Functional genomic hypothesis generation and experimentation by a robot scientist

King R. D., Whelan, K. E., Jones, F. M., Reiser, P. G. K., Bryant, C. H., Muggleton, S., Kell, D. B. and Oliver, S. G. (2004) Functional genomic hypothesis generation and experimentation by a robot scientist. Nature 427 (6971) p247-252

Photonic integrated circuits for the generation of coherent optical signals

The demand for optical bandwidth continues to increase year on year and is being driven primarily by entertainment services and video streaming to the home. Current photonic systems are coping with this demand by increasing data rates through faster modulation techniques, spectrally efficient transmission systems and by increasing the number of modulated optical channels per fibre strand. Such photonic systems are large and power hungry due to the high number of discrete components required in their operation. Photonic integration offers excellent potential for combining otherwise discrete system components together on a single device to provide robust, power efficient and cost effective solutions. In particular, the design of optical modulators has been an area of immense interest in recent times. Not only has research been aimed at developing modulators with faster data rates, but there has also a push towards making modulators as compact as possible. Mach-Zehnder modulators (MZM) have proven to be highly successful in many optical communication applications. However, due to the relatively weak electro-optic effect on which they are based, they remain large with typical device lengths of 4 to 7 mm while requiring a travelling wave structure for high-speed operation. Nested MZMs have been extensively used in the generation of advanced modulation formats, where multi-symbol transmission can be used to increase data rates at a given modulation frequency. Such nested structures have high losses and require both complex fabrication and packaging. In recent times, it has been shown that Electro-absorption modulators (EAMs) can be used in a specific arrangement to generate Quadrature Phase Shift Keying (QPSK) modulation. EAM based QPSK modulators have increased potential for integration and can be made significantly more compact than MZM based modulators. Such modulator designs suffer from losses in excess of 40 dB, which limits their use in practical applications. The work in this thesis has focused on how these losses can be reduced by using photonic integration. In particular, the integration of multiple lasers with the modulator structure was considered as an excellent means of reducing fibre coupling losses while maximising the optical power on chip. A significant difficultly when using multiple integrated lasers in such an arrangement was to ensure coherence between the integrated lasers. The work investigated in this thesis demonstrates for the first time how optical injection locking between discrete lasers on a single photonic integrated circuit (PIC) can be used in the generation of coherent optical signals. This was done by first considering the monolithic integration of lasers and optical couplers to form an on chip optical power splitter, before then examining the behaviour of a mutually coupled system of integrated lasers. By operating the system in a highly asymmetric coupling regime, a stable phase locking region was found between the integrated lasers. It was then shown that in this stable phase locked region the optical outputs of each laser were coherent with each other and phase locked to a common master laser.

All-optical signal processing using semiconductor optical amplifiers for next generation optical networks

This thesis details an experimental and simulation investigation of some novel all-optical signal processing techniques for future optical communication networks. These all-optical techniques include modulation format conversion, phase discrimination and clock recovery. The methods detailed in this thesis use the nonlinearities associated with semiconductor optical amplifiers (SOA) to manipulate signals in the optical domain. Chapter 1 provides an introduction into the work detailed in this thesis, discusses the increased demand for capacity in today’s optical fibre networks and finally explains why all-optical signal processing may be of interest for future optical networks. Chapter 2 discusses the relevant background information required to fully understand the all-optical techniques demonstrated in this thesis. Chapter 3 details some pump-probe measurement techniques used to calculate the gain and phase recovery times of a long SOA. A remarkably fast gain recovery is observed and the wavelength dependent nature of this recovery is investigated. Chapter 4 discusses the experimental demonstration of an all-optical modulation conversion technique which can convert on-off- keyed data into either duobinary or alternative mark inversion. In Chapter 5 a novel phase sensitive frequency conversion scheme capable of extracting the two orthogonal components of a quadrature phase modulated signal into two separate frequencies is demonstrated. Chapter 6 investigates a novel all-optical clock recovery technique for phase modulated optical orthogonal frequency division multiplexing superchannels and finally Chapter 7 provides a brief conclusion.

