Ultracam - An Ultra-Fast Triple-Beam CCD Camera

ULTRACAM is a high-speed three-colour CCD camera designed to provide imaging photometry at high temporal resolutions. The instrument is highly portable and will be used at a number of large telescopes around the world. ULTRACAM was successfully commissioned on the 4.2-m William Herschel Telescope on La Palma on 16 May 2002 over 3 months ahead of schedule and within budget. The instrument was funded by PPARC and designed and built by a consortium involving the Universities of Sheffield Southampton and the UKATC Edinburgh. We present an overview of the design and performance characteristics of ULTRACAM and highlight some of its most recent scientific results.

First development and characterisation of polyclonal and monoclonal antibodies to the emerging fresh water toxin cylindrospermopsin

As increasing incidences in the occurrence of cylindrospermopsin (CYN) appear, in addition to further research on its toxicological nature, improved rapid methods to detect this toxin are required. Antibody based assays are renowned for their ability to provide rapid, portable, simple to use tests. As yet however there are no publications outlining how an antibody to CYN can be produced. A range of chemical approaches was investigated to synthesise CYN immunogens for antibody production but failed to generate a response. Finally, a modified Mannich reaction for immunogen synthesis was employed to couple the toxin to two carrier proteins. Both protein conjugates were successfully used to raise both polyclonal and monoclonal antibodies of high sensitivity to CYN. These antibodies were characterised employing competitive indirect ELISA and an optical biosensor assay. By ELISA the sensitivity achieved ranged from 27 to 131. pg/mL and by SPR 4.4 to 11.1. ng/mL thus demonstrating that the selection of immunoassay platform is important for the detection level required by the end user for their application. Low cross-reactivity to the much less toxic metabolite deoxyCYN was observed. This is the first reported production of antibodies to this toxin. © 2013 Elsevier B.V.

Extremely Complex Populations of Small RNAs in the Mouse Retina and RPE/Choroid

Purpose: MicroRNAs (miRNAs) are small non-coding RNAs of ~18-22 nucleotides in length that regulate gene expression. They are widely expressed in the retina, being both required for its normal development and perturbed in disease. The aim of this study was to apply new high-throughput sequencing techniques to more fully characterise the microRNAs and other small RNAs expressed in the retina and retinal pigment epithelium (RPE)/choroid of the mouse.

Methods: Retina and RPE/choroid were dissected from eyes of 3 month-old C57BL/6J mice. Small RNA libraries were prepared and deep sequencing performed on a Genome Analyzer (Illumina). Reads were annotated by alignment to miRBase, other non-coding RNA databases and the mouse genome.

Results: Annotation of 9 million reads to 320 microRNAs in retina and 340 in RPE/choroid provides the most comprehensive profiling of microRNAs to date. Two novel microRNAs were identified in retina. Members of the sensory organ specific miR-183,-182,-96 cluster were amongst the most highly expressed, retina-enriched microRNAs. Remarkably, microRNA 'isomiRs', which vary slightly in length and are differentially detected by Taqman RT-PCR assays, existed for all the microRNAs identified in both tissues. More variation occurred at the 3' ends, including non-templated additions of T and A. Drosha-independent mirtron microRNAs and other small RNAs derived from snoRNAs were also detected.

Conclusions: Deep sequencing has revealed the complexity of small RNA expression in the mouse retina and RPE/choroid. This knowledge will improve the design and interpretation of future functional studies of the role of microRNAs and other small RNAs in retinal disease.

