Experimental quantification and modelling of attrition of infant formulae during pneumatic conveying

Infant formula is often produced as an agglomerated powder using a spray drying process. Pneumatic conveying is commonly used for transporting this product within a manufacturing plant. The transient mechanical loads imposed by this process cause some of the agglomerates to disintegrate, which has implications for key quality characteristics of the formula including bulk density and wettability. This thesis used both experimental and modelling approaches to investigate this breakage during conveying. One set of conveying trials had the objective of establishing relationships between the geometry and operating conditions of the conveying system and the resulting changes in bulk properties of the infant formula upon conveying. A modular stainless steel pneumatic conveying rig was constructed for these trials. The mode of conveying and air velocity had a statistically-significant effect on bulk density at a 95% level, while mode of conveying was the only factor which significantly influenced D[4,3] or wettability. A separate set of conveying experiments investigated the effect of infant formula composition, rather than the pneumatic conveying parameters, and also assessed the relationships between the mechanical responses of individual agglomerates of four infant formulae and their compositions. The bulk densities before conveying, and the forces and strains at failure of individual agglomerates, were related to the protein content. The force at failure and stiffness of individual agglomerates were strongly correlated, and generally increased with increasing protein to fat ratio while the strain at failure decreased. Two models of breakage were developed at different scales; the first was a detailed discrete element model of a single agglomerate. This was calibrated using a novel approach based on Taguchi methods which was shown to have considerable advantages over basic parameter studies which are widely used. The data obtained using this model compared well to experimental results for quasi-static uniaxial compression of individual agglomerates. The model also gave adequate results for dynamic loading simulations. A probabilistic model of pneumatic conveying was also developed; this was suitable for predicting breakage in large populations of agglomerates and was highly versatile: parts of the model could easily be substituted by the researcher according to their specific requirements.

The detuning effects of a wrist-worn antenna and design of a custom antenna measurement system

This paper investigates the effects of antenna detuning on wireless devices caused by the presence of the human body,particularly the wrist. To facilitate repeatable and consistent antenna impedance measurements, an accurate and low cost human phantom arm, that simulates human tissue at 433MHz frequencies, has been developed and characterized. An accurate and low cost hardware prototype system has been developed to measure antenna return loss at a frequency of 433MHz and the design, fabrication and measured results are presented. This system provides a flexible means of evaluating closed-loop reconfigurable antenna tuning circuits for use in wireless mote applications.

Antenna tuning for wearable wireless sensors

When miniaturized wireless sensors are placed on or close to the human body, they can experience a significant loss inperformance due to antenna detuning, resulting in degradationof wireless performance as well as decreased battery lifetime.Several antenna tuning technologies have been proposed formobile wireless devices but devices suitable for widespread integration have yet to emerge. This paper highlights the possible advantages of antenna tuning for wearable wireless sensors and presents the design and characterization of a prototype 433MHz tuner module.

Investigating the influence of the sulfur oxidation state on solid state conformation

Design, synthesis and structural characterization of a series of diphenylacetylene derivatives bearing organosulfur, amide and amine moieties has been achieved in which the molecular conformation is controlled through variation of the hydrogen bond properties on alteration of the oxidisation level of sulfur.

Victimisation of street children in Addis Ababa: factors of resilience and susceptibility

Cross-cultural variations in conceptions of childhood are discussed, particularly with regard to child abuse and child labour. Regardless of cultural background, a universal minimum standard of child rearing is required. The street child literature is reviewed, culminating in an analysis of Ethiopian street children. Theoretically this work is informed by victimology. Concepts shared by victimology and rational choice perspective are discussed, after Fattah (1993a). Victim surveys are described, highlighting their accuracy of crime estimates. Juvenile prostitution, runaways and rape are examined, particularly with regard to their relevance in Addis Ababa. Fifty five male and 135 female street children were interviewed. Interviews with boys focused on delinquency. An age-related pattern emerged, with younger boys less likely to drink, chew khat, steal or be sexually active. Interviews with street girls focused on the differences between girls living on the streets (girls of the street), girls working on the streets (girls on the street) and a sample of homebased girls. Girls of the street come to the street come to the streets for many reasons. Conflicts with a parent or guardian account for almost 50%. They are highly vulnerable to sexual assaults, particularly those 43% who have worked as prostitutes. Girls on the street experience considerably less victimisation. Urban poor girls live in socio-economic circumstances akin to girls on the street but enjoy almost universal protection from victimisation because they do not spend time on the streets. Unprotected by the stability which a family provides, girls of the street experience high victimisation levels. Such victimisation is often the result of reliance on types of work, such as prostitution, which brings the girls into contact with exploitative adults. Resistance to such victimisation is provided by a secure place to sleep, companions, and relatively safe types of work. Such protective factors are more readily available to family based children as compared to those living independently.

