Discovery of Aporphine Analogues as Potential Antiplatelet and Antioxidant Agents: Design,Synthesis, Structure–Activity Relationships,Biological Evaluations,and in silico Molecular Docking Studies

To explore the potential of aporphine alkaloids, a novel series of functionalized aporphine analogues with alkoxy (OCH₃, OC₂H₅, OC₃H₇) functional groups at C1/C2 of ring A and an acyl (COCH₃ and COPh) or phenylsulfonyl (SO₂Ph and SO₂C₆H₄‐3‐CH₃) functionality at the N6 position of ring B of the aporphine scaffold were synthesized and evaluated for their arachidonic acid (AA)‐induced antiplatelet aggregation inhibitory activity and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) free‐radical‐scavenging antioxidant activity, with acetylsalicylic acid and ascorbic acid as standard references, respectively. The preliminary structure–activity relationship related to AA‐induced platelet aggregation inhibitory activity results showed that the aporphine analogues 1‐[1,2,9,10‐tetramethoxy‐6a,7‐dihydro‐4H‐dibenzo[de,g]quinolin‐6(5H)‐yl]ethanone and 1‐[2‐(benzyloxy)‐1,9,10‐trimethoxy‐6a,7‐dihydro‐4H‐dibenzo[de,g]quinolin‐6(5H)‐yl]ethanone to be the best compounds of the series. Moreover, the DPPH free‐radical‐scavenging antioxidant activity results demonstrated that the aporphine analogues 1,2,9,10‐tetramethoxy‐6‐(methylsulfonyl)‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline, 2‐ethoxy‐1,9,10‐trimethoxy‐6‐(methylsulfonyl)‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline, 1‐ethoxy‐2,9,10‐trimethoxy‐6‐(methylsulfonyl)‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline, 2,9,10‐trimethoxy‐6‐(methylsulfonyl)‐1‐propoxy‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline, and 1‐(benzyloxy)‐2,9,10‐trimethoxy‐6‐(methylsulfonyl)‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline were the best compounds of the series. Moreover, in silico molecular docking simulation studies of the active analogues were also performed.     

A Simple D 2-Sampling Based PTAS for k-Means and Other Clustering Problems

Given a set of points \(P \subset\mathbb{R}^{d}\) , the k-means clustering problem is to find a set of k centers \(C = \{ c_{1},\ldots,c_{k}\}, c_{i} \in\mathbb{R}^{d}\) , such that the objective function ∑ _x∈P e(x,C)², where e(x,C) denotes the Euclidean distance between x and the closest center in C, is minimized. This is one of the most prominent objective functions that has been studied with respect to clustering. D ²-sampling (Arthur and Vassilvitskii, Proceedings of the Eighteenth Annual ACM-SIAM Symposium on Discrete Algorithms, SODA’07, pp. 1027–1035, SIAM, Philadelphia, 2007) is a simple non-uniform sampling technique for choosing points from a set of points. It works as follows: given a set of points \(P \subset\mathbb{R}^{d}\) , the first point is chosen uniformly at random from P. Subsequently, a point from P is chosen as the next sample with probability proportional to the square of the distance of this point to the nearest previously sampled point. D ²-sampling has been shown to have nice properties with respect to the k-means clustering problem. Arthur and Vassilvitskii (Proceedings of the Eighteenth Annual ACM-SIAM Symposium on Discrete Algorithms, SODA’07, pp. 1027–1035, SIAM, Philadelphia, 2007) show that k points chosen as centers from P using D ²-sampling give an O(logk) approximation in expectation. Ailon et al. (NIPS, pp. 10–18, 2009) and Aggarwal et al. (Approximation, Randomization, and Combinatorial Optimization. Algorithms and Techniques, pp. 15–28, Springer, Berlin, 2009) extended results of Arthur and Vassilvitskii (Proceedings of the Eighteenth Annual ACM-SIAM Symposium on Discrete Algorithms, SODA’07, pp. 1027–1035, SIAM, Philadelphia, 2007) to show that O(k) points chosen as centers using D ²-sampling give an O(1) approximation to the k-means objective function with high probability. In this paper, we further demonstrate the power of D ²-sampling by giving a simple randomized (1+?)-approximation algorithm that uses the D ²-sampling in its core.     

Forensic image analysis using inconsistent noise pattern

With the advancement of image acquisition devices and social networking services, a huge volume of image data is generated. Using different image and video processing applications, these image data are manipulated, and thus, original images get tampered. These tampered images are the prime source of spreading fake news, defaming the personalities and in some cases (when used as evidence) misleading the law bodies. Hence before relying totally on the image data, the authenticity of the image must be verified. Works of the literature are reported for the verification of the authenticity of an image based on noise inconsistency. However, these works suffer from limitations of confusion between edges and noise, post-processing operation for localization and need of prior knowledge about an image. To handle these limitations, a noise inconsistency-based technique has been presented here to detect and localize a false region in an image. This work consists of three major steps of pre-processing, noise estimation and post-processing. For the experimental purpose two, publicly available datasets are used. The result is discussed in terms of precision, recall, accuracy and f1-score on the pixel level. The result of the presented work is also compared with the recent state-of-the-art techniques. The average accuracy of the proposed work on datasets is 91.70%, which is highest among state-of-the-art techniques.

