An Interactive Visualisation System for Engineering Design using Evolutionary Computing

This thesis describes a system designed to promote collaboration between the human and computer during engineering design tasks. Evolutionary algorithms (in particular the genetic algorithm) can find good solutions to engineering design problems in a small number of iterations, but a review of the interactive evolutionary computing literature reveals that users would benefit from understanding the design space and having the freedom to direct the search. The main objective of this research is to fulfil a dual requirement: the computer should generate data and analyse the design space to identify high performing regions in terms of the quality and robustness of solutions, while at the same time the user should be allowed to interact with the data and use their experience and the information provided to guide the search inside and outside regions already found. To achieve these goals a flexible user interface was developed that links and clarifies the research fields of evolutionary computing, interactive engineering design and multivariate visualisation. A number of accessible visualisation techniques were incorporated into the system. An innovative algorithm based on univariate kernel density estimation is introduced that quickly identifies the relevant clusters in the data from the point of view of the original design variables or a natural coordinate system such as the principal or independent components. The robustness of solutions inside a region can be investigated by novel use of 'negative' genetic algorithm search to find the worst case scenario. New high performance regions can be discovered in further runs of the evolutionary algorithm; penalty functions are used to avoid previously found regions. The clustering procedure was also successfully applied to multiobjective problems and used to force the genetic algorithm to find desired solutions in the trade-off between objectives. The system was evaluated by a small number of users who were asked to solve simulated engineering design scenarios by finding and comparing robust regions in artificial test functions. Empirical comparison with benchmark algorithms was inconclusive but it was shown that even a devoted hybrid algorithm needs help to solve a design task. A critical analysis of the feedback and results suggested modifications to the clustering algorithm and a more practical way to evaluate the robustness of solutions. The system was also shown to experienced engineers working on their real world problems, new solutions were found in pertinent regions of objective space; links to the artefact aided comparison of results. It was confirmed that in practice a lot of design knowledge is encoded into design problems but experienced engineers use subjective knowledge of the problem to make decisions and evaluate the robustness of solutions. So the full potential of the system was seen in its ability to support decision making by supplying a diverse range of alternative design options, thereby enabling knowledge discovery in a wide-ranging number of applications

Metabolic targets of watercress and PEITC in MCF-7 and MCF-10A cells explain differential sensitisation responses to ionising radiation

Watercress is a rich source of phytochemicals with anticancer potential, including phenethyl isothiocyanate (PEITC). We examined the potential for watercress extracts and PEITC to increase the DNA damage caused by ionising radiation (IR) in breast cancer cells and to be protective against radiation-induced collateral damage in healthy breast cells. The metabolic events that mediate such responses were explored using metabolic profiling. H nuclear magnetic resonance spectroscopy-based metabolic profiling was coupled with DNA damage-related assays (cell cycle, Comet assay, viability assays) to profile the comparative effects of watercress and PEITC in MCF-7 breast cancer cells and MCF-10A non-tumorigenic breast cells with and without exposure to IR. Both the watercress extract and PEITC-modulated biosynthetic pathways of lipid and protein synthesis and resulted in changes in cellular bioenergetics. Disruptions to the redox balance occurred with both treatments in the two cell lines, characterised by shifts in the abundance of glutathione. PEITC enhanced the sensitivity of the breast cancer cells to IR increasing the effectiveness of the cancer-killing process. In contrast, watercress-protected non-tumorigenic breast cells from radiation-induced damage. These effects were driven by changes in the cellular content of the antioxidant glutathione following exposure to PEITC and other phytochemicals in watercress. These findings support the potential prophylactic impact of watercress during radiotherapy. Extracted compounds from watercress and PEITC differentially modulate cellular metabolism collectively enhancing the therapeutic outcomes of radiotherapy