Effects of synbiotics on cancer risk biomarkers

Colorectal cancer (CRC) is the fourth most common cause of death from cancer in the world and second most common (behind lung cancer) in developed countries. In recent years there has been much interest in the potential use of prebiotics, probiotics and synbiotics in the prevention and treatment of CRC. We have previously shown that synbiotic consumption in Azoxymethane treated rats modulates the immune system, influences the genotoxic potential of caecal contents and reduces the number of colonic tumours compared to control rats who did not receive the synbiotic. The aim of the current study was to identify biomarkers suitable for use as cancer risk markers and as intervention markers. A second aim was to determine the influence of synbiotic consumption on cancer risk biomarkers such as in vivo colonic mucosal proliferation and genotoxic damage along with examining the genotoxic, cytotoxic and tumour promoting potential of faecal water (FW). Synbiotic consumption altered the composition of the gastrointestinal flora and reduced in vivo genotoxic damage and the genotoxic potential of FW in cancer and polyp subjects. Synbiotic consumption also reduced the proliferative activity in the colonic mucosa in polyp subjects. In both cancer and polyp subjects gene expression in the colonic mucosa was modulated in synbiotic consuming subjects. In this and other studies the activity of natural killer cells, the level of PGE2 in FW, IL-12 production by PBMCs, genotoxic damage in the colonic mucosa and the tumour promoting activities of FW have been identified as possible biomarkers of cancer risk. Future large scale studies investigating these parameters in healthy and diseased individuals are needed to confirm the suitability of these markers in assessing cancer risk and the role of synbiotics in modulating them.

Targeting aberrant kinase activity in myeloid leukaemias

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults. Its treatment has remained largely unchanged for the past 30 years. Chronic myeloid leukaemia (CML) represents a tremendous success story in the era of targeted therapy but significant challenges remain including the development of drug resistance and disease persistence due to presence of CML stem cells. The Aurora family of kinases is essential for cell cycle regulation and their aberrant expression in cancer prompted the development of small molecules that selectively inhibit their activity. Chapter 2 of this thesis outlines the efficacy and mechanism of action of alisertib, a novel inhibitor of Aurora A kinase, in preclinical models of CML. Alisertib possessed equipotent activity against CML cells expressing unmutated and mutated forms of BCR-ABL. Notably, this agent retained high activity against the T315I and E255K BCR-ABL mutations, which confer the greatest degree of resistance to standard CML therapy. Chapter 3 explores the activity of alisertib in preclinical models of AML. Alisertib disrupted cell viability, diminished clonogenic survival, induced expression of the forkhead box O3 (FOXO3a) targets p27 and BCL-2 interacting mediator (BIM), and triggered apoptosis. A link between Aurora A expression and sensitivity to ara-C was established. Chapter 4 outlines the role of the proto-oncogene serine/threonine-protein (PIM) kinases in resistance to ara-C in AML. We report that the novel small molecule PIM kinase inhibitor SGI-1776 disrupted cell viability and induced apoptosis in AML. We establish a link between ara-C resistance and PIM over-expression. Finally, chapter 5 explores how the preclinical work outlined in this thesis may be translated into clinical studies that may lead to novel therapeutic approaches for patients with refractory myeloid leukaemia.

