Computerized Protein Modeling and Molecular Docking Analysis of Human Proto Oncogene Tyrosine Protein Kinase YES for Discovery of Novel Lead Molecules

Human proto-oncogene tyrosine-protein kinase YES (YES) is a non receptor kinase belongs to Src family. This gene lies in close proximity to thymidylate synthase gene on chromosome 18, and a corresponding pseudogene has been found on chromosome 22. In hepatocellular carcinoma and colorectal carcinoma elevated human YES activity was observed. Inhibitors of human YES reported till date are in clinical trials and associated with several side effects. The present study was mainly aimed in homology modeling of human YES and discovery of novel lead molecules that inhibit YES kinase more efficiently with fewer side effects. Virtual screening and docking techniques were applied to identify novel lead molecule of YES kinase. As there was no reported human YES crystal structural data, the three dimensional structure of human YES was constructed based on template structure (PDB ID: 2H8H) obtained through homology search using MODELLER 9V7. The model was refined, energy minimized and assessed through PROCHECK. Active site residues of human YES were identified from the homology model in complex with template ligand AZD0530 and were further confirmed using CASTp. Five published inhibitors of YES family (Dasatinib, Bosutinib, SU6656, AZD0530 and CGP77675) were identified through literature search. High throughput virtual screening method at Ligand.Info was applied for these five inhibitors to establish a library of 1932 structural analogs. LigPrep was used to generate possible conformations of each ligand molecules from structural analog library. The ligand duplicates conformers, ligands having reactive functional group and poor ADME properties were rejected from the prepared dataset. Glide 5.5 was used to generate a grid box by picking the active site residues of human YES protein. Through sequential applications of stringent mode glide docking procedures from Glide HTVS to SP to XP respectively, 13 potential inhibitors were proposed. The docking complexes of each inhibitor with human YES protein were analyzed and lead ‘1’ molecule was identified to have higher binding affinity to human YES protein (XP Gscore: -12.07 Kcal/mol) compared to existing published inhibitors and other 12 lead molecules. The lead ‘1’ - human YES docking complex was highly stabilized through hydrogen bond network with amino acid residues Thr348, Asp358, Asp414 and Phe415. Moreover, from the results obtained we could decipher that lead ‘1’ molecule can be raised into potential inhibitors after binding assays, substantiated experimental investigations and passing several phases of clinical trials

Efficient Digital System Management using IEEE 1451.0 Enabled Control Architecture

The IEEE and National Institute of Standards and Technology have formulated an open universal standard called IEEE 1451 for ‘Smart Transducer Interface’ with digital systems. The objectives of this paper is to propose IEEE 21450 enabled control architectures for efficient management of power system with embedded system parameters as electronic documentation. The control architecture accommodates appropriate number of transducer interface module along with transducer electronic data sheet, which enables active calibration, adaptive tuning and failure proof operation of system management

A Design Thinking Based Study to Assess the Effectiveness of Computer Assisted Teaching on Knowledge and Attitude Regarding Organ Donation Among Non-Health Professional Students at Selected College in Coimbatore

Design thinking is generally defined as an analytic and creative process that engages a person in opportunities to experiment, create and prototype models, gather feedback, and redesign. Design Thinking Approach is adopted to carry out the research to correlate the knowledge and attitude among non-health professional students. Objectives: (a) To assess the pre-test and post-test level of knowledge and attitude regarding organ donation among non-health professional students. (b) To assess the effectiveness of computer assisted teaching on knowledge and attitude regarding organ donation among non-health professional students. (c)To find out the association between post-test level of knowledge and attitude regarding organ donation and the selected demographic variables among non-health professional students. (d)To assess the correlation between knowledge and attitude regarding organ donation. Methodology: The research design used was a pre-experimental one group pretest and posttest design. The samples for the study were chosen by using convenient sampling technique, The sample size was 50. Results: Karl Pearson correlation test was used. It reveals that there is effectiveness present in the group. Conclusion: Organ donation is a huge public health concern worldwide. The biggest advantage to organ donation is, it saves lives that would otherwise be lost. A single organ donor has the chance to save the lives or improve the quality of life for several people. So, the organ donation should be encouraged and the people should be motivated to donate their organs by conducting periodical educational programmed regarding organ donation

