Identification of RNA editing in the human exome and development of DARNED DatabaseSF

RNA editing is a biological phenomena that alters nascent RNA transcripts by insertion, deletion and/or substitution of one or a few nucleotides. It is ubiquitous in all kingdoms of life and in viruses. The predominant editing event in organisms with a developed central nervous system is Adenosine to Inosine deamination. Inosine is recognized as Guanosine by the translational machinery and reverse-transcriptase. In primates, RNA editing occurs frequently in transcripts from repetitive regions of the genome. In humans, more than 500,000 editing instances have been identified, by applying computational pipelines on available ESTs and high-throughput sequencing data, and by using chemical methods. However, the functions of only a small number of cases have been studied thoroughly. RNA editing instances have been found to have roles in peptide variants synthesis by non-synonymous codon substitutions, transcript variants by alterations in splicing sites and gene silencing by miRNAs sequence modifications. We established the Database of RNA EDiting (DARNED) to accommo-date the reference genomic coordinates of substitution editing in human, mouse and fly transcripts from published literatures, with additional information on edited genomic coordinates collected from various databases e.g. UCSC, NCBI. DARNED contains mostly Adenosine to Inosine editing and allows searches based on genomic region, gene ID, and user provided sequence. The Database is accessible at http://darned.ucc.ie RNA editing instances in coding region are likely to result in recoding in protein synthesis. This encouraged me to focus my research on the occurrences of RNA editing specific CDS and non-Alu exonic regions. By applying various filters on discrepancies between available ESTs and their corresponding reference genomic sequences, putative RNA editing candidates were identified. High-throughput sequencing was used to validate these candidates. All predicted coordinates appeared to be either SNPs or unedited.

Development of inversion-mode and junctionless Indium-Gallium-Arsenide MOSFETs

This PhD covers the development of planar inversion-mode and junctionless Al2O3/In0.53Ga0.47As metal-oxidesemiconductor field-effect transistors (MOSFETs). An implant activation anneal was developed for the formation of the source and drain (S/D) of the inversionmode MOSFET. Fabricated inversion-mode devices were used as test vehicles to investigate the impact of forming gas annealing (FGA) on device performance. Following FGA, the devices exhibited a subthreshold swing (SS) of 150mV/dec., an ION/IOFF of 104 and the transconductance, drive current and peak effective mobility increased by 29%, 25% and 15%, respectively. An alternative technique, based on the fitting of the measured full-gate capacitance vs gate voltage using a selfconsistent Poisson-Schrödinger solver, was developed to extract the trap energy profile across the full In0.53Ga0.47As bandgap and beyond. A multi-frequency inversion-charge pumping approach was proposed to (1) study the traps located at energy levels aligned with the In0.53Ga0.47As conduction band and (2) separate the trapped charge and mobile charge contributions. The analysis revealed an effective mobility (μeff) peaking at ~2850cm2/V.s for an inversion-charge density (Ninv) = 7*1011cm2 and rapidly decreasing to ~600cm2/V.s for Ninv = 1*1013 cm2, consistent with a μeff limited by surface roughness scattering. Atomic force microscopy measurements confirmed a large surface roughness of 1.95±0.28nm on the In0.53Ga0.47As channel caused by the S/D activation anneal. In order to circumvent the issue relative to S/D formation, a junctionless In0.53Ga0.47As device was developed. A digital etch was used to thin the In0.53Ga0.47As channel and investigate the impact of channel thickness (tInGaAs) on device performance. Scaling of the SS with tInGaAs was observed for tInGaAs going from 24 to 16nm, yielding a SS of 115mV/dec. for tInGaAs = 16nm. Flat-band μeff values of 2130 and 1975cm2/V.s were extracted on devices with tInGaAs of 24 and 20nm, respectively

WriteSim TCExam--an open source text simulation environment for training novice researchers in scientific writing.

BACKGROUND: The ability to write clearly and effectively is of central importance to the scientific enterprise. Encouraged by the success of simulation environments in other biomedical sciences, we developed WriteSim TCExam, an open-source, Web-based, textual simulation environment for teaching effective writing techniques to novice researchers. We shortlisted and modified an existing open source application - TCExam to serve as a textual simulation environment. After testing usability internally in our team, we conducted formal field usability studies with novice researchers. These were followed by formal surveys with researchers fitting the role of administrators and users (novice researchers) RESULTS: The development process was guided by feedback from usability tests within our research team. Online surveys and formal studies, involving members of the Research on Research group and selected novice researchers, show that the application is user-friendly. Additionally it has been used to train 25 novice researchers in scientific writing to date and has generated encouraging results. CONCLUSION: WriteSim TCExam is the first Web-based, open-source textual simulation environment designed to complement traditional scientific writing instruction. While initial reviews by students and educators have been positive, a formal study is needed to measure its benefits in comparison to standard instructional methods.