     

Distortion in a 2-D scan pattern generated by combining a plane mirror and a regular polygon scanner

The distortion in a 2-D scan pattern generated by a system of a plane mirror and a regular polygon scanner was investigated using the matrix formulation of reflection by plane mirrors. A particular configuration involving the two scan elements was identified which does not introduce any distortion in its 2-D scan pattern.     

An indigenously developed electronic control system for Langmuir-Blodgett film deposition set-up

An indigenous and simple electronic control system for Langmuir-Blodgett (LB) film deposition set-up has been developed. This set-up consists of a microstepping circuit to drive the stepper motors with precision and smooth motion, essential for controlled movement of the barriers and substrate in the LB set-up. Linear variable differential transformer (LVDT)-based displacement measuring device has been developed and used to measure the surface pressure of the monolayer material spread on the water surface. A control program is written which incorporates all operational modes required to drive the set-up and to acquire the datain situ using a set of user-friendly commands. This control set-up has been successfully used to plot the pressure-area isotherm of various amphiphilic compounds such as ferric stearate, zinc arachidate etc. and for deposition of ordered LB films of ferric stearate.     

Location prediction algorithm for a nonlinear vehicular movement in VANET using extended Kalman filter

Vehicular ad-hoc network (VANET) is an essential component of the intelligent transportation system, that facilitates the road transportation by giving a prior alert on traffic condition, collision detection warning, automatic parking and cruise control using vehicle to vehicle (V2V) and vehicle to roadside unit (V2R) communication. The accuracy of location prediction of the vehicle is a prime concern in VANET which enhances the application performance such as automatic parking, cooperative driving, routing etc. to give some examples. Generally, in a developed country, vehicle speed varies between 0 and 60 km/h in a city due to traffic rules, driving skills and traffic density. Likewise, the movement of the vehicle with steady speed is highly impractical. Subsequently, the relationship between time and speed to reach the destination is nonlinear. With reference to the previous work on location prediction in VANET, nonlinear movement of the vehicle was not considered. Thus, a location prediction algorithm should be designed by considering nonlinear movement. This paper proposes a location prediction algorithm for a nonlinear vehicular movement using extended Kalman filter (EKF). EKF is more appropriate contrasted with the Kalman filter (KF), as it is designed to work with the nonlinear system. The proposed prediction algorithm performance is measured with the real and model based mobility traces for the city and highway scenarios. Also, EKF based prediction performance is compared with KF based prediction on average Euclidean distance error (AEDE), distance error (DE), root mean square error (RMSE) and velocity error (VE).     

Flow of power law liquids through particle assemblages at intermediate reynolds numbers

The complete equations of motion and continuity have been solved numerically using the finite element method for the flow of power law liquids through assemblages of rigid spherical particles. The inter-particle interactions have been simulated using the free surface cell model. Extensive results on drag coefficients have been obtained under a wide range of physical and operating conditions (0.9999 ≥ 0.3), 1 ≥ n ≥ 0.4 and 20 ≥ Re ≥ 1. The observed dependence of drag coefficient on voidage and non-Newtonian flow behaviour index have been explained qualitatively with the aid of order of magnitude considerations. Finally, the theoretical predictions have been validated using suitable experimental data available in the literature.     

Efficient in vitro repair of 7-hydro-8-oxodeoxyguanosine by human cell extracts: involvement of multiple pathways

To investigate the repair of oxidative damage in DNA, we have established an in vitro assay utilizing human lymphoblastoid whole cell extracts and plasmid DNA damaged by exposure to methylene blue and visible light. This treatment has been shown to produce predominantly 7-hydro-8-oxodeoxyguanosine (8-oxodG) in double-stranded DNA at low levels of modification. DNA containing 1. 6 lesions per plasmid is substrate for efficient repair synthesis by cell extracts. The incorporation of dGMP is 2.7 +/- 0.5 times greater than the incorporation of dCMP, indicating an average repair patch of 3-4 nucleotides. Damage-specific nicking occurs within 15 min, while resynthesis is slower. The incorporation of dGMP increases linearly, while the incorporation of dCMP exhibits a distinct lag. Extracts from xeroderma pigmentosum (XP) complementation groups A and B exhibit 25 and 40%, respectively, of the incorporation of dCMP compared with normal extracts, but extracts from an XP-D cell line exhibit twice the activity. These data suggest that the efficient repair of 8-oxodG lesions observed in human cell extracts involves more than one pathway of base excision repair.     

Design and implementation of a secure multi-agent marketplace

A multi-agent marketplace, MAGNET (Multi-AGent Negotiation Testbed), is a promising solution for conducting online combinatorial auctions. The trust model of MAGNET is somewhat different from other on-line auction systems since the marketplace, which mediates all communications between agents, acts as a partially trusted third party. We identify the security vulnerabilities of MAGNET and present a solution that overcomes these weaknesses. Our solution makes use of three different existing technologies with standard cryptographic techniques: a publish/subscribe system to provide simple and general messaging, time-release cryptography to provide guaranteed non-disclosure of the bids, and anonymous communication to hide the identity of the bidders until the end of the auction. Using these technologies, we successfully minimize the trust on the market as well as increase the security of the whole system. The protocol that we have developed can be adapted for use by other agent-based auction systems, that use a third party to mediate transactions.