Integrated magnetic components for high-power high-current dc-dc converters

This thesis is focused on the design and development of an integrated magnetic (IM) structure for use in high-power high-current power converters employed in renewable energy applications. These applications require low-cost, high efficiency and high-power density magnetic components and the use of IM structures can help achieve this goal. A novel CCTT-core split-winding integrated magnetic (CCTT IM) is presented in this thesis. This IM is optimized for use in high-power dc-dc converters. The CCTT IM design is an evolution of the traditional EE-core integrated magnetic (EE IM). The CCTT IM structure uses a split-winding configuration allowing for the reduction of external leakage inductance, which is a problem for many traditional IM designs, such as the EE IM. Magnetic poles are incorporated to help shape and contain the leakage flux within the core window. These magnetic poles have the added benefit of minimizing the winding power loss due to the airgap fringing flux as they shape the fringing flux away from the split-windings. A CCTT IM reluctance model is developed which uses fringing equations to accurately predict the most probable regions of fringing flux around the pole and winding sections of the device. This helps in the development of a more accurate model as it predicts the dc and ac inductance of the component. A CCTT IM design algorithm is developed which relies heavily on the reluctance model of the CCTT IM. The design algorithm is implemented using the mathematical software tool Mathematica. This algorithm is modular in structure and allows for the quick and easy design and prototyping of the CCTT IM. The algorithm allows for the investigation of the CCTT IM boxed volume with the variation of input current ripple, for different power ranges, magnetic materials and frequencies. A high-power 72 kW CCTT IM prototype is designed and developed for use in an automotive fuelcell-based drivetrain. The CCTT IM design algorithm is initially used to design the component while 3D and 2D finite element analysis (FEA) software is used to optimize the design. Low-cost and low-power loss ferrite 3C92 is used for its construction, and when combined with a low number of turns results in a very efficient design. A paper analysis is undertaken which compares the performance of the high-power CCTT IM design with that of two discrete inductors used in a two-phase (2L) interleaved converter. The 2L option consists of two discrete inductors constructed from high dc-bias material. Both topologies are designed for the same worst-case phase current ripple conditions and this ensures a like-for-like comparison. The comparison indicates that the total magnetic component boxed volume of both converters is similar while the CCTT IM has significantly lower power loss. Experimental results for the 72 kW, (155 V dc, 465 A dc input, 420 V dc output) prototype validate the CCTT IM concept where the component is shown to be 99.7 % efficient. The high-power experimental testing was conducted at General Motors advanced technology center in Torrence, Los Angeles. Calorific testing was used to determine the power loss in the CCTT IM component. Experimental 3.8 kW results and a 3.8 kW prototype compare and contrast the ferrite CCTT IM and high dc-bias 2L concepts over the typical operating range of a fuelcell under like-for-like conditions. The CCTT IM is shown to perform better than the 2L option over the entire power range. An 8 kW ferrite CCTT IM prototype is developed for use in photovoltaic (PV) applications. The CCTT IM is used in a boost pre-regulator as part of the PV power stage. The CCTT IM is compared with an industry standard 2L converter consisting of two discrete ferrite toroidal inductors. The magnetic components are compared for the same worst-case phase current ripple and the experimental testing is conducted over the operation of a PV panel. The prototype CCTT IM allows for a 50 % reduction in total boxed volume and mass in comparison to the baseline 2L option, while showing increased efficiency.

