Masters

Investigation of a Metal Complexing Route to Arene trans - Dihydrodiols

Crystal O'Connor [Thesis] — Thu, 14 Mar 2013 08:31:47 PDT

In this work, a route for the conversion of arene cis-dihydrodiols to their trans
isomers was examined. Arene trans-dihydrodiols are potentially important chiral
building blocks in synthetic chemistry and are more stable than their cis analogues.
While the cis-arene dihydrodiols can be produced on a relatively large scale by
fermentation, their trans isomers cannot. The principal aim of this work was to
carry out studies in tandem to inform the development of the synthetic pathway to
convert arene cis-dihydrodiols to their trans isomers by (a) the synthesis of
organometallic intermediates and (b) investigation of their reactivity by means of
kinetic and equilibrium studies. A number of analogues based on sevenmembered ring systems instead of six were also investigated as a comparison. The four-step synthetic route being investigated involved formation of a tricarbonyl iron complex of the arene cis-dihydrodiol substrate, followed by reaction in acid to form a carbocation intermediate. This cation complex is trapped stereoselectively using hydroxide to give a trans isomer and decomplexation to remove the iron tricarbonyl moiety is the final step. Two substrates were examined, 3- bromocyclohexa-3,5-diene-1 ,2-diol and 3-trifluoromethylcyclohexa-3,5-diene-1 ,2- diol. The first three steps in the route were successfully performed on each compound in yields of 52 % and 43 % overall for the 3-bromo and 3-trifluoromethyl starting materials respectively. The final decomplexation step was not successful however and will require optimisation of the conditions. The ionisation of the tricarbonyl iron cis-dihydrodiol intermediates was investigated kinetically in strong acid, and the corresponding rate constant for the bromo substituted complex was
determined to be 8.0 x 1 o-s M-1 s-1 showing a significant lack of reactivity towards cation complex formation. This is expected based on previous work that reports low reactivity towards ionisation for any complexes that have hydroxyl groups endo to the iron centre, as is the case here. The reverse reaction, hydrolysis of the bromo-substituted cation, was too fast to measure but a pKR of 0.5 was estimated. It can be concluded that ionisation of the coordinated endo (i.e. cis-) diol to form the corresponding cation is the difficult step in the route to convert arene cis - dihydrodiols to their trans isomers. Among the seven-membered ring complexes synthesised were salts of the cation
species, tricarbonyl (115-cyclohepta-1 ,3-dienyl) iron and tricarbonyl (117-
cycloheptatrienyl) chromium. Rate constants for the nucleophilic reaction of the
former cation complex with water to give tricarbonyl (115-cyclohepta-2,4-diene-1-ol
iron) and conversion of this complex back to the cation were measured, allowing a
pH profile (log k versus pH) to be constructed. From this, an equilibrium constant,
pKR, = 4.2 was determined for the interconversion between the cycloheptadienyl
complex [R+] and the corresponding hydrolysis product [ROH] in which the
hydroxyl group is exo to the iron centre.
Comparison of this equilibrium constant to that reported for the uncoordinated
cycloheptadienyl cation shows that the iron tricarbonyl moiety is highly stabilising
(~PKR = 15.8). The uncoordinated tropylium (or cycloheptatrienyl) ion however
shows a similar stability to tricarbonyl (115-cyclohepta-1 ,3-dienyl) iron due to
aromatic stabilisation. The effect of having one less methylene group in the ring
was found to be negligible as ~PKR = 0.4 for the coordinated cycloheptadienyl and
cyclohexadienyl cations.
It is proposed that, in weak base, the tricarbonyl cycloheptatrienyl chromium
complex gives a zwitterionic complex in which a carbonyl ligand is converted to a
carboxylate ion. Equilibrium between this zwitterion and a cationic form in which
the carboxylate has been protonated to give the carboxylic acid is postulated to
occur in weakly acid solutions. An acid dissociation constant, pKa of 4.8 was
determined for this equilibrium spectrophotometrically.

Effect of Reduction of Breath-Holding Time In The Single-Breath Method To Assess Carbon Monoxide Diffusing Capacity