Examining the Neurocognitive Validity of Commercially Available, Smartphone-Based Puzzle Games

Cognitive assessment typically involves assessing a person’s cognitive performance in unfamiliar and ar-guably unnatural clinical surroundings. User-centred approaches to assessment and monitoring, driven by issues such as enjoyability and familiarity, are largely absent. Everyday technologies, for example, smartphones represent an opportunity to obtain an objective assessment of a person’s cognitive capabili-ties in a non-threatening, discreet and familiar way, e.g. by everyday puzzle games undertaken as a leisure activity at home. We examined the strength of relationships that exist between performance on common puzzle games and standard measures of neuropsychological performance. Twenty-nine participants, aged 50 - 65 years, completed a comprehensive neuropsychological test battery and played three smart-phone-based puzzle games in triplicate: a picture puzzle [Matches Plus], a word puzzle [Jumbline] and a number puzzle [Sudoku]. As anticipated, a priori, significant correlations were observed between scores on a picture puzzle and visual memory test (r = 0.49; p = 0.007); a word puzzle and estimated verbal IQ (r = 0.53; p = 0.003) and verbal learning (r = 0.30; p = 0.039) tests; and a number puzzle and reason-ing/problem solving test (r = 0.42; p = 0.023). Further analyses making allowance for multiple compari-sons identified a significant unanticipated correlation (r = 0.49; p = 0.007) between number puzzle scores and a measure of nonverbal working memory. Performance on these smartphone-based games was in-dicative of relative cognitive ability across several cognitive domains at a fixed time point. Smart-phone-based, everyday puzzle games may offer a valid, portable measure of assessing and monitoring cognition in older adults.

Hybrid address spaces: A methodology for implementing scalable high-level programming models on non-coherent many-core architectures

This paper introduces hybrid address spaces as a fundamental design methodology for implementing scalable runtime systems on many-core architectures without hardware support for cache coherence. We use hybrid address spaces for an implementation of MapReduce, a programming model for large-scale data processing, and the implementation of a remote memory access (RMA) model. Both implementations are available on the Intel SCC and are portable to similar architectures. We present the design and implementation of HyMR, a MapReduce runtime system whereby different stages and the synchronization operations between them alternate between a distributed memory address space and a shared memory address space, to improve performance and scalability. We compare HyMR to a reference implementation and we find that HyMR improves performance by a factor of 1.71× over a set of representative MapReduce benchmarks. We also compare HyMR with Phoenix++, a state-of-art implementation for systems with hardware-managed cache coherence in terms of scalability and sustained to peak data processing bandwidth, where HyMR demon- strates improvements of a factor of 3.1× and 3.2× respectively. We further evaluate our hybrid remote memory access (HyRMA) programming model and assess its performance to be superior of that of message passing.

Containing the Nanometer "Pandora-Box": Cross-Layer Design Techniques for Variation Aware Low Power Systems

The demand for richer multimedia services, multifunctional portable devices and high data rates can only been visioned due to the improvement in semiconductor technology. Unfortunately, sub-90 nm process nodes uncover the nanometer Pandora-box exposing the barriers of technology scaling-parameter variations, that threaten the correct operation of circuits, and increased energy consumption, that limits the operational lifetime of today's systems. The contradictory design requirements for low-power and system robustness, is one of the most challenging design problems of today. The design efforts are further complicated due to the heterogeneous types of designs ( logic, memory, mixed-signal) that are included in today's complex systems and are characterized by different design requirements. This paper presents an overview of techniques at various levels of design abstraction that lead to low power and variation aware logic, memory and mixed-signal circuits and can potentially assist in meeting the strict power budgets and yield/quality requirements of future systems.

Role of saphenous vein wall in the pathogenesis of primary varicose veins

UNLABELLED: Varicose veins may be due to weakness of the vein wall as a result of structural problems. There are conflicting findings in the literature about these problems especially concerning collagen, elastin and smooth muscle cells content. The aim of this study was to look at the structural abnormalities of varicose veins (with and without valvular incompetence).

MATERIALS AND METHODS: We studied 70 specimens of long saphenous veins from 35 patients (24 with varicose and 11 with normal veins). Two specimens were taken from each vein approximately 3-4 cm from the saphenofemoral junction. Vein specimens were processed for histological and electron microscopic studies. Both qualitative and quantitative analyses were performed to assess the degree of wall changes. Using the image analyzer, contents of collagen, elastin and smooth muscle cells, in addition to intimal and medial thickness, were measured.

RESULTS: Light microscopy revealed significant increase in intimal and medial thickness and collagen content of media and significant decrease in elastin content in varicose veins compared with normal veins. There was no statistical significant difference between varicose veins with and without saphenofemoral valve incompetence. Electron microscopy showed marked degenerative changes in intima and media of varicose veins.

