Hazard and early warning analysis based on domain specific modeling technologies

An aim of proactive risk management strategies is the timely identification of safety related risks. One way to achieve this is by deploying early warning systems. Early warning systems aim to provide useful information on the presence of potential threats to the system, the level of vulnerability of a system, or both of these, in a timely manner. This information can then be used to take proactive safety measures. The United Nation’s has recommended that any early warning system need to have four essential elements, which are the risk knowledge element, a monitoring and warning service, dissemination and communication and a response capability. This research deals with the risk knowledge element of an early warning system. The risk knowledge element of an early warning system contains models of possible accident scenarios. These accident scenarios are created by using hazard analysis techniques, which are categorised as traditional and contemporary. The assumption in traditional hazard analysis techniques is that accidents are occurred due to a sequence of events, whereas, the assumption of contemporary hazard analysis techniques is that safety is an emergent property of complex systems. The problem is that there is no availability of a software editor which can be used by analysts to create models of accident scenarios based on contemporary hazard analysis techniques and generate computer code that represent the models at the same time. This research aims to enhance the process of generating computer code based on graphical models that associate early warning signs and causal factors to a hazard, based on contemporary hazard analyses techniques. For this purpose, the thesis investigates the use of Domain Specific Modeling (DSM) technologies. The contributions of this thesis is the design and development of a set of three graphical Domain Specific Modeling languages (DSML)s, that when combined together, provide all of the necessary constructs that will enable safety experts and practitioners to conduct hazard and early warning analysis based on a contemporary hazard analysis approach. The languages represent those elements and relations necessary to define accident scenarios and their associated early warning signs. The three DSMLs were incorporated in to a prototype software editor that enables safety scientists and practitioners to create and edit hazard and early warning analysis models in a usable manner and as a result to generate executable code automatically. This research proves that the DSM technologies can be used to develop a set of three DSMLs which can allow user to conduct hazard and early warning analysis in more usable manner. Furthermore, the three DSMLs and their dedicated editor, which are presented in this thesis, may provide a significant enhancement to the process of creating the risk knowledge element of computer based early warning systems.

A post-structuralist analysis of Irish youth crime prevention policy with specific emphasis on the Garda youth diversion projects

Garda Youth Diversion Projects (GYDPs) have since their beginnings in the early 1990s gained an increasingly important role and now constitute a central feature of Irish youth justice provision. Managed by the Irish Youth Justice Service and implemented by the Gardai and a variety of youth work organisations as well as independent community organisations, GYDPs are located at the crossroads of welfarist and corporatist approaches to youth justice, combining diversionary and preventative aspects in their work. To date, these projects have been subjected to very little systematic analysis and they have thus largely escaped critical scrutiny. To address this gap, this thesis locates the analysis of GYDP policy and practice within a post-structuralist theoretical framework and deploys discourse analysis primarily based on the work of Michel Foucault. It makes visible the official youth crime prevention and GYDP policy discourses and identifies how official discourses relating to youth crime prevention, young people and their offending behaviour, are drawn upon, negotiated, rejected or re-contextualised by project workers and JLOs. It also lays bare how project workers and JLOs draw upon a variety of other discourses, resulting in multi-layered, complex and sometimes contradictory constructions of young people, their offending behaviour and corresponding interventions. At a time when the projects are undergoing significant changes in terms of their repositioning to operate as the support infrastructure underpinning the statutory Garda Youth Diversion Programme, the thesis traces the discursive shifts and the implications for practice that are occurring as the projects move away from a youth work orientation towards a youth justice orientation. A key contribution of this thesis is the insight it provides into how young people and their families are being constituted in individualising and sometimes pathologising ways in GYDP discourses and practices. It reveals the part played by the GYDP intervention in favouring individual and narrow familial causes of offending behaviour while broader societal contexts are sidelined. By explicating the very assumptions upon which contemporary youth crime prevention policy, as well as GYDP policy and practice are based, this thesis offers a counterpoint to the prevailing evidence-based agenda of much research in the field of Irish youth justice theory and youth studies more generally. Rather, it encourages the reader to take a step back and examine some of the most fundamental and unquestioned assumptions about the construction of young people, their offending behaviour and ways of addressing this, in contemporary Irish youth crime prevention policy and practice.