Development and usability testing of a Web-based decision aid for families of patients receiving prolonged mechanical ventilation.

BACKGROUND: Web-based decision aids are increasingly important in medical research and clinical care. However, few have been studied in an intensive care unit setting. The objectives of this study were to develop a Web-based decision aid for family members of patients receiving prolonged mechanical ventilation and to evaluate its usability and acceptability. METHODS: Using an iterative process involving 48 critical illness survivors, family surrogate decision makers, and intensivists, we developed a Web-based decision aid addressing goals of care preferences for surrogate decision makers of patients with prolonged mechanical ventilation that could be either administered by study staff or completed independently by family members (Development Phase). After piloting the decision aid among 13 surrogate decision makers and seven intensivists, we assessed the decision aid's usability in the Evaluation Phase among a cohort of 30 surrogate decision makers using the Systems Usability Scale (SUS). Acceptability was assessed using measures of satisfaction and preference for electronic Collaborative Decision Support (eCODES) versus the original printed decision aid. RESULTS: The final decision aid, termed 'electronic Collaborative Decision Support', provides a framework for shared decision making, elicits relevant values and preferences, incorporates clinical data to personalize prognostic estimates generated from the ProVent prediction model, generates a printable document summarizing the user's interaction with the decision aid, and can digitally archive each user session. Usability was excellent (mean SUS, 80 ± 10) overall, but lower among those 56 years and older (73 ± 7) versus those who were younger (84 ± 9); p = 0.03. A total of 93% of users reported a preference for electronic versus printed versions. CONCLUSIONS: The Web-based decision aid for ICU surrogate decision makers can facilitate highly individualized information sharing with excellent usability and acceptability. Decision aids that employ an electronic format such as eCODES represent a strategy that could enhance patient-clinician collaboration and decision making quality in intensive care.

Overview of FEED, the feeding experiments end-user database.

The Feeding Experiments End-user Database (FEED) is a research tool developed by the Mammalian Feeding Working Group at the National Evolutionary Synthesis Center that permits synthetic, evolutionary analyses of the physiology of mammalian feeding. The tasks of the Working Group are to compile physiologic data sets into a uniform digital format stored at a central source, develop a standardized terminology for describing and organizing the data, and carry out a set of novel analyses using FEED. FEED contains raw physiologic data linked to extensive metadata. It serves as an archive for a large number of existing data sets and a repository for future data sets. The metadata are stored as text and images that describe experimental protocols, research subjects, and anatomical information. The metadata incorporate controlled vocabularies to allow consistent use of the terms used to describe and organize the physiologic data. The planned analyses address long-standing questions concerning the phylogenetic distribution of phenotypes involving muscle anatomy and feeding physiology among mammals, the presence and nature of motor pattern conservation in the mammalian feeding muscles, and the extent to which suckling constrains the evolution of feeding behavior in adult mammals. We expect FEED to be a growing digital archive that will facilitate new research into understanding the evolution of feeding anatomy.

A design pattern for integration of business process management systems

A cross-domain workflow application may be constructed using a standard reference model such as the one by the Workflow Management Coalition (WfMC) [7] but the requirements for this type of application are inherently different from one organization to another. The existing models and systems built around them meet some but not all the requirements from all the organizations involved in a collaborative process. Furthermore the requirements change over time. This makes the applications difficult to develop and distribute. Service Oriented Architecture (SOA) based approaches such as the BPET (Business Process Execution Language) intend to provide a solution but fail to address the problems sufficiently, especially in the situations where the expectations and level of skills of the users (e.g. the participants of the processes) in different organisations are likely to be different. In this paper, we discuss a design pattern that provides a novel approach towards a solution. In the solution, business users can design the applications at a high level of abstraction: the use cases and user interactions; the designs are documented and used, together with the data and events captured later that represents the user interactions with the systems, to feed an intermediate component local to the users -the IFM (InterFace Mapper) -which bridges the gaps between the users and the systems. We discuss the main issues faced in the design and prototyping. The approach alleviates the need for re-programming with the APIs to any back-end service thus easing the development and distribution of the applications

Reading the landscape: the development of a typology of literary trails to inform experiential design

This article explores the under-researched field of self-guided trails. The focus of the research is on the experiential aspects of self-guided literary trails from the perspective of both the developer and user. An examination of existing literature on self-guided trails and literary tourism was undertaken and supplemented with a review of experiential design principles. Content analysis of a sample of literary heritage trails was then carried out and three distinctive typologies were developed, informed by aspects of experiential design. The research reveals that few literary trails developers utilise these principles and the article concludes with proposals for the design of more effective literary trail experiences.

