Transient Enhancement Research Articles

Transient Synaptic Enhancement Triggered by Exogenously Supplied Monocarboxylate in Drosophila Motoneuron Synapse

Current evidence suggests that glial cells provide C3 carbon sources to fuel neuronal activity; however, this notion has become challenged by biosensor studies carried out in acute brain slices or in vivo, showing that neuronal activity does not rely on the import of astrocyte-produced L-lactate. Rather, stimulated neurons become net lactate exporters, as it was also shown in Drosophila neurons, in which astrocyte-provided lactate returns as lipid droplets to be stored in glial cells. In this view, we investigate whether exogenously supplied monocarboxylates can support Drosophila motoneuron neurotransmitter release (NTR). By assessing the excitatory post-synaptic current (EPSC) amplitude under voltage-clamp as NTR indicative, we found that both pyruvate and L-lactate, as the only carbon sources in the synapses bathing-solution, cause a large transient NTR enhancement, which declines to reach a synaptic depression state, from which the synapses do not recover. The FM1-43 pre-synaptic loading ability, however, is maintained under monocarboxylate, suggesting that SV cycling should not contribute to the synaptic depression state. The NTR recovery was reached by supplementing the monocarboxylate medium with sucrose. However, monocarboxylate addition to sucrose medium does not enhance NTR, but it does when the disaccharide concentration becomes too reduced. Thus, when pyruvate concentrations become too reduced, exogenously supplied L-lactate could be converted to pyruvate and metabolized by the neural mitochondria, triggering the NTR enhancement. Significance statementThe question of whether monocarboxylic acids can fuel the Drosophila motoneuron NTR was challenged. Our findings show that exogenously supplied monocarboxylates trigger a large transient synaptic enhancement just under extreme glycolysis reduction but fail to maintain NTR under sustained synaptic demand, still at low frequency stimulation, driven to the synapses to a synaptic depression state. Glycolysis activation, by adding sucrose to the monocarboxylate bath solution, restores the motoneuron NTR ability, giving place to a hexoses role in SV recruitment. Moreover these results suggest exogenously supplied C3 carbon sources could have an additional role beyond providing energetic support for neural activity.

Vaccine-Boosted CCP Decreases Virus Replication and Hastens Resolution of Infection Despite Transiently Enhancing Disease in SARS-CoV-2-Infected Hamsters.

Definitive data demonstrating the utility of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) for treating immunocompromised patients remains elusive. To better understand the mechanism of action of CCP, we studied viral replication and disease progression in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected hamsters treated with CCP obtained from recovered COVID-19 patients that were also vaccinated with an mRNA vaccine, hereafter referred to as Vaxplas. Vaxplas transiently enhanced disease severity and lung pathology in hamsters treated near peak viral replication due to immune complex and activated complement deposition in pulmonary endothelium, and recruitment of M1 proinflammatory macrophages into the lung parenchyma. However, aside from one report, transient enhanced disease has not been reported in CCP recipient patients, and the transient enhanced disease in Vaxplas hamsters may have been due to mismatched species IgG-FcR interactions, infusion timing, or other experimental factors. Despite transient disease enhancement, Vaxplas dramatically reduced virus replication in lungs and improved infection outcome in SARS-CoV-2-infected hamsters.

Functional neuroimaging and behavioral correlates of multisite tDCS as an add-on to language training in a person with post-stroke non-fluent aphasia: a year-long case study

ABSTRACT Mary, who experienced non-fluent aphasia as a result of an ischemic stroke, received 10 years of personalized language training (LT), resulting in transient enhancements in speech and comprehension. To enhance these effects, multisite transcranial Direct Current Stimulation (tDCS) was added to her LT regimen for 15 sessions. Assessment using the Reliable Change Index showed that this combination improved her left inferior frontal connectivity and speech production for two months and significantly improved comprehension after one month. The results indicate that using multisite transcranial direct current stimulation (tDCS) can improve the effectiveness of language therapy (LT) for individuals with non-fluent aphasia.