Cereal products for specific dietary requirements. Evaluation and improvement of technological and nutritional properties of gluten free raw materials and end products

Coeliac disease is one of the most common food intolerances worldwide and at present the gluten free diet remains the only suitable treatment. A market overview conducted as part of this thesis on nutritional and sensory quality of commercially available gluten free breads and pasta showed that improvements are necessary. Many products show strong off-flavors, poor mouthfeel and reduced shelf-life. Since the life-long avoidance of the cereal protein gluten means a major change to the diet, it is important to also consider the nutritional value of products intending to replace staple foods such as bread or pasta. This thesis addresses this issue by characterising available gluten free cereal and pseudocereal flours to facilitate a better raw material choice. It was observed that especially quinoa, buckwheat and teff are high in essential nutrients, such as protein, minerals and folate. In addition the potential of functional ingredients such as inulin, β-glucan, HPMC and xanthan to improve loaf quality were evaluated. Results show that these ingredients can increase loaf volume and reduce crumb hardness as well as rate of staling but that the effect diverges strongly depending on the bread formulation used. Furthermore, fresh egg pasta formulations based on teff and oat flour were developed. The resulting products were characterised regarding sensory and textural properties as well as in vitro digestibility. Scanning electron and confocal laser scanning microscopy was used throughout the thesis to visualise structural changes occurring during baking and pasta making

The expression and regulation of pregnancy-specific glycoproteins in the mouse

Pregnancy-Specific Glycoproteins (PSG) are the most abundant fetally expressed proteins in the maternal bloodstream at term. This multigene family are immunoglobulin superfamily members and are predominantly expressed in the syncytiotrophoblast of human placenta and in giant cells and spongiotrophoblast of rodent placenta. PSGs are encoded by seventeen genes in the mouse and ten genes in the human. Little is known about the function of this gene family, although they have been implicated in immune modulation and angiogenesis through the induction of cytokines such as IL-10 and TGFβ1 in monocytes, and more recently, have been shown to inhibit the platelet-fibrinogen interaction. I provide new information concerning the evolution of the murine Psg genomic locus structure and organisation, through the discovery of a recent gene inversion event of Psg22 within the major murine Psg cluster. In addition to this, I have performed an examination of the expression patterns of individual Psg genes in placental and non-placental tissues. This study centres on Psg22, which is the most abundant murine Psg transcript detected in the first half of pregnancy. A novel alternative splice variant transcript of Psg22 lacking the protein N1-domain was discovered, and similar to the full length isoform induces TGFβ1 in macrophage and monocytic cell lines. The identification of a bidirectional antisense long non-coding RNA transcript directly adjacent to Psg22 and its associated active local chromatin conformation, suggests an interesting epigenetic gene-specific regulatory mechanism that may be responsible for the high level of Psg22 expression relative to the other Psg family members upon trophoblast giant cell differentiation

