The research was aimed to unravel the enzymatic potential of sequentially transformed new triazoles by chemically converting 4-methoxybenzoic acid via Fischer's esterification to 4-methoxybenzoate which underwent hydrazinolysis and the corresponding hydrazide (1) was cyclized with phenyl isothiocyanate (2) via 2-(4-methoxybenzoyl)-N-phenylhydrazinecarbothioamide (3); an intermediate to 5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazol-3-thiol (4). The electrophiles; alkyl halides 5(a-g) were further reacted with nucleophilic S-atom to attain a series of S-alkylated 5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazole-3-thiols 6(a-g). Characterization of synthesized compounds was accomplished by contemporary spectral techniques such as FT-IR, 1H-NMR, 13C-NMR and EI-MS. Excellent cholinesterase inhibitory potential was portrayed by 3-(n-heptylthio)-5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazole; 6g against AChE (IC50; 38.35±0.62μM) and BChE (IC50; 147.75±0.67μM) enzymes. Eserine (IC50; 0.04±0.01μM) was used as reference standard. Anti-proliferative activity results ascertained that derivative encompassing long straight chain substituted at S-atom of the moiety was the most potent with 4.96 % cell viability (6g) at 25μM and with 2.41% cell viability at 50μMamong library of synthesized derivatives. In silico analysis also substantiated the bioactivity statistics.
The 2-amino-5-(3/4-fluorostyryl)acetophenones were prepared and reacted with benzaldehyde derivatives to afford the corresponding 5-styryl-2-aminochalcone hybrids. The trans geometry of the styryl and α,β-unsaturated carbonyl arms, and the presence of NH…O intramolecular hydrogen bond were validated using 1H-NMR and X-ray data. The 2-amino-5-styrylacetophenones and their 5-styryl-2-aminochalcone derivatives were screened in vitro for their capability to inhibit α-glucosidase and/or α-amylase activities. Their antioxidant properties were evaluated in vitro through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) free radical scavenging assays. Kinetic studies of the most active derivatives from each series against α-glucosidase and/or α-amylase activities have been performed supported by molecular docking studies to determine plausible protein-ligand interactions on a molecular level. The key aspects of the pharmacokinetics of these compounds, i.e., absorption, distribution, metabolism, and excretion have also been simulated at theoretical level. The most active compounds from each series, namely, 2a and 3e, were evaluated for cytotoxicity against the normal monkey kidney cells (Vero cells) and the adenocarcinomic human epithelial (A549) cell line to establish their safety profile at least in vitro.
The current study describes the discovery of novel inhibitors of α-glucosidase and α-amylase enzymes. For that purpose, new hybrid analogs of N-hydrazinecarbothioamide substituted indazoles 4-18 were synthesized and fully characterized by EI-MS, FAB-MS, HRFAB-MS, 1H-, and 13C NMR spectroscopic techniques. Stereochemistry of the imine double bond was established by NOESY measurements. All derivatives 4-18 with their intermediates 1-3, were evaluated for in vitro α-glucosidase and α-amylase enzyme inhibition. It is worth mentioning that all synthetic compounds showed good inhibition potential in the range of 1.54 ± 0.02-4.89 ± 0.02 µM for α-glucosidase and for α-amylase 1.42 ± 0.04-4.5 ± 0.18 µM in comparison with the standard acarbose (IC50 value of 1.36 ± 0.01 µM). In silico studies were carried out to rationalize the mode of binding interaction of ligands with the active site of enzymes. Moreover, enzyme inhibitory kinetic characterization was also performed to understand the mechanism of enzyme inhibition.
