Suppression of TRPV1/TRPM8/P2Y Nociceptors by Withametelin via Downregulating MAPK Signaling in Mouse Model of Vincristine-Induced Neuropathic Pain

Vincristine (VCR) is a widely used chemotherapy drug that induced peripheral painful neuropathy. Yet, it still lacks an ideal therapeutic strategy. The transient receptor potential (TRP) channels, purinergic receptor (P2Y), and mitogen-activated protein kinase (MAPK) signaling play a crucial role in the pathogenesis of neuropathic pain. Withametelin (WMT), a potential Phytosteroid isolated from datura innoxa, exhibits remarkable neuroprotective properties. The present investigation was designed to explore the effect of withametelin on VCR-induced neuropathic pain and its underlying molecular mechanism. Initially, the neuroprotective potential of WMT was confirmed against hydrogen peroxide (H₂O₂)-induced PC12 cells. To develop potential candidates for neuropathic pain treatment, a VCR-induced neuropathic pain model was established. Vincristine (75 μg/kg) was administered intraperitoneally (i.p.) for 10 consecutive days (day 1–10) for the induction of neuropathic pain. Gabapentin (GBP) (60 mg/kg, i.p.) and withametelin (0.1 and 1 mg/kg i.p.) treatments were given after the completion of VCR injection on the 11th day up to 21 days. The results revealed that WMT significantly reduced VCR-induced pain hypersensitivity, including mechanical allodynia, cold allodynia, and thermal hyperalgesia. It reversed the VCR-induced histopathological changes in the brain, spinal cord, and sciatic nerve. It inhibited VCR-induced changes in the biochemical composition of the myelin sheath of the sciatic nerve. It markedly downregulated the expression levels of TRPV1 (transient receptor potential vanilloid 1); TRPM8 (Transient receptor potential melastatin 8); and P2Y nociceptors and MAPKs signaling, including ERK (Extracellular Signal-Regulated Kinase), JNK (c-Jun N-terminal kinase), and p-38 in the spinal cord. It suppressed apoptosis by regulating Bax (Bcl2-associated X-protein), Bcl-2 (B-cell-lymphoma-2), and Caspase-3 expression. It considerably attenuated inflammatory cytokines, oxidative stress, and genotoxicity. This study suggests that WMT treatment suppressed vincristine-induced neuropathic pain by targeting the TRPV1/TRPM8/P2Y nociceptors and MAPK signaling.     

Analysis and Simulation of Capsule Dissolution Problem Encountered During Prodkt Scale-Up

An in vitro capsule dissolution rate problem was encountered during scale-up of cofadroxil monohydrate, a water-soluble drug product. Initial formulation development had been carried out on a Zanasi LZ-64 with a blend containing 1.0% magnesium stearate lubricant. Scale-up capsules manufactured using a Hoflinger-Karg model GFK-1500 (H&K) showed a significantly slower dissolution rate when compared to those produced on a Zanasi LZ-64. Analysis of the problem indicated that during encepsulation on the H&K capsule machine, powder was being sheared resulting in slower in vitro capsule dissolution rate.

Shear simulation studies were conducted to select the level of magnesium stearate for encapsulation on the H&K which would maintain a satisfactory in capsule dissolution rate. A 0.3% level of magnesium stearate was selected on the basis of the simulation studies. At this lubricant level, capsules have been routinely produced on the H&K with satisfactory dissolution and encapsulation characteristics.     

Erratum to: Conductivity Sensors Based System Development and Application to Investigate the Interfacial Behaviour between Supersonic Steam Jet and Water

Instruments and Experimental Techniques - An Erratum to this paper has been published: https://doi.org/10.1134/S0020441221050249     

Road Oriented Traffic Information System for Vehicular Ad hoc Networks

Over the last few years, vehicular ad hoc networks (VANETs) have gained popularity for their interesting applications. To make efficient routing decisions, VANET routing protocols require road traffic density information for which they use density estimation schemes. This paper presents a distributed mechanism for road vehicular density estimation that considers multiple road factors, such as road length and junctions. Extensive simulations are carried out to analyze the effectiveness of the proposed technique. Simulation results suggested that, the proposed technique is more accurate compared to the existing technique. Moreover, it facilitate VANET routing protocols to increase packet delivery ratio and reduce end-to-end delay.     