Characterisation of bacteriophage-host interactions in Lactococcus lactis

Lactococcus lactis is used extensively world-wide for the production of fermented dairy products. Bacteriophages (phages) infecting L. lactis can result in slow or incomplete fermentations, or may even cause total fermentation failure. Therefore, bacteriophages disrupting L. lactis fermentation are of economic concern. This thesis employed a multifaceted approach to investigate various molecular aspects of phage-host interaction in L. lactis. The genome sequence of an Irish dairy starter strain, the prophage-cured L. lactis subsp. cremoris UC509.9, was studied. The 2,250,427 bp circular chromosome represents the smallest among its sequenced lactococcal equivalents. The genome displays clear genetic adaptation to the dairy niche in the form of extensive reductive evolution. Gene prediction identified 2066 protein-encoding genes, including 104 which showed significant homology to transposase-specifying genes. Over 9 % of the identified genes appear to be inactivated through stop codons or frame shift mutations. Many pseudogenes were found in genes that are assigned to carbohydrate and amino acid transport and metabolism orthologous groups, reflecting L. lactis UC509.9’s adaptation to the lactose and casein-rich dairy environment. Sequence analysis of the eight plasmids of L. lactis revealed extensive adaptation to the dairy environment. Key industrial phenotypes were mapped and novel lactococcal plasmid-associated genes highlighted. In addition to chromosomally-encoded bacteriophage resistance systems, six functional such systems were identified, including two abortive infection systems, AbiB and AbiD1, explaining the observed phage resistance of L. lactis UC509.9 Molecular analysis suggests that the constitutive expression of AbiB is not lethal to cells, suggesting the protein is expressed in an un/inactivated form. Analysis of 936 species phage sk1-escape mutants of AbiB revealed that all such mutants harbour mutations in orf6, which encodes the major capsid protein. Results suggest that the major capsid protein is required for activation of the AbiB system, although this requires furrther investigations. Temporal transcriptomes of L. lactis UC509.9 undergoing lytic infection with either one of two distinct bacteriophages, Tuc2009 and c2, was determined and compared to the transcriptome of uninfected UC509.9 cells. Whole genome microarrays performed at various time-points post-infection demonstrated a rather modest impact on host transcription. Alterations in the UC509.9 transcriptome during lytic infection appear phage-specific, with a relatively small number of differentially transcribed genes shared between infection with either Tuc2009 or c2. Transcriptional profiles of both bacteriophages during lytic infection was shown to generally correlate with previous studies and allowed the confirmation of previously predicted promoter sequences. Bioinformatic analysis of genomic regions encoding the presumed cell wall polysaccharide (CW PS) biosynthesis gene cluster of several strains of L. lactis was performed. Results demonstrate the presence of three dominant genetic types of this gene cluster, termed type A, B and C. These regions were used for the development of a multiplex PCR to identify CW PS genotype of various lactococcal strains. Analysis of 936 species phage receptor binding protein phylogeny (RBP) and CW PS genotype revealed an apparent correlation between RBP phylogeny and CW PS type, thereby providing a partial explanation for the observed narrow host range of 936 phages. Further analysis of the genetic locus encompassing the presumed CW PS biosynthesis operon of eight strains identified as belonging to the CW PS C (geno)type, revealed the presence of a variable region among the examined strains. The obtained comparative analysis allowed for the identification of five subgroups of the C type, named C1 to C5. We purified an acidic polysaccharide from the cell wall of L. lactis 3107 (C2 subtype) and confirmed that it is structurally different from the CW PS of the C1 subtype L. lactis MG1363. Combinations of genes from the variable region of C2 subtype were amplified from L. lactis 3107 and introduced into a mutant of the C1 subtype L. lactis NZ9000 (a direct derivative of MG1363) deficient in CW PS biosynthesis. The resulting recombinant mutant synthesized a CW PS with a composition characteristic for that of the C2 subtype L. lactis 3107 and not the wildtype C1 L. lactis NZ9000. The recombinant mutant exhibited a changed phage resistance/sensitivity profile consistent with that of L. lactis 3107, which unambiguously demonstrated that L. lactis 3107 CW PS is the host cell surface receptor of two bacteriophages belonging to the P335 species as well as phages that are member of the 936 species. The research presented in this thesis has significantly advanced our understanding of L. lactis bacteriophage-host interactions in several ways. Firstly, the examination of plasmidencoded bacteriophage resistance systems has allowed inferences to be made regarding the mode of action of AbiB, thereby providing a platform for further elucidation of the molecular trigger of this system. Secondly, the phage infection transcriptome data presented, in addition to previous work, has made L. lactis a model organism in terms of transcriptomic studies of bacteriophage-host interactions. And finally, the research described in this thesis has for the first time explicitly revealed the nature of a carbohydrate bacteriophage receptor in L. lactis, while also providing a logical explanation for the observed narrow host ranges exhibited by 936 and P335 phages. Future research in discerning the structures of other L. lactis CW PS, combined with the determination of the molecular interplay between receptor binding proteins of these phages and CW PS will allow an in depth understanding of the mechanism by which the most prevalent lactococcal phages identify and adsorb to their specific host.

