Gröbner basis techniques for certain problems in coding and systems theory

There is much common ground between the areas of coding theory and systems theory. Fitzpatrick has shown that a Göbner basis approach leads to efficient algorithms in the decoding of Reed-Solomon codes and in scalar interpolation and partial realization. This thesis simultaneously generalizes and simplifies that approach and presents applications to discrete-time modeling, multivariable interpolation and list decoding. Gröbner basis theory has come into its own in the context of software and algorithm development. By generalizing the concept of polynomial degree, term orders are provided for multivariable polynomial rings and free modules over polynomial rings. The orders are not, in general, unique and this adds, in no small way, to the power and flexibility of the technique. As well as being generating sets for ideals or modules, Gröbner bases always contain a element which is minimal with respect tot the corresponding term order. Central to this thesis is a general algorithm, valid for any term order, that produces a Gröbner basis for the solution module (or ideal) of elements satisfying a sequence of generalized congruences. These congruences, based on shifts and homomorphisms, are applicable to a wide variety of problems, including key equations and interpolations. At the core of the algorithm is an incremental step. Iterating this step lends a recursive/iterative character to the algorithm. As a consequence, not all of the input to the algorithm need be available from the start and different "paths" can be taken to reach the final solution. The existence of a suitable chain of modules satisfying the criteria of the incremental step is a prerequisite for applying the algorithm.

Modular average case analysis: Language implementation and extension

Motivated by accurate average-case analysis, MOdular Quantitative Analysis (MOQA) is developed at the Centre for Efficiency Oriented Languages (CEOL). In essence, MOQA allows the programmer to determine the average running time of a broad class of programmes directly from the code in a (semi-)automated way. The MOQA approach has the property of randomness preservation which means that applying any operation to a random structure, results in an output isomorphic to one or more random structures, which is key to systematic timing. Based on original MOQA research, we discuss the design and implementation of a new domain specific scripting language based on randomness preserving operations and random structures. It is designed to facilitate compositional timing by systematically tracking the distributions of inputs and outputs. The notion of a labelled partial order (LPO) is the basic data type in the language. The programmer uses built-in MOQA operations together with restricted control flow statements to design MOQA programs. This MOQA language is formally specified both syntactically and semantically in this thesis. A practical language interpreter implementation is provided and discussed. By analysing new algorithms and data restructuring operations, we demonstrate the wide applicability of the MOQA approach. Also we extend MOQA theory to a number of other domains besides average-case analysis. We show the strong connection between MOQA and parallel computing, reversible computing and data entropy analysis.

Biodiscovery of natural products from microbes associated with Irish coastal sponges