In this study, we have investigated a series of indole-based compounds for their inhibitory study against pancreatic α-amylase and intestinal α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes appear to have an essential role as antidiabetic drugs. All analogous exhibited good to moderate α-amylase (IC50 = 3.80 to 47.50 μM), and α-glucosidase inhibitory interactions (IC50 = 3.10-52.20 μM) in comparison with standard acarbose (IC50 = 12.28 μM and 11.29 μM). The analogues 4, 11, 12, 15, 14 and 17 had good activity potential both for enzymes inhibitory interactions. Structure activity relationships were deliberated to propose the influence of substituents on the inhibitory potential of analogues. Docking studies revealed the interaction of more potential analogues and enzyme active site. Further, we studied their kinetic study of most active compounds showed that compounds 15, 14, 12, 17 and 11 are competitive for α-amylase and non- competitive for α-glucosidase.
Diabetes mellitus (DM) is a chronic disorder and has affected a large number of people worldwide. Insufficient insulin production causes an increase in blood glucose level that results in DM. To lower the blood glucose level, various drugs are employed that block the activity of the α-glucosidase enzyme, which is considered responsible for the breakdown of polysaccharides into monosaccharides leading to an increase in the intestinal blood glucose level. We have synthesized novel 2-(3-(benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides and have screened them for their in silico and in vitro α-glucosidase inhibition activity. The derivatives 11c, 12a, 12d, 12e, and 12g emerged as potent inhibitors of the α-glucosidase enzyme. These compounds exhibited good docking scores and excellent binding interactions with the selected residues (Asp203, Asp542, Asp327, His600, Arg526) during in silico screening. Similarly, these compounds also showed good in vitro α-glucosidase inhibitions with IC50 values of 30.65, 18.25, 20.76, 35.14, and 24.24 μM, respectively, which were better than the standard drug, acarbose (IC50 = 58.8 μM). Furthermore, a good agreement was observed between in silico and in vitro modes of study.
A series of 16 oxadiazole and triazolothiadiazole derivatives were designed, synthesized and evaluated as mushroom tyrosinase inhibitors. Five derivatives were found to display high inhibition on the tyrosinase activity ranging from 0.87 to 1.49 microM. Compound 5 exhibited highest tyrosinase inhibitory activity with an IC(50) value of 0.87+/-0.16 microM. The in silico protein-ligand docking using AUTODOCK 4.1 was successfully performed on compound 5 with significant binding energy value of -5.58 kcal/mol. The docking results also showed that the tyrosinase inhibition might be due to the metal chelating effect by the presence of thione functionality in compounds 1-5. Further studies revealed that the presence of hydrophobic group such as cycloamine derivatives played a major role in the inhibition. Piperazine moiety in compound 5 appeared to be involved in an extensive hydrophobic contact and a 2.9A hydrogen bonding with residue Glu 182 in the active site.
Surface phonon polariton (SPP) characteristics of In(0.04)Al(0.06)Ga(0.90)N/AlN/Al(2)O(3) heterostructure are investigated by means of p-polarized infrared (IR) attenuated total reflection spectroscopy. Two absorption dips corresponding to In(0.04)Al(0.06)Ga(0.90)N SPP modes are observed. In addition, two prominent dips and one relatively weak and broad dip corresponding to the Al(2)O(3) SPP mode, In(0.04)Al(0.06)Ga(0.90)N/Al(2)O(3) interface mode, and Al(2)O(3) bulk polariton mode, respectively, are clearly seen. No surface mode feature originating from the AlN layer is observed because it is too thin. Overall, the observations are in good agreement with the theoretical predictions.
Under the restriction of ecological and environmental factors, our requirements have improved for the development path of gymnasium construction. According to the previous way to carry out the development path of gymnasium construction will make our construction work encounter a lot of unnecessary troubles, so we can improve the success rate of the development path of gymnasium construction under the constraints of the ecological environment by carrying out relevant evasive operations according to the constraints of ecological environment. The topological path and path algorithm used to improve the efficiency of stadium construction and development path under the constraints of ecological environment, TEG algorithm, Q-TEG model, Q-TEG algorithm, Dtra algorithm, TraD algorithm, ResR algorithm, and Q-TED algorithm used in resource reservation plus time slot plus hosting bring the following advantages: (1) we use topological path and path algorithm to explore topological representation methods suitable for development path. The overview provides a theoretical basis for guidance, for forwarding technology scheduling mechanisms and multi-path forwarding mechanisms to provide higher flexibility. (2) We use the TEG algorithm of resource reservation plus time slot plus trusteeship, Q-TEG model, and Q-TEG algorithm under multi-model model can deal with the capacity and link of queue in each stadium construction development path well. It is more convenient to set the packet loss threshold for the propagation experiment tested in the simulation. Better help gymnasium construction and development path transmission is successful. (3) The use of the Dtra algorithm, TraD algorithm, ResR algorithm, and Q-TED algorithm in our stadium construction development path of a good deal of the transmission link structure between each node, so that the transmission efficiency between nodes becomes higher, making our stadium construction development path operation more efficient and convenient.