Optimizing Cervical Cancer Classification with SVM and Improved Genetic Algorithm on Pap Smear Images

This study presents an approach to optimize cervical cancer classification using Support Vector Machines (SVM) and an improved Genetic Algorithm (GA) on Pap smear images. The proposed methodology involves preprocessing the images, extracting relevant features, and employing a genetic algorithm for feature selection. An SVM classifier is trained using the selected features and optimized using the genetic algorithm. The performance of the optimized model is evaluated, demonstrating improved accuracy and efficiency in cervical cancer classification. The findings hold the potential for assisting healthcare professionals in early cervical cancer diagnosis based on Pap smear images

Inhibition of dipeptidyl peptidase IV and xanthine oxidase by amino acids and dipeptides

peer-reviewedXanthine oxidase (XO) and dipeptidyl peptidase IV (DPP-IV) inhibition by amino acids and dipeptides was studied. Trp and Trp-containing dipeptides (Arg-Trp, Trp-Val, Val-Trp, Lys-Trp and Ile-Trp) inhibited XO. Three amino acids (Met, Leu and Trp) and eight dipeptides (Phe-Leu, Trp-Val, His-Leu, Glu-Lys, Ala-Leu, Val-Ala, Ser-Leu and Gly-Leu) inhibited DPP-IV. Trp and Trp-Val were multifunctional inhibitors of XO and DPP-IV. Lineweaver and Burk analysis showed that Trp was a non-competitive inhibitor of XO and a competitive inhibitor of DPP-IV. Molecular docking with Autodock Vina was used to better understand the interaction of the peptides with the active site of the enzyme. Because of the non-competitive inhibition observed, docking of Trp-Val to the secondary binding sites of XO and DPP-IV is required. Trp-Val was predicted to be intestinally neutral (between 25% and 75% peptide remaining after 60 min simulated intestinal digestion). These results are of significance for the reduction of reactive oxygen species (ROS) and the increase of the half-life of incretins by food-derived peptides. (C) 2013 Elsevier Ltd. All rights reserved.ACCEPTEDpeer-reviewe

Zinc intake, status and indices of cognitive function in adults and children: a systematic review and meta-analysis

In developing countries, deficiencies of micronutrients are thought to have a major impact on child development; however, a consensus on the specific relationship between dietary zinc intake and cognitive function remains elusive. The aim of this systematic review was to examine the relationship between zinc intake, status and indices of cognitive function in children and adults. A systematic literature search was conducted using EMBASE, MEDLINE and Cochrane Library databases from inception to March 2014. Included studies were those that supplied zinc as supplements or measured dietary zinc intake. A meta-analysis of the extracted data was performed where sufficient data were available. Of all of the potentially relevant papers, 18 studies met the inclusion criteria, 12 of which were randomised controlled trials (RCTs; 11 in children and 1 in adults) and 6 were observational studies (2 in children and 4 in adults). Nine of the 18 studies reported a positive association between zinc intake or status with one or more measure of cognitive function. Meta-analysis of data from the adult’s studies was not possible because of limited number of studies. A meta-analysis of data from the six RCTs conducted in children revealed that there was no significant overall effect of zinc intake on any indices of cognitive function: intelligence, standard mean difference of <0.001 (95% confidence interval (CI) –0.12, 0.13) P=0.95; executive function, standard mean difference of 0.08 (95% CI, –0.06, 022) P=0.26; and motor skills standard mean difference of 0.11 (95% CI –0.17, 0.39) P=0.43. Heterogeneity in the study designs was a major limitation, hence only a small number (n=6) of studies could be included in the meta-analyses. Meta-analysis failed to show a significant effect of zinc supplementation on cognitive functioning in children though, taken as a whole, there were some small indicators of improvement on aspects of executive function and motor development following supplementation but high-quality RCTs are necessary to investigate this further