Contributions to High-Throughput Computing Based on the Peer-to-Peer Paradigm

XII, 116 p.

Explicit DNase sequence bias modeling enables high-resolution transcription factor footprint detection.

DNaseI footprinting is an established assay for identifying transcription factor (TF)-DNA interactions with single base pair resolution. High-throughput DNase-seq assays have recently been used to detect in vivo DNase footprints across the genome. Multiple computational approaches have been developed to identify DNase-seq footprints as predictors of TF binding. However, recent studies have pointed to a substantial cleavage bias of DNase and its negative impact on predictive performance of footprinting. To assess the potential for using DNase-seq to identify individual binding sites, we performed DNase-seq on deproteinized genomic DNA and determined sequence cleavage bias. This allowed us to build bias corrected and TF-specific footprint models. The predictive performance of these models demonstrated that predicted footprints corresponded to high-confidence TF-DNA interactions. DNase-seq footprints were absent under a fraction of ChIP-seq peaks, which we show to be indicative of weaker binding, indirect TF-DNA interactions or possible ChIP artifacts. The modeling approach was also able to detect variation in the consensus motifs that TFs bind to. Finally, cell type specific footprints were detected within DNase hypersensitive sites that are present in multiple cell types, further supporting that footprints can identify changes in TF binding that are not detectable using other strategies.

Retrofit versus new-build house using life-cycle assessment

This paper reports the findings of research on the environmental performance of two case-study houses, a retrofit and new build. The retrofit was completed to a Passivhaus standard while the new build was completed to current Irish building regulations. Environmental performance of the retrofit and new build was measured using life-cycle assessments, examining the assembly, operational and end-of-life stage over life spans of 50 and 80 years. Using primary information, life-cycle assessment software and life-cycle assessment databases the environmental impacts of each stage were modelled. The operational stage of both case studies was found to be the source of the most significant environmental damage, followed by the assembly and the end-of-life stage respectively. The relative importance of the assembly and end-of-life stage decreased as the life span increased. It was found that the retrofit house studied outperformed the new build in the assembly and operational stage, whereas the new build performed better in the end-of-life stage; however, this is highly sensitive, depending on the standards to which both are completed. Operational energy savings pre- and post-retrofit were significant, indicating the future potential for adoption of high-quality retrofitting practices.

A techno-economic feasibility study of high altitude wind power in Northern Ireland

Globally the amount of installed terrestrial wind power both onshore and offshore has grown rapidly over the last twenty years. Most large onshore and offshore wind turbines are designed to harvest winds within the atmospheric boundary layer, which can be vary variable due to terrain and weather effects. The height of the neutral atmospheric boundary layer is estimated at above 1300m. A relatively new concept is to harvest more consistent wind conditions above the atmospheric boundary layer using high altitude wind harvesting devices such as tethered kites, air foils and dirigible rotors. This paper presents a techno-economic feasibility study of high altitude wind power in Northern Ireland. First this research involved a state of the art review of the resource and the technologies proposed for high altitude wind power. Next the techno-economic analysis involving four steps is presented. In step one, the potential of high altitude wind power in Northern Ireland using online datasets (e.g. Earth System Research Laboratory) is estimated. In step two a map for easier visualisation of geographical limitations (e.g. airports, areas of scenic beauty, flight paths, military training areas, settlements etc.) that could impact on high altitude wind power is developed. In step three the actual feasible resource available is recalculated using the visualisation map to determine the ‘optimal’ high altitude wind power locations in Northern Ireland. In the last step four the list of equipment, resources and budget needed to build a demonstrator is provided in the form of a concise techno-economic appraisal using the findings of the previous three steps.

