Nucleoside diphosphate kinase A as a controller of AMP-kinase in airway epithelia

This review integrates recent understanding of a novel role for NDPK-A in two related directions: Firstly, its role in an airway epithelial cell when bound to the luminal (apical) membrane and secondly in the cytosol of many different cells (epithelial and non-epithelial) where an isoform-specific interaction occurs with a regulatory partner, AMPKα1. Thus NDPK-A is present in both a membrane and cytosolic environment but in the apical membrane, its roles are not understood in detail; preliminary data suggest that it co-localises with the cystic fibrosis protein (CFTR). In cytosol, we find that NDPK-A is coupled to the catalytic alpha1 isoform of the AMP-activated protein kinase (AMPKα subunit), which is part of a heterotrimeric protein complex that responds to cellular energy status by switching off ATP-consuming pathways and switching on ATP-generating pathways when ATP is limiting. We find that ATP is located within this complex and ‘fed’ from NDPK to AMPK without ever ‘seeing’ bulk solution. Importantly, the reverse can also happen such that AMPK activity can be made to decline when NDPK-A ‘steals’ ATP from AMPK. Thus we propose a novel paradigm in NDPK-A function by suggesting that AMP-kinase can be regulated by NDPK-A, independently of AMP

Screen or not to screen for peripheral arterial disease: Guidance from a decision model

__Abstract__ Background: Asymptomatic Peripheral Arterial Disease (PAD) is associated with greater risk of acute cardiovascular events. This study aims to determine the cost-effectiveness of one time only PAD screening using Ankle Brachial Index (ABI) test and subsequent anti platelet preventive treatment (low dose aspirin or clopidogrel) in individuals at high risk for acute cardiovascular events compared to no screening and no treatment using decision analytic modelling. Methods. A probabilistic Markov model was developed to evaluate the life time cost-effectiveness of the strategy of selective PAD screening and consequent preventive treatment compared to no screening and no preventive treatment. The analysis was conducted from the Dutch societal perspective and to address decision uncertainty, probabilistic sensitivity analysis was performed. Results were based on average values of 1000 Monte Carlo simulations and using discount rates of 1.5% and 4% for effects and costs respectively. One way sensitivity analyses were performed to identify the two most influential model parameters affecting model outputs. Then, a two way sensitivity analysis was conducted for combinations of values tested for these two most influential parameters. Results: For the PAD screening strategy, life years and quality adjusted life years gained were 21.79 and 15.66 respectively at a lifetime cost of 26,548 Euros. Compared to no screening and treatment (20.69 life years, 15.58 Quality Adjusted Life Ye

A Novel Universal Primer-Multiplex-PCR Method with Sequencing Gel Electrophoresis Analysis

In this study, a novel universal primer-multiplex-PCR (UP-M-PCR) method adding a universal primer (UP) in the multiplex PCR reaction system was described. A universal adapter was designed in the 5′-end of each specific primer pairs which matched with the specific DNA sequences for each template and also used as the universal primer (UP). PCR products were analyzed on sequencing gel electrophoresis (SGE) which had the advantage of exhibiting extraordinary resolution. This method overcame the disadvantages rooted deeply in conventional multiplex PCR such as complex manipulation, lower sensitivity, self-inhibition and amplification disparity resulting from different primers, and it got a high specificity and had a low detection limit of 0.1 ng for single kind of crops when screening the presence of genetically modified (GM) crops in mixture samples. The novel developed multiplex PCR assay with sequencing gel electrophoresis analysis will be useful in many fields, such as verifying the GM status of a sample irrespective of the crop and GM trait and so on

Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201)

Objectives: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification. Methods: Thirty-four participants with virologic suppression ≥48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3+CD56 +CD16+) cells and cell-associated markers (HLA-DR, CD's 38/69/94/95/158/279). Results: Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) <50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL <50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92-55.3). Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels. Conclusions: Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring. Trial Registration: ClinicalTrials.gov NCT00084019

Influence of Matrix Polarity on the Properties of Ethylene Vinyl Acetate–Carbon Nanofiller Nanocomposites

A series of ethylene vinyl acetate (EVA) nanocomposites using four kinds of EVA with 40, 50, 60, and 70 wt% vinyl acetate (VA) contents and three different carbon-based nanofillers—expanded graphite (EG), multi-walled carbon nanotube (MWCNT), and carbon nanofiber (CNF) have been prepared via solution blending. The influence of the matrix polarity and the nature of nanofillers on the morphology and properties of EVA nanocomposites have been investigated. It is observed that the sample with lowest vinyl acetate content exhibits highest mechanical properties. However, the enhancement in mechanical properties with the incorporation of various nanofillers is the highest for EVA with high VA content. This trend has been followed in both dynamic mechanical properties and thermal conductivity of the nanocomposites. EVA copolymer undergoes a transition from partial to complete amorphousness between 40 and 50 wt% VA content, and this changes the dispersion of the nanofillers. The high VA-containing polymers show more affinity toward fillers due to the large free volume available and allow easy dispersion of nanofillers in the amorphous rubbery phase, as confirmed from the morphological studies. The thermal stability of the nanocomposites is also influenced by the type of nanofiller

Mammographic density adds accuracy to both the Tyrer-Cuzick and Gail breast cancer risk models in a prospective UK screening cohort

This work was supported by the National Institute for Health Research (NIHR) and Genesis Breast Cancer Prevention Appeal (references GA10-033 and GA13-006). This article presents independent research funded by the NIHR under its Programme Grants for Applied Research (grant RP-PG-0707-10031). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors also acknowledge the support of Medical Research Council Health eResearch Centre grant MR/K006665/1

Combined artificial bee colony algorithm and machine learning techniques for prediction of online consumer repurchase intention

A novel paradigm in the service sector i.e. services through the web is a progressive mechanism for rendering offerings over diverse environments. Internet provides huge opportunities for companies to provide personalized online services to their customers. But prompt novel web services introduction may unfavorably affect the quality and user gratification. Subsequently, prediction of the consumer intention is of supreme importance in selecting the web services for an application. The aim of study is to predict online consumer repurchase intention and to achieve this objective a hybrid approach which a combination of machine learning techniques and Artificial Bee Colony (ABC) algorithm has been used. The study is divided into three phases. Initially, shopping mall and consumer characteristic’s for repurchase intention has been identified through extensive literature review. Secondly, ABC has been used to determine the feature selection of consumers’ characteristics and shopping malls’ attributes (with > 0.1 threshold value) for the prediction model. Finally, validation using K-fold cross has been employed to measure the best classification model robustness. The classification models viz., Decision Trees (C5.0), AdaBoost, Random Forest (RF), Support Vector Machine (SVM) and Neural Network (NN), are utilized for prediction of consumer purchase intention. Performance evaluation of identified models on training-testing partitions (70-30%) of the data set, shows that AdaBoost method outperforms other classification models with sensitivity and accuracy of 0.95 and 97.58% respectively, on testing data set. This study is a revolutionary attempt that considers both, shopping mall and consumer characteristics in examine the consumer purchase intention.N/