Isoeugenol is a selective potentiator of camptothecin cytotoxicity in vertebrate cells lacking TDP1

Camptothecin (CPT), a topoisomerase I (TOP1) inhibitor, exhibits anti-tumor activity against a wide range of tumors. Redundancy of TOP1-mediated repair mechanisms is a major challenge facing the efficiency of TOP1-targetting therapies. This study aims to uncover new TOP1 targeting approaches utilising a selection of natural compounds in the presence or absence of tyrosyl DNA phosphodiesterase I (TDP1); a key TOP1-mediated protein-linked DNA break (PDB) repair enzyme. We identify, isoeugenol, a phenolic ether found in plant essential oils, as a potentiator of CPT cytotoxicity in Tdp1 deficient but not proficient cells. Consistent with our cellular data, isoeugenol did not inhibit Tdp1 enzymatic activity in vitro nor it sensitized cells to the PARP1 inhibitor olaparib. However, biochemical analyses suggest that isoeugenol inhibits TDP2 catalytic activity; a pathway that can compensate for the absence of TDP1. Consistent with this, isoeugenol exacerbated etoposide-induced cytotoxicity, which generates TOP2-mediated PDBs for which TDP2 is required for processing. Together, these findings identify isoeugenol as a potential lead compound for developing TDP2 inhibitors and encourage structure-activity relationship studies to shed more light on its utility in drug discovery programs

Energy management strategy in dynamic distribution network reconfiguration considering renewable energy resources and storage

© 2010-2012 IEEE. Penetration of renewable energy sources (RESs) and electrical energy storage (EES) systems in distribution systems is increasing, and it is crucial to investigate their impact on systems' operation scheme, reliability, and security. In this paper, expected energy not supplied (EENS) and voltage stability index (VSI) of distribution networks are investigated in dynamic balanced and unbalanced distribution network reconfiguration, including RESs and EES systems. Furthermore, due to the high investment cost of the EES systems, the number of charge and discharge is limited, and the state-of-health constraint is included in the underlying problem to prolong the lifetime of these facilities. The optimal charging/discharging scheme for EES systems and optimal distribution network topology are presented in order to optimize the operational costs, and reliability and security indices simultaneously. The proposed strategy is applied to a large-scale 119-bus distribution test network in order to show the economic justification of the proposed approach

Did Ebola emerge in West Africa by a policy-driven phase change in agroecology? Ebola's social context

SCOPUS: no.jinfo:eu-repo/semantics/publishe

Brownian diffusion and thermophoresis mechanisms in Casson fluid over a moving wedge

The effect of Brownian diffusion and thermophoresis on electrically conducting mixed convection flow of Casson fluid induced by moving wedge is investigated in this paper. It is assumed that the wedge is saturated in a porous medium and experiences the thermal radiation and chemical reaction effects. The transformed nonlinear governing equations are solved numerically by Keller box scheme. Findings reveal that increase in Casson and magnetic parameters reduced the boundary layer thickness. The effect of Brownian motion and thermophoresis parameters are more pronounced on temperature profile as compared to nanoparticles concentration. The presence of thermal radiation assisted the heat transfer rate significantly. The influence of magnetic parameter is observed less significant on temperature and nanoparticles concentration

Anthocyanins in chokeberry and purple maize attenuate diet-induced metabolic syndrome in rats

Objective: Increased consumption of fruits and vegetables as functional foods leads to the reduction of signs of metabolic syndrome. The aim of this study was to measure and compare cardiovascular, liver, and metabolic parameters following chronic administration of the same dose of anthocyanins either from chokeberry (CB) or purple maize (PM) in rats with diet-induced metabolic syndrome. Methods: Male Wistar rats were fed a maize starch (C) or high-carbohydrate, high-fat diet (H) and divided into six groups for 16 wk. The rats were fed C, C with CB or PM for the last 8 wk (CCB or CPM), H, H with CB or PM for the last 8 wk (HCB or HPM); CB and PM rats received ∼8 mg anthocyanins/kg daily. The rats were monitored for changes in blood pressure, cardiovascular and hepatic structure and function, glucose tolerance, and adipose tissue mass. Results: HCB and HPM rats showed reduced visceral adiposity index, total body fat mass, and systolic blood pressure; improved glucose tolerance, liver, and cardiovascular structure and function; decreased plasma triacylglycerols and total cholesterol compared with H rats. Inflammatory cell infiltration was reduced in heart and liver. Conclusion: CB and PM interventions gave similar responses, suggesting that anthocyanins are the bioactive molecules in the attenuation or reversal of metabolic syndrome by prevention of inflammation-induced damage