An evaluation of reovirus as an effective therapeutic for cancer

Cancer is a global problem. Despite the significant advances made in recent years, a definitively effective therapeutic has yet to be developed. Oncolytic virology has fallen back into favour for the treatment of cancer with several viruses and viral vectors currently under investigation including vesicular stomatitis virus (VSV), adenovirus vectors and herpes simplex virus (HSV) vectors. Reovirus has an advantage over many viral vectors in that its wild-type form is non-pathogenic and will selectively infect transformed cells, particularly those mutated in the Ras pathway. These advantages make Reovirus an ideal candidate as a safe and non-toxic therapeutic. The aim of the first part of this study was to determine the effect, if any, of Reovirus on cell lines derived from cancers of the gastrointestinal tract. These cancers, particularly those of the oesophagus and stomach, have extremely poor prognoses and little improvement has been seen in survival of these patients in recent years. Reovirus as a single therapy showed promising results in cell lines of oesophageal, gastric and colorectal origin. Further study of partially resistant cell lines using a combination of Reovirus and conventional therapies, either chemotherapy or radiation, showed that a multi-modal approach to therapy is possible with Reovirus and no antagonism between Reovirus and other treatments was observed. The second part of this study focused on investigating a novel use of Reovirus in an in vivo setting. Cancer vaccination or the use of vaccines in cancer therapy is gaining momentum and success has been seen both in a prophylactic approach and a therapeutic approach. A cell-based Reovirus vaccine was used in both these approaches with encouraging success. When used as a prophylactic vaccine tumour development was subsequently inhibited even upon exposure to a tumorigenic dose of cells. The use of the cell-based Reovirus vaccine as a therapeutic for established tumours showed significant delay in tumour growth and a prolongation of survival in all models. This study has proven that Reovirus is an effective therapeutic in a range of cancers and the successful use of a cell-based Reovirus vaccine leads the way for new advancements in cancer immunotherapy.

Investigation of the genetic susceptibility to osteoporosis in the Irish population

Osteoporosis is a complex skeletal disorder characterized by compromised bone strength. Variation in bone mineral density (BMD) is a contributing factor. The aim of this research as to select informative single nucleotide polymorphisms (SNPs) in potential candidate genes from loci suggestively linked to BMD variation for fine mapping. The gene regulated by oestrogen in breast cancer 1 (GREB1), located at 2p25.1, was selected. GREB1 transcription is initiated early in the oestrogen receptor alpha regulated pathway. There was significant association between GREB1_03 and BMD variation at the lumbar spine and femoral neck (FN) in the discovery cohort. Significant association was observed between GREB1_04 and FN BMD in the replication cohort. The development and differentiation enhancing factor 2, the integrin cytoplasmic domain associated protein 1 and A-disintegrin and metalloprotease 17 were selected due to their respective roles in cell mobility and adhesion. There was no linkage or association observed between the Chr2 cluster SNPs and BMD. Two factors in bone remodelling are the attraction of bone cell precursors and endocrine regulation of the process, primarily through the action of parathyroid hormone (PTH). The C-C chemokine receptor type 3 (CCR3) encodes a CC chemokine receptor expressed in osteoclast precursors. The PTH receptor type 1 (PTHR1) encodes a G-protein coupled receptor for PTH. Association was observed between CCR3 haplotypes and BMD variation at the FN. There was no linkage or association observed between PTHR1 SNPs and BMD variation. Population genetic studies with complex phenotypes endeavour to elucidate the traits genetic architecture. This study presents evidence of association between GREB1 and BMD variation and as such, introduces GREB1 as a novel gene target for osteoporosis genetics studies. It affirms that common genomic variants in PTHR1 are not associated with BMD variation in Caucasians and supports the evidence that CCR3 may be contributing to BMD variation