Marine sponges have been an abundant source of new metabolites in recent years. The symbiotic association between the bacteria and the sponge has enabled scientists to access the bacterial diversity present within the bacterial/sponge ecosystem. This study has focussed on accessing the bacterial diversity in two Irish coastal marine sponges, namely Amphilectus fucorum and Eurypon major. A novel species from the genus Aquimarina has been isolated from the sponge Amphilectus fucorum. The study has also resulted in the identification of an α–Proteobacteria, Pseudovibrio sp. as a potential producer of antibiotics. Thus a targeted based approach to specifically cultivate Pseudovibrio sp. may prove useful for the development of new metabolites from this particular genus. Bacterial isolates from the marine sponge Haliclona simulans were screened for anti–fungal activity and one isolate namely Streptomyces sp. SM8 displayed activity against all five fungal strains tested. The strain was also tested for anti–bacterial activity and it showed activity against both against B. subtilis and P. aeruginosa. Hence a combinatorial approach involving both biochemical and genomic approaches were employed in an attempt to identify the bioactive compounds with these activities which were being produced by this strain. Culture broths from Streptomyces sp. SM8 were extracted and purified by various techniques such as reverse–phase HPLC, MPLC and ash chromatography. Anti–bacterial activity was observed in a fraction which contained a hydroxylated saturated fatty acid and also another compound with a m/z 227 but further structural elucidation of these compounds proved unsuccessful. The anti–fungal fractions from SM8 were shown to contain antimycin–like compounds, with some of these compounds having different retention times from that of an antimycin standard. A high–throughput assay was developed to screen for novel calcineurin inhibitors using yeast as a model system and three putative bacterial extracts were found to be positive using this screen. One of these extracts from SM8 was subsequently analysed using NMR and the calcineurin inhibition activity was con rmed to belong to a butenolide type compound. A H. simulans metagenomic library was also screened using the novel calcineurin inhibitor high–throughput assay system and eight clones displaying putative calcineurin inhibitory activity were detected. The clone which displayed the best inhibitory activity was subsequently sequenced and following the use of other genetic based approaches it became clear that the inhibition was being caused by a hypothetical protein with similarity to a hypothetical Na+/Ca2+ exchanger protein. The Streptomyces sp. SM8 genome was sequenced from a fragment library using Roche 454 pyrosequencing technology to identify potential secondary metabolism clusters. The draft genome was annotated by IMG/ER using the Prodigal pipeline. The Whole Genome Shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession AMPN00000000. The genome contains genes which appear to encode for several polyketide synthases (PKS), non–ribosomal peptide synthetases (NRPS), terpene and siderophore biosynthesis and ribosomal peptides. Transcriptional analyses led to the identification of three hybrid clusters of which one is predicted to be involved in the synthesis of antimycin, while the functions of the others are as yet unknown. Two NRPS clusters were also identified, of which one may be involved in gramicidin biosynthesis and the function of the other is unknown. A Streptomyces sp. SM8 NRPS antC gene knockout was constructed and extracts from the strain were shown to possess a mild anti–fungal activity when compared to the SM8 wild–type. Subsequent LCMS analysis of antC mutant extracts confirmed the absence of the antimycin in the extract proving that the observed anti–fungal activity may involve metabolite(s) other than antimycin. Anti–bacterial activity in the antC gene knockout strain against P. aeruginosa was reduced when compared to the SM8 wild–type indicating that antimycin may be contributing to the observed anti–bacterial activity in addition to the metabolite(s) already identified during the chemical analyses. This is the first report of antimycins exhibiting anti–bacterial activity against P. aeruginosa. One of the hybrid clusters potentially involved in secondary metabolism in SM8 that displayed high and consistent levels of gene–expression in RNA studies was analysed in an attempt to identify the metabolite being produced by the pathway. A number of unusual features were observed following bioinformatics analysis of the gene sequence of the cluster, including a formylation domain within the NRPS cluster which may add a formyl group to the growing chain. Another unusual feature is the lack of AT domains on two of the PKS modules. Other unusual features observed in this cluster is the lack of a KR domain in module 3 of the cluster and an aminotransferase domain in module 4 for which no clear role has been hypothesised.

Work experience in transition year: a mixed methods study of subject and career choices

Transition Year (TY) has been a feature of the Irish Education landscape for 39 years. Work experience (WE) has become a key component of TY. WE is defined as a module of between five and fifteen days duration where students engage in a work placement in the broader community. It places a major emphasis on building relationships between schools and their external communities and concomitantly between students and their potential future employers. Yet, the idea that participation in a TY work experience programme could facilitate an increased awareness of potential careers has drawn little attention from the research community. This research examines the influence WE has on the subsequent subjects choices made by students along with the effects of that experience on the students’ identities and emerging vocational identities. Socio-cultural Learning Theory and Occupational Choice Theory frame the overall study. A mixed methods approach to data collection was adopted through the administration of 323 quantitative questionnaires and 32 individual semi-structured interviews in three secondary schools. The analysis of the data was conducted using a grounded theory approach. The findings from the research show that WE makes a significant contribution to the students’ sense of agency in their own lives. It facilitates the otherwise complex process of subject choice, motivates students to work harder in their senior cycle, introduces them to the concepts of active, experience-based and self-directed learning, while boosting their self-confidence and nurturing the emergence of their personal and vocational identities. This research is a gateway to further study in this field. It also has wide reaching implications for students, teachers, school authorities, parents and policy makers regarding teaching and learning in our schools and the value of learning beyond the walls of the classroom.