Voltage-Adaptive Strategy for Transient Stability Enhancement of Power Systems With 100% Renewable Energy

Voltage-Adaptive Strategy for Transient Stability Enhancement of Power Systems With 100% Renewable Energy

Stability Constrained Transient Overcurrent Capability Enhancement of Grid Forming Converters based on Switching Frequency Adjustment

Stability Constrained Transient Overcurrent Capability Enhancement of Grid Forming Converters based on Switching Frequency Adjustment

Investigation on Transient Stability Enhancement of Multi-VSG System Incorporating Resistive SFCLs Based on Deep Reinforcement Learning

Investigation on Transient Stability Enhancement of Multi-VSG System Incorporating Resistive SFCLs Based on Deep Reinforcement Learning

Clinical Pharmacology of Oral Octreotide Capsules for the Treatment of Acromegaly.

The primary goal of acromegaly treatment is to normalize biochemical parameters as it significantly reduces the risks of complications and comorbidities associated with the disease. First-line medical treatment is commonly represented by injectable somatostatin analogues (SRLs) after surgery. In June 2020, with the integration of Transient Permeation Enhancer® technology, oral octreotide capsules (OOCs) received regulatory approval from the US Food and Drug Administration for long-term maintenance treatment in patients with acromegaly who have responded to and tolerated treatment with octreotide or lanreotide. We reviewed the clinical pharmacological data on the development and clinical use of OOCs. The pharmacokinetic and pharmacodynamic data on OOCs showed a dose-dependent increase in octreotide levels and remarkable suppression of growth hormone secretion. The efficacy and safety of OOCs were investigated in four clinical trials conducted on patients with complete or partially controlled acromegaly. The trials resulted in the maintenance of biochemical control after switching from injectable SRLs to OOCs, with a comparable side-effect profile. Moreover, the acromegaly symptoms improved in patients on OOC. The data showed a patient preference to continue in the OOC arm for the extension phase of the trials. From the clinical pharmacological perspective, oral formulation of octreotide has the advantage of efficacy and safety with respect to injectable octreotide.

Transient Stability Enhancement of Current Limited-GFM Inverters Based on Varying Virtual Impedance

Transient Stability Enhancement of Current Limited-GFM Inverters Based on Varying Virtual Impedance

Transient Worsening of Pain After Administration of Immune Checkpoint Inhibitors - A Case Series.

Transient pain enhancement or flare pain, is observed following the administration of immune checkpoint inhibitors (ICIs). However, the detailed mechanism of this phenomenon remains unclear. In this report, we present our experience of documenting the course of flare pain following ICI administration in six cases. Six patients with advanced solid tumors received ICI monotherapy between July 2017 and November 2019. Their pain increased within hours of ICI administration despite being stable before ICI administration. We evaluated the changes in the numerical rating scale (NRS) score over 72 h after ICI administration. Four non-small cell lung cancer patients, one gastric cancer patient, and one renal cell cancer patient were included. Four patients experienced an increase in NRS, as evidenced by scores on two or more scales compared to the day before administration, whereas two patients showed an increase only on one scale. The NRS score decreased to almost the same level as that on the day before administration. Flare pain is observed in the same area as the primary site. Most of the pain was alleviated without the need for rescue analgesics, although one patient experienced a 4-point increase in the NRS scale. Flare pain may occur following ICI administration. Healthcare providers should be aware of these events and provide patients with suitable information and coping techniques.

Transient Stability Analysis and Enhancement of Inverter-Based Microgrid Considering Current Limitation

Transient Stability Analysis and Enhancement of Inverter-Based Microgrid Considering Current Limitation

Power Supporting Control of Grid-forming Converters under Grid Voltage Sags for Transient Stability Enhancement and Overcurrent Limitation

Power Supporting Control of Grid-forming Converters under Grid Voltage Sags for Transient Stability Enhancement and Overcurrent Limitation

Transient Stability Enhancement Control for Virtual Synchronous Generator Controlled Isolated Power Grid

Transient Stability Enhancement Control for Virtual Synchronous Generator Controlled Isolated Power Grid