Elsa Magro — Thu, 24 Jan 2013 08:36:00 PST

Measurement of the diffusing capacity of the lung is part of the routine
pulmonary function assessment in every patient and the single breath method is the most commonly used method. This method requires a subject to inspire a gas mixture followed by a 10 second (s) breath-hold. However dyspnoea may preclude measurement in patients with advanced pulmonary disease. We sought to determine if breath-hold time reduction had a significant effect on measured DLco values.
Forced spirometry and CO-diffusion by the single breath method were
performed by a respiratory scientist with a Jaeger master-screen PFT equipment, in duplicate with breath-holding of 10 , 8 and 6 s in 30 control subjects (FEV1 107 ± 12.04% predicted), 30 severe COPD patients (FEV1 37.2 ± 7.92% predicted), and 30 patients with interstitial lung disease (ILD) (FEV1 69.5 ± 17.61% predicted).
There was no significant difference between DLcoSB and KCO measured at 10,
8 and 6 s in the control group (p=0.4431) and ILD group (p=0.5915). However, there was a significant difference between DLcoSB (p=0.0003) and DLco (VA) (p=0.0183) measured at 10, 8 and 6 s in the COPD group. In the presence of severe airway obstruction the DLco decreases with breath-hold time reduction.
In the control group and patients with ILD, there was no significant change in
the DLcoSB when breath-hold time was reduced from 10 to 6 s. This could allow a reduction in breath-hold time when measuring the DLco in patients with advanced ILD who are unable to breath-hold for 10 s, but not in patients with severe COPD.

Evaluation of Smoking Cessation Services in Ireland: Design and Pilot of a Smoking Cessation Treatment Database

Sheila Keogan — Wed, 23 Jan 2013 02:44:59 PST

A reduction in tobacco use is one of the stated aims of the National Health Promotion Strategy
(2000-2005) (Department of Health and Children, 2000a) as well being the core activity of
membership for all health promoting hospitals (HPH).
AIMS OF THE STUDY

1. To develop a database of smoking cessation services in Ireland.

2. Do a census of the smoking cessation services in Ireland and evaluate the range and
availability of them.
3. Develop a database for use in smoking cessation treatment services which would schedule
consultations with patients and gather all relevant demographics, treatments and their outcomes,
(cessation treatment database) and pilot its use over a 3 month period.
4. Conduct a patient satisfaction survey of the service users.

RESEARCH METHODS:

1. The database of services was compiled from existing information supplemented by further enquiry
and validation. It was then used as the population base for a survey of services using a
specially developed, structured self-administered questionnaire which was completed by the smoking
cessation service providers identified from the database.
2. Having developed an “Excel” based smoking cessation treatment database, workshops were held
around the country and used to further develop and demonstrate it. At these workshops smoking
cessation service providers were encouraged to (SPs) into pilot its use for a 3 month period. Data
on patients was entered into the database by SPs during the 3 month pilot and was subsequently
analysed.
3. A patient satisfaction survey was also carried out during this 3 month period using a custom
built survey instrument with the cooperation of the SPs.

Role of Vascular Endothelial Growth Factor, Placental Growth Factor and Cytokines on outer Blood Retinal Barrier Breakdown.

Sangeetha Sukumaran — Mon, 01 Oct 2012 09:04:10 PDT

The aim of this thesis was to investigate the effect of the VEGF family of growth factors and
cytokines TNF- α and IL-1β on oBRB function. The human RPE line ARPE-19 was
employed as an in vitro model of the oBRB. Two-Dimensional gel electrophoresis was
employed to study the effect of growth factors on the RPE proteome. The barrier properties of
the oBRB were evaluated by expression of the TJ proteins occludin or Zo-1, or claudins-1, 2,
3 and 4, determined by western blotting analysis. Claudins 2, 3 and 4 were found to be
significantly up-regulated by TNF-α, while interleukin 1 β-treated RPE showed increased
expression of Claudins 1 and 3.

Assessment of Fire Safety and Evacuation Management in Nursning Homes

John Moore — Fri, 27 Jul 2012 08:25:45 PDT

The Nutritional Status of Patients with Clostridium Difficile Associeated Disease and Dietetic Practices Concerning the Management of These Patients

Yvonne Hickey (Thesis) — Fri, 27 Jul 2012 08:02:10 PDT

Background: Clostridium difficile is a leading cause of noscomial infection and is responsible for increased morbidity and mortality (Hookman & Barkin, 2009). There are limited data available on the nutritional status and dietetic management of these patients. Aims: 1. To carry out an observational study to assess the prevalence of the risk of malnutrition in patients with Clostridium difficile associated disease (CDAD) and compare it to a group of patients in the same hospital. 2. To investigate dietitians’ beliefs and recommendations of probiotics in CDAD and determine the probiotic products and strains being used in this patient group. To assess the current enteral feeding practices of dietitians in patients with CDAD. Methods: The Malnutrition Screening Tool (MUST) was used to assess the prevalence of risk of malnutrition in the patients with CDAD and a hospital comparison group. A questionnaire was sent to members of the Irish Nutrition and Dietetic Institute to gather information on dietitians’ opinions and use of probiotics and their enteral feeding practices in patients with CDAD. Results: There was no significant difference in the prevalence of malnutrition risk (MUST of 1 or more) between the CDAD group (75.5%) compared to the hospital comparison group (66.7%). The questionnaire response rate was 41% with 215 questionnaires undergoing analysis. One-third (34.5%) of dietitians considered probiotics to have a role in the prevention of CDAD yet only 11% used them in practice. Almost two-thirds (65.4%) believed that they have a role in the treatment of CDAD but only 40% regularly used them in practice. A yogurt drink containing Lactobacillus rhamnosus GG was mostly commonly available probiotic product for use by dietitians. When enterally feeding patients with CDAD, the majority of dietitians use a polymeric feed (79.6%). Conclusion: Both patient groups studied were at similar nutritional risk. There are mixed beliefs among Irish dietitians on the role of probiotics in CDAD. Probiotics are frequently recommended by dietitians in their clinical practice with little standardisation in practice. The probiotic strain that is most commonly being used in patients with CDAD does not have strong evidence to support its use.

