Zebrafish as a genetic model in pre-clinical drug testing and screening

The traditional drug discovery pipeline for the identification and development of compounds that selectively target specific molecules to ameliorate disease remains a major focus for medical research. However, the zebrafish is increasingly providing alternative strategies for various components of this pipeline. Zebrafish and their embryos are small, easily accessible and relatively low cost, making them applicable to high-throughput, small molecule screening. Zebrafish can also be manipulated by a range of forward and reverse genetics techniques to facilitate gene discovery and functional studies. Moreover, their physiological and developmental complexity provides accurate models of human disease to underpin mechanism of action and in vivo validation studies. Finally, several of these biological characteristics make zebrafish eminently suitable for toxicity testing, including eco-toxicology. Here we review the application of zebrafish to preclinical drug development and toxicity testing, including recent advances in mutant generation, drug screening and toxicology that serve to further enhance the capabilities of this valuable model organism in drug discovery.

Corrosion monitoring under disbonded coatings

Localized corrosion can occur under disbonded coatings threatening the safe operation of industry infrastructures such as underground oil and gas pipelines. Currently the assessment of localised corrosion under coating defects is a major technical challenge. The application of corrosion probes to monitor corrosion under disbonded coating also remains a difficulty. This paper presents a new corrosion sensor concept capable of electrochemically measuring corrosion rates under disbonded coatings on cathodically protected structures such as energy pipelines. Examples of its capabilities are illustrated with experimental data obtained in low conductivity aqueous solutions.

The effects of mechanical stress, environment and cathodic protection on the degradation and failure of coatings: An overview

Organic coatings have been used in conjunction with cathodic protection as the most economical method of corrosion protection by the oil and gas pipeline industry. In a bid to prolong the life of the pipelines, the degradation and failure of pipeline coatings under the effects of major influencing factors including mechanical stress, the environmental corrosivity and cathodic protection have been extensively investigated over the past decades. This paper provides an overview of recent research for understanding coating degradation under the effect of these factors, either individually or in combination. Electrochemical impedance spectroscopy remains the primary and the most commonly used technique of studying the degradation of organic coatings, although there have been attempts to use other techniques such as electrochemical polarization (both dynamic and static), electrochemical noise, Scanning Kelvin Probe, Fourier Transform Infrared Spectroscopy, Differential Scanning Calorimetry and Dynamic Mechanical Analyser. Major knowledge and technological gaps in the investigation of the combined effects of mechanical stress, environmental corrosivity and cathodic protection on coating degradation have been identified.

Studying the cathodic disbondment of coatings using electrochemical impedance spectroscopy

The disbondment of protective organic coatings is a widely reported pipeline coating failure mode in the oil and gas industry. Traditional methods of evaluating cathodic disbondment of pipeline coatings are based on visual inspection of pipeline conditions, and laboratory testing of cathodic disbondment resistance (CDR) using standard methods such as ASTM G8. Although some other laboratory-based techniques, such as scanning kelvin probe and scanning acoustic microscopy have been used to study the cathodic disbondment (CD) of coatings, these are often difficult to apply in practical testing. Over the past decade, electrochemical impedance spectroscopy (EIS) has been employed as a potential method for measuring CD. This paper reports preliminary results from an EIS study designed to characterise CD behaviour of epoxy coatings under excessive cathodic protection. EIS data correlated well with the area of disbonded coating. Analysis of EIS data can provide valuable information on the initiation and rates of CD.

Understanding the effects of electrical interference signals and the environment on the effectiveness of cathodic protection

Cathodic protection (CP) failure due to excursions from safe CP levels is a challenge for the protection and maintenance of buried energy pipelines. Although research shows that stray current is a major factor contributing to CP failure, there is little consensus on how 'big' the excursions (either in magnitude, length or frequency) need to be in order to cause pipeline corrosion problems. This uncertainty has caused difficulties in selecting suitable parameters in relevant industry standards. This paper provides a brief review of past research on different factors affecting CP efficiency. Preliminary results from new electrochemical cells designed to develop an understanding of how CP excursions away from the 'safe' level can lead to corrosion problems are also presented.

