Effect of OATP-binding on the prediction of biliary excretion

1.Biliary excretion of compounds is dependant on several transporter proteins for the active uptake of compounds from the blood into the hepatocytes. Organic anion-transporting polypeptides (OATPs) are some of the most abundant transporter proteins in the sinusoidal membrane and have been shown to have substrate specificity similar to the structural characteristics of cholephilic compounds. 2.In this study, we sought to use measures of OATP binding as predictors of biliary excretion in conjunction with molecular descriptors in a quantitative structure-activity relationship (QSAR) study. Percentage inhibitions of three subtypes of OATPs were used as surrogate indicators of OATP substrates. Several statistical modelling techniques were incorporated including classification and regression trees, boosted trees, random forest and multivariate adaptive regression splines (MARS) in order to first develop QSARs for the prediction of OATP inhibition of compounds. The predicted OATP percentage inhibition using selected models were then used as features of the QSAR models for the prediction of biliary excretion of compounds in rat. 3.The results indicated that incorporation of predicted OATP inhibition improves accuracy of biliary excretion models. The best result was obtained from a simple regression tree that used predicted OATP1B1 percentage inhibition at the root node of the tree

Development of models for predicting Torsade de Pointes cardiac arrhythmias using perceptron neural networks

Blockage of some ion channels and in particular, the hERG cardiac potassium channel delays cardiac repolarization and can induce arrhythmia. In some cases it leads to a potentially life-threatening arrhythmia known as Torsade de Pointes (TdP). Therefore recognizing drugs with TdP risk is essential. Candidate drugs that are determined not to cause cardiac ion channel blockage are more likely to pass successfully through clinical phases II and III trials (and preclinical work) and not be withdrawn even later from the marketplace due to cardiotoxic effects. The objective of the present study is to develop an SAR model that can be used as an early screen for torsadogenic (causing TdP arrhythmias) potential in drug candidates. The method is performed using descriptors comprised of atomic NMR chemical shifts and corresponding interatomic distances which are combined into a 3D abstract space matrix. The method is called 3D-SDAR (3 dimensional spectral data-activity relationship) and can be interrogated to identify molecular features responsible for the activity, which can in turn yield simplified hERG toxicophores. A dataset of 55 hERG potassium channel inhibitors collected from Kramer et al. consisting of 32 drugs with TdP risk and 23 with no TdP risk was used for training the 3D-SDAR model.An ANN model with multilayer perceptron was used to define collinearities among the independent 3D-SDAR features. A composite model from 200 random iterations with 25% of the molecules in each case yielded the following figures of merit: training, 99.2 %; internal test sets, 66.7%; external (blind validation) test set, 68.4%. In the external test set, 70.3% of positive TdP drugs were correctly predicted. Moreover, toxicophores were generated from TdP drugs. A 3D-SDAR was successfully used to build a predictive model for drug-induced torsadogenic and non-torsadogenic drugs.Comment: Accepted for publication in BMC Bioinformatics (Springer) July 201

Study the effectiveness of cognitive-behavioral intervention on the quality of life, job satisfaction, and nurses' organizational performance

Background and aims: Quality of life is an important concept in how to play the role of nursing care. In addition, the performance and job satisfaction of nurses as components of the effective health systems to provide better services to clients are in a particular significance. The aim of this study was to investigate the effectiveness of cognitive-behavioral intervention on the quality of life, organizational performance, and job satisfaction of nurses. Methods: The current study is a quasi-experimental research with pre-test and post-test with control group. The first experimental group received cognitive-behavioral training and the second group without training is studied. Both groups response the pre-test and post-test at the same time. The population studied in this research study comprised nurses who were working in Tabriz hospitals in the second half 2016. The primary samples in this study were 205 nurses who were determined in convenience after the implementation of a pilot study. 40 nurses first with lower scores on tests were selected and divided into two experimental and control groups (each 20 people). Tools of the research were questionnaires of The World Health Organization Quality of Life, Paterson Organizational Performance, Berry Field and Ruth job satisfaction questionnaire and Content of the Sessions of Cognitive Therapy Group. Data were analyzed using SPSS software and multivariate covariance analysis test. Results: The results of the research showed that the education of cognitive-behavioral intervention on the variables of quality of life, job satisfaction and organizational performance nurses have a significant positive effect (P<0.05). Conclusion: Regarding the effectiveness of cognitive-behavioral intervention training, it is recommended interventional programs for nurses be used in order to improve quality of life and increase job satisfaction and their organizational performance

