Unlocking the potential of RNA interference as a therapeutic tool

The existence of an intrinsic biochemical pathway enabling specified regulation of gene expression was unheard of until the final years of the last decade. The identification of ribonucleic acid interference (RNAi) in mammalian cells has nowadays become of extreme importance in the field of functional genomics and translational medicine. The advent of RNAi technology has brought to the scientific research and pharmaceutical communities the ability to regulate expression of any desired gene in a reproducible manner. Consequently, such technology may be utilised in the design of novel therapeutics for clinical conditions having dys-regulated gene expression. Since most RNAi-based therapies in the drug development pipeline of pharmaceutical companies utilise short interfering RNA (siRNA), this review will focus on the role of siRNA in drug development.peer-reviewe

Resistance of a compartmented surface-effect ship

A series of carefully controlled experiments on the resistance of a model of a compartmented surface-effect ship has been conducted in a towing tank. Configurations of the model included cases encompassing one subcushion and two subcushions, as well as differing values of the pressures in the subcushions. It was shown that a reduced total resistance in the appropriate range of Froude number could be achieved in this manner. Furthermore, the previously developed theory for the resistance of a surface-effect ship was verified for the model for a Froude number greater than 0.40

An investigation into the cognitive effects of delayed visual feedback

Abstract unavailable please refer to PD

Reach modelling for drive-up self-service

People using a self-service terminal such as an automated teller machine (ATM) tend to adjust their physical position throughout a transaction. This is particularly apparent with terminals that are designed to be used from a vehicle (i.e. drive up automated teller machines or ATMs). Existing predictive tools tend to focus on static reach and provide limited predictions for how far people are willing to stretch to complete a task. Drive-up self-service products have 3 main challenges: the variability of vehicles, people and driver behaviour. Such conventional tools are therefore of limited use in understanding how much people are willing to move to use a self-service terminal. Work is described to build in-house predictive models based on 2 large empirical studies of reach in a drive up installation. These 2 studies assessed comfortable and extended reach from 10 vehicle categories. Extended reach was defined as stretching/leaning as far as participants would normally be willing to in order to complete a drive-up transaction. Findings from these studies indicated that participants are prepared to adopt more extreme postures at drive-up than in other situations with extended reach at drive-up being significantly different to what might be seen at a walk-up kiosk

Can aggregate quarry silt lagoons provide resources for wading birds?

Wading birds have declined across Europe as the intensification of lowland agriculture has resulted in the loss and degradation of wetland areas. Lowland aggregate extraction sites that incorporate areas of fine, waste sediments deposited in silt lagoons have the potential to be restored for wader conservation. We set out to determine the potential value of silt lagoons to wading birds by comparing the water quality, sediment profiles, aquatic invertebrate abundance and diversity (prey availability) and wader site use at five sites representing various stages of active aggregate extraction and restoration for conservation purposes. Wader counts were conducted monthly over a twelve month period using replicated scan samples, and the invertebrate communities studied during the breeding and autumn migration season (June–September). Water quality variables were similar between sites, but sediments from active quarries were dominated by moderately sorted fine sands in comparison to the coarser sediment profiles of restored areas. June and September there was no significant difference in invertebrate diversity between sites, however richness was significantly lower on quarry sites and total abundance a factor of ten higher at restored sites than on silt lagoons, with the dominant taxa similar across all sites. Waders used all sites; albeit at lower abundance and richness on silt lagoons and two species were recorded breeding on active silting sites. We conclude that the fine, uniform sediments of modern silt lagoons limited invertebrate diversity and abundance, diminishing the value of silt lagoons to waders. Simple low-cost intervention measures increasing substrate heterogeneity and creating temporary ponds could increase invertebrate richness and abundance, and enhance the conservation potential of these sites

Expression stability of commonly used reference genes in canine articular connective tissues

<p>Abstract</p> <p>Background</p> <p>The quantification of gene expression in tissue samples requires the use of reference genes to normalise transcript numbers between different samples. Reference gene stability may vary between different tissues, and between the same tissue in different disease states. We evaluated the stability of 9 reference genes commonly used in human gene expression studies. Real-time reverse transcription PCR and a mathematical algorithm were used to establish which reference genes were most stably expressed in normal and diseased canine articular tissues and two canine cell lines stimulated with lipolysaccaride (LPS).</p> <p>Results</p> <p>The optimal reference genes for comparing gene expression data between normal and diseased infrapatella fat pad were <it>RPL13A </it>and <it>YWHAZ </it>(M = 0.56). The ideal reference genes for comparing normal and osteoarthritic (OA) cartilage were <it>RPL13A </it>and <it>SDHA </it>(M = 0.57). The best reference genes for comparing normal and ruptured canine cranial cruciate ligament were <it>B2M </it>and <it>TBP </it>(M = 0.59). The best reference genes for normalising gene expression data from normal and LPS stimulated cell lines were <it>SDHA </it>and <it>YWHAZ </it>(K6) or <it>SDHA </it>and <it>HMBS </it>(DH82), which had expression stability (M) values of 0.05 (K6) and 0.07 (DH82) respectively. The number of reference genes required to reduce pairwise variation (V) to <0.20 was 4 for cell lines, 5 for cartilage, 7 for cranial cruciate ligament and 8 for fat tissue. Reference gene stability was not related to the level of gene expression.</p> <p>Conclusion</p> <p>The reference genes demonstrating the most stable expression within each different canine articular tissue were identified, but no single reference gene was identified as having stable expression in all different tissue types. This study underlines the necessity to select reference genes on the basis of tissue and disease specific expression profile evaluation and highlights the requirement for the identification of new reference genes with greater expression stability for use in canine articular tissue gene expression studies.</p