CONCLUSION: The findings in our study supported the theory of primary weakness of the vein wall as a cause of varicosity. This weakness is due to intimal changes, disturbance in the connective tissue components and smooth muscle cells.

Rapid design of discrete orthonormal wavelet transforms using silicon IP components

A rapid design methodology for orthonormal wavelet transform cores has been developed. This methodology is based on a generic, scaleable architecture utilising time-interleaved coefficients for the wavelet transform filters. The architecture has been captured in VHDL and parameterised in terms of wavelet family, wavelet type, data word length and coefficient word length. The control circuit is embedded within the cores and allows them to be cascaded without any interface glue logic for any desired level of decomposition. Case studies for stand alone and cascaded silicon cores for single and multi-stage wavelet analysis respectively are reported. The design time to produce silicon layout of a wavelet based system has been reduced to typically less than a day. The cores are comparable in area and performance to handcrafted designs. The designs are portable across a range of foundries and are also applicable to FPGA and PLD implementations.

Synthesisable FFT cores

Methods are presented for developing synthesisable FFT cores. These are based on a modular approach in which parameterisable blocks are cascaded to implement the computations required across a range of typical FFT signal flow graphs. The underlying architectural approach combines the use of a digital serial data organisation with generic commutator blocks to produce systems that offer 100% processor utilisation with storage requirements less than previous designs. The approach has been used to create generators for the automated synthesis of FFT cores that are portable across a broad range of silicon technologies. Resulting chip designs are competitive with manual methods but with significant reductions in design times.

Laboratizing the border: The production, translation and anticipation of security technologies

This paper critically interrogates how borders are produced by scientists, engineers and security experts in advance of the actual deployment of technical devices they develop. This paper explores the prior stages of translation and decision-making as a socio-technical device is conceived and developed. Drawing on in-depth interviews, observations and ethnographic research of the EU-funded Handhold project (consisting of nine teams in five countries), it explores how assumptions about the way security technologies will and should perform at the border shape the way that scientists, engineers, and security experts develop a portable, integrated device to detect CBRNE threats at borders. In disaggregating the moments of sovereign decision making across multiple sites and times, this paper questions the supposed linearity of how science comes out of and feeds back into the world of border security. An interrogation of competing assumptions and understandings of security threats and needs, of competing logics of innovation and pragmatism, of the demands of differentiated temporalities in detection and interrogation, and of the presumed capacities, behaviours, and needs of phantasmic competitors and end-users reveals a complex, circulating and co-constitutive process of device development that laboratises the border itself. We trace how sovereign decisions are enacted as assemblages in the antecedent register of device development itself through the everyday decisions of researchers in the laboratory, and the material components of the Handhold device itself.

A quality-scalable and energy-efficient approach for spectral analysis of heart rate variability

Today there is a growing interest in the integration of health monitoring applications in portable devices necessitating the development of methods that improve the energy efficiency of such systems. In this paper, we present a systematic approach that enables energy-quality trade-offs in spectral analysis systems for bio-signals, which are useful in monitoring various health conditions as those associated with the heart-rate. To enable such trade-offs, the processed signals are expressed initially in a basis in which significant components that carry most of the relevant information can be easily distinguished from the parts that influence the output to a lesser extent. Such a classification allows the pruning of operations associated with the less significant signal components leading to power savings with minor quality loss since only less useful parts are pruned under the given requirements. To exploit the attributes of the modified spectral analysis system, thresholding rules are determined and adopted at design- and run-time, allowing the static or dynamic pruning of less-useful operations based on the accuracy and energy requirements. The proposed algorithm is implemented on a typical sensor node simulator and results show up-to 82% energy savings when static pruning is combined with voltage and frequency scaling, compared to the conventional algorithm in which such trade-offs were not available. In addition, experiments with numerous cardiac samples of various patients show that such energy savings come with a 4.9% average accuracy loss, which does not affect the system detection capability of sinus-arrhythmia which was used as a test case. 