Exploring the Zionist evolution of Robert Briscoe: History and memory

Robert Briscoe was the Dublin born son of Lithuanian and German-Jewish immigrants. As a young man he joined Sinn Féin and was an important figure in the War of Independence due to a role as one of the IRA’s main gun-procuring agents. He took the anti-Treaty side during an internecine Civil War, mainly due to the influence of Eamon de Valera and retained a filial devotion towards him for the rest of his life. In 1926 he was a founding member of Fianna Fáil, de Valera’s breakaway republican party, which would dominate twentieth-century Irish politics. He was first elected as a Fianna Fáil T.D. (Teachta Dála, Deputy to the Dáil) in 1927, and successfully defended his seat eleven times becoming the first Jewish Lord Mayor of Dublin in 1956, an honour that was repeated in 1961. On this basis alone, it can be argued that Briscoe was a significant presence in an embryonic Irish political culture; however, when his role in the 1930s Jewish immigration endeavor is acknowledged, it is clear that he played a unique part in one of the most contentious political and social discourses of the pre-war years. This was reinforced when Briscoe embraced Zionism in a belated realisation that the survival of his European co-religionists could only be guaranteed if an independent Jewish state existed. This information is to a certain degree public knowledge; however, the full extent of his involvement as an immigration advocate for potential Jewish refugees, and the seniority he achieved in the New Zionist Organisation (Revisionists) has not been fully recognised. This is partly explicable because researchers have based their assessment of Briscoe on an incomplete political archive in the National Library of Ireland (NLI). The vast majority of documentation pertaining to his involvement in the immigration endeavor has not been available to scholars and remains the private property of Robert Briscoe’s son, Ben Briscoe. The lack of immigration files in the NLI was reinforced by the fact that information about Briscoe’s Revisionist engagement was donated to the Jabotinsky Institute in Tel Aviv and can only be accessed physically by visiting Israel. Therefore, even though these twin endeavors have been commented on by a number of academics, their assessments have tended to be based on an incomplete archive, which was supplemented by Briscoe’s autobiographical memoir published in 1958. This study will attempt to fill in the missing gaps in Briscoe’s complex political narrative by incorporating the rarely used private papers of Robert Briscoe, and the difficult to access Briscoe files in Tel Aviv. This undertaking was only possible when Mr.Ben Briscoe graciously granted me full and unrestricted access to his father’s papers, and after a month-long research trip to the Jabotinsky Institute in Tel Aviv. Access to this rarely used documentation facilitated a holistic examination of Briscoe’s complex and multifaceted political reality. It revealed the full extent of Briscoe’s political and social evolution as the Nazi instigated Jewish emigration crisis reached catastrophic proportions. He was by turn Fianna Fáil nationalist, Jewish immigration advocate and senior Revisionist actor on a global stage. The study will examine the contrasting political and social forces that initiated each stage of Briscoe’s Zionist awakening, and in the process will fill a major gap in Irish-Jewish historiography by revealing the full extent of his Revisionist engagement.

The treatment of landfill leachate using natural systems

Leachate may be defined as any liquid percolating through deposited waste and emitted from or contained within a landfill. If leachate migrates from a site it may pose a severe threat to the surrounding environment. Increasingly stringent environmental legislation both at European level and national level (Republic of Ireland) regarding the operation of landfill sites, control of associated emissions, as well as requirements for restoration and aftercare management (up to 30 years) has prompted research for this project into the design and development of a low cost, low maintenance, low technology trial system to treat landfill leachate at Kinsale Road Landfill Site, located on the outskirts of Cork city. A trial leachate treatment plant was constructed consisting of 14 separate treatment units (10 open top cylindrical cells [Ø 1.8 m x 2.0 high] and four reed beds [5.0m x 5.0m x 1.0m]) incorporating various alternative natural treatment processes including reed beds (vertical flow [VF] and horizontal flow [HF]), grass treatment planes, compost units, timber chip units, compost-timber chip units, stratified sand filters and willow treatment plots. High treatment efficiencies were achieved in units operating in sequence containing compost and timber chip media, vertical flow reed beds and grass treatment planes. Pollutant load removal rates of 99% for NH4, 84% for BOD5, 46% for COD, 63% for suspended solids, 94% for iron and 98% for manganese were recorded in the final effluent of successfully operated sequences at irrigation rates of 945 l/m2/day in the cylindrical cells and 96 l/m2/day in the VF reed beds and grass treatment planes. Almost total pathogen removal (E. coli) occurred in the final effluent of the same sequence. Denitrification rates of 37% were achieved for a limited period. A draft, up-scaled leachate treatment plant is presented, based on treatment performance of the trial plant.