Placement of Small Vertical Axis Wind Turbine to Maximize Power Generation Influenced by Architectural and Geographic Interfaces in Urban Areas

Current methods for large-scale wind collection are unviable in urban areas. In order to investigate the feasibility of generating power from winds in these environments, we sought to optimize placements of small vertical-axis wind turbines in areas of artificially-generated winds. We explored both vehicular transportation and architecture as sources of artificial wind, using a combination of anemometer arrays, global positioning system (GPS), and weather report data. We determined that transportation-generated winds were not significant enough for turbine implementation. In addition, safety and administrative concerns restricted the implementation of said wind turbines along roadways for transportation-generated wind collection. Wind measurements from our architecture collection were applied in models that can help predict other similar areas with artificial wind, as well as the optimal placement of a wind turbine in those areas.

Automatic parallel code generation for message passing on distributed memory systems

The availability of a very accurate dependence graph for a scalar code is the basis for the automatic generation of an efficient parallel implementation. The strategy for this task which is encapsulated in a comprehensive data partitioning code generation algorithm is described. This algorithm involves the data partition, calculation of assignment ranges for partitioned arrays, addition of a comprehensive set of execution control masks, altering loop limits, addition and optimisation of communications for all data. In this context, the development and implementation of strategies to merge communications wherever possible has proved an important feature in producing efficient parallel implementations for numerical mesh based codes. The code generation strategies described here are embedded within the Computer Aided Parallelisation tools (CAPTools) software as a key part of a toolkit for automating as much as possible of the parallelisation process for mesh based numerical codes. The algorithms used enables parallelisation of real computational mechanics codes with only minor user interaction and without any prior manual customisation of the serial code to suit the parallelisation tool.

Podcasting - delivering learning to the iTunes generation

The Guardian newspaper (21st October 2005) informed its readers that: "Stanford University in California is to make its course content available on iTunes...The service, Stanford on iTunes, will provide…downloads of faculty lectures, campus events, performances, book readings, music recorded by Stanford students and even podcasts of Stanford football games". The emergence of Podcasting as means of sending audio data to users has clearly excited educational technologists around the world. This paper will explore the technologies behind Podcasting and how this could be used to develop and deliver new E-Learning material. The paper refers to the work done to create Podcasts of lectures for University of Greenwich students.

On efficient data integrity and data origin authentication for wireless sensor networks utilising block cipher design techniques

Analysis of the generic attacks and countermeasures for block cipher based message authentication code algorithms (MAC) in sensor applications is undertaken; the conclusions are used in the design of two new MAC constructs Quicker Block Chaining MAC1 (QBC-MAC1) and Quicker Block Chaining MAC2 (QBC-MAC2). Using software simulation we show that our new constructs point to improvements in usage of CPU instruction clock cycle and energy requirement when benchmarked against the de facto Cipher Block Chaining MAC (CBC-MAC) based construct used in the TinySec security protocol for wireless sensor networks.

Towards Data Management Planning Support for Research Data

Görzig, H., Engel, F., Brocks, H., Vogel, T. & Hemmje, M. (2015, August). Towards Data Management Planning Support for Research Data. Paper presented at the ASE International Conference on Data Science, Stanford, United States of America.

Annual westward propagating anomalies near 26 degrees N and eddy generation south of the Canary Islands: remote sensing (altimeter/SeaWIFS) and in situ measurement

Seasonal changes in altimeter data are derived for the North Atlantic Ocean. Altimeter data are then used to examine annually propagating structure along 26 degree N. By averaging the altimeter data into monthly values or by Fourier analysis, a positive anomaly can be followed from 17 degree W to similar to 50 degree W along similar to 26 degree N. The methods give a westward travel speed of 1 degree of longitude a month and a half-life of one year for the average decaying structure. At similar to 50 degree W 26 degree N, the average structure is about 2.8 years old with an elevation signal of similar to 1 cm, having gravelled similar to 3300 km westward. The mean positive anomaly results from the formation of anticyclonic eddies which are generally formed annually south of the Canary Islands by late summer and which then travel westward near 26 degree N. Individual eddy structure along 26 degree N is examined and related to in situ measurements and anomalies in the annual seasonal concentration cycle of SeaWiFS chlorophyll-a.