Development of a rapid multiplexed assay for the direct screening of antimicrobial residues in raw milk

Antimicrobial residues found to be present in milk can have both health and economic impacts. For these reasons, the widespread routine testing of milk is required. Due to delays with sample handling and test scheduling, laboratory-based tests are not always suited for making decisions about raw material intake and product release, especially when samples require shipping to a central testing facility. Therefore, rapid on-site screening tests that can produce results within a matter of minutes are required to facilitate rapid intake and product release processes. Such tests must be simple for use by non-technical staff. There is increasing momentum towards the development and implementation of multiplexing tests that can detect a range of important antimicrobial residues simultaneously. A simple in situ multiplexed planar waveguide device that can simultaneously detect chloramphenicol, streptomycin and desfuroylceftiofur in raw dairy milk, without sample preparation, has been developed. Samples are simply mixed with antibody prior to an aliquot being passed through the detection cartridge for 5 min before reading on a field-deployable portable instrument. Multiplexed calibration curves were produced in both buffer and raw milk. Buffer curves, for chloramphenicol, streptomycin and desfuroylceftiofur, showed linear ranges (inhibitory concentration (IC)₂₀–IC₈₀) of 0.1–0.9, 3–129 and 12–26 ng/ml, whilst linear range in milk was 0.13–0.74, 11–376 and 2–12 ng/ml, respectively, thus meeting European legislated concentration requirements for both chloramphenicol and streptomycin, in milk, without the need for any sample preparation. Desfuroylceftiofur-contaminated samples require only simple sample dilution to bring positive samples within the range of quantification. Assay repeatability and reproducibility were lower than 12 coefficient of variation (%CV), whilst blank raw milk samples (n = 9) showed repeatability ranging between 4.2 and 8.1 %CV when measured on all three calibration curves.

On-site monitoring and cartographical mapping of heavy metals

This paper presents a portable electrochemical instrument capable of real-time in situ detection and automatic identification of heavy metals. The instrument is equipped with an embedded Geographical Position System and is capable of storing the geographical position of the sample under test. Software has been developed to combine pollutant results with geographical position, in order to produce a cartographical presentation of the pollution of an area. The electrochemical instrument provides the facilities found in a traditional lab based instrument in a portable design for on-site measurements. The instrument is capable of detecting lead, cadmium, zinc, nickel, mercury, and copper with good sensitivity and precision. The system is reliable, easy to use, safe, and it may be used in a variety of situations to help environmental assessment and control.

Intelligent potentiostat for identification of heavy metals in situ

This article presents a low-cost portable electrochemical instrument capable of on-site identification of heavy metals. The instrument acquires metal-specific voltage and current signals by the application of differential pulse anodic stripping voltammetry. This technique enhances the analytical current and rejects the background current, resulting in a higher signal-to-noise ratio for a better detection limit. The identification of heavy metals is based on an intelligent machine-based method using a multilayer perceptron neural network consisting of three layers of neurons. The neural network is implemented using a 16 bit microcontroller. The system is developed for use in the field in order to avoid expensive and time-consuming procedures and can be used in a variety of situations to help environmental assessment and control. 

Use of Inhaled Tobramycin in Cystic Fibrosis

Chronic infection with Pseudomonas aeruginosa is associated with poor outcomes in patients with cystic fibrosis (CF). It leads to a reduced quality of life, acceleration of the decline in lung function, and increased frequency and severity of pulmonary exacerbations. Tobramycin, administered by inhalation as a long-term therapy, decreases bacterial density in airways, reduces exacerbation frequency, and improves quality of life and lung function in patients with chronic P. aeruginosa infection. In the last decade, tobramycin inhalation has become an important contributor to CF treatment as a means to control chronic infection and as a first-line treatment for the eradication of early acquisition of P. aeruginosa. Recently, a dry powder inhalation (DPI) form of tobramycin has become available, which is more convenient for administration and has comparable efficacy to the tobramycin solution. This DPI, the Podhaler™ (Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA), requires less time for treatment delivery and is more portable than a nebulizer, and so is a welcome additional therapeutic option for many patients.