Immobilized Candida rugosa lipase was used for the synthesis of citronellyl laurate from citronellol and lauric acid. Screening of different types of support (Amberlite MB-1 and Celite) for immobilization of lipase and solvent (n-hexane, n-heptane, and iso-octane) and optimization of reaction conditions, such as catalyst loading, effect of substrates molar ratio and temperature, have been studied. The maximum enzyme activity was obtained at 310 K. The immobilized C. rugosa lipase onto Amberlite MB-1 support was found to be the best support with a conversion of 89% of citronellyl laurate ester in iso-octane compared to Celite 545. Deactivation of C. rugosa lipase at 313, 318 and 323 K were observed. Ordered bi bi mechanism with dead end complex of lauric acid was found to fit the initial rate data and the kinetic parameters were obtained by non-linear regression analysis.
Different dental post designs and materials affect the stability of restoration of a tooth. This study aimed to analyse and compare the stability of two shapes of dental posts (parallel-sided and tapered) made of five different materials (titanium, zirconia, carbon fibre and glass fibre) by investigating their stress transfer through the finite element (FE) method. Ten three-dimensional (3D) FE models of a maxillary central incisor restored with two different designs and five different materials were constructed. An oblique loading of 100 N was applied to each 3D model. Analyses along the centre of the post, the crown-cement/core and the post-cement/dentine interfaces were computed, and the means were calculated. One-way ANOVAs followed by post hoc tests were used to evaluate the effectiveness of the post materials and designs (p=0.05). For post designs, the tapered posts introduced significantly higher stress compared with the parallel-sided post (p<0.05), especially along the centre of the post. Of the materials, the highest level of stress was found for stainless steel, followed by zirconia, titanium, glass fibre and carbon fibre posts (p<0.05). The carbon and glass fibre posts reduced the stress distribution at the middle and apical part of the posts compared with the stainless steel, zirconia and titanium posts. The opposite results were observed at the crown-cement/core interface.
Seed dispersals deal with complex systems through which the data collected using advanced seed tracking facilities pose challenges to conventional approaches, such as empirical and deterministic models. The use of stochastic models in current seed dispersal studies is encouraged. This review describes three existing stochastic models: the birth-death process (BDP), a 2 dimensional ( 2
D
) symmetric random walks and a 2
D
intermittent walks. The three models possess Markovian property, which make them flexible for studying natural phenomena. Only a few of applications in ecology are found in seed dispersals. The review illustrates how the models are to be used in seed dispersals context. Using the nonlinear BDP, we formulate the individual-based models for two competing plant species while the cover time model is formulated by the symmetric and intermittent random walks. We also show that these three stochastic models can be formulated using the Gillespie algorithm. The full cover time obtained by the symmetric random walks can approximate the Gumbel distribution pattern as the other searching strategies do. We suggest that the applications of these models in seed dispersals may lead to understanding of many complex systems, such as the seed removal experiments and behaviour of foraging agents, among others.