IMP: Imperial Metagenomics Pipeline for high-throughput sequence data

We have developed an in-house pipeline for the processing and analyses of sequence data generated during Illumina technology-based metagenomic studies of the human gut microbiota. Each component of the pipeline has been selected following comparative analysis of available tools; however, the modular nature of software facilitates replacement of any individual component with an alternative should a better tool become available in due course. The pipeline consists of quality analysis and trimming followed by taxonomic filtering of sequence data allowing reads associated with samples to be binned according to whether they represent human, prokaryotic (bacterial/archaeal), viral, parasite, fungal or plant DNA. Viral, parasite, fungal and plant DNA can be assigned to species level on a presence/absence basis, allowing – for example – identification of dietary intake of plant-based foodstuffs and their derivatives. Prokaryotic DNA is subject to taxonomic and functional analyses, with assignment to taxonomic hierarchies (kingdom, class, order, family, genus, species, strain/subspecies) and abundance determination. After de novo assembly of sequence reads, genes within samples are predicted and used to build a non-redundant catalogue of genes. From this catalogue, per-sample gene abundance can be determined after normalization of data based on gene length. Functional annotation of genes is achieved through mapping of gene clusters against KEGG proteins, and InterProScan. The pipeline is undergoing validation using the human faecal metagenomic data of Qin et al. (2014, Nature 513, 59–64). Outputs from the pipeline allow development of tools for the integration of metagenomic and metabolomic data, moving metagenomic studies beyond determination of gene richness and representation towards microbial-metabolite mapping. There is scope to improve the outputs from viral, parasite, fungal and plant DNA analyses, depending on the depth of sequencing associated with samples. The pipeline can easily be adapted for the analyses of environmental and non-human animal samples, and for use with data generated via non-Illumina sequencing platforms.

Evaluation of a treatment program for individuals with an intellectual disability who have high risk behaviours

In the past two decades numerous programs have emerged to treat individuals with developmental disabilities who have sexual offending behaviours. There has, however been very few studies that systematically examine the effectiveness of long term treatment with this population. The present research examines the therapeutic outcomes of a multi-modal behaviour approach with six individuals with intellectual disabilities previously charged with sexual assault. The participants also exhibited severe behavioural challenges that included verbal aggression, physical aggression, destruction and self-injury. These six participants (5 males, 1 female) were admitted to a Long Term Residential Treatment Program (LTRTP), due to the severity of their behaviours and due to their lack of treatment success in other programs. Individualized treatment plans focused on the reduction of maladaptive behaviours and the enhancing of skills such as positive coping strategies, socio-sexual knowledge, life skills, recreation and leisure skills. The treatment program also included psychiatric, psychological, medical, behavioural and educational interventions. The participants remained in the Long Term Residential Treatment Program (LTRTP) program from 181 to 932 days (average of 1.5 years). Pre and post treatment evaluations were conducted using the following tools: frequency of target behaviours, Psychopathology Inventory for Mentally Retarded Adults (PIMRA), Emotional Problems Scale (EPS), Socio-Sexual Knowledge and Attitudes Assessment Tool (SSKAAT-R) and Quality of Life Questionnaire (QOL-Q). Recidivism rates and the need for re-hospitalization were also noted for each participant. By offering high levels of individualized interventions, all six participants showed a 37 % rate of reduction in maladaptive behaviours with zero to low rates of inappropriate sexualbehaviour, there were no psychiatric hospitalizations, and there was no recidivism for 5 of 6 participants. In addition, medication was reduced. Mental health scores on the PIMRA were reduced across all participants by 25 % and scores on the Quality of Life Questionnaire increased for all participants by an average of 72 %. These findings add to and build upon the existing literature on long term treatment benefits for individuals with a intellectual disability who sexually offend. By utilizing an individualized and multimodal treatment approach to reduce severe behavioural challenges, not only can the maladaptive behaviours be reduced, but adaptive behaviours can be increased, mental health concerns can be managed, and overall quality of life can be improved.