A Study of the Factors that Influence Early Stages Technology Investment by Food Enterprises

Grainne Kavanagh (Thesis) — Fri, 27 Jul 2012 06:31:45 PDT

To promote industry sustainability and to catalyze links between publicly-funded knowledge providers and companies, the Irish government has invested significantly in food-orientated research and development. This project aims to facilitate a greater understanding of the motivations and barriers influencing the decision by small and medium-sized food enterprises (SME) to invest in technological innovation, emanating from research conducted in publicly-funded organisations. A critical review of the literature was used to develop a framework for investigating the uptake of technological innovations from sources external to the company. In order to ground this framework within the specific context of the Irish food industry, a series of in-depth interviews were conducted with key food industry representatives (n=7). Building from the literature and exploratory interviews, a postal survey of Irish food SMEs was undertaken (n=399). A response rate of 31.8% (n=117) was achieved. An open innovation scale was constructed from measures of the perceived relevance of academia, support agencies and publicly-funded research. Results of t-tests for independence indicated that companies which showed a propensity towards open innovation were more likely to have performed product [F(1, 118)=3.9, p=0.05] and process [F(1, 111)=3.7, p<0.001] innovations in the last three years. The proclivity towards open innovation varied significantly across sectors, with the preparedconsumer goods (x̅=3.9, SD=0.61) sector scoring a significantly higher open innovation mean than the others sector i.e. beverage, seafood and fresh produce (x̅=3.4, SD=0.57). Issues arising from earlier research steps were further clarified in a number of followup, in-depth interviews, with representatives from SMEs (n=6). By understanding the barriers and drivers to industry uptake of publicly-funded food research, targeted supports can be constructed to facilitate technological innovation within food SMEs, and in doing so, maximise return from the States investment in food-orientated R&D.

The Clinical Utility of Forced Vital Capacity Measured at Six Seconds in the Spirometric Detection of Airways Obstruction

Janine Kelly (Thesis) — Tue, 28 Feb 2012 06:58:05 PST

Synthesis, Characterisation and Anti-Candida Activity of Inorganic and Organic Derivatives of 1,10-Phenanthroline

Ruth Cogan (Thesis) — Wed, 02 Nov 2011 08:30:02 PDT

This thesis reports results in three areas: (i) the synthesis, characterisation and biological activity of simple metal salts incorporating 1,10-phenanthroline (phen) and 1,10 phenanthroline- 5,6-dione (phendione) ligands, (ii) the synthesis, characterisation and biological activity of three different organic derivatives of phendione, and (iii) the synthesis or attempted synthesis, characterisation and biological activity of phendione-amino acid conjugates.

Functional Characterization of Nuclear Receptor and Co-activator Binding Loci in the Human Genome

Kim Maguire (Thesis) — Wed, 02 Nov 2011 06:00:55 PDT

Steroid hormones, such as oestrogen, mediate their effects via activation of oestrogen regulated genes using nuclear receptors. Selective oestrogen receptor modulators (SERMs), such as Tamoxifen, are used to treat oestrogen responsive breast cancers, hctioning to act as oestrogen antagonists, preventing the oestrogen receptor biding DNA and blocking gene expression. However, Tamoxifen has been identified as an oestrogen agonist in other tissues which can often lead to secondary tumors in the years following the treatment. Identification of the genomic regions where SERMs can act as oestrogen agonists can possibly lead to the development of gene targeted therapies or other alternatives to prevent this from occurring. Investigations of a previously constructed ERE reporter library were directed towards the isolation of SERM responsive plasmids. Identified SERM responsive plasmids were compared to oestrogen responsive reporter piasmids on the basis of their ability to mediate trauscription in conjunction with other nuclear -tors and coactivators to establish potential novel interactions. ERa mutation analysis was performed to attempt to identify the mechanism by which these sequences have the ability to be activated with the addition of SERMs. It was found that SRC-3, a member of the SRC family of coactivators, had the ability to corepress SERMs via oestrogen receptors, a response not documented previously. Further to results obtained from the investigations of the SERM responsive reporter plasmids, DamID technology was employed to attempt to construct two libraries of sequences that associated, indirectly, with SRC-1A or SRC-3, via ligand bound oestrogen or progesterone. Gateway technology was used to transfer cloned sequences in to reporter plasmids to enable the luciferase assay to be employed in order to determine the functionality of the isolated sequences. - ~.... - Transactivation assays suggested that the attempt to direct the SRC-1A:Dam fusion protein to bind to DNA via either ligand bound oestrogen or progesterone failed, however following reporter plasmid sequencing bioinformatical studies were performed q d a number of possible transcription factor binding,motifs were identified in the sequences. Further transactivation assays indicated SRC-1A:Dam had, in a subset of the reporter plasmids, bound via the orphan nuclear receptors RORa and COUP TFI. Results suggest that SRC-1A may mediate this association and coactivate gene transcription; the mechanism behind this novel finding remains to be elucidated.