Pregnancy-specific glycoprotein function, conservation and receptor investigation

Pregnancy-specific glycoproteins (PSGs) are highly glycosylated secreted proteins encoded by multi-gene families in some placental mammals. They are carcinoembryonic antigen (CEA) family and immunoglobulin (Ig) superfamily members. PSGs are immunomodulatory, and have been demonstrated to possess antiplatelet and pro-angiogenic properties. Low serum levels of these proteins have been correlated with adverse pregnancy outcomes. Objectives: Main research goals of this thesis were: 1). To attempt to replicate previously reported cytokine responses to PSG-treatment of immune cells and subsequently to investigate functionally important amino acids within PSG1. 2). To determine whether candidate receptor, integrin αvβ3, was a binding partner for PSG1 and to investigate whether PSG1 possessed functionality in a leukocyte-endothelial interaction assay. 3). To determine whether proteins generated from recently identified putative PSG genes in the horse shared functional properties with PSGs from other species. Outcomes: 1). Sequential domain deletion of PSG1 as well as mutation of conserved residues within the PSG1 Ndomain did not affect PSG1-induced TGF-β1. The investigated response was subsequently found to be the result of latent TGF-β1 contaminating the recombinant protein. Protein further purified by SEC to remove this showed no induction of TGF-β1. The most N-terminal glycosylation site was demonstrated to have an important role in PSG N domain secretion. PSG1 attenuated LPS-induced IL-6 and TNF-α. Investigations into signalling underpinning this proved inconclusive. 2). Integrin αvβ3 was identified as a novel PSG1 receptor mediating an as yet unknown function. Preliminary investigations into a role for PSGs as inhibitors of leukocyte endothelial interactions showed no effect by PSG1. 3). Horse PSG protein, CEACAM49, was shown to be similarly contaminated by latent TGF-β1 particle and once removed did not demonstrate TGF-β1 release. Interestingly horse PSG did show anti-platelet properties through inhibition of the plateletfibrinogen interaction as previously published for mouse and human PSGs.

A cultural study on communication and technology with specific reference to media in China

This dissertation examines the role of communications technology in social change. It examines secondary data on contemporary China arguing that many interpretations of events in China are unsuitable at best and at worst conceptually damages our understanding of social change in China. This is especially the case in media studies under the ‘democratic framework’. It proposes that there is an alternative framework in studying the media and social change. This alternative conceptual framework is termed a zone of interpretative development offering a means by which to discuss events that take place in a mediated environment. Taking a theoretical foundation using the philosophy of Mikhail Bakhtin this dissertation develops a platform with which to understand communication technology from an anthropological perspective. Three media events from contemporary China are examined. The first examines the Democracy Wall event and the implications of using a public sphere framework. The second case examines the phenomenon of the Grass Mud Horse, a symbol that has gained popular purchase as a humorous expression of political dissatisfaction and develops the problems seen in the first case but with some solutions. Using a modification of Lev Vygotskiĭ’s zone of proximal development this symbol is understood as an expression of the collective recognition of a shared experience. In the second example from the popular TV talent show contests in China further expressions of collective experience are introduced. With the evidence from these media events in contemporary China this dissertation proposes that we can understand certain modes of communication as occurring in a zone of interpretative development. This proposed anthropological feature of social change via communication and technology can fruitfully describe meaning-formation in society via the expression and recognition of shared experiences.

Dealing with emergent design science research projects in IS

Multiple models, methods and frameworks have been proposed to guide Design Science Research (DSR) application to address relevant classes of problems in Information Systems (IS) discipline. While much of the ambiguity around the research paradigm has been removed, only the surface has been scratched on DSR efforts where researcher takes an active role in organizational and industrial engagement to solve a specific problem and generalize the solution to a class of problems. Such DSR projects can have a significant impact on practice, link theories to real contexts and extend the scope of DSR. Considering these multiform settings, the implications to theorizing nor the crucial role of researcher in the interplay of DSR and IS projects have not been properly addressed. The emergent nature of such projects needs to be further investigated to reach such contributions for both theory and practice. This paper raises multiple theoretical, organizational and managerial considerations for a meta-level monitoring model for emergent DSR projects.