Creating a Generation of Upstanders: Curriculum Resource to Help Ontario Educators Build Safe Schools

This project focuses on the bullying found in the 21st century elementary classrooms, more specifically in grades 4-8. These grades were found to have high levels of bullying because of major shifts in a student’s life that may place a student of this age at risk for problems with their peer relationships (Totura et al., 2009). Supporting the findings in the literature review, this handbook was created for Ontario grade 4-8 classroom teachers. The resource educates teachers on current knowledge of classroom bullying, and provides them with information and resources to share with their students so that they can create a culture of upstanders. Upstanders are students who stand up for the victims of bullying, and have the self-esteem and strategies to stand up to classroom bullies. These upstanders, with the support of their classroom teachers and their peers, will be a force strong enough to build the government-mandated Safe School environment.

Creating a Generation of Upstanders: Curriculum Resource to Help Ontario Educators Build Safe Schools

This project focuses on the bullying found in the 21st century elementary classrooms, more specifically in grades 4-8. These grades were found to have high levels of bullying because of major shifts in a student’s life that may place a student of this age at risk for problems with their peer relationships (Totura et al., 2009). Supporting the findings in the literature review, this handbook was created for an Ontario grade 4-8 classroom teachers. The resource educates teachers on current knowledge of classroom bullying, and provides them with information and resources to share with their students so that they can create a culture of upstanders. Upstanders are students who stand up for the victims of bullying, and have the self-esteem and strategies to stand up to classroom bullies. These upstanders, with the support of their classroom teachers and their peers, will be a force strong enough to build the government-mandated Safe School environment.

Studies on the Effect of High Energy Ball Milling On the Structural, Electrical and Magnetic Properties of Some Normal Spinets in the Ultrafine Regime

The present work is an attempt to understand the characteristics of high energy ball milling on the structural, electrical and magnetic properties of some normal spinets in the ultra fine regime, Magnetism and magnetic materials have been a fascinating subject for the mankind ever since the discovery of lodestone. Since then, man has been applying this principle of magnetism to build devices for various applications. Magnetism can be classified broadly into five categories. They are diamagnetic, paramagnetic, ferromagnetic antiferromagnetic and ferrimagnetic. Of these, ferro and ferri magnetic materials assume great commercial importance due to their unique properties like appropriate magnetic characteristics, high resistivity and low eddy current losses. The emergence of nanoscience and nanotechnology during the last decade had its impact in the field of magnetism and magnetic materials too. Now, it is common knowledge that materials synthesized in the nanoregime exhibit novel and superlative properties with respect to their coarser sized counterparts in the micron regime. These studies reveal that dielectric properties can be varied appreciably by high-energy ball milling in nanosized zinc ferrites produced by coprecipitation method. A semi conducting behaviour was observed in these materials with the Oxygen vacancies acting as the main charge carrier for conduction, which was produced at the time of coprecipitation and milling. Thus through this study, it was possible to successfully investigate the finite size effects on the structural, electrical and magnetic properties of normal spinels in the ultra fine regime

Trace elements biogeochemistry in high mountain lake catchments: identifying anthropogenic versus natural components from the atmospheric contamination legacy in remote natural areas

Human activities have been interfering with the natural biogeochemical cycles of trace elements since the ancient civilizations. Although they are inaccessible and remote, high mountain lake catchments are irrefutably trace-element contaminated by anthropogenic emissions, which can travel by long-range atmospheric transport before they are deposited. This has been revealed by several natural archives. High mountain lake catchments are thus excellent sentinels of long-range contamination. Continuous accumulation can lead to a build up of potentially toxic trace elements in these remote, or relatively remote, ecosystems. The thesis focuses on the biogeochemistry of a suite of trace elements of environmental concern (Ni, Cu, Zn, As, Se, Cd and Pb) in Pyrenean lake catchments, with special emphasis on discerning the “natural” components from the “anthropogenic” contributions. Five other metallic elements (Al, Fe, Ti, Mn and Zr) have also been studied to trace natural fluxes and biogeochemical processes within the lake catchment systems.