Composite front maps for improved visibility of dynamic sea-surface features on cloudy SeaWiFS and AVHRR data

Novel techniques have been developed for increasing the value of cloud-affected sequences of Advanced Very High Resolution Radiometer (AVHRR) sea-surface temperature (SST) data and Sea-viewing Wide Field-of-view Sensor (SeaWiFS) ocean colour data for visualising dynamic physical and biological oceanic processes such as fronts, eddies and blooms. The proposed composite front map approach is to combine the location, strength and persistence of all fronts observed over several days into a single map, which allows intuitive interpretation of mesoscale structures. This method achieves a synoptic view without blurring dynamic features, an inherent problem with conventional time-averaging compositing methods. Objective validation confirms a significant improvement in feature visibility on composite maps compared to individual front maps. A further novel aspect is the automated detection of ocean colour fronts, correctly locating 96% of chlorophyll fronts in a test data set. A sizeable data set of 13,000 AVHRR and 1200 SeaWiFS scenes automatically processed using this technique is applied to the study of dynamic processes off the Iberian Peninsula such as mesoscale eddy generation, and many additional applications are identified. Front map animations provide a unique insight into the evolution of upwelling and eddies.

Next Generation Sequencing Reveals the Hidden Diversity of Zooplankton Assemblages

Zooplankton play an important role in our oceans, in biogeochemical cycling and providing a food source for commercially important fish larvae. However, difficulties in correctly identifying zooplankton hinder our understanding of their roles in marine ecosystem functioning, and can prevent detection of long term changes in their community structure. The advent of massively parallel next generation sequencing technology allows DNA sequence data to be recovered directly from whole community samples. Here we assess the ability of such sequencing to quantify richness and diversity of a mixed zooplankton assemblage from a productive time series site in the Western English Channel. Methodology/Principle Findings Plankton net hauls (200 µm) were taken at the Western Channel Observatory station L4 in September 2010 and January 2011. These samples were analysed by microscopy and metagenetic analysis of the 18S nuclear small subunit ribosomal RNA gene using the 454 pyrosequencing platform. Following quality control a total of 419,041 sequences were obtained for all samples. The sequences clustered into 205 operational taxonomic units using a 97% similarity cut-off. Allocation of taxonomy by comparison with the National Centre for Biotechnology Information database identified 135 OTUs to species level, 11 to genus level and 1 to order, <2.5% of sequences were classified as unknowns. By comparison a skilled microscopic analyst was able to routinely enumerate only 58 taxonomic groups. Conclusions Metagenetics reveals a previously hidden taxonomic richness, especially for Copepoda and hard-to-identify meroplankton such as Bivalvia, Gastropoda and Polychaeta. It also reveals rare species and parasites. We conclude that Next Generation Sequencing of 18S amplicons is a powerful tool for elucidating the true diversity and species richness of zooplankton communities. While this approach allows for broad diversity assessments of plankton it may become increasingly attractive in future if sequence reference libraries of accurately identified individuals are better populated.

Modelling and Prediction of NOx Emission in a Coal-Fired Power Generation Plant

In this paper NOx emissions modelling for real-time operation and control of a 200 MWe coal-fired power generation plant is studied. Three model types are compared. For the first model the fundamentals governing the NOx formation mechanisms and a system identification technique are used to develop a grey-box model. Then a linear AutoRegressive model with eXogenous inputs (ARX) model and a non-linear ARX model (NARX) are built. Operation plant data is used for modelling and validation. Model cross-validation tests show that the developed grey-box model is able to consistently produce better overall long-term prediction performance than the other two models.

Effects of the novel (Pro(3))GIP antagonist and exendin(9-39)amide on GIP- and GLP-1-induced cyclic AMP generation, insulin secretion and postprandial insulin release in obese diabetic (ob/ob) mice: evidence that GIP is the major physiological incretin

AIMS/HYPOTHESIS: This study examined the biological effects of the GIP receptor antagonist, (Pro3)GIP and the GLP-1 receptor antagonist, exendin(9-39)amide.

METHODS: Cyclic AMP production was assessed in Chinese hamster lung fibroblasts transfected with human GIP or GLP-1 receptors, respectively. In vitro insulin release studies were assessed in BRIN-BD11 cells while in vivo insulinotropic and glycaemic responses were measured in obese diabetic ( ob/ ob) mice.