Identification of new reference genes for the normalisation of canine osteoarthritic joint tissue transcripts from microarray data

<p>Abstract</p> <p>Background</p> <p>Real-time reverse transcriptase quantitative polymerase chain reaction (real-time RT-qPCR) is the most accurate measure of gene expression in biological systems. The comparison of different samples requires the transformation of data through a process called normalisation. Reference or housekeeping genes are candidate genes which are selected on the basis of constitutive expression across samples, and allow the quantification of changes in gene expression. At present, no reference gene has been identified for any organism which is universally optimal for use across different tissue types or disease situations. We used microarray data to identify new reference genes generated from total RNA isolated from normal and osteoarthritic canine articular tissues (bone, ligament, cartilage, synovium and fat). RT-qPCR assays were designed and applied to each different articular tissue. Reference gene expression stability and ranking was compared using three different mathematical algorithms.</p> <p>Results</p> <p>Twelve new potential reference genes were identified from microarray data. One gene (mitochondrial ribosomal protein S7 [<it>MRPS7</it>]) was stably expressed in all five of the articular tissues evaluated. One gene HIRA interacting protein 5 isoform 2 [<it>HIRP5</it>]) was stably expressed in four of the tissues evaluated. A commonly used reference gene glyceraldehyde-3-phosphate dehydrogenase (<it>GAPDH</it>) was not stably expressed in any of the tissues evaluated. Most consistent agreement between rank ordering of reference genes was observed between <it>Bestkeeper©</it> and geNorm, although each method tended to agree on the identity of the most stably expressed genes and the least stably expressed genes for each tissue. New reference genes identified using microarray data normalised in a conventional manner were more stable than those identified by microarray data normalised by using a real-time RT-qPCR methodology.</p> <p>Conclusion</p> <p>Microarray data normalised by a conventional manner can be filtered using a simple stepwise procedure to identify new reference genes, some of which will demonstrate good measures of stability. Mitochondrial ribosomal protein S7 is a new reference gene worthy of investigation in other canine tissues and diseases. Different methods of reference gene stability assessment will generally agree on the most and least stably expressed genes, when co-regulation is not present.</p

A proposed increase in retinal field-of-view may lead to spatial shifts in images

Visual information determines majority of our spatial behavior. The eye projects a 2-D image of the world on the retina. We demonstrate that when a monocular-like imaging system operates entirely with optically dense fluids, an increase in field-of-view (FOV) is observed compared to an experimental condition, where the ocular medium is optically neutral. Resulting spatial shifts in the retinal image towards the fovea complement the photoreceptor distribution pattern, incidentally revealing a new role for ocular fluids in the image space. Possible effects on the perceived egocentric object location are discussed.Comment: 13 pages, 2 figures, 1 tabl

Automated design analysis, assembly planning and motion study analysis using immersive virtual reality

Previous research work at Heriot-Watt University using immersive virtual reality (VR) for cable harness design showed that VR provided substantial productivity gains over traditional computer-aided design (CAD) systems. This follow-on work was aimed at understanding the degree to which aspects of this technology were contributed to these benefits and to determine if engineering design and planning processes could be analysed in detail by nonintrusively monitoring and logging engineering tasks. This involved using a CAD-equivalent VR system for cable harness routing design, harness assembly and installation planning that can be functionally evaluated using a set of creative design-tasks to measure the system and users' performance. A novel design task categorisation scheme was created and formalised which broke down the cable harness design process and associated activities. The system was also used to demonstrate the automatic generation of usable bulkhead connector, cable harness assembly and cable harness installation plans from non-intrusive user logging. Finally, the data generated from the user-logging allowed the automated activity categorisation of the user actions, automated generation of process flow diagrams and chronocyclegraphs

Using digital logs to reduce academic misdemeanour by students in digital forensic assessments

Identifying academic misdemeanours and actual applied effort in student assessments involving practical work can be problematic. For instance, it can be difficult to assess the actual effort that a student applied, the sequence and method applied, and whether there was any form of collusion or collaboration. In this paper we propose a system of using digital logs generated by selected software tools (such as FTK- Forensic Toolkit and EnCase), for the purpose of identifying the effort and sequence of events that students followed to complete their learning activities, (say, arriving at conclusions relating to an assessment question) and thereby determining whether it is likely that an academic misdemeanour may have occurred. The paper elaborates on an assessment exercise conducted with a cohort of 67 students in a specific class of disciplinary learning, highlighting the process that students have to follow, and then proceeds to show in some details how selected logging facilities can be used to provide evidence that students may have committed an academic misdemeanour