Over the past few decades, Escherichia coli (E. coli) remains the most favorable host among the microbial cell factories for the production of soluble recombinant proteins. Recombinant protein production (RPP) via E. coli is optimized at the level of gene expression (expression level) and the process condition of fermentation (process level). Presently, the reported studies do not give a clear view on the selection of methods employed in the optimization of RPP. Here, we have reviewed various optimization methods and their preferences with respect to the factors at expression and process levels to achieve the optimal levels of soluble RPP. With a greater understanding of these optimization methods, we proposed a stepwise methodology linking the factors from both levels for optimizing the production of soluble recombinant protein in E. coli. The proposed methodology is further explained through five sets of examples demonstrating the optimization of RPP at both expression and process levels.Key Points• Stepwise methodology of optimizing recombinant protein production is proposed.• In silico tools can facilitate the optimization of gene- and protein-based factors.• Optimization of gene- and protein-based factors aids host-vector selection.• Statistical optimization is preferred for achieving optimal levels of process factors.
DNA computing, or more generally, molecular computing, is a recent development on computations using biological molecules, instead of the traditional silicon-chips. Some computational models which are based on different operations of DNA molecules have been developed by using the concept of formal language theory. The operations of DNA molecules inspire various types of formal language tools which include sticker systems, grammars and automata. Recently, the grammar counterparts of Watson-Crick automata known as Watson-Crick grammars which consist of regular, linear and context-free grammars, are defined as grammar models that generate double-stranded strings using the important feature of Watson-Crick complementarity rule. In this research, a new variant of static Watson-Crick linear grammar is introduced as an extension of static Watson-Crick regular grammar. A static Watson-Crick linear grammar is a grammar counterpart of sticker system that generates the double-stranded strings and uses rule as in linear grammar. The main result of the paper is to determine some computational properties of static Watson-Crick linear grammars. Next, the hierarchy between static Watson-Crick languages, Watson-Crick languages, Chomsky languages and families of languages generated by sticker systems are presented.
Thermophilic treatment of palm oil mill effluent (POME) was studied in a novel integrated anaerobic-aerobic bioreactor (IAAB). The IAAB was subjected to a program of steady-state operation over a range of organic loading rate (OLR)s, up to 30 g COD/L day in order to evaluate its treatment capacity. The thermophilic IAAB achieved high chemical oxygen demand (COD), biochemical oxygen demand (BOD) and total suspended solids (TSS) removal efficiencies of more than 99% for OLR up to 18.5 g COD/L day. High methane yield of 0.32 LCH(4) (STP)/g COD(removed) with compliance of the final treated effluent to the discharge limit were achieved. This is higher than that of the mesophilic system due to the higher maximum specific growth rate (μ(max)) of the thermophilic microorganisms. Besides, coupling the model of Grau second order model (anaerobic system) with the model of Monod (aerobic system) will completely define the IAAB system.
The performance of a compost biofilter inoculated with mixed microbial consortium was optimized for treating a gas-phase mixture of benzene and toluene. The biofilter was acclimated to these VOCs for a period of ∼18d. The effects of concentration and flow rate on the removal efficiency (RE) and elimination capacity (EC) were investigated by varying the inlet concentration of benzene (0.12-0.95g/m(3)), toluene (0.14-1.48g/m(3)) and gas-flow rate (0.024-0.072m(3)/h). At comparable loading rates, benzene removal in the mixture was reduced in the range of 6.6-41% in comparison with the individual benzene degradation. Toluene removal in mixture was even more affected as observed from the reductions in REs, ranging from 18.4% to 76%. The results were statistically interpreted by performing an analysis of variance (ANOVA) to elucidate the main and interaction effects.
This research focuses on creating a standardized nasal cavity model of adult Malaysian females. The methodology implemented in this research is a new approach compared to other methods used by previous researchers. This study involves 26 females who represent the test subjects for this preliminary study. Computational fluid dynamic (CFD) analysis was carried out to better understand the characteristics of the standardized model and to compare it to the available standardized Caucasian model. This comparison includes cross-sectional areas for both half-models as well as velocity contours along the nasal cavities. The Malaysian female standardized model is larger in cross-sectional area compared to the standardized Caucasian model thus leading to lower average velocity magnitudes. The standardized model was further evaluated with four more Malaysian female test subjects based on its cross-sectional areas and average velocity magnitudes along the nasal cavities. This evaluation shows that the generated model represents an averaged and standardized model of adult Malaysian females.