RESULTS: In GIP receptor-transfected fibroblasts, (Pro(3))GIP or exendin(9-39)amide inhibited GIP-stimulated cyclic AMP production with maximal inhibition of 70.0+/-3.5% and 73.5+/-3.2% at 10(-6) mol/l, respectively. In GLP-1 receptor-transfected fibroblasts, exendin(9-39)amide inhibited GLP-1-stimulated cyclic AMP production with maximal inhibition of 60+/-0.7% at 10(-6) mol/l, whereas (Pro(3))GIP had no effect. (Pro(3))GIP specifically inhibited GIP-stimulated insulin release (86%; p<0.001) from clonal BRIN-BD11 cells, but had no effect on GLP-1-stimulated insulin release. In contrast, exendin(9-39)amide inhibited both GIP and GLP-1-stimulated insulin release (57% and 44%, respectively; p<0.001). Administration of (Pro(3))GIP, exendin(9-39)amide or a combination of both peptides (25 nmol/kg body weight, i.p.) to fasted (ob/ob) mice decreased the plasma insulin responses by 42%, 54% and 49%, respectively (p<0.01 to p<0.001). The hyperinsulinaemia of non-fasted (ob/ob) mice was decreased by 19%, 27% and 18% (p<0.05 to p<0.01) by injection of (Pro3)GIP, exendin(9-39)amide or combined peptides but accompanying changes of plasma glucose were small.

CONCLUSIONS/INTERPRETATION: These data show that (Pro(3))GIP is a specific GIP receptor antagonist. Furthermore, feeding studies in one commonly used animal model of obesity and diabetes, (ob/ob) mice, suggest that GIP is the major physiological component of the enteroinsular axis, contributing approximately 80% to incretin-induced insulin release.

Development of complex classical force fields through force matching to ab initio data: Application to a room-temperature ionic liquid

Recent experimental neutron diffraction data and ab initio molecular dynamics simulation of the ionic liquid dimethylimidazolium chloride ([dmim]Cl) have provided a structural description of the system at the molecular level. However, partial radial distribution functions calculated from the latter, when compared to previous classical simulation results, highlight some limitations in the structural description offered by force fieldbased simulations. With the availability of ab initio data it is possible to improve the classical description of [dmim]Cl by using the force matching approach, and the strategy for fitting complex force fields in their original functional form is discussed. A self-consistent optimization method for the generation of classical potentials of general functional form is presented and applied, and a force field that better reproduces the observed first principles forces is obtained. When used in simulation, it predicts structural data which reproduces more faithfully that observed in the ab initio studies. Some possible refinements to the technique, its application, and the general suitability of common potential energy functions used within many ionic liquid force fields are discussed.

Enhanced cAMP generation and insulin-releasing potency of two novel Tyr(1)-modified enzyme-resistant forms of glucose-dependent insulinotropic polypeptide is associated with significant antihyperglycaemic activity in spontaneous obesity-diabetes

Glucose-dependent insulinotropic polypeptide (GIP) is an important incretin hormone, which potentiates glucose-induced insulin secretion. Antihyperglycaemic actions of GIP provide significant potential in Type 11 diabetes therapy. However, inactivation of GIP by the enzyme dipeptidyl peptidase IV (DPP IV) and its consequent short circulating half-life limit its therapeutic use. Therefore two novel Tyr(1)-Modified analogues of GIP, N-Fmoc-GIP (where Fmoc is 9-fluorenylmethoxycarbonyl) and N-palmitate-GIP, were synthesized and tested for metabolic stability and biological activity. Both GIP analogues were resistant to degradation by DPP IV and human plasma. In Chinese hamster lung (CHL) cells expressing the cloned human GIP receptor, both analogues exhibited a 2-fold increase in cAMP-generating potency compared with native GIP (EC50 values of 9.4, 10.0 and 18.2 nM respectively). Using clonal BRIN-BD11 cells, both analogues demonstrated strong insulinotropic activity compared with native GIP (P <0.01 to P <0.001). In obese diabetic (ob/ob) mice, administration of N-Fmoc-GIP or N-palmitate-GIP (25 nmol/kg) together with glucose (18 mmol/kg) significantly reduced the peak 15 min glucose excursion (1.4- and 1.5-fold respectively; P <0.05 to P <0.01) compared with glucose alone. The area under the curve (AUC) for glucose was significantly lower after administration of either analogue compared with glucose administered alone or in combination with native GIP (1.5-fold; P <0.05). This was associated with a significantly greater AUC for insulin (2.1-fold; P <0.001) for both analogues compared with native GIP. A similar pattern of in vivo responsiveness was evident in lean control mice. These data indicate that novel N-terminal Tyr(1) modification of GIP with an Fmoc or palmitate group confers resistance to degradation by DPP IV in plasma, which is reflected by increased in vitro potency and greater insulinotropic and antihyperglycaemic activities in an animal model of Type 11 diabetes mellitus.