Update in Pathophysiology and Management of Helicobacter pylori in Children

Abstract: Objective: The aim of this study is to review Helicobacter pylori in children describing its epidemiology, pathophysiology, clinical presentations and management. Data summary Helicobacter pylori is one of the most common chronic bacterial infection worldwide. Helicobacter pylori infection is the main etiological factor for chronic gastritis, most peptic ulcers and gastric adenocarcinoma and lymphoma. Recently a potential role of Helicobacter pylori in other gastrointestinal as well as several extra-intestinal pathologies is being evaluated. Standard triple therapy should be abandoned in areas of high clarithromycin resistance. Conclusion: Several diseases have been reported to be associated with Helicobacter pylori infection. Its role in some hematologic conditions has been fully validated and included in the current guidelines. Further studies are still needed to evaluate the role of Helicobacter pylori in other diseases. Choice of the diagnostic test for each patient depends on several factors. Clarithromycin is critically important as it negatively impacts the efficacy of the chosen therapeutic regimen

Model-based test case prioritization using selective and even-spread count-based methods with scrutinized ordering criterion

Regression testing is crucial in ensuring that modifications made did not introduce any adverse effect on the software being modified. However, regression testing suffers from execution cost and time consumption problems. Test case prioritization (TCP) is one of the techniques used to overcome these issues by re-ordering test cases based on their priorities. Model-based TCP (MB-TCP) is an approach in TCP where the software models are manipulated to perform prioritization. The issue with MB-TCP is that most of the existing approaches do not provide satisfactory faults detection capability. Besides, their granularity of test selection criteria is not very good and this can affect prioritization effectiveness. This study proposes an MB-TCP approach that can improve the faults detection performance of regression testing. It combines the implementation of two existing approaches from the literature while incorporating an additional ordering criterion to boost prioritization efficacy. A detailed empirical study is conducted with the aim to evaluate and compare the performance of the proposed approach with the selected existing approaches from the literature using the average of the percentage of faults detected (APFD) metric. Three web applications were used as the objects of study to obtain the required test suites that contained the tests to be prioritized. From the result obtained, the proposed approach yields the highest APFD values over other existing approaches which are 91%, 86% and 91% respectively for the three web applications. These higher APFD values signify that the proposed approach is very effective in revealing faults early during testing. They also show that the proposed approach can improve the faults detection performance of regression testing

An evaluation of existent methods for estimation of embankment dam breach parameters

The study of dam-break analysis is considered important to predict the peak discharge during dam failure. This is essential to assess economic, social and environmental impacts downstream and to prepare the emergency response plan. Dam breach parameters such as breach width, breach height and breach formation time are the key variables to estimate the peak discharge during dam break. This study presents the evaluation of existing methods for estimation of dam breach parameters. Since all of these methods adopt regression analysis, uncertainty analysis of these methods becomes necessary to assess their performance. Uncertainty was performed using the data of more than 140 case studies of past recorded failures of dams, collected from different sources in the literature. The accuracy of the existing methods was tested, and the values of mean absolute relative error were found to be ranging from 0.39 to 1.05 for dam breach width estimation and from 0.6 to 0.8 for dam failure time estimation. In this study, artificial neural network (ANN) was recommended as an alternate method for estimation of dam breach parameters. The ANN method is proposed due to its accurate prediction when it was applied to similar other cases in water resources