In this paper, we propose two different control strategies for the position control of the ball of the ball and beam system (BBS). The first control strategy uses the proportional integral derivative-second derivative with a proportional integrator PIDD2-PI. The second control strategy uses the tilt integral derivative with filter (TID-F). The designed controllers employ two distinct metaheuristic computation techniques: grey wolf optimization (GWO) and whale optimization algorithm (WOA) for the parameter tuning. We evaluated the dynamic and steady-state performance of the proposed control strategies using four performance indices. In addition, to analyze the robustness of proposed control strategies, a comprehensive comparison has been performed with a variety of controllers, including tilt integral-derivative (TID), fractional order proportional integral derivative (FOPID), integral-proportional derivative (I-PD), proportional integral-derivative (PI-D), and proportional integral proportional derivative (PI-PD). By comparing different test cases, including the variation in the parameters of the BBS with disturbance, we examine step response, set point tracking, disturbance rejection analysis, and robustness of proposed control strategies. The comprehensive comparison of results shows that WOA-PIDD2-PI-ISE and GWO-TID-F- ISE perform superior. Moreover, the proposed control strategies yield oscillation-free, stable, and quick response, which confirms the robustness of the proposed control strategies to the disturbance, parameter variation of BBS, and tracking performance. The practical implementation of the proposed controllers can be in the field of under actuated mechanical systems (UMS), robotics and industrial automation. The proposed control strategies are successfully tested in MATLAB simulation.
This paper proposes non-Gaussian models for parametric spectral estimation with application to event-related desynchronization (ERD) estimation of nonstationary EEG. Existing approaches for time-varying spectral estimation use time-varying autoregressive (TVAR) state-space models with Gaussian state noise. The parameter estimation is solved by a conventional Kalman filtering. This study uses non-Gaussian state noise to model autoregressive (AR) parameter variation with estimation by a Monte Carlo particle filter (PF). Use of non-Gaussian noise such as heavy-tailed distribution is motivated by its ability to track abrupt and smooth AR parameter changes, which are inadequately modeled by Gaussian models. Thus, more accurate spectral estimates and better ERD tracking can be obtained. This study further proposes a non-Gaussian state space formulation of time-varying autoregressive moving average (TVARMA) models to improve the spectral estimation. Simulation on TVAR process with abrupt parameter variation shows superior tracking performance of non-Gaussian models. Evaluation on motor-imagery EEG data shows that the non-Gaussian models provide more accurate detection of abrupt changes in alpha rhythm ERD. Among the proposed non-Gaussian models, TVARMA shows better spectral representations while maintaining reasonable good ERD tracking performance.
This paper proposes the African Buffalo Optimization (ABO) which is a new metaheuristic algorithm that is derived from careful observation of the African buffalos, a species of wild cows, in the African forests and savannahs. This animal displays uncommon intelligence, strategic organizational skills, and exceptional navigational ingenuity in its traversal of the African landscape in search for food. The African Buffalo Optimization builds a mathematical model from the behavior of this animal and uses the model to solve 33 benchmark symmetric Traveling Salesman's Problem and six difficult asymmetric instances from the TSPLIB. This study shows that buffalos are able to ensure excellent exploration and exploitation of the search space through regular communication, cooperation, and good memory of its previous personal exploits as well as tapping from the herd's collective exploits. The results obtained by using the ABO to solve these TSP cases were benchmarked against the results obtained by using other popular algorithms. The results obtained using the African Buffalo Optimization algorithm are very competitive.
Two-point four step direct implicit block method is presented by applying the simple form of Adams- Moulton method for solving directly the general third order ordinary differential equations (ODEs) using variable step size. This method is implemented to get the solutions of initial value problems (IVPs) at two points simultaneously in a block using four backward steps. The numerical results showed that the performance of the developed method is better in terms of maximum error at all tested tolerances and lesser total number of steps as the tolerances getting smaller compared to the existence direct method.