DNA molecules and human therapeutics

Nucleic acid molecules are championing a new generation of reverse engineered biopharmaceuticals. In terms of potential application in gene medicine, plasmid DNA (pDNA) vectors have exceptional therapeutic and immunological profiles as they are free from safety concerns associated with viral vectors, display non-toxicity and are simpler to develop. This review addresses the potential applications of pDNA molecules in vaccine design/development and gene therapy via recombinant DNA technology as well as a staged delivery mechanism for the introduction of plasmid-borne gene to target cells via the nasal route.

The suitability of DEAE-Cl active groups on customized poly(GMA-co-EDMA) continuous stationary phase for fast enzyme-free isolation of plasmid DNA

The creation of a commercially viable and a large-scale purification process for plasmid DNA (pDNA) production requires a whole-systems continuous or semi-continuous purification strategy employing optimised stationary adsorption phase(s) without the use of expensive and toxic chemicals, avian/bovine-derived enzymes and several built-in unit processes, thus affecting overall plasmid recovery, processing time and economics. Continuous stationary phases are known to offer fast separation due to their large pore diameter making large molecule pDNA easily accessible with limited mass transfer resistance even at high flow rates. A monolithic stationary sorbent was synthesised via free radical liquid porogenic polymerisation of ethylene glycol dimethacrylate (EDMA) and glycidyl methacrylate (GMA) with surface and pore characteristics tailored specifically for plasmid binding, retention and elution. The polymer was functionalised with an amine active group for anion-exchange purification of pDNA from cleared lysate obtained from E. coli DH5α-pUC19 pellets in RNase/protease-free process. Characterization of the resin showed a unique porous material with 70% of the pores sizes above 300 nm. The final product isolated from anion-exchange purification in only 5 min was pure and homogenous supercoiled pDNA with no gDNA, RNA and protein contamination as confirmed with DNA electrophoresis, restriction analysis and SDS page. The resin showed a maximum binding capacity of 15.2 mg/mL and this capacity persisted after several applications of the resin. This technique is cGMP compatible and commercially viable for rapid isolation of pDNA.

Electropolymerisation of catalytically active PEDOT from an ionic liquid on a flexible carbon cloth using a sandwich cell configuration

We report the electropolymerization of poly(3,4-ethylenedioxythiopene) (PEDOT) from an ionic liquid, butyl-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide (C4mpyrTFSI) onto flexible carbon cloth electrodes. A continuous, homogeneous and well adhered coating of the individual cloth fibres is achieved by employing a sandwich cell arrangement where the carbon cloth which is soaked with electrolyte is placed between two indium tin oxide electrodes isolated from each other by a battery separator. The resultant PEDOT modified carbon cloth electrode demonstrates excellent activity for the oxygen reduction reaction which is due to the doping level, conductivity and morphology of the PEDOT layer and is also tolerant to the presence of methanol in the electrolyte. This simple approach therefore offers a route to fabricate flexible polymer electrodes that could be used in various electronic applications.

Application of TS-Fuzzy Controller for Active Power and DC Capacitor Voltage Control in DFIG-Based Wind Energy Conversion Systems

This chapter focuses on the implementation of the TS (Tagaki-Sugino) fuzzy controller for the Doubly Fed Induction Generator (DFIG) based wind generator. The conventional PI control loops for mantaining desired active power and DC capacitor voltage is compared with the TS fuzzy controllers. DFIG system is represented by a third-order model where electromagnetic transients of the stator are neglected. The effectiveness of the TS-fuzzy controller on the rotor speed oscillations and the DC capacitor voltage variations of the DFIG damping controller on converter ratings is also investigated. The results from the time domain simulations are presented to elucidate the effectiveness of the TS-fuzzy controller over the conventional PI controller in the DFIG system. The proposed TS-fuzzy con-troller can improve the fault ride through capability of DFIG compared to the conventional PI controller.

DNA molecules and future blockbuster therapeutics

Deoxyribonucleic acid molecules are heralding a new generation of reverse - engineered biopharmaceuticals. In terms of potential application in gene medicine, plasmid DNA (pDNA) vectors have exceptional therapeutic and immunological profiles as they are free from safety concerns associated with viral vectors, display non-toxicity and are simpler to develop. This presentation will discuss the potential applications of pDNA molecules in vaccine development and gene therapy, pilot-scale production of pDNA-based biopharmaceuticals and the controlled delivery of therapeutic sequences in biodegradable polymers to different target cells via the nasal route.