The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog

Chronic spinal cord dysfunction occurs in dogs as a consequence of diverse aetiologies, including long-standing spinal cord compression and insidious neurodegenerative conditions. One such neurodegenerative condition is canine degenerative myelopathy (DM), which clinically is a challenge to differentiate from other chronic spinal cord conditions. Although the clinical diagnosis of DM can be strengthened by the identification of the Sod1 mutations that are observed in affected dogs, genetic analysis alone is insufficient to provide a definitive diagnosis. There is a requirement to identify biomarkers that can differentiate conditions with a similar clinical presentation, thus facilitating patient diagnostic and management strategies. A comparison of the cerebrospinal fluid (CSF) protein gel electrophoresis profile between idiopathic epilepsy (IE) and DM identified a protein band that was more prominent in DM. This band was subsequently found to contain a multifunctional protein clusterin (apolipoprotein J) that is protective against endoplasmic reticulum (ER) stress-mediated apoptosis, oxidative stress, and also serves as an extracellular chaperone influencing protein aggregation. Western blot analysis of CSF clusterin confirmed elevated levels in DM compared to IE (p < 0.05). Analysis of spinal cord tissue from DM and control material found that clusterin expression was evident in neurons and that the clusterin mRNA levels from tissue extracts were elevated in DM compared to the control. The plasma clusterin levels was comparable between these groups. However, a comparison of clusterin CSF levels in a number of neurological conditions found that clusterin was elevated in both DM and chronic intervertebral disc disease (cIVDD) but not in meningoencephalitis and IE. These findings indicate that clusterin may potentially serve as a marker for chronic spinal cord disease in the dog; however, additional markers are required to differentiate DM from a concurrent condition such as cIVDD

Trace-elemental and multi-isotopic (Sr-Nd-Pb) discrimination of jade in the circum-Caribbean: Implications for pre-colonial inter-island exchange networks

Dense and strong, hydrothermal-metasomatic jadeitite and jadeite-omphacite rocks were used as tools and adornments throughout the wider Caribbean since initial inhabitation. Regionally, rich sources of jadeitite and jadeite-omphacite jade are known only in Guatemala (north and south of the Motagua Fault Zone), eastern Cuba and the northern Dominican Republic, establishing that humans transported jadeitic material over vast distances. This study validates that geochemical fingerprinting is a viable provenance method for Caribbean pre-colonial jadeitic lithologies. An assemblage of 101 source rocks has been characterised for trace element and combined Sr-Nd-Pb isotope compositions. Four statistical approaches (Principal Component Analysis, t-Distributed Stochastic Neighbour Embedding, Decision Tree, and Multiclass Regression) were assessed, employing source-distinct trace element ratios. A multiclass regression technique based on trace element ratios of immobile high field strength, light to medium rare earth and fluid-mobile, large-ion-lithophile elements is shown to be most effective in discriminating the four source regions. Ninety-one % of the Guatemalan samples can be discriminated from the Dominican and Cuban sources using La/Th, Zr/Hf and Y/Th ratios. Jadeitic rocks cropping out in the Dominican Republic can be distinguished from Cuban jades employing Er/Yb, Nb/Ta and Ba/Rb ratios with 71% certainty. Furthermore, the two Guatemala sources, north and south of the Motagua Fault Zone, can be discriminated by using (among others) Zr/Hf, Ta/Th, La/Sm and Dy/Y ratios with an 89% success rate. This raises the possibility of determining, in detail, former trading and mobility networks between different islands and the Meso- and Central American mainland within the Greater Caribbean. The provenance technique was applied to 19 pre-colonial jade celts excavated from the Late Ceramic Age Playa Grande archaeological site in the northern Dominican Republic. Three artefacts are discriminated as derived from the Guatemalan source, indicating that, despite a source of jade within 25 km, material was traded from Guatemala. The presence of Guatemalan jade in the Playa Grande lithic assemblage provides further evidence of large scale (>3000 km), regional trading and indigenous knowledge transfer networks.This research received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013)/ERC grant agreement No 319209 (ERC-Synergy NEXUS 1492) and the European Union’s Horizon 2020 research and innovation programme under grant agreement No 654208 (Europlanet 2020 RI). We are grateful to the Museo del Hombre Dominicano for providing the Playa Grande samples. Thanks to Richard Smeets, Bas van der Wagt, Kirsten van Zuilen, Bouke Lacet, Eva Kelderman and Quinty Boosten for analytical assistance