Making sense of game based user data: learning analytics in applied games

Digital learning games are useful educational tools with high motivational potential. With the application of games for instruction there comes the need of acknowledging learning game experiences also in the context of educational assessment. Learning analytics provides new opportunities for supporting assessment in and of educational games. We give an overview of current learning analytics methods in this field and reflect on existing challenges. An approach of providing reusable software assets for interaction assessment and evaluation in games is presented. This is part of a broader initiative of making available advanced methodologies and tools for supporting applied game development.

Gov 2.0: Towards a User Generated State?

New elements associated withWeb 2.0 relating to interactivity and end-user focus have combined with the availability of newlevels of information to encourage the development of what may be termed a Gov 2.0 approach.This, in combination with recent initiatives in the modernising government programme, has emphasised new levels of public participation and engagement with government as well as a re-engineering of public services tomake them more responsive to their end users. Adopting a governmentality perspective, it is argued that this involves a wider process of governing through constructing and reconstructing ideas of the public, community and individual citizen-consumers who take on a role in their own governance. It is argued that this fundamental re-working of the nature of what is public represents a constitutional change that is perhaps more signi¢cant than the constitutional reform programme directed to formal government which attracts more attention

Championing the interface between mental health and child protection: evaluation of a service initiative to improve joint working in Northern Ireland

The importance of establishing effective interagency working between adult mental health services and child care services in order to safeguard children has been repeatedly identified by research, policy, inquiries and inspection reports. This article reports on the evaluation of an initiative in one Health and Social Care Trust in Northern Ireland that aimed to facilitate joint working and so improve service provision and protection for children and families. The Champions Initiative involved identifying a champion in each multi-disciplinary community mental health team and in each family and child care team who would have responsibility for providing information, promoting joint working and identifying any obstacles to better co-operation. The evaluation of this initiative assessed levels of experience, training, confidence, understanding and awareness in the Champions and their team members at baseline. The Champions and their Team Leaders were then followed-up after six months to obtain their qualitative views of the impact of the initiative. The results include comparisons between mental health and child care staff, and crucially, views about whether the initiative has had any impact on working together. This study also generated recommendations for further service development in this complex and important area of practice.

'Like walking on eggshells': Service user views and expectations of the child protection system

This paper reports on a study of service users' views on Irish child protection services. Qualitative interviews were conducted with 67 service users, including young people between 13 and 23. The findings showed that despite refocusing and public service management reforms, service users still experience involvement with the services as intimidating and stressful and while they acknowledged opportunities to participate in the child protection process, they found the experience to be very difficult. Their definition of ‘needs’ was somewhat at odds with that suggested in official documentation, and they viewed the execution of a child protection plan more as a coercive requirement to comply with ‘tasks’ set by workers than a conjoint effort to enhance their children's welfare. As in previous studies, the data showed how the development of good relationships between workers and service users could compensate for the harsher aspects of involvement with child protection. In addition, this study demonstrated a high level of discernment on the part of service users, highlighting their expectation of quality standards in respect of courtesy, respect, accountability, transparency and practitioner expertise.

Effects of particle plasticity characteristics on local interface stress in particle reinforced composite during uniaxial tension

For elastoplastic particle reinforced metal matrix composites, failure may originate from interface debonding between the particles and the matrix, both elastoplastic and matrix fracture near the interface. To calculate the stress and strain distribution in these regions, a single reinforcing particle axisymmetric unit cell model is used in this article. The nodes at the interface of the particle and the matrix are tied. The development of interfacial decohesion is not modelled. Finite element modelling is used, to reveal the effects of particle strain hardening rate, yield stress and elastic modulus on the interfacial traction vector (or stress vector), interface deformation and the stress distribution within the unit cell, when the composite is under uniaxial tension. The results show that the stress distribution and the interface deformation are sensitive to the strain hardening rate and the yield stress of the particle. With increasing particle strain hardening rate and yield stress, the interfacial traction vector and internal stress distribution vary in larger ranges, the maximum interfacial traction vector and the maximum internal stress both increase, while the interface deformation decreases. In contrast, the particle elastic modulus has little effect on the interfacial traction vector, internal stress and interface deformation.