A review of techniques for the monitoring of cathodic shielding and corrosion under disbonded coatings

The mitigation of external corrosion of energy pipelines by a combination of barrier coatings and Cathodic Protection (CP) is not always effective. Even when design specifications are properly met, the shielding of cathodic protection current from reaching steel surface by disbonded barrier coatings, often referred to as cathodic shielding, may lead to severe corrosion problems such as deep pitting, high and near neutral pH Stress Corrosion Cracking (SCC) and Microbiologically Induced Corrosion (MIC). Unfortunately, current indirect assessment methods used in the pipeline industry have serious difficulties in detecting such corrosion problems. This paper provides a brief review of current techniques and their limitations when being applied under complex buried pipeline environmental conditions. The main purpose is to identify potential methods that could be utilised in the design of new monitoring probes specific for the monitoring of cathodic shielding and corrosion of disbonded coatings in the pipeline industry.

Non-referenced genome assembly from epigenomic short-read data

Current computational methods used to analyze changes in DNA methylation and chromatin modification rely on sequenced genomes. Here we describe a pipeline for the detection of these changes from short-read sequence data that does not require a reference genome. Open source software packages were used for sequence assembly, alignment, and measurement of differential enrichment. The method was evaluated by comparing results with reference-based results showing a strong correlation between chromatin modification and gene expression. We then used our de novo sequence assembly to build the DNA methylation profile for the non-referenced Psammomys obesus genome. The pipeline described uses open source software for fast annotation and visualization of unreferenced genomic regions from short-read data.

Automated quantification of neurite outgrowth orientation distributions on patterned surfaces

Objective. We have developed an image analysis methodology for quantifying the anisotropy of neuronal projections on patterned substrates. Approach. Our method is based on the fitting of smoothing splines to the digital traces produced using a non-maximum suppression technique. This enables precise estimates of the local tangents uniformly along the neurite length, and leads to unbiased orientation distributions suitable for objectively assessing the anisotropy induced by tailored surfaces. Main results. In our application, we demonstrate that carbon nanotubes arrayed in parallel bundles over gold surfaces induce a considerable neurite anisotropy; a result which is relevant for regenerative medicine. Significance. Our pipeline is generally applicable to the study of fibrous materials on 2D surfaces and should also find applications in the study of DNA, microtubules, and other polymeric materials.

Granitic coastal geomorphology: Applying integrated terrestrial and bathymetric LiDAR with multibeam sonar to examine coastal landscape evolution

Coasts composed of resistant lithologies such as granite are generally highly resistant to erosion. They tend to evolve over multiple sea level cycles with highstands acting to remove subaerially weathered material. This often results in a landscape dominated by plunging cliffs with shore platforms rarely occurring. The long-term evolution of these landforms means that throughout the Quaternary these coasts have been variably exposed to different sea level elevations which means erosion may have been concentrated at different elevations from today. Investigations of the submarine landscape of granitic coasts have however been hindered by an inability to accurately image the nearshore morphology. Only with the advent of multibeam sonar and aerial laser surveying can topographic data now be seamlessly collected from above and below sea level. This study tests the utility of these techniques and finds that very accurate measurements can be made of the nearshore thereby allowing researchers to study the submarine profile with the same accuracy as the subaerial profile. From a combination of terrestrial and marine LiDAR data with multibeam sonar data, it is found that the morphology of granite domes is virtually unaffected by erosion at sea level. It appears that evolution of these landscapes on the coast is a very slow process with modern sea level acting only to remove subaerially weathered debris. The size and orientation of the joints determines the erosional potential of the granite. Where joints are densely spaced (<2 m apart) or the bedrock is highly weathered can semi-horizontal surfaces form.

