In vivo imaging of hydrogen peroxide with chemiluminescent nanoparticles

The overproduction of hydrogen peroxide is implicated in the development of numerous diseases and there is currently great interest in developing contrast agents that can image hydrogen peroxide in vivo. In this report, we demonstrate that nanoparticles formulated from peroxalate esters and fluorescent dyes can image hydrogen peroxide in vivo with high specificity and sensitivity. The peroxalate nanoparticles image hydrogen peroxide by undergoing a three-component chemiluminescent reaction between hydrogen peroxide, peroxalate esters and fluorescent dyes. The peroxalate nanoparticles have several attractive properties for in vivo imaging, such as tunable wavelength emission (460-630 nm), nanomolar sensitivity for hydrogen peroxide and excellent specificity for hydrogen peroxide over other reactive oxygen species. The peroxalate nanoparticles were capable of imaging hydrogen peroxide in the peritoneal cavity of mice during a lipopolysaccharide-induced inflammatory response. We anticipate numerous applications of peroxalate nanoparticles for in vivo imaging of hydrogen peroxide, given their high specificity and sensitivity and deep-tissue-imaging capability.     

Steady state behaviour of three phase air lift bioreactors – an integrated model and experimental verification

Beneckea natriegens growing both in suspension and immobilised on diatomaceous earth (silica) support particles, in a 3 dm three phase air lift bioreactor (TPALB), was employed to demonstrate the relationship between substrate loading rate and immobilised biomass loading at steady state. Sterile conditions were maintained during the experiments, while the hydraulic conditions and the inlet flowrate remained constant. The experiment ran for 12 days, whilst the inlet substrate (n‐propanol) concentration was varied both upwards and downwards between 250 and 750 mg dm⁻³. The bulk liquid substrate concentration and the immobilised biomass loading were found to vary between 6–120 mg dm⁻³ and 71–159 mg(dry biomass) g⁻¹ (silica), respectively. The experimental results demonstrated that there is a positive relationship between substrate loading and immobilised biomass loading. A mathematical model is proposed to calculate biofilm thickness and bulk liquid substrate concentration (for steady state) using the inlet flowrate and the inlet substrate concentration as input parameters. The model was able to predict both biofilm thickness and immobilised biomass loading for the lower substrate loading rates applied. © 1999 Society of Chemical Industry     

Differential Expression of the Host Lipid Regulators ANGPTL-3 and ANGPTL-4 in HCV Infection and Treatment

Host lipid metabolism reprogramming is essential for hepatitis C virus (HCV) infection and progression to severe liver disease. Direct-acting antivirals (DAAs) achieve a sustained virological response (SVR) in most patients, but virus eradication does not always protect against hepatocellular carcinoma (HCC). Angiopoietin-like protein-3 (ANGPTL-3) and angiopoietin-like protein-4 (ANGPTL-4) regulate the clearance of plasma lipids by inhibiting cellular lipase activity and possess emerging roles in tumourigenesis. We used ELISA and RT-qPCR to investigate ANGPTL-3 and ANGPTL-4 expression in HCV patients with characterised fibrosis throughout the natural history of hepatitis C and in long-term HCV infection in vitro, before and after DAA treatment. ANGPTL-3 was decreased in patients with advanced fibrosis compared to other disease stages, while ANGPTL-4 was progressively increased from acute infection to cirrhosis and HCC, peaking at the advanced fibrosis stage. Only ANGPTL-3 mRNA was down-regulated during early infection in vitro, although both ANGPTLs were increased later. DAA treatment did not alter ANGPTL-3 levels in advanced fibrosis/cirrhosis and in HCV infection in vitro, in contrast to ANGPTL-4. The association between ANGPTLs and fibrosis in HCV infection was underlined by an inverse correlation between the levels of ANGPTLs and serum transforming growth factor- β (TGF-β). Collectively, we demonstrate the pivotal role of advanced fibrosis in defining the expression fate of ANGPTLs in HCV infection and after treatment and propose a role for ANGPTL-3 as a contributor to post-treatment deregulation of lipid metabolism that could predispose certain individuals to HCC development.     

Optimization of a parallel permutation testing function for the SPRINT R package

The statistical language R and its Bioconductor package are favoured by many biostatisticians for processing microarray data. The amount of data produced by some analyses has reached the limits of many common bioinformatics computing infrastructures. High Performance Computing systems offer a solution to this issue. The Simple Parallel R Interface (SPRINT) is a package that provides biostatisticians with easy access to High Performance Computing systems and allows the addition of parallelized functions to R. Previous work has established that the SPRINT implementation of an R permutation testing function has close to optimal scaling on up to 512 processors on a supercomputer. Access to supercomputers, however, is not always possible, and so the work presented here compares the performance of the SPRINT implementation on a supercomputer with benchmarks on a range of platforms including cloud resources and a common desktop machine with multiprocessing capabilities. Copyright © 2011 John Wiley & Sons, Ltd.     

Three-dimensional nonlinear invisible boundary detection.

The human vision system can discriminate regions which differ up to the second-order statistics only. We present an algorithm designed to reveal "hidden" boundaries in gray level images, by computing gradients in higher order statistics of the data. We demonstrate it by applying it to the identification of possible "hidden" boundaries of glioblastomas as manifest themselves in three-dimensional (3-D) MRI scans, using a model driven approach. We also demonstrate the method using a nonmodel driven approach where we have no prior information about the location of possible boundaries. In this case, we use 3-D MRI data concerning schizophrenic patients and normal controls.     

Ambient particulate matter exhibits direct inhibitory effects on oxidative stress enzymes

A primary mechanistic hypothesis by which ambient air particles have a significant negative impact on human health is via the induction of pulmonary inflammatory responses mediated through the generation of reactive oxygen species (ROS). Development of a biosensor for the assessment of particulate ROS activity would be a significant advance in air pollution monitoring. The objective of this study was to evaluate whether air particulates interact directly with protective enzymes involved in oxidative stress responses. We performed enzyme activity assays on four enzymes involved in oxidative stress responses (Cu/Zn superoxide dismutase, Mn superoxide dismutase, glutathione peroxidase, and glutathione reductase) in the presence of particles of varying toxicities and found distinctive inhibition patterns. On the basis of these findings, we suggest a strategy for an enzyme bioassay that could be used to assess the potential of particles to generate ROS-induced responses.     

A model for the development of a power production system in Greece,Part I: Where RES do not meet EU targets

This paper studies the electricity production system of the Greek Interconnected Electric Production System using a model created with the software package WASP-IV. The period of study is from 2009 to 2030. It consists of three scenarios using three different criteria: energy, environmental and economic. The three scenarios are the business as usual, the lignite and the natural gas. Subsequently, a sensitivity analysis is carried out for the annual growth rate of electricity consumption and load demand. The paper examines how the three criteria change, when there are no other energy sources beyond those already in use (lignite, oil, natural gas, biomass, solar, wind and hydropower) with no CO₂ capture policies and with the electricity production from Renewable Energy Sources not to reach the targets of the European Union for 2020. In a second paper, three other scenarios examine production with the Renewable Energy Sources to reach the targets of the European Union for 2020.