Comparing the effect of lecture and rescue training methods with the war maneuvers on the public aid preparedness in the personnel of the navy's military barracks

Aims: Simulation is one of active learning techniques that learners are encouraged to acquire skills and knowledge. This study aimed to determine comparing the effect of lecture and rescue training methods with the war maneuvers on the public aid preparedness in the personnel of the navy's military barracks in 2014. At first, Kolmogorov Smirnov test was used to detect normal data, and independent t-test was performed for normal data, and Mann-Whitney and Wilcoxon tests were used for non-normal data to examine the proposal. Methods: This research was a quasi-experimental study. 132 military personnel were selected by stratified sampling and divided identically in two groups into lectures and training along with combat maneuvers. Multiple-choice test made by researcher was used to determine the level of knowledge before and after the intervention. After gathering information and bringing them into the SPSS software, version 19, data were analyzed using descriptive statistics (Mean and Standard deviation) and inferential statistics. Results: The mean score of the subjects before and after intervention was obtained 12.81 ± 3 and 20.59 ± 3.34, respectively. The results of the comparison between the two groups before and after intervention showed that there were significant differences both lectures and practical groups (P <0.001). Moreover, both groups after intervention indicated an increased score, but the score of operation group increased more than lecture group. Conclusion: The practical training of military forces with war maneuvers has more impact than lecture training method on the amount of preparation and rescue. It is recommended to be used practical training method of military forces along with war maneuvers for military preparedness

Macrophage migration inhibitory factor -173 G/C polymorphism is associated with an increased risk of pulmonary tuberculosis in Zahedan, Southeast Iran

Macrophage migration inhibitory factor (MIF) has an important role in controlling infection. The aim of this study was to evaluate the possible association between MIF -173 G/C functional polymorphism and pulmonary tuberculosis (PTB) in an Iranian population from Zahedan Southeast Iran. This case-control study was done on 161 PTB and 142 healthy subjects. Genomic DNA was extracted from all participants by salting out method. The MIF -173 G/C variant was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The finding showed that the MIF -173 G/C polymorphism increased the risk of PTB in codominant (OR=1.76, 95 % CI=1.05-2.95, p=0.038, GC vs GG) and dominant (OR=1.78, 95 % CI=1.09-2.91, p=0.027, GC+CC vs GG) tested inheritance models. Furthermore, the minor allele frequency (MAF) increased the risk of PTB in comparison with G allele (OR=1.63, 95 % CI=1.07-2.48, p=0.028). In conclusion, the present study provides evidence that -173 G/C polymorphism may increase the risk of PTB

A Proposed Architecture for Continuous Web Monitoring Through Online Crawling of Blogs

Getting informed of what is registered in the Web space on time, can greatly help the psychologists, marketers and political analysts to familiarize, analyse, make decision and act correctly based on the society`s different needs. The great volume of information in the Web space hinders us to continuously online investigate the whole space of the Web. Focusing on the considered blogs limits our working domain and makes the online crawling in the Web space possible. In this article, an architecture is offered which continuously online crawls the related blogs, using focused crawler, and investigates and analyses the obtained data. The online fetching is done based on the latest announcements of the ping server machines. A weighted graph is formed based on targeting the important key phrases, so that a focused crawler can do the fetching of the complete texts of the related Web pages, based on the weighted graph.Comment: 10 pages, 2 figure

Activity-based Criteria on Internationalization

The world economy is moving ever faster toward a highly interdependent state in which international business is creating a global market. Often, in this environment, growth or even survival of a business hinges on its successful internationalization. Therefore, firms need to ask the vital question of how internationalized are their operations? To answer such question requires, among other things, measuring the extent of global involvement. This paper is an attempt toward constructing an internationalization measure by using financial performance and market engagement data outside firm’s home country

Rapid Implementation Of ERP Financials Into The Curriculum: A Success Story

Most academic institutions wish to provide current, up to date and real world software applications to their students and this causes a number of common difficulties.  This is especially true as those applications become far larger and more complex, such as in Enterprise Resource Planning (ERP) systems, more recently referred to as Enterprise Systems.  The authors’ institution has a degree program in accounting information systems, and the authors believed that it was critical that ERP skills and applications be included in order to maintain the stature of the program.  Although difficulties were expected, the authors nonetheless pursued various classroom ERP alternatives.  This paper reports on those efforts, which culminated in the creation and offering of an ERP financial applications class in a six month time period.  It is believed that such information will provide encouragement and useful information to other institutions that are considering such implementations