Supporting therapist engagement in evidence based practice: Developing a continuing education programme through participatory action research

Therapists find it challenging to integrate research evidence into their clinical decision-making because it may involve modifying their existing practices. Although continuing education (CE) programmes for evidence-based practice (EBP) have employed various approaches to increase individual practitioner’s knowledge and skills, these have been shown to have little impact in changing customary behaviours. To date, there has been little attempt to actively engage therapists as collaborators in developing educational processes concerning EBP. The researcher collaborated with seven clinical therapists (one occupational therapist, four physiotherapists and two speech and language therapists) enrolled in a new post-qualification Implementing Evidence in Therapy Practice (IETP) MSc module to monitor and adapt the learning programme over ten weeks. The participating therapists actively engaged in participatory action research (PAR) iterative cycles of reflecting→ planning→ acting→ observing→ reflecting with the researcher. Mixed methods were used to evaluate the IETP module and its influence on therapists’ subsequent engagement in EBP activities. Data were gathered immediately on completion of the module and five months later. Immediate post-module findings revealed four components as being important to the therapists: 1) characteristics of the learning environment; 2) acquisition of relevant EBP skills; 3) nature of the learning process; and 4) acquiring confidence. The two themes and sub-themes which emerged from individual interviews conducted five months post-module expanded on the four components already identified. Theme 1: Experiencing the learning (sub-themes: module organisation; learning is relational; improving the module); and theme 2: Enacting the learning through a new way of being (sub-themes: criticality and reflection; self agency; modelling EBP behaviours; positioning self in an EB work culture). The therapists’ perspectives had by then shifted from that of a learner to that of a clinician constructing a new sense of self as an evidence-based practitioner. Findings from this study underline the importance of the process of socially constructed knowledge and of empowering learners through collaboratively designed continuing education programmes. In the student-driven learning environment, therapists chose repetitive skill-building and authentic problem-solving activities which reflected the complexity of the environments to which they were expected to transfer their learning. These findings have implications for educators designing EBP continuing education programmes, during which students develop professional ways of being.

Research and design of high-speed advanced analogue front-ends for fibre-optic transmission systems

In the last decade, we have witnessed the emergence of large, warehouse-scale data centres which have enabled new internet-based software applications such as cloud computing, search engines, social media, e-government etc. Such data centres consist of large collections of servers interconnected using short-reach (reach up to a few hundred meters) optical interconnect. Today, transceivers for these applications achieve up to 100Gb/s by multiplexing 10x 10Gb/s or 4x 25Gb/s channels. In the near future however, data centre operators have expressed a need for optical links which can support 400Gb/s up to 1Tb/s. The crucial challenge is to achieve this in the same footprint (same transceiver module) and with similar power consumption as today’s technology. Straightforward scaling of the currently used space or wavelength division multiplexing may be difficult to achieve: indeed a 1Tb/s transceiver would require integration of 40 VCSELs (vertical cavity surface emitting laser diode, widely used for short‐reach optical interconnect), 40 photodiodes and the electronics operating at 25Gb/s in the same module as today’s 100Gb/s transceiver. Pushing the bit rate on such links beyond today’s commercially available 100Gb/s/fibre will require new generations of VCSELs and their driver and receiver electronics. This work looks into a number of state‐of-the-art technologies and investigates their performance restraints and recommends different set of designs, specifically targeting multilevel modulation formats. Several methods to extend the bandwidth using deep submicron (65nm and 28nm) CMOS technology are explored in this work, while also maintaining a focus upon reducing power consumption and chip area. The techniques used were pre-emphasis in rising and falling edges of the signal and bandwidth extensions by inductive peaking and different local feedback techniques. These techniques have been applied to a transmitter and receiver developed for advanced modulation formats such as PAM-4 (4 level pulse amplitude modulation). Such modulation format can increase the throughput per individual channel, which helps to overcome the challenges mentioned above to realize 400Gb/s to 1Tb/s transceivers.