Integrated Data-Driven Power System Transient Stability Monitoring and Enhancement

While many promising data-driven power system transient stability assessment (TSA) studies have been recently reported, very few of them further propose efficient data-driven solutions for follow-up control actions, e.g., generator tripping, against potential instability. To address this inadequacy, this work develops an integrated data-driven transient stability monitoring and enhancement (TSMAE) approach that can reliably and efficiently handle various emergency situations in real time. First, by introducing the emerging spatial-temporal synchronous graph convolutional network (STSGCN), wide-area spatial-temporal features w.r.t. system stability are sufficiently learned to reliably implement online TSA. Then, to handle impending instability in a tractable manner, remedial actions are quickly taken based on intelligent critical generator identification (CGI). Specifically, with the help of the STSGCN again, the potential effects of tripping individual generators on system stabilization are efficiently predicted from the spatial-temporal perspective. Based upon that, the most critical generators for tripping are adaptively selected to enhance system stability. Numerical test results on a realistic provincial power grid of China illustrate the efficacy of the proposed TSMAE approach.

Experiences and Translatability of In Vitro and In Vivo Models to Evaluate Caprate as a Permeation Enhancer.

Transient permeation enhancers (PEs) have been widely used to improve the oral absorption of macromolecules. During pharmaceutical development, the correct selection of the macromolecule, PE, and the combination needs to be made to maximize oral bioavailability and ensure successful clinical development. Various in vitro and in vivo methods have been investigated to optimize this selection. In vitro methods are generally preferred by the pharmaceutical industry to reduce the use of animals according to the "replacement, reduction, and refinement" principle commonly termed "3Rs," and in vitro methods typically have a higher throughput. This paper compares two in vitro methods that are commonly used within the pharmaceutical industry, being Caco-2 and an Ussing chamber, to two in vivo models, being in situ intestinal instillation to rats and in vivo administration via an endoscope to pigs. All studies use solution formulation of sodium caprate, which has been widely used as a PE, and two macromolecules, being FITC-dextran 4000 Da and MEDI7219, a GLP-1 receptor agonist peptide. The paper shares our experiences of using these models and the challenges with the in vitro models in mimicking the processes occurring in vivo. The paper highlights the need to consider these differences when translating data generated using these in vitro models for evaluating macromolecules, PE, and combinations thereof for enabling oral delivery.

A Novel Data-Driven Self-Tuning SVC Additional Fractional-Order Sliding Mode Controller for Transient Voltage Stability With Wind Generations

This paper proposes a novel data-driven self-tuning additional sliding mode controller for power system transient voltage stability enhancement considering wind integration. We first develop a new additional fractional-order sliding mode controller (FOSMC) for the static var compensator (SVC). The tuning of FOSMC parameter settings is then reformulated as a Markov decision process (MDP) and solved by the deep reinforcement learning (DRL) algorithm. In addition, a data-driven estimation method is proposed for the identification of an equivalent transfer function that is further used to calculate reward during the training process, yielding the model-free training. After that, the well-trained agent allows us to tune the controller parameters considering system uncertainties and achieve robustness against various operating conditions. Comparative results with other state-of-art methods demonstrate that the proposed method can effectively suppress the chattering issue of the sliding mode controller and ensure transient voltage stability under different operating conditions.

A transient stability enhancement framework based on rapid fault-type identification for virtual synchronous generators

The virtual synchronous generator (VSG) control, widely used for voltage source inverters, is prone to the loss of synchronization (LOS) under large disturbances such as grid voltage sags. Despite the significant amount of research that has been conducted on the transient stability of VSGs, the existing conclusions on the influence of virtual inertia under different fault conditions remain controversial. In this paper, the conflicting effect of virtual inertia on VSG transient stability under different severities of grid voltage sag is comprehensively investigated. Faults, like grid voltage sags, are classified into two types in this paper: transient tolerable faults and transient intolerable faults. Moreover, a unified control framework for rapid fault-type identification and transient stability improvement is proposed. The Learning vector quantization (LVQ) neural networks are used to distinguish fault types within 5 ms. Based on the fault-type identification results, the proposed control strategies are applied to enhance the transient stability of VSG. Finally, simulations and control-hardware-in-loop experimental validations are carried out to demonstrate the effectiveness of the proposed framework.

