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Ballast plays an important role in the stability of railway track systems. The effectiveness of the ballast in maintaining the track stability is very much dependent on its mechanical conditions. The available ballast maintenance approaches are mainly based on only track geometry conditions (such as track profile) which do not sufficiently reflect the ballast mechanical behaviors. That is, the ballast potential of degradation (i.e., ballast long term behaviors) has been omitted. This makes the effectiveness of the current ballast maintenance approach questionable, indicating a need for a more comprehensive and effective ballast conditions assessment technique. In response to this need, two ballast condition indices based on ballast geometry degradation (BGI) and the level of ballast fouling (BFI) as the main indicators of ballast mechanical behavior were developed. The BGI is a function of the standard deviations of track alignment, unevenness and twist. The BFI was developed based on the data obtained from the ground penetration radar (GPR). Making use of the new indices, a more reliable maintenance algorithm was developed. Through illustrations of the applicability of the new maintenance algorithm in a railway line, it was shown that the new algorithm causes a considerable improvement in the maintenance effectiveness and an increase in the life cycle of railway tracks by making more effective allocation of resources and more accurate maintenance planning. [ABSTRACT FROM AUTHOR]

In this article, different s-substituted benzimidazole-thioquinoline derivatives were designed, synthesized, and evaluated for their possible α-glucosidase inhibitory activities. The most active compound in this series, 6j (X = 4-bromobenzyl) exhibited significant potency with an IC 50 value of 28.0 ± 0.6 µM compared to acarbose as the positive control with an IC 50 value of 750.0 µM. The kinetic study showed a competitive inhibition pattern against α-glucosidase for the 6j derivative. Also, the molecular dynamic simulations were performed to determine key interactions between compounds and the targeted enzyme. The in silico pharmacodynamics and ADMET properties were executed to illustrate the druggability of the novel derivatives. In general, it can be concluded that these derivatives can serve as promising leads to the design of potential α-glucosidase inhibitors., (© 2023. The Author(s).)