The impact of saving and credit cooperatives on food security in the West Amhara Region of Ethiopia

In rural Ethiopia, among other things, lack of adequate financial service is considered as the basic problem to alleviate rural poverty and to solve the problem of food insecurity. Commercial banks are restricted to urban centres. Providing rural financial service through RUSACCO to the poor has been proposed as a tool for economic development and for achieving food security. Evidence from research in this regard has been so far scanty, especially in rural Ethiopia. The aims of this study are to analyze the determinants of membership, to identify socioeconomic and demographic factors that influence members’ participation in RUSACCOs and to quantify the impact of RUSACCOs on member households’ food security. The study was conducted in two purposely selected woredas in the Amhara region one from food insecure (Lay Gayint woreda) and the other from food secure (Dejen woreda). Six RUSACCOs were selected randomly from these two woredas. Both qualitative and quantitative data were collected. Key informant interviews, focus group discussions and survey techniques were used to collect primary data. Collected data was then analyzed using mixed methods depending on the nature of data. For quantitative data analysis appropriate statistical models were used. The study result reveals that the number of members in each RUSACCO is very small. However, the majority of non-member respondents are willing to join RUSACCO. Lack of information about the benefits of RUSACCO membership is the main problem why many rural poor do not join RUSACCOs. Members participate in different aspects of the cooperatives, starting from attending general assembly up to board membership. They also participate actively in saving and borrowing activities of RUSACCO. The majority of the respondents believe the RUSACCO is a vital instrument in combating food insecurity. The empirical findings indicate that gender, marital status, occupation, educational level, participation in local leadership and participation in other income generation means determine the decision of rural poor to join a RUSACCO or not. The amount of saving is determined by household head occupation, farming experience and income level. While age of household head, primary occupation, farming experience, date of membership, annual total consumption expenditure, amount of saving and participation in other income generation activities influence members’ amount of borrowing by RUSACCO members. Finally, the study confirms that RUSACCO participation improves household food security. RUSACCO membership has made positive impact on household total consumption expenditure and food expenditure.

Mechanically stacked solar cells for concentrator photovoltaics

The power output of dual-junction mechanically stacked solar cells comprising different sub-cell materials in a terrestrial concentrating photovoltaic module has been evaluated. The ideal bandgap combination of both cells in a stack was found using EtaOpt. A combination of 1.4 eV and 0.7 eV has been found to produce the highest photovoltaic conversion efficiency under the AM1.5 Direct Solar Spectrum with x500 concentration. As EtaOpt does not consider the absorption profile of solar cell materials; the practical power output per unit area of a dual junction mechanically stacked solar cell has been modelled considering the optical absorption co-efficients and thicknesses of the individual solar cells. The model considered a GaAs top cell and a Ge, GaSb, Ga0.47In0.53As or Si bottom cell. It was found that GaSb gives the highest power contribution as a bottom cell in a dual junction configuration followed by Ge and GaInAs. While the additional power provided by a Si bottom cell is less than these it remains a suitable candidate for a bottom cell owing to its lower cost

"I have nothing to say, only to show": appropriation in the poetries of Trevor Joyce, Alan Halsey, and Susan Howe

This thesis studies contemporary poetry’s innovations in textual borrowing and the range and scope of its appropriative practices. The restrictions of the inherited definitions of appropriation include a limited capacity for expression and meaningfulness, a partial concept of appropriation’s critical capacity, and an inadequate sense of the poet’s individual and unique practice of appropriation. This thesis resolves the problematic constraints limiting contemporary definitions of appropriation by tracing the history of the practice to reveal an enduring relation between appropriation and poetic expression. Close readings of Trevor Joyce’s, Alan Halsey’s, and Susan Howe’s poetry serve as evidence of contemporary poetry’s development of appropriation beyond the current ascriptions and offer some direction on how the critical understanding of appropriation might be extended and redefined. Here, appropriation is recognized as another source of lyric expression, critical innovation, and conceptual development in contemporary poetry. This thesis encourages a new perspective on the purpose and processes of poetic appropriation and the consequences of its declarative potential for both poet and poem.