A Low Noise Neural Recording Frontend IC With Power Management for Closed-Loop Brain-Machine Interface Application.

Brain-machine Interface (BMI) with implantable bioelectronics systems can provide an alternative way to cure neural diseases, while a power management system plays an important role in providing a stable voltage supply for the implanted chip. a prototype system of power management integrated circuit (PMIC) with heavy load capability supplying artifacts tolerable neural recording integrated circuit (ATNR-IC) is presented in this work. A reverse nested miller compensation (RNMC) low dropout regulator (LDO) with a transient enhancer is proposed for the PMIC. The power consumption is 0.55 mW and 22.5 mW at standby (SB) and full stimulation (ST) load, respectively. For a full load transition, the overshoot and downshoot of the LDO are 110 mV and 71 mV, respectively, which help improve the load transient response during neural stimulation. With the load current peak-to-peak range is about 560 μA supplied by a 4-channel stimulator, the whole PMIC can output a stable 3.3 V supply voltage, which indicates that this PMIC can be extended for more stimulating channels' scenarios. When the ATNR-IC is supplied for presented PMIC through a voltage divider network, it can amplify the signal consisting of 1 mVpp simulated neural signal and 20 mVpp simulated artifact by 28 dB with no saturation.

A Transient-Enhanced Autonomous Current Adaptation Buffer Amplifier

This paper proposes a transient enhanced autonomous current adaptation buffer amplifier (ACABA) that effectively resolves the slew rate degradation problem observed in the previous design. The proposed circuit enhances the transient responses, achieving faster step responses, superior linearity, and higher power efficiency. The cause of the degradation in the previous work has been elucidated, and a transient enhancement circuit is proposed to circumvent the slewing bottleneck. A prototype chip has been designed and fabricated in a 0.35μm CMOS process. From measurements, the proposed circuit improves settling time by 62.1%, enhances slew rate by 3.1 times, and reduces total harmonic distortion (THD) by 17 dB without extra static power consumption. With a 2.5V supply voltage, the proposed buffer amplifier allows a maximum input signal amplitude of 2.3 V with the THD below -60dB. Furthermore, the enhanced buffer amplifier exhibits the best power efficiency in both small-signal and large-signal performance compared to other state-of-the-art designs.

Optimized PID controller using Archimedes optimization algorithm for transient stability enhancement

Optimized PID controller using Archimedes optimization algorithm for transient stability enhancement

Time-dependent analysis of heat transfer enhancement and entropy generation of hybrid nanofluids in a tube with a solid and elliptical‑cut twisted tape insert with non-uniform heat flux

ABSTRACT This numerical study investigates the improvement of transient heat transfer in a plain tube using hybrid nanofluids consisting of solid particles and twisted tapes with elliptical cuts, under non-uniform heat flux conditions. The analysis includes the calculation of the Bejan number and entropy production. Different working fluids, including water, CuO/water nanofluid, and a hybrid nanofluid with a 2% volume concentration of Al2O3-Cu/water, are used with varying concentrations of the hybrid nanofluid ranging from 1% to 4%. Effects of heat flux distribution and local concentration ratio (LCR) are investigated. The computational results indicate that conventional and elliptical cut twisted tapes enhance transient heat transmission. A slight rise in the heat transfer coefficient is observed when the fluid has higher thermal conductivity. The flow velocity gradually stabilizes over time. The hybrid nanofluid of (Al2O3-Cu/water) significantly affects transient heat transmission, reducing the maximum temperature difference by approximately 4.1% compared to water and 6.2% compared to the nanofluid. Transient heat transmission is further intensified by TECT. Moreover, frictional entropy production dominates the system’s irreversibility. This study contributes to the understanding of transient heat transfer enhancement and its dependence on hybrid nanofluids, providing insights for engineering applications.