Voltage source inverters are extensively used in the grid connection of renewable energy-sourced generators, and multilevel converters, in particular, have attracted a great deal of attention in recent years. This paper investigates the application of a novel passivity-based sliding mode (PSM) control scheme on three-level grid-tie active Neutral-Point-Clamped (ANPC) inverters that yield fast and stable responses to grid impedance variations. Simulation studies confirm that this control scheme can produce high tracking performance and is also robust against grid load variations. Furthermore, to enhance ANPC efficiency, the loss distribution of switching devices controlled by the proposed strategy is evaluated. An optimal scheme is finally proposed for allocating silicon and Wide-Band-Gap switching devices, resulting in a hybrid ANPC inverter capable of achieving a desirable trade-off between the power losses and the device cost. Full article

Human observation of the ocean has gradually evolved from the sea surface to systematic monitoring and sampling through seafloor observation networks, and constant current power supply has become the main power supply method for seafloor observation networks due to its high reliability. There are some studies on current source to voltage source converters, but there are few studies on current source to current source (CS/CS) converters, which affects the expansion of power supply networks for seafloor observation networks. In this paper, by employing input current sharing and output voltage doubling circuits, an active clamp dual-inductor isolated CS/CS converter which uses a single-stage conversion circuit to realize constant current source conversion with a wide output voltage range is proposed. Active clamp technology at the primary side of the proposed circuit is employed to recover energy stored in leakage inductance, suppress voltage spikes of the primary side switches, and achieve zero-voltage switching of the primary side switches. The secondary side’s output voltage doubling circuit resonates with transformer leakage inductance to achieve zero-current switching of the secondary side diodes, which can reduce losses and enhance efficiency. The operating principles of the proposed circuit are analyzed in detail, and the characteristic and parameter design analysis, including current conversion ratio, transformer turn ratio, power inductors, and resonant capacitors and inductor, are presented. Finally, the experimental results based on a 100 W experimental prototype validate the feasibility of the proposed converter. Full article

The signaling complex around voltage-gated sodium (Nav) channels includes accessory proteins and kinases crucial for regulating neuronal firing. Previous studies showed that one such kinase, WEE1—critical to the cell cycle—selectively modulates Nav1.2 channel activity through the accessory protein fibroblast growth factor 14 (FGF14). Here, we tested whether WEE1 exhibits crosstalk with the AKT/GSK3 kinase pathway for coordinated regulation of FGF14/Nav1.2 channel complex assembly and function. Using the in-cell split luciferase complementation assay (LCA), we found that the WEE1 inhibitor II and GSK3 inhibitor XIII reduce the FGF14/Nav1.2 complex formation, while the AKT inhibitor triciribine increases it. However, combining WEE1 inhibitor II with either one of the other two inhibitors abolished its effect on the FGF14/Nav1.2 complex formation. Whole-cell voltage-clamp recordings of sodium currents (I_Na) in HEK293 cells co-expressing Nav1.2 channels and FGF14-GFP showed that WEE1 inhibitor II significantly suppresses peak I_Na density, both alone and in the presence of triciribine or GSK3 inhibitor XIII, despite the latter inhibitor’s opposite effects on I_Na. Additionally, WEE1 inhibitor II slowed the tau of fast inactivation and caused depolarizing shifts in the voltage dependence of activation and inactivation. These phenotypes either prevailed or were additive when combined with triciribine but were outcompeted when both WEE1 inhibitor II and GSK3 inhibitor XIII were present. Concerted regulation by WEE1 inhibitor II, triciribine, and GSK3 inhibitor XIII was also observed in long-term inactivation and use dependency of Nav1.2 currents. Overall, these findings suggest a complex role for WEE1 kinase—in concert with the AKT/GSK3 pathway—in regulating the Nav1.2 channelosome. Full article

To protect the battery, radio energy transmission charging typically uses constant current (CC) charging before switching to constant voltage (CV) charging to enhance battery durability. This paper proposes adding an auxiliary clamp coil to the original circuit topology. The IPT battery charger designed with the auxiliary clamp coil can achieve both constant current (CC) and constant voltage (CV) outputs. The mutual inductance between the auxiliary clamp coil and the primary side coil greatly influences the output performance of the entire IPT system, so the auxiliary clamp coil should not be too large. To solve this problem, an S-S-PS circuit with secondary compensation topology in the secondary coil is proposed. This circuit topology reduces the size of the auxiliary clamp coil, allowing it to be placed in an optimal position. When the constant voltage output critical position is reached, the IPT system can still automatically, continuously, and smoothly switch between CC and CV modes. Consequently, this approach avoids increased cost consumption associated with detecting CC-CV switching thresholds, adding wireless transmission communication modules, real-time control of the power transmitter, and active protection of the circuit during constant current charging. Finally, a 48 V/2.5 A prototype was built to verify that the IPT system has CC-CV conversion functionality. Full article

Strain clamps are critical components in high-voltage overhead transmission lines, and detection of their defects becomes an important part of regular inspection of transmission lines. A dual UAV (unmanned aerial vehicle) system was proposed to detect strain clamps in multiple split-phase conductors. The main UAV was equipped with a digital radiography (DR) imaging device, a mechanical arm, and an edge intelligence module with visual sensors. The slave UAV was equipped with a digital imaging board and visual sensors. A workflow was proposed for this dual UAV system. Target detection and distance detection of the strain clamps, as well as detection of the defects of strain clamps in DR images, are the main procedures of this workflow. To satisfy the demands of UAV-borne and real-time deployment, the improved YOLOv8-TR algorithm was proposed for the detection of strain clamps (the mAP@50 was 60.9%), and the KD-ResRPA algorithm is used for detecting defects in DR images (the average AUCROC of the three datasets was 82.7%). Field experiments validated the suitability of our dual UAV-based system for charged detection of strain clamps in double split-phase conductors, demonstrating its potential for practical application in live detecting systems. Full article

This paper analyzes, designs and implements a reconfigurable phase-shifted full-bridge (PSFB) converter. It adopts the topology of the traditional PSFB converter and incorporates clamping circuits to solve some fundamental problems of conventional topology. In addition, auxiliary switches are employed for output reconfiguration, which allows expanding the output voltage range without compromising the system efficiency. Single pole double throw (SPDT) mechanical switches are used to realize series and parallel connections. In this paper, the characterization of the PSFB converter with clamping circuit and its design considerations are discussed. A 10 kW prototype with a power density of 0.485 W/cm³, 900 V input voltage and 400/800 V nominal output voltage was manufactured. The experimental results validated the analysis and confirmed the high conversion efficiency for a wide load range; an efficiency of 96.69% was obtained for the full load condition. Full article

This letter derives and discusses the superiority of a simple dc-link capacitor voltage control configuration for multilevel neutral-point-clamped converters with any number of levels. The control involves n − 2 control loops regulating the difference between the voltage of neighbor capacitors. These control loops are inherently decoupled, i.e., they are independent and the control action of one loop does not affect the others. This method is proven to be equivalent to previously published approaches, with the added advantages of increased simplicity and scalability to a higher number of levels, all while imposing a lower computational burden. The good performance of such control is confirmed through simulations and experiments. Full article