SV40 Infection in Human Lymphocyte Cell Lines

Aoife Kelly (Thesis) — Wed, 02 Nov 2011 03:20:18 PDT

The oncogenic DNA virus Simian virus 40 (SV40) was introduced into the human population as an inadvertent contaminant of polio vaccines that were prepared in cultures of primary monkey kidney cells. It is estimated that, as a result, millions of people worldwide were exposed to SV40 between the years 1955-1 963. Research indicates that the virus is still present in the human population today, based on the finding of neutralising antibodies and viral DNA sequences in children and adults. Of concern is that SV40 has also been detected in human tumours including primary brain cancer, malignant mesothelioma, bone tumours and systemic lymphomas. Recent studies have found a significant association of SV40 with certain types of Non-Hodgkin's Lymphoma (NHL). However, the interaction between SV40 and lymphocytes has not yet been fully characterised. In this study, the characteristics of SV40 infections were evaluated in human B and T lymphocyte cell lines. Three strains of SV40 were compared: wild type 776-1E with a single enhancer, 776-2E with a duplicated enhancer and a micro RNA mutant virus, 776-2E-SM. Following infection, cell proliferation and viability, cell surface marker expression, viral large tumour antigen (T-ag) expression, and quantification of viral genomes were measured. The results showed increased B cell proliferation and cell activation as shown by the upregulation of CD69. Downregulation of CD80, a co-stitnulatory molecule, was also observed. T-ag expression was detected in a small percentage of B cells and RQ-PCR analysis showed maintenance of the viral genome in B cells during passage of the cultures. In all, these initial observations indicate that some human B lymphocyte cell lines are susceptible to SV40 infection. Viral maintenance and oncoprotein expression in lymphocytes may bear relevance to SV40 persistence in the host and the detection of the virus in human lymphomas.

Collagen Binding Proteins in Helicobacter Pylori

Carmel Cremin (Thesis) — Thu, 20 Oct 2011 01:24:15 PDT

Helicobacter pylori is a human pathogen and the causative agent of chronic gastritis, peptic ulcer and gastric malignancies. A number of H. pylori virulence factors have been described including, CagA, VacA, neutrophil activating protein, and expression of receptors for binding to extracellular matrix proteins (adhesins). H. pylori interacts with extracellular matrix (ECM) proteins such as collagen IV, laminin, vitronectin and fibronectin, that can be exposed due to loss of integrity of the gastric epithelial cell layer. These interactions may be important in the pathogenesis of the organism. This study examines the interaction of H. pylori with collagen IV in an attempt to identify a H. pylori collagen IV adhesin. Collagen IV makes up a large proportion of the basement membranes, and has been implicated in microbial adherence. FITC labelling of bacteria and a bacteria overlay method showed binding of H. pylori to ECM proteins collagen IV, laminin and fibronectin. Binding was observed under a variety of culture conditions. Receptor activity-directed tagging known as “Retagging” was employed in an attempt to purify the collagen IV adhesin. H. pylori catalase was identified as a possible collagen adhesin, This enzyme was isolated and its interaction with collagen IV in vitro was studied. However, in vitro binding of collagen IV to catalase could not be demonstrated despite repeated attempts. Immunoblot and receptor overlay techniques were investigated in further attempts to identify the H. pylori collagen IV binding protein. The role of collagen IV in H. pylori ECM binding is discussed.

Is there a Benefit to Screening for Abdominal Aortic Aneurysm in the Irish Male Population between the ages of 55 to 75 years; an Ideal Opportunity Group for Evaluating Cardiovascular Risk Factors?

Mairead Brosnan (Thesis) — Mon, 03 Oct 2011 03:59:32 PDT

Introduction