Microfluidic platforms for biomarker analysis

Biomarkers have been described as characteristics, most often molecular, that provide information about biological states, whether normal, pathological, or therapeutically modified. They hold great potential to assist diagnosis and prognosis, monitor disease, and assess therapeutic effectiveness. While a few biomarkers are routinely utilised clinically, these only reflect a very small percentage of all biomarkers discovered. Numerous factors contribute to the slow uptake of these new biomarkers, with challenges faced throughout the biomarker development pipeline. Microfluidics offers two important opportunities to the field of biomarkers: firstly, it can address some of these developmental obstacles, and secondly, it can provide the precise and complex platform required to bridge the gap between biomarker research and the biomarker-based analytical device market. Indeed, adoption of microfluidics has provided a new avenue for advancement, promoting clinical utilisation of both biomarkers and their analytical platforms. This review will discuss biomarkers and outline microfluidic platforms developed for biomarker analysis.

Selective visuo-haptic rendering of heterogeneous objects in 'parallel universes'

 Haptic rendering of complex models is usually prohibitive due to its much higher update rate requirement compared to visual rendering. Previous works have tried to solve this issue by introducing local simulation or multi-rate simulation for the two pipelines. Although these works have improved the capacity of haptic rendering pipeline, they did not take into consideration the situation of heterogeneous objects in one scenario, where rigid objects and deformable objects coexist in one scenario and close to each other. In this paper, we propose a novel idea to support interactive visuo-haptic rendering of complex heterogeneous models. The idea incorporates different collision detection and response algorithms and have them seamlessly switched on and off on the fly, as the HIP travels in the scenario. The selection of rendered models is based on the hypothesis of “parallel universes”, where the transition of rendering one group of models to another is totally transparent to users. To facilitate this idea, we proposed a procedure to convert the traditional single universe scenario into a “multiverse” scenario, where the original models are grouped and split into each parallel universe, depending on the scenario rendering requirement rather than just locality. We also proposed to add simplified visual objects as background avatars in each parallel universe to visually maintain the original scenario while not overly increase the scenario complexity. We tested the proposed idea in a haptically-enabled needle thoracostomy training environment and the result demonstrates that our idea is able to substantially accelerate visuo-haptic rendering with complex heterogeneous scenario objects.

Gender differences in conference presentations: a consequence of self-selection?

Women continue to be under-represented in the sciences, with their representation declining at each progressive academic level. These differences persist despite long-running policies to ameliorate gender inequity. We compared gender differences in exposure and visibility at an evolutionary biology conference for attendees at two different academic levels: student and post-PhD academic. Despite there being almost exactly a 1:1 ratio of women and men attending the conference, we found that when considering only those who presented talks, women spoke for far less time than men of an equivalent academic level: on average student women presented for 23% less time than student men, and academic women presented for 17% less time than academic men. We conducted more detailed analyses to tease apart whether this gender difference was caused by decisions made by the attendees or through bias in evaluation of the abstracts. At both academic levels, women and men were equally likely to request a presentation. However, women were more likely than men to prefer a short talk, regardless of academic level. We discuss potential underlying reasons for this gender bias, and provide recommendations to avoid similar gender biases at future conferences.

Monitoring cathodic shielding and corrosion under disbonded coatings

This work presents a novel corrosion monitoring probe designed for simulating the conditions developed under disbonded coatings and for measuring current densities and their distribution over a simulated pipeline surface. The probe’s concept was experimentally evaluated via immersion tests under Cathodic Protection (CP) in high resistivity aqueous solution. Under the disbonded area, anodic currents as well as cathodic currents were both measured. Anodic current densities were used to calculate metal losses by means of Faraday’s law. Calculated corrosion patterns were compared with corrosion damage observed at the probe’s surface after a period of test. The probe’s working principles are explained in terms of simple electrochemistry.

Synthesis of norbornane bisether antibiotics via silver-mediated alkylation

A small series of norbornane bisether diguanidines have been synthesized and evaluated as antibacterial agents. The key transformation-bisalkylation of norbornane diol 6-was not successful using Williamson methodology but has been accomplished using Ag2O mediated alkylation. Further functionalization to incorporate two guanidinium groups gave rise to a series of structurally rigid cationic amphiphiles; several of which (16d, 16g and 16h) exhibited antibiotic activity. For example, compound 16d was active against a broad range of bacteria including Pseudomonas aeruginosa (MIC = 8 µg/mL), Escherichia coli (MIC = 8 µg/mL) and methicillin-resistant Staphylococcus aureus (MIC = 8 µg/mL).