Strategies to prevent potentially inappropriate prescribing and adverse drug reactions in older patients

INTRODUCTION: Potentially inappropriate prescribing (PIP) is a major contributor to adverse drug reactions and overall increased healthcare costs. The aim of this thesis was to identify, develop and implement strategies with the potential to prevent PIP and ADRs in older patients. METHODS: A systematic review of the qualitative literature (Meta-synthesis); A qualitative study in Irish hospitals; A randomised controlled trial (RCT) to assess the impact of an online educational module on doctors’ prescribing knowledge and confidence; Exploration of the potential for a frailty index score to enable doctors identify patients at increased risk of PIP and ADRs; Exploration of the potential for the SHiM tool to enable doctors to optimise prescribing for older patients. RESULTS: The meta-synthesis identified four key concepts: (i) Desire to please the patient; (ii) Feeling of being forced to prescribe; (iii) Tension between experience and guidelines; (iv) Prescriber fear. Similar themes also emerged from the qualitative study. In the RCT, the online educational module resulted in a highly significant 22% difference in test scores between intervention and control groups. The studies exploring the frailty index score showed a significant positive relationship between a patient’s frailty status and their likelihood of experiencing PIP/ADRs. Patients above a frailty threshold of 0.16 were at least twice as likely to experience PIP/ADRs. SHiM was found to be a useful tool in terms of reconciling patients’ medications. However, the evidence for it being capable of preventing clinically relevant adverse events was poor. CONCLUSION:Qualitative research in this thesis has proposed novel theories relating to the causative factors of PIP in older patients. In doing so, it has identified several areas for intervention and laid down a road map for future research.

Randomized, controlled trial investigating short-term health-related quality of life with doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer: European Organization for Research and Treatment of Cancer Breast Cancer Group, Investigational Drug Branch for Breast Cancer and the New Drug Development Group Study.

PURPOSE: To compare health-related quality of life (HRQOL) in patients with metastatic breast cancer receiving the combination of doxorubicin and paclitaxel (AT) or doxorubicin and cyclophosphamide (AC) as first-line chemotherapy treatment. PATIENTS AND METHODS: Eligible patients (n = 275) with anthracycline-naive measurable metastatic breast cancer were randomly assigned to AT (doxorubicin 60 mg/m(2) as an intravenous bolus plus paclitaxel 175 mg/m(2) as a 3-hour infusion) or AC (doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2)) every 3 weeks for a maximum of six cycles. Dose escalation of paclitaxel (200 mg/m(2)) and cyclophosphamide (750 mg/m(2)) was planned at cycle 2 to reach equivalent myelosuppression in the two groups. HRQOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and the EORTC Breast Module at baseline and the start of cycles 2, 4, and 6, and 3 months after the last cycle. RESULTS: Seventy-nine percent of the patients (n = 219) completed a baseline measure. However, there were no statistically significant differences in HRQOL between the two treatment groups. In both groups, selected aspects of HRQOL were impaired over time, with increased fatigue, although some clinically significant improvements in emotional functioning were seen, as well as a reduction in pain over time. Overall, global quality of life was maintained in both treatment groups. CONCLUSION: This information is important when advising women patients of the expected HRQOL consequences of treatment regimens and should help clinicians and their patients make informed treatment decisions.

Baseline health-related quality-of-life data as prognostic factors in a phase III multicentre study of women with metastatic breast cancer.

The potential value of baseline health-related quality-of-life (HRQOL) and clinical factors in predicting prognosis was examined using data from an international randomised phase III trial which compared doxorubicin and paclitaxel with doxorubicin and cylophosphamide as first line chemotherapy in 275 women with metastatic breast cancer. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and the related breast module (QLQ-BR23) were used to assess baseline HRQOL data. The Cox proportional-hazards regression model was used for both univariate and multivariate analyses of survival. In the univariate analyses, performance status (P<0.001) and number of sites involved (P=0.001) were the most important clinical prognostic factors. The HRQOL variables at baseline most strongly associated with longer survival were better appetite, physical and role functioning, as well as less fatigue (P<0.001). The final multivariate model retained performance status (P<0.001) and appetite loss (P=0.005) as the variables best predicting survival. Substantial loss of appetite was the only independent HRQOL factor predicting poor survival and was strongly correlated (/r/>0.5) with fatigue, role and physical functioning. In addition to known clinical factors, appetite loss appears to be a significant prognostic factor for survival in women with metastatic breast cancer. However, the mechanism underlying this association remains to be precisely defined in future studies.

