Earticle

The p21-activated kinase-1 (PAK1) has emerged as a potential target for anticancer therapy. It is overexpressed in ovarian, breast and bladder cancers. This suggests that PAK1 may contribute to tumorigenesis. 4-azaindole derivatives are reported as potent PAK1 inhibitors. The present work deals with the molecular docking studies of 4-azaindoles with PAK1. Probable binding mode of these inhibitors has been identified by molecular modeling. Docking results indicated that hydrogen bonding interactions with Glu345 and Leu347 are responsible for governing inhibitor potency of the compounds. Additionally, Val284, Val328, Met344 and Leu396 were found to be accountable for hydrophobic interactions inside the active site of PAK1

Collagen plays a vital role in the maintenance of structure and function of a human body. It has been widely applied in various fields including biomedical, cosmeceutical, food, pharmaceutical and tissue engineering. In the present study, the docking behaviour of type I collagen with 15 different ligands namely hydroxymethylfurfural, methylglyoxal, methylsyringate, O-methoxyacetophenone, 3-phenyllactic acid, 4- hydroxybenzoic acid, kojic acid, lumichrome, galangin, artoindonesianin F, caffeic acid, 4-coumaric acid, origanol A, thymoquinone and quercetin was evaluated along with their putative binding sites using Discovery Studio Version 3.1. Docking studies and binding free energy calculations revealed that origanol A has maximum interaction energy (-40.48 kcal/mol) and quercetin with the least interaction energy (-15.44 kcal/mol) as compared to the other investigated ligands. Three ligands which are galangin, methylsyringate and origanol A were shown to interact with Asp21 amino acid residue of chain B (type I collagen). Therefore, it is strongly suggested that the outcomes from the present study might provide new insight in understanding these 15 ligands as potential type I collagen modulators for the prevention of collagen associate disorders.

Rap1 is a key regulator of cell adhesion and migration. Although increasing evidence indicates that the Rap1 signaling pathway is involved in the process of bone remodeling, the mechanism by which Rap1 regulates osteoblastic differentiation and cell adhesion remains unknown. Here, we investigated the morphological characteristics and osteoblastic differentiation of cells expressing constitutively activated form of Rap1A (Rap1ACA) or Rap1 GTPase activating protein Rap1GAP and found that activated Rap1 induces osteoblastic differentiation and cell adhesion as well as cell spreading. When osteoblastic differentiation was induced, Rap1ACA cells showed considerably higher levels of calcium deposits than the wild-type and Rap1GAP-overexpressing cells did. Rap1ACA cells showed increased spreading and size, as well as strong cell adhesion and significantly decreased growth rates. F-actin staining using phalloidin revealed several thin thread-like filopodia around the protrusions in Rap1ACA cells, which possibly contribute to the increased cell adhesion.

CXC chemokine receptor 2 (CXCR2) is a prominent chemokine receptor on neutrophils and it regulates the neutrophilic inflammation in the lung diseases. CXCR2 antagonist may reduce the neutrophil chemotaxis and alter the inflammatory response. Hence, in the present study, ligand based Comparative Molecular Similar Indices Analysis (CoMSIA) was performed on a series of CXCR2 antagonist named pyrimidine-5- carbonitrile-6-alkyl derivatives. The optimum CoMSIA model was obtained with statistically significant cross-validated coefficients (q2) of 0.582 and conventional coefficients (r2) of 0.987 with steric, electrostatic, hydrophobic, donor and acceptor fields. The contour maps suggest the important structural modifications and this study can be used to guide the development of potent CXCR2 antagonist.

Urotensin-2 receptor (UTS2R) is the most potent vasoconstrictor and plays a major role in the pathophysiology of various cardiovascular diseases and becomes a potential target for human pharmacotherapy. The crystal structure of Urotension-2 receptor has not yet been resolved. Hence, in the current study homology modelling of UTS2R was done utilizing the crystal structure of human delta opioid receptor as the template. Since the template has low sequence identity, we have incorporated both comparative modelling and threading approach to generate the three dimensional structure. 10 models were generated and validated. The reported models can be used to characterize the critical amino acid residues in the binding site of UTS2R.

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organsincluding the liver, gut, lung, kidney, heart, brain and plasma. It is involved in gout pathogenesis. In this study, we have performed Comparative Molecular Field Analysis (CoMSIA) on a series of 2-(indol- 5-yl) thiazole derivatives as xanthine oxidase (XO) inhibitors to identify the structural variations with their inhibitory activities. Ligand based CoMSIA models were generated based on atom-by- atom matching alignment. In atom-by-atom matching, the bioactive conformation of highly active molecule 11 was generated using systematic search. Compounds were aligned using the bioactive conformation and it is used for model generation. Different CoMSIA models were generated using different alignments and the best model yielded across- validated q2 of 0.698 with five components and non-cross-validated correlation coefficient (r2) of 0.992 with Fisher value as 236.431, and an estimated standard error of 0.068. The predictive ability of the best CoMSIA models was found to be r2 pred 0.653. The study revealed the important structural features required for the biological activity of the inhibitors and could provide useful for the designing of novel and potent drugs for the inhibition of Xanthine oxidase.

In this paper, we established ZIGBEE home network and combined smart-grid and u-Healthcare system. We assisted for amount of electricity management of household by interlocking home devices of wireless sensor, PLC modem, DCU and realized smart grid and u-Healthcare at the same time by verifying body heat, pulse, blood pressure change and proceeded living body signal by using SVM algorithm and variety of ZIGBEE network channel and enabled it to check real-time through IHD which is developed by user interface. In addition, we minimized the rate of energy consumption of each sensor node when living body signal is processed and realized Query Processor which is able to optimize accuracy and speed of query. We were able to check the result that is accuracy of classification 0.848 which is less accounting for average 17.9% of storage more than the real input data by using Mjoin, multiple query process and SVM algorithm.

The basic goal of software development is to produce high quality software at low cost. Therefore, when to stop software testing and release the software product is a significant point in the software development. The software cost model is an effective tool used to help software developers control costs and determine the release time. In this paper, we discuss the cost model to apply all 6 models with consideration of time to remove errors, cost of removing each error and risk cost due to software failure. We show the impact of cost coefficients and parameter values on the expected total cost by changing the values and comparing the optimal release times.

When the linear correlation of the quality variables are considerably high, multivariate control charts may be a more effective way than univariate charts which operate quality variables and process parameters individually. Performances and efficiencies of the multivariate control charts under multivariate normal process has been considered. Some numerical results are presented under small scale of the shifts in the process to see the improvement of the efficiency of EWMA chart and CUSUM chart, which use past quality information, comparing to Shewart chart, which do not use quality information. We can know that the decision of the optimum value of the smoothing constant in EWMA structure or the reference value in CUSUM structure are very important whether we adopt combine-accumulate technique or accumulatecombine technique under the given condition of process.