Recovery Time and Fault Tolerance Improvement for Circuits mapped on SRAM-based FPGAs

The rapid adoption of FPGA-based systems in space and avionics demands dependability rules from the design to the layout phases to protect against radiation effects. Triple Modular Redundancy is a widely used fault tolerance methodology to protect circuits against radiation-induced Single Event Upsets implemented on SRAM-based FPGAs. The accumulation of SEUs in the configuration memory can cause the TMR replicas to fail, requiring a periodic write-back of the configuration bit-stream. The associated system downtime due to scrubbing and the probability of simultaneous failures of two TMR domains are increasing with growing device densities. We propose a methodology to reduce the recovery time of TMR circuits with increased resilience to Cross-Domain Errors. Our methodology consists of an automated tool-flow for fine-grain error detection, error flags convergence and non-overlapping domain placement. The fine-grain error detection logic identifies the faulty domain using gate-level functions while the error flag convergence logic reduces the overwhelming number of flag signals. The non-overlapping placement enables selective domain reconfiguration and greatly reduces the number of Cross-Domain Errors. Our results demonstrate an evident reduction of the recovery time due to fast error detection time and selective partial reconfiguration of faulty domains. Moreover, the methodology drastically reduces Cross-Domain Errors in Look-Up Tables and routing resources. The improvements in recovery time and fault tolerance are achieved at an area overhead of a single LUT per majority voter in TMR circuits.     

Influence of sintering temperature on secondary phases formation and microwave dielectric properties of Ca2Ce2Ti5O16 ceramics

Ca₂Ce₂Ti₅O₁₆ dielectric ceramics prepared by conventional solid-state ceramic route was investigated. Phase composition and microwave dielectric properties were measured using XRD and Vector network analyzer, respectively. XRD analysis of the calcined and sintered samples revealed the formation of CeO₂ and another unidentified phase (that vanished at ? 1400 °C) as secondary phases along with the parent Ca₂Ce₂Ti₅O₁₆ phase. The amount of the parent Ca₂Ce₂Ti₅O₁₆ phase increased with increasing sintering temperature from 1350 °C to 1450 °C accompanied by a decrease in the apparent density. The density decreased but ? _r and Q _u f _o increased with sintering temperature. An ? _r ～ 81.5, Q _u f _o ～ 5915 GHz and τ _f ～ 219 GHz were achieved for the sample sintered at 1450 °C.     

Variable Speed Wind Turbines for Power System Stability Enhancement

This paper investigates possible improvements in grid voltage stability and transient stability with wind energy converter units using modified P/Q control. The voltage source converter (VSC) in modern variable speed wind turbines is utilized to achieve this enhancement. The findings show that using only available hardware for variable-speed turbines improvements could be obtained in all cases. Moreover, it was found that power system stability improvement is often larger when the control is modified for a given variable speed wind turbine rather than when standard variable speed turbines are used instead of fixed speed turbines. To demonstrate that the suggested modifications can be incorporated in real installations, a real situation is presented where short-term voltage stability is improved as an additional feature of an existing VSC high voltage direct current (HVDC) installation     

Classification of Diabetic Macular Edema and Its Stages Using Color Fundus Image

Diabetic macular edema(DME)is a retinal thickening involving the center of the macula.It is one of the serious eye diseases which affects the central vision and can lead to partial or even complete visual loss.The only cure is timely diagnosis,prevention,and treatment of the disease.This paper presents an automated system for the diagnosis and classification of DME using color fundus image.In the proposed technique,first the optic disc is removed by applying some preprocessing steps.The preprocessed image is then passed through a classifier for segmentation of the image to detect exudates.The classifier uses dynamic thresholding technique by using some input parameters of the image.The stage classification is done on the basis of an early treatment diabetic retinopathy study(ETDRS)given criteria to assess the severity of disease.The proposed technique gives a sensitivity,specificity,and accuracy of 98.27%,96.58%,and 96.54%,respectively on publically available database.