High value information in engineering organisations

The management of information in engineering organisations is facing a particular challenge in the ever-increasing volume of information. It has been recognised that an effective methodology is required to evaluate information in order to avoid information overload and to retain the right information for reuse. By using, as a starting point, a number of the current tools and techniques which attempt to obtain ‘the value’ of information, it is proposed that an assessment or filter mechanism for information is needed to be developed. This paper addresses this issue firstly by briefly reviewing the information overload problem, the definition of value, and related research work on the value of information in various areas. Then a “characteristic” based framework of information evaluation is introduced using the key characteristics identified from related work as an example. A Bayesian Network diagram method is introduced to the framework to build the linkage between the characteristics and information value in order to quantitatively calculate the quality and value of information. The training and verification process for the model is then described using 60 real engineering documents as a sample. The model gives a reasonable accurate result and the differences between the model calculation and training judgements are summarised as the potential causes are discussed. Finally, several further issues including the challenge of the framework and the implementations of this evaluation assessment method are raised.

Teachers as researchers and teachers as software developers: how use-case analysis helps build better educational software

A series of government initiatives has raised both the profile of ICT in the curriculum and the expectation that high quality teaching and learning resources will be accessible across electronic networks. In order for e-learning resources such as websites to have the maximum educational impact, teachers need to be involved in their design and development. Use-case analysis provides a means of defining user requirements and other constraints in such a way that software developers can produce e-learning resources which reflect teachers' professional knowledge and support their classroom practice. It has some features in common with the participatory action research used to develop other aspects of classroom practice. Two case-studies are presented: one involves the development of an on-line resource centred on transcripts of original historical documents; the other describes how 'Learning how to Learn', a major, distributed research project funded under the ESRC Teaching and Learning Research Programme is using use-case analysis to develop web resources and services.

Numerical-asymptotic boundary integral methods in high-frequency acoustic scattering

In this article we describe recent progress on the design, analysis and implementation of hybrid numerical-asymptotic boundary integral methods for boundary value problems for the Helmholtz equation that model time harmonic acoustic wave scattering in domains exterior to impenetrable obstacles. These hybrid methods combine conventional piecewise polynomial approximations with high-frequency asymptotics to build basis functions suitable for representing the oscillatory solutions. They have the potential to solve scattering problems accurately in a computation time that is (almost) independent of frequency and this has been realized for many model problems. The design and analysis of this class of methods requires new results on the analysis and numerical analysis of highly oscillatory boundary integral operators and on the high-frequency asymptotics of scattering problems. The implementation requires the development of appropriate quadrature rules for highly oscillatory integrals. This article contains a historical account of the development of this currently very active field, a detailed account of recent progress and, in addition, a number of original research results on the design, analysis and implementation of these methods.

High leverage interventions: three cases of defensive action and their lessons for OR/MS today.

This paper has two aims. First, to present cases in which scientists developed a defensive system for their homeland: Blackett and the air defense of Britain in WWII, Forrester and the SAGE system for North America in the Cold War, and Archimedes’ work defending Syracuse during the Second Punic War. In each case the historical context and the individual’s other achievements are outlined, and a description of the contribution’s relationship to OR/MS is given. The second aim is to consider some of the features the cases share and examine them in terms of contemporary OR/MS methodology. Particular reference is made to a recent analysis of the field’s strengths and weaknesses. This allows both a critical appraisal of the field and a set of potential responses for strengthening it. Although a mixed set of lessons arise, the overall conclusion is that the cases are examples to build on and that OR/MS retains the ability to do high stakes work.

Proposal of redundant drive wire mechanism for producing motions with high acceleration and high precision

A new wire mechanism called Redundant Drive Wire Mechanism (RDWM) is proposed. The purpose of this paper is to build up the theory of a RDWM with fast motion and fine motion. First, the basic concepts of the proposed mechanism is presented. Second, the vector closure condition for the proposed mechanism is developed. Next, we present the basic equations, propose the basic structure of RDWM with the Internal DOF module, Double Actuation Modules and Precision Modules together with the properties of the mechanism. Finally, we conduct the simulation to show the validity of the RDWM.