Bikeshare's impact on active travel: Evidence from the United States, Great Britain, and Australia

Over 800 cities globally now offer bikeshare programs. One of their purported benefits is increased physical activity. Implicit in this claim is that bikeshare replaces sedentary modes of transport, particularly car use. This paper estimates the median changes in physical activity levels as a result of bikeshare in the cities of Melbourne, Brisbane, Washington, D.C., London, and Minneapolis/St. Paul. This study is the first known multi-city evaluation of the active travel impacts of bikeshare programs. To perform the analysis, data on mode substitution (i.e. the modes that bikeshare replaces) were used to determine the extent of shift from sedentary to active transport modes (e.g. when a car trip is replaced by bikeshare). Potentially offsetting these gains, reductions in physical activity when walking trips are replaced by bikeshare was also estimated. Finally a Markov Chain Monte Carlo analysis was conducted to estimate confidence bounds on estimated impacts on active travel given uncertainties in data sources. The results indicate that on average 60% of bikeshare trips replace sedentary modes of transport (from 42% in Minneapolis/St. Paul to 67% in Brisbane). When bikeshare replaces a walking trip, there is a reduction in active travel time because walking a given distance takes longer than cycling. Considering the active travel balance sheet for the cities included in this analysis, bikeshare activity in 2012 has an overall positive impact on active travel time. This impact ranges from an additional 1.4 million minutes of active travel for the Minneapolis/St. Paul bikeshare program, to just over 74 million minutes of active travel for the London program The analytical approach adopted to estimate bikeshare’s impact on active travel may act as the basis for future bikeshare evaluations or feasibility studies.

The role of non-thermal plasma technique in {NOx} treatment: A review

Non-thermal plasma (NTP) has been introduced over the past several years as a promising method for nitrogen oxide (NOx) removal. The intent, when using NTP, is to selectively transfer input electrical energy to the electrons, and to not expend this in heating the entire gas stream, which generates free radicals through collisions, and promotes the desired chemical changes in the exhaust gases. The generated active species react with the pollutant molecules and decompose them. This paper reviews and summarizes relevant literature regarding various aspects of the application of {NTP} technology on {NOx} removal from exhaust gases. A comprehensive description of available scientific literature on {NOx} removal using {NTP} technology is presented, including various types of NTP, e.g. dielectric barrier discharge, corona discharge and electron beam. Furthermore, the combination of {NTP} with catalyst and adsorbent for better {NOx} removal efficiency is presented in detail. The removal of {NOx} from both simulated gases and real diesel engines is also considered in this review paper. As {NTP} is a new technique and is not yet commercialized, there is a need for more studies to be performed in this field.

Active aging: Exploration into self-ratings of "being active," out-of-home physical activity, and participation among older Australian adults living in four different settings

We examined whether self-ratings of “being active” among older people living in four different settings (major city high and lower density suburbs, a regional city, and a rural area) were associated with out-of-home participation and outdoor physical activity. A mixed-methods approach (survey, travel diary, and GPS tracking over a one-week period) was used to gather data from 48 individuals aged over 55 years. Self-ratings of “being active” were found to be positively correlated with the number of days older people spent time away from home but unrelated to time traveled by active means (walking and biking). No significant differences in active travel were found between the four study locations, despite differences in their respective built environments.The findings suggest that additional strategies to the creation of “age-friendly” environments are needed if older people are to increase their levels of outdoor physical activity. “Active aging” promotion campaigns may need to explicitly identify the benefits of walking outdoors to ambulatory older people as a means of maintaining their overall health, functional ability, and participation within society in the long-term and also encourage the development of community-based programs in order to facilitate regular walking for this group.

Learning choices, older Australians and active ageing

This paper reports on the findings of qualitative, semi-structured interviews conducted with 40 older Australian participants who either did or did not engage in organized learning. Phenomenology was used to guide the interviews and analysis to explore the lived learning experiences and perspectives of these older people. Their experiences of learning can be described in two main categories of pleasure and leisure or purpose and relevance. Almost all the activities described in these categories have the potential to support health and wellbeing. Organisers of activities should take these reasons into account.