Land use and vegetation change on the Long Mynd

The plant communities of the Long Mynd plateau are the culmination of over 3000 years of human intervention that largely deforested the uplands, and subsequently maintained the generally treeless heath and grassland communities now extant. The capacity of these communities to respond to directional change is well known, indeed the traditional mode of heathland management, burning, depends on the regenerative capacity of the target species, generally heather (Calluna vulgaris), for its success. However, changes in post WW2 stocking practice; the loss of ponies followed by an increase in the numbers of sheep and a change to them being overwintered on the hill, led to excessive grazing and damage to the heath. This coincided with the spread over the hill by bracken (Pteridium aquilinum) and other changes in the distribution and nature of the vegetation. A sequence of vegetation surveys made by various individuals and organisations over the past 75 years or so has been analysed in an attempt to delineate spatial and temporal changes in the vegetation. This demonstrated the need for a standardised survey methodology to allow consistent monitoring. The analysis showed that bracken had been infiltrating most of the communities from its origins outside the lower limits of the Common as well as from some of the valley sides. Within the last decade, this expansion has apparently been contained in line with the current management plan for control. A survey of 730 quadrats in some 30 stands was made to characterise the variation of the vegetation on the plateau, and to relate it to some of the associated environmental factors. Classification, unconstrained ordination and ordination constrained by the abiotic environmental variables, showed that, a) the strongest trend in the vegetation distinguished water-flushed communities, b) non-wetland communities differentiate between heathland and grassland, c) this trend can be only partly be attributed to the measured abiotic environmental variables, d) the amount of pure Pteridietum [U20] is limited, although much of the heathland and grassland has bracken within it. There are indications that invasion by bracken often correlates with a loss of dominance of Calluna in favour of Deschampsia flexuosa and Vaccinium myrtillus. Difficulties in associating these trends with measured abiotic variables suggests, other factors probably management processes, are critical in driving this trend. Distribution of ‘heathland’ bryophytes was found to be associated more with the structure of their ‘host’ vascular communities rather than with abiotic factors. Finally, this investigation considers the practical implications with regard to the future encouragement of heather and the control of bracken. Cutting rather than burning appears to be the ecologically most suitable method for heather regeneration and bracken control.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

An HST Morphological Survey of Faint EROs

We present the results from a survey for Extremely Red Objects (EROs) in deep, high resolution optical images taken from the Hubble Space Telescope (HST) Medium Deep Survey. We have surveyed 35 deep F814W HST/WFPC2 fields in the near-infrared to a typical depth of K~20. From a total area of 206 arcmin^2 and to a limit of K=20.0 we identify 224 EROs ((1.14+/-0.08) arcmin^-2) with (I_{814}-K)=>4.0 and 83 ((0.41+/-0.05) arcmin^-2) with (I_{814}-K)=>5.0. We find that the slope of the number counts of the (I_{814}-K)=>4.0 EROs flattens beyond K~19, in line with results from previous surveys, and the typical colours of the EROs become redder beyond the break magnitude. We morphologically classify our ERO sample using visual and quantitative schemes and find that 35% of our sample exhibit clear disk components, 15% are disturbed or irregular, a further 30% are either spheroidal or compact and the remaining 20% are unclassifiable. Using a quantitative measure of morphology, we find that the ERO morphological distribution evolves across the break in their counts, such that low concentration (disk-like) galaxies decline. We relate the morphological and colour information for our EROs and conclude that those EROs morphologically classified as bulges do indeed possess SEDs consistent with passive stellar populations; while EROs with dusty star-forming SEDs are mostly associated with disk-like and peculiar galaxies. However, ~30% of disk EROs reside in the passive region of I/J/K colour-colour space. These could be either genuinely passive systems, lower redshift contaminants to the high-z ERO population, or systems with composite star-forming and passive SEDs.Comment: 20 pages, 14 figures. MNRAS submitted, revised in response to referee's comment

Confirmation of TNIP1 and IL23A as susceptibility loci for psoriatic arthritis

Objectives: To investigate a shared genetic aetiology for skin involvement in psoriasis and psoriatic arthritis (PsA) by genotyping single-nucleotide polymorphisms (SNPs), reported to be associated in genome-wide association studies of psoriasis, in patients with PsA. Methods: SNPs with reported evidence for association with psoriasis were genotyped in a PsA case and control collection from the UK and Ireland. Genotype and allele frequencies were compared between PsA cases and controls using the Armitage test for trend. Results: Seven SNPs mapping to the IL1RN, TNIP1, TNFAIP3, TSC1, IL23A, SMARCA4 and RNF114 genes were successfully genotyped. The IL23A and TNIP1 genes showed convincing evidence for association (rs2066808, p = 9.1 x 10 ?7 ; rs17728338, p = 3.5 x 10 ?5 , respectively) whilst SNPs mapping to the TNFAIP3, TSC1 and RNF114 genes showed nominal evidence for association (rs610604, p = 0.03; rs1076160, p = 0.03; rs495337, p = 0.0025). No evidence for association with IL1RN or SMARCA4 was found but the power to detect association was low. Conclusions: SNPs mapping to previously reported psoriasis loci show evidence for association to PSA, thus supporting the hypothesis that the genetic aetiology of skin involvement is the same in both PsA and psoriasi

Evidence to support IL-13 as a risk locus for psoriatic arthritis but not psoriasis vulgaris