In the development of novel anti-α-glucosidase agents, we synthesized novel thieno[2,3-b]quinoline-hydrazones 9a-n by facile and efficient conventional chemical reactions. These compounds were characterized by IR, 1 H NMR, 13 C NMR, and elemental analysis. Inhibitory activities of the title compounds were evaluated against yeast α-glucosidase. In particular, compounds 9c, 9d, and 9h exhibited high anti-α-glucosidase activity. Representatively, compound 9c with IC 50  = 1.3 µM, was 576-times more potent than positive control acarbose. Molecular docking study of the most active compounds showed that these compounds formed important binding interactions at α-glucosidase active site. Molecular dynamics study of compound 9c was also performed and the obtained results were compared with acarbose. Compounds 9c, 9d, and 9h were also evaluated for in silico druglikeness properties and ADMET prediction. These studies showed that the title most potent compounds could be exploited as drug candidates., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: α-Glucosidase is a hydrolyzing enzyme that plays a crucial role in the degradation of carbohydrates and starch to glucose. Hence, α-glucosidase is an important target in carbohydrate mediated diseases such as diabetes mellitus., Objective: In this study, novel coumarin containing dithiocarbamate derivatives 4a-n were synthesized and evaluated against α-glucosidase in vitro and in silico., Methods: These compounds were obtained from the reaction between 4-(bromomethyl)-7- methoxy-2H-chromen-2-one 1, carbon disulfide 2, and primary or secondary amines 3a-n in the presence of potassium hydroxide and ethanol at room temperature. In vitro α-glucosidase inhibition and kinetic study of these compounds were performed. Furthermore, a docking study of the most potent compounds was also performed by Auto Dock Tools (version 1.5.6)., Results: Obtained results showed that all the synthesized compounds exhibited prominent inhibitory activities (IC50 = 85.0 ± 4.0-566.6 ± 8.6 μM) in comparison to acarbose as a standard inhibitor (IC50 = 750.0 ± 9.0 μM). Among them, the secondary amine derivative 4d with pendant indole group was the most potent inhibitor. Enzyme kinetic study of the compound 4d revealed that this compound competes with a substrate to connect to the active site of α-glucosidase and therefore is a competitive inhibitor. Moreover, a molecular docking study predicted that this compound interacted with the α-glucosidase active site pocket., Conclusion: Our results suggest that the coumarin-dithiocarbamate scaffold can be a promising lead structure for designing potent α-glucosidase inhibitors for the treatment of type 2 diabetes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A new series of benzyl pyridinium-2,4-dioxochroman derivatives 7a-o was synthesized and evaluated as new anti-Alzheimer agents. Among the synthesized compounds, the compounds 7f and 7i exhibited the most potent anti-AChE and anti-BuChE activities, respectively. The kinetic study of the compound 7f revealed that this compound inhibited AChE in a mixed-type inhibition mode. Furthermore, the docking study of the compounds 7f and 7i showed that these compounds bound to both the catalytic site (CS) and peripheral anionic site (PAS) of AChE and BuChE, respectively. The compound 7f also exhibited a greater self-induced Aβ peptide aggregation inhibitory activity in compare to donepezil. Furthermore, the neuroprotective activity of this compound at 20 μM was comparable to that of the standard neuroprotective agent (quercetin)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We present a bidirectional neural interface with a 4-channel biopotential analog-to-digital converter (bioADC) and a 4-channel current-mode stimulator in 180 nm CMOS. The bioADC directly transduces microvolt biopotentials into a digital representation without a voltage-amplification stage. Each bioADC channel comprises a continuous-time first-order ∆Σ modulator with a chopper-stabilized OTA input and current feedback, followed by a second-order comb-filter decimator with programmable oversampling ratio. Each stimulator channel contains two independent digital-to-analog converters for anodic and cathodic current generation. A shared calibration circuit matches the amplitude of the anodic and cathodic currents for charge balancing. Powered from a 1.5 V supply, the analog and digital circuits in each recording channel draw on average [Formula: see text] and [Formula: see text] of supply current, respectively. The bioADCs achieve an SNR of [Formula: see text] and a SFDR of [Formula: see text] , for better than 9-b ENOB. Intracranial EEG recordings from an anesthetized rat are shown and compared to simultaneous recordings from a commercial reference system to validate performance in-vivo . Additionally, we demonstrate bidirectional operation by recording cardiac modulation induced through vagus nerve stimulation, and closed-loop control of cardiac rhythm. The micropower operation, direct digital readout, and integration of electrical stimulation circuits make this interface ideally suited for closed-loop neuromodulation applications.

A few kinematic synergies identified by principal component analysis (PCA) account for most of the variance in the coordinated joint rotations of the fingers and wrist used for a wide variety of hand movements. To examine the possibility that motor cortex might control the hand through such synergies, we collected simultaneous kinematic and neurophysiological data from monkeys performing a reach-to-grasp task. We used PCA, jPCA and isomap to extract kinematic synergies from 18 joint angles in the fingers and wrist and analyzed the relationships of both single-unit and multiunit spike recordings, as well as local field potentials (LFPs), to these synergies. For most spike recordings, the maximal absolute cross-correlations of firing rates were somewhat stronger with an individual joint angle than with any principal component (PC), any jPC or any isomap dimension. In decoding analyses, where spikes and LFP power in the 100- to 170-Hz band each provided better decoding than other LFP-based signals, the first PC was decoded as well as the best decoded joint angle. But the remaining PCs and jPCs were predicted with lower accuracy than individual joint angles. Although PCs, jPCs or isomap dimensions might provide a more parsimonious description of kinematics, our findings indicate that the kinematic synergies identified with these techniques are not represented in motor cortex more strongly than the original joint angles. We suggest that the motor cortex might act to sculpt the synergies generated by subcortical centers, superimposing an ability to individuate finger movements and adapt the hand to grasp a wide variety of objects., (Copyright © 2014 the American Physiological Society.)