Peptide-functionalized polymeric nanoparticles for active targeting of damaged tissue in animals with experimental autoimmune encephalomyelitis

Increased permeability of blood vessels is an indicator for various injuries and diseases, including multiple sclerosis (MS), of the central nervous system. Nanoparticles have the potential to deliver drugs locally to sites of tissue damage, reducing the drug administered and limiting associated side effects, but efficient accumulation still remains a challenge. We developed peptide-functionalized polymeric nanoparticles to target blood clots and the extracellular matrix molecule nidogen, which are associated with areas of tissue damage. Using the induction of experimental autoimmune encephalomyelitis in rats to provide a model of MS associated with tissue damage and blood vessel lesions, all targeted nanoparticles were delivered systemically. In vivo data demonstrates enhanced accumulation of peptide functionalized nanoparticles at the injury site compared to scrambled and naive controls, particularly for nanoparticles functionalized to target fibrin clots. This suggests that further investigations with drug laden, peptide functionalized nanoparticles might be of particular interest in the development of treatment strategies for MS.

Active learning: A step towards automating medical concept extraction

Objective This paper presents an automatic active learning-based system for the extraction of medical concepts from clinical free-text reports. Specifically, (1) the contribution of active learning in reducing the annotation effort, and (2) the robustness of incremental active learning framework across different selection criteria and datasets is determined. Materials and methods The comparative performance of an active learning framework and a fully supervised approach were investigated to study how active learning reduces the annotation effort while achieving the same effectiveness as a supervised approach. Conditional Random Fields as the supervised method, and least confidence and information density as two selection criteria for active learning framework were used. The effect of incremental learning vs. standard learning on the robustness of the models within the active learning framework with different selection criteria was also investigated. Two clinical datasets were used for evaluation: the i2b2/VA 2010 NLP challenge and the ShARe/CLEF 2013 eHealth Evaluation Lab. Results The annotation effort saved by active learning to achieve the same effectiveness as supervised learning is up to 77%, 57%, and 46% of the total number of sequences, tokens, and concepts, respectively. Compared to the Random sampling baseline, the saving is at least doubled. Discussion Incremental active learning guarantees robustness across all selection criteria and datasets. The reduction of annotation effort is always above random sampling and longest sequence baselines. Conclusion Incremental active learning is a promising approach for building effective and robust medical concept extraction models, while significantly reducing the burden of manual annotation.

External knowledge and query strategies in active learning: A study in clinical information extraction

This paper presents a new active learning query strategy for information extraction, called Domain Knowledge Informativeness (DKI). Active learning is often used to reduce the amount of annotation effort required to obtain training data for machine learning algorithms. A key component of an active learning approach is the query strategy, which is used to iteratively select samples for annotation. Knowledge resources have been used in information extraction as a means to derive additional features for sample representation. DKI is, however, the first query strategy that exploits such resources to inform sample selection. To evaluate the merits of DKI, in particular with respect to the reduction in annotation effort that the new query strategy allows to achieve, we conduct a comprehensive empirical comparison of active learning query strategies for information extraction within the clinical domain. The clinical domain was chosen for this work because of the availability of extensive structured knowledge resources which have often been exploited for feature generation. In addition, the clinical domain offers a compelling use case for active learning because of the necessary high costs and hurdles associated with obtaining annotations in this domain. Our experimental findings demonstrated that 1) amongst existing query strategies, the ones based on the classification model’s confidence are a better choice for clinical data as they perform equally well with a much lighter computational load, and 2) significant reductions in annotation effort are achievable by exploiting knowledge resources within active learning query strategies, with up to 14% less tokens and concepts to manually annotate than with state-of-the-art query strategies.

Active fibers: Matching deformable tract templates to diffusion tensor images

Reliable quantitative analysis of white matter connectivity in the brain is an open problem in neuroimaging, with common solutions requiring tools for fiber tracking, tractography segmentation and estimation of intersubject correspondence. This paper proposes a novel, template matching approach to the problem. In the proposed method, a deformable fiber-bundle model is aligned directly with the subject tensor field, skipping the fiber tracking step. Furthermore, the use of a common template eliminates the need for tractography segmentation and defines intersubject shape correspondence. The method is validated using phantom DTI data and applications are presented, including automatic fiber-bundle reconstruction and tract-based morphometry. © 2009 Elsevier Inc. All rights reserved.

Generation of catalytically active materials from a liquid metal precursor

A facile route to prepare catalystically active materials from a galinstan liquid metal alloy is introduced. Sonicating liquid galinstan in alkaline solution or treating it in reducing media results in the creation of solid In/Sn rich microspheres that show catalytic activity toward both potassium ferricyanide and 4-nitrophenol reduction.