MyRoom: A user-centred model of affective responsive architecture

Can my immediate physical environment affect how I feel? The instinctive answer to this question must be a resounding “yes”. What might seem a throwaway remark is increasingly borne out by research in environmental and behavioural psychology, and in the more recent discipline of Evidence-Based Design. Research outcomes are beginning to converge with findings in neuroscience and neurophysiology, as we discover more about how the human brain and body functions, and reacts to environmental stimuli. What we see, hear, touch, and sense affects each of us psychologically and, by extension, physically, on a continual basis. The physical characteristics of our daily environment thus have the capacity to profoundly affect all aspects of our functioning, from biological systems to cognitive ability. This has long been understood on an intuitive basis, and utilised on a more conscious basis by architects and other designers. Recent research in evidence-based design, coupled with advances in neurophysiology, confirm what have been previously held as commonalities, but also illuminate an almost frightening potential to do enormous good, or alternatively, terrible harm, by virtue of how we make our everyday surroundings. The thesis adopts a design methodology in its approach to exploring the potential use of wireless sensor networks in environments for elderly people. Vitruvian principles of “commodity, firmness and delight” inform the research process and become embedded in the final design proposals and research conclusions. The issue of person-environment fit becomes a key principle in describing a model of continuously-evolving responsive architecture which makes the individual user its focus, with the intention of promoting wellbeing. The key research questions are: What are the key system characteristics of an adaptive therapeutic single-room environment? How can embedded technologies be utilised to maximise the adaptive and therapeutic aspects of the personal life-space of an elderly person with dementia?.

Substance misuse in young people in Ireland - a focus on benzodiazepines

Benzodiazepines are a class of drugs that are prescribed for the treatment of anxiety and insomnia. Due to the powerful tolerance that can develop as a result of sustained use, benzodiazepines can also be dependence-forming. Benzodiazepine dependence can occur from prescribed and from recreational use, and is a significant issue for young people. The consequences of benzodiazepine dependence include cognitive and learning impairment, depressive symptoms, and increased suicide risk. Despite these risks, the nature of youth benzodiazepine use has not been explored to the same extent as other drugs. A review of existing Irish literature revealed that benzodiazepines are one of the five most recreationally-used drugs among young people. Analyses of young people attending a treatment centre indicated that young attendees from urban areas were more likely to be referred to the centre because of benzodiazepines than rural attendees. Further examination of the centre’s attendees showed that regular benzodiazepine users experienced more paranoia, loss of interest in sport, and pallor than non-regular users. Analysis of benzodiazepine prescribing to young people revealed that approximately one in seven young people were prescribed benzodiazepines for periods greater than recommended by national guidelines. Young benzodiazepine users discussed in interviews that they took benzodiazepines to escape from negative feelings and that they are generally taken in a social setting. Further interviews with youth counsellors and general practitioners highlighted that both family and community attitude to benzodiazepine use can impact on a young person’s benzodiazepine usage. Suggestions for reducing benzodiazepine use such as psychological alternatives to medication, public awareness campaigns and prescribing restrictions are provided. Future research can elaborate upon this work to determine other methods of reducing youth benzodiazepine use and the damage that it causes to the young people themselves, but also to their families, their community, and society at large.

The impact of host-microbe interactions on murine colonic secretomotor function

The overall objective of this thesis was to gain further insight into the mechanisms underlying commensal microbial influences on intestinal ion transport. In this regard, I examined the impact of commensal host-microbe interactions on colonic secretomotor function in mouse. I first examined the influence of two different probiotic (microorganisms which, when given in adequate amounts, can confer health benefits upon the host) strains, Bifidobacterium infantis 35624 and L. salivarius UCC118 on active colonic ion transport in the mouse, using the Ussing Chamber. I found that both probiotics appear to have converging effects on ion transport at a functional level. However, L. salivarius UCC118 may preferentially inhibit neurally-evoked ion transport. Next I examined the impact of the host microbiota itself on both baseline and stimulated colonic secretomotor function as well as probiotic induced changes in ion transport. I provide further evidence that the microbiota is capable of mediating alterations in colonic ion transport, and specifically suggests that it can influence cAMP-mediated responses. Finally, it has been well documented that many probiotics elicit their effects via secreted bioactives, therefore, I studied the effects of microbially produced GABA, contained in supernatants from the commensal microbe Lactobacillus brevis DPC6108, on colonic secretomotor function. In conclusion, I believe that commensal microbes have an important and strain specific functional influence on colonic ion transport and secretomotor function and these effects can be mediated via extracellular bioactives. Moreover, I believe that functional ex-vivo studies such as those carried out in this thesis have a critical role to play in our future understanding of host-microbe interactions in the gut.