HDAC6 and Ubp-M BUZ domains recognize specific C-terminal sequences of proteins.

The BUZ/Znf-UBP domain is a protein module found in the cytoplasmic deacetylase HDAC6, E3 ubiquitin ligase BRAP2/IMP, and a subfamily of ubiquitin-specific proteases. Although several BUZ domains have been shown to bind ubiquitin with high affinity by recognizing its C-terminal sequence (RLRGG-COOH), it is currently unknown whether the interaction is sequence-specific or whether the BUZ domains are capable of binding to proteins other than ubiquitin. In this work, the BUZ domains of HDAC6 and Ubp-M were subjected to screening against a one-bead-one-compound (OBOC) peptide library that exhibited random peptide sequences with free C-termini. Sequence analysis of the selected binding peptides as well as alanine scanning studies revealed that the BUZ domains require a C-terminal Gly-Gly motif for binding. At the more N-terminal positions, the two BUZ domains have distinct sequence specificities, allowing them to bind to different peptides and/or proteins. A database search of the human proteome on the basis of the BUZ domain specificities identified 11 and 24 potential partner proteins for Ubp-M and HDAC6 BUZ domains, respectively. Peptides corresponding to the C-terminal sequences of four of the predicted binding partners (FBXO11, histone H4, PTOV1, and FAT10) were synthesized and tested for binding to the BUZ domains by fluorescence polarization. All four peptides bound to the HDAC6 BUZ domain with low micromolar K(D) values and less tightly to the Ubp-M BUZ domain. Finally, in vitro pull-down assays showed that the Ubp-M BUZ domain was capable of binding to the histone H3-histone H4 tetramer protein complex. Our results suggest that BUZ domains are sequence-specific protein-binding modules, with each BUZ domain potentially binding to a different subset of proteins.

Generalized sampling using a compound-eye imaging system for multi-dimensional object acquisition.

In this paper, we propose generalized sampling approaches for measuring a multi-dimensional object using a compact compound-eye imaging system called thin observation module by bound optics (TOMBO). This paper shows the proposed system model, physical examples, and simulations to verify TOMBO imaging using generalized sampling. In the system, an object is modulated and multiplied by a weight distribution with physical coding, and the coded optical signal is integrated on to a detector array. A numerical estimation algorithm employing a sparsity constraint is used for object reconstruction.

Display of cell surface sites for fibronectin assembly is modulated by cell adherence to (1)F3 and C-terminal modules of fibronectin.

BACKGROUND: Fibronectin-null cells assemble soluble fibronectin shortly after adherence to a substrate coated with intact fibronectin but not when adherent to the cell-binding domain of fibronectin (modules (7)F3-(10)F3). Interactions of adherent cells with regions of adsorbed fibronectin other than modules (7)F3-(10)F3, therefore, are required for early display of the cell surface sites that initiate and direct fibronectin assembly. METHODOLOGY/PRINCIPAL FINDINGS: To identify these regions, coatings of proteolytically derived or recombinant pieces of fibronectin containing modules in addition to (7)F3-(10)F3 were tested for effects on fibronectin assembly by adherent fibronectin-null fibroblasts. Pieces as large as one comprising modules (2)F3-(14)F3, which include the heparin-binding and cell adhesion domains, were not effective in supporting fibronectin assembly. Addition of module (1)F3 or the C-terminal modules to modules (2)F3-(14)F3 resulted in some activity, and addition of both (1)F3 and the C-terminal modules resulted in a construct, (1)F3-C, that best mimicked the activity of a coating of intact fibronectin. Constructs (1)F3-C V0, (1)F3-C V64, and (1)F3-C Delta(V(15)F3(10)F1) were all able to support fibronectin assembly, suggesting that (1)F3 through (11)F1 and/or (12)F1 were important for activity. Coatings in which the active parts of (1)F3-C were present in different proteins were much less active than intact (1)F3-C. CONCLUSIONS: These results suggest that (1)F3 acts together with C-terminal modules to induce display of fibronectin assembly sites on adherent cells.