Objective: There is great interest in the identification of genetic factors that differentiate psoriatic arthritis (PsA) from psoriasis vulgaris (PsV), as such discoveries could lead to the identification of distinct underlying aetiological pathways. Recent studies identified single nucleotide polymorphisms (SNPs) in the interleukin 13 (IL-13) gene region as risk factors for PsV. Further investigations in one of these studies found the effect to be primarily restricted to PsA, thus suggesting the discovery of a specific genetic risk factor for PsA. Given this intriguing evidence, association to this gene was investigated in large collections of PsA and PsV patients and healthy controls. Methods: Two SNPs (rs20541 and rs1800925) mapping to the IL-13 gene were genotyped in 1057 PsA and 778 type I PsV patients using the Sequenom genotyping platform. Genotype frequencies were compared to those of 5575 healthy controls. Additional analyses were performed in phenotypic subgroups of PsA (type I or II PsV and in those seronegative for rheumatoid factor). Results: Both SNPs were found to be highly associated with susceptibility to PsA (rs1800925 ptrend = 6.1×10−5 OR 1.33, rs20541 ptrend = 8.0×10−4 OR 1.27), but neither SNP was significantly associated with susceptibility to PsV. Conclusions: This study confirms that the effect of IL-13 risk locus is specific for PsA, thus highlighting a key biological pathway that differentiates PsA from PsV. The identification of markers that differentiate the two diseases raises the possibility in future of allowing screening of PsV patients to identify those at risk of developing PsA

Training of Instrumentalists and Development of New Technologies on SOFIA

This white paper is submitted to the Astronomy and Astrophysics 2010 Decadal Survey (Astro2010)1 Committee on the State of the Profession to emphasize the potential of the Stratospheric Observatory for Infrared Astronomy (SOFIA) to contribute to the training of instrumentalists and observers, and to related technology developments. This potential goes beyond the primary mission of SOFIA, which is to carry out unique, high priority astronomical research. SOFIA is a Boeing 747SP aircraft with a 2.5 meter telescope. It will enable astronomical observations anywhere, any time, and at most wavelengths between 0.3 microns and 1.6 mm not accessible from ground-based observatories. These attributes, accruing from the mobility and flight altitude of SOFIA, guarantee a wealth of scientific return. Its instrument teams (nine in the first generation) and guest investigators will do suborbital astronomy in a shirt-sleeve environment. The project will invest $10M per year in science instrument development over a lifetime of 20 years. This, frequent flight opportunities, and operation that enables rapid changes of science instruments and hands-on in-flight access to the instruments, assure a unique and extensive potential - both for training young instrumentalists and for encouraging and deploying nascent technologies. Novel instruments covering optical, infrared, and submillimeter bands can be developed for and tested on SOFIA by their developers (including apprentices) for their own observations and for those of guest observers, to validate technologies and maximize observational effectiveness.Comment: 10 pages, no figures, White Paper for Astro 2010 Survey Committee on State of the Professio

Multiply-imaged submm galaxy in a z~2.5 group

We present observations of a remarkable submillimetre-selected galaxy, SMMJ16359+6612. This distant galaxy lies behind the core of a massive cluster of galaxies, A2218, and is gravitationally lensed by the foreground cluster into three discrete images which were identified in deep submillimetre maps of the cluster core at both 450 and 850micron. Subsequent follow-up using deep optical and NIR images identify a faint counterpart to each of the 3 images, with similar red optical--NIR colours and HST morphologies. By exploiting a detailed mass model for the cluster lens we estimate that the combined images of this galaxy are magnified by a factor of ~45, implying that this galaxy would have un-lensed magnitudes K_s=22.9 and I=26.1, and an un-lensed 850micron flux density of only 0.8mJy. Moreover, the highly constrained lens model predicted the redshift of SMMJ16359+6612 to be z=2.6+/-0.4. We confirm this estimate using deep optical and NIR Keck spectroscopy, measuring a redshift of z=2.516. SMMJ16359+6612 is the faintest submm-selected galaxy so far identified with a precise redshift. Thanks to the large gravitational magnification of this source, we identify 3 sub-components in this submm galaxy, which are also seen in the NIRSPEC data, arguing for either a strong dust (lane) absorption or a merger. Interestingly, there are 2 other highly-amplified galaxies at almost identical redshifts in this field (although neither is a strong submm emitter). The 3 galaxies lie within a ~100kpc region on the background sky, suggesting this submm galaxy is located in a dense high-redshift group.Comment: 7 pages, 1 JPEG figure, MNRAS in pres