‘Multi View Graphing’: Linked Multi Visualization utilising Brushing, Binning and Clustering

Visualization can provide a distinctly advantageous overview of data, enabling the rapid identification of anomalies, patterns or correlations that would not otherwise be obvious. Different visualization techniques each offer their own unique insight into the same data; however the similarities that exist between them are not always clear. High data density can also be a very evident issue when exploring data using visualization. The densest datasets can ensure that even well suited visualization methodologies succumb to usability issues. The most powerful data analysis environments are arguably those that provide interactive exploration, however visual feedback in such environments is sometimes undesirably limited. The concept of linking different visualization styles using interactive techniques, such as brushing, is currently evident in multiple publically available software environments. To explore the concept of linked visualization a prototype application was produced, allowing up to four unique visual styles to be generated using the same data, at the same time. Current brushing methodologies were extended and included, in order to provide the ability to affect each visualization from within every other. The issue of data density was tackled through the use of a novel approach to binning based around a uniform grid. Visual cues were used extensively throughout the prototype, ranging from representing a brushing area through to defining the basic starting parameters of a clustering algorithm. Three distinctly different test cases are presented to demonstrate the techniques showcased within the prototype, each in conjunction with external collaborators. Results suggest that using linked multi visualization is a more effective method of data analysis, offering greater insight than using a lone visualization technique. In tackling data density, the grid based binning has the ability to offer an easily disseminated overview of even extremely cluttered visualizations. The extensive use of visual cues in the prototype vindicated the theory that offering clear feedback within interactive environments is of the utmost importance. Also the interactive definition of clustering parameters via visual cues shows promise as a concept but one requiring further research. This study highlights that the current trend towards linking multiple visualization techniques within advanced data analysis environments is correct; it also introduces novel brushing, binning and clustering concepts worthy of further investigation

Numerical Modelling and Visualization of the Evolution of Extensional Fault Systems

The purpose of this work is split into two categories, the first was to analyse the application of real-time Physics Engine software libraries for use in calculating a geological numerical model. Second was the analysis of the applicability of glyph and implicit surface based visualization techniques to explore fault systems produced by the model. The current state of the art in Physics Engines was explored by redeveloping a Discrete Element Model to be calculated using NVIDIA’s PhysX engine. Analyses regarding the suitability of the engine in terms of numerical accuracy and developmental capabilities is given, as well as the definition of a specialised and bespoke parallelisation technique. The use of various glyph based visualizations is explored to define a new standardised taxonomy for geological data and the MetaBall visualization technique was applied to reveal three dimensional fault structures as an implicit surface. Qualitative analysis was undertaken in the form of a user study, comprising of interviews with expert geologists. The processing pipeline used by many Physics Engines was found to be comparable to the design of Discrete Element Model software, however, aspects of their design, such as integration accuracy, limitation to single precision floating point and imposed limits on the scale of n-body problem means their suitability is restricted to specific modelling cases. Glyph and implicit surface based visualization have been shown to be an effective way to present a geological Discrete Element Model, with the majority of experts interviewed able to perceive the fault structures that it contained. Development of a new engine, or modification of one that exists in accordance with the findings of this thesis would result in a library extremely well suited to the problem of rigid-body simulation for the sciences

Visualizing a spherical geological discrete element model of fault evolution

Discrete Element Modelling (DEM) is a numerical technique that uses a system of interacting discrete bodies to simulate the movement of material being exposed to external forces. This technique is often used to simulate granular systems; however by adding further elements that inter-connect the bodies, it can be used to simulate the deformation of a large volume of material. This method has precedent for use in the Earth Sciences and recently, with the increase of available computing power, it has been put to good use simulating the evolution of extensional faults in large scale crustal experiments that involve over half a million individual spherical bodies. An interactive environment that provides high quality rendering is presented, showing that interactivity is key in allowing the intelligent application of visualization methods such as colour-mapping and visibility thresholds in order to extract fault information from a geological DEM. It is also shown that glyph representation alone is not sufficient to provide full insight into the complex three dimensional geometries of the faults found within the model. To overcome this, a novel use of the MetaBall method is described, which results in implicit surface representations of sphere sub-sets. The surfaces produced are shown to provide greater insight into the faults found within the data but also raise questions as to their meaning. © The Eurographics Association 2012

Analysing the use of Real-time Physics Engines for Scientific Simulation: Exploring the Theoretical and Practical Benefits for Discrete Element Modelling

Within computer science, reusability of specific modular software components is generally accepted as best practice. Simulation techniques such as Discrete Element Modelling (DEM) rely on the well defined problems of Newtonian physics, and while differences exist in the methods defined to compute solutions to these problems, each method follows the same basic set of premises. Recently, libraries termed Physics Engines (PE) have been released that are designed to solve physics based problems. This paper considers the features of a range PEs and explores whether the techniques and design methodologies can be applicable to the design and implementation of a working simulation. The NVIDIA PhysX engine has been utilised in a practical DEM implementation to simulate the evolution of extensional fault systems in rock. Through understanding the general processing pipeline implemented by a PE, obvious similarities with a range of DEM implementations has became apparent. Discussed are areas that are compatible and also areas within the PE that have been proved unsuited to large scale DEM simulation. It is shown that current versions of PEs may not provide access to techniques giving high enough numerical accuracy for certain applications, but the basic premise of an easy to use and highly optimised library, designed to allow researchers to construct complex simulation scenarios is compelling

Discrete element modelling using a parallelised physics engine

Discrete Element Modelling (DEM) is a technique used widely throughout science and engineering. It offers a convenient method with which to numerically simulate a system prone to developing discontinuities within its structure. Often the technique gets overlooked as designing and implementing a model on a scale large enough to be worthwhile can be both time consuming and require specialist programming skills. Currently there are a few notable efforts to produce homogenised software to allow researchers to quickly design and run DEMs with in excess of 1 million elements. However, these applications, while open source, are still complex in nature and require significant input from their original publishers in order for them to include new features as a researcher needs them. Recently software libraries notably from the computer gaming and graphics industries, known as physics engines, have emerged. These are designed specifically to calculate the physical movement and interaction of a system of independent rigid bodies. They provide conceptual equivalents of real world constructions with which an approximation of a realistic scenario can be quickly built. This paper presents a method to utilise the most notable of these engines, NVIDIAs PhysX, to produce a parallelised geological DEM capable of supporting in excess of a million elements. © The Eurographics Association 2009

Association of Fidaxomicin with C. difficile spores: Effects of Persistence on Subsequent Spore Recovery, Outgrowth and Toxin Production.

Background: We have previously shown that fidaxomicin instillation prevents spore recovery in an in-vitro gut model, whereas vancomycin does not. The reasons for this are unclear. Here, we have investigated persistence of fidaxomicin and vancomycin on C. difficile spores, and examined post-antibiotic exposure spore recovery, outgrowth and toxin production. Methods: Prevalent UK C. difficile ribotypes (n=10) were incubated with 200mg/L fidaxomicin, vancomycin or a non-antimicrobial containing control for 1 h in faecal filtrate or Phosphate Buffered Saline. Spores were washed three times with faecal filtrate or phosphate buffered saline, and residual spore-associated antimicrobial activity was determined by bioassay. For three ribotypes (027, 078, 015), antimicrobial-exposed, faecal filtrate-washed spores and controls were inoculated into broth. Viable vegetative and spore counts were enumerated on CCEYL agar. Percentage phase bright spores, phase dark spores and vegetative cells were enumerated by phase contrast microscopy at 0, 3, 6, 24 and 48 h post-inoculation. Toxin levels (24 and 48h) were determined by cell cytotoxicity assay. Results: Fidaxomicin, but not vancomycin persisted on spores of all ribotypes following washing in saline (mean=10.1mg/L; range= 4.0-14mg/L) and faecal filtrate (mean =17.4mg/L; 8.4-22.1mg/L). Outgrowth and proliferation rates of vancomycin-exposed spores were similar to controls, whereas fidaxomicin-exposed spores showed no vegetative cell growth after 24 and 48 h. At 48h, toxin levels averaged 3.7 and 3.3 relative units (RU) in control and vancomycin-exposed samples, respectively, but were undetectable in fidaxomicin-exposed samples. Conclusion: Fidaxomicin persists on C. difficile spores, whereas vancomycin does not. This persistence prevents subsequent growth and toxin production in vitro. This may have implications on spore viability, thereby impacting CDI recurrence and transmission rates

Unsaturated fatty acids are inhibitors of bacterial conjugation

This report describes a high-throughput assay to identify substances that reduce the frequency of conjugation in Gram-negative bacteria. Bacterial conjugation is largely responsible for the spread of multiple antibiotic resistances in human pathogens. Conjugation inhibitors may provide a means to control the spread of antibiotic resistance. An automated conjugation assay was developed that used plasmid R388 and a laboratory strain of Escherichia coli as a model system, and bioluminescence as a reporter for conjugation activity. Frequencies of conjugation could be measured continuously in real time by the amount of light produced, and thus the effects of inhibitory compounds could be determined quantitatively. A control assay, run in parallel, allowed elimination of compounds affecting cell growth, plasmid stability or gene expression. The automated conjugation assay was used to screen a database of more than 12 000 microbial extracts known to contain a wide variety of bioactive compounds (the NatChem library). The initial hit rate was 1·4 %. From these, 48 extracts containing active compounds and representing a variety of organisms and extraction conditions were subjected to fractionation (24 fractions per extract). The 52 most active fractions were subjected to a secondary analysis to determine the range of plasmid inhibition. Plasmids R388, R1 and RP4 were used as representatives of a variety of plasmid transfer systems. Only one fraction (of complex composition) affected transfer of all three plasmids, while four other fractions were active against two of them. Two separate compounds were identified from these fractions: linoleic acid and dehydrocrepenynic acid. Downstream analysis showed that the chemical class of unsaturated fatty acids act as true inhibitors of conjugation

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

The ClosER study: results from a three-year pan-European longitudinal surveillance of antibiotic resistance among prevalent Clostridium difficile ribotypes, 2011–2014

Objectives: Until the introduction of fidaxomicin, antimicrobial treatment for Clostridium difficile infection (CDI) was limited to metronidazole and vancomycin. The changing epidemiology of CDI and the emergence of epidemic C. difficile PCR ribotype 027 necessitate continued surveillance to identify shifts in antibiotic susceptibility. ClosER, currently the largest pan-European epidemiological study of C. difficile ribotype distribution and antibiotic susceptibility, aimed to undertake antimicrobial resistance surveillance pre- and post-introduction of fidaxomicin. Methods: Between July 2011 and July 2014, 39 sites across 22 European countries submitted 2830 C. difficile isolates for ribotyping, toxin testing and susceptibility testing to metronidazole, vancomycin, fidaxomicin, rifampicin, moxifloxacin, clindamycin, imipenem, chloramphenicol and tigecycline. Results: Ribotypes 027, 014, 001, 078, 020, 002, 126, 015 and 005 were most frequently isolated, and emergent ribotypes 198 and 356 were identified in Hungary and Italy, respectively. All isolates were susceptible to fidaxomicin, with scarce resistance to metronidazole (0.2%, 6/2694), vancomycin (0.1%, 2/2694) and tigecycline (0%). Rifampicin, moxifloxacin and clindamycin resistance was evident in multiple ribotypes. Lack of ribotype diversity correlated with greater antimicrobial resistance. Epidemic ribotypes (027/001) were associated with multiple antimicrobial resistance, and ribotypes 017, 018 and 356 with high-level resistance. Additional factors may also influence local ribotype prevalence. Conclusions: Fidaxomicin susceptibility was retained post-introduction, and resistance to metronidazole and vancomycin was rare. Continued surveillance is needed, with more accurate classification and clarification of ribotype subtypes to further understand their role in the spread of resistance. Other factors may also influence changes in prevalence of C. difficile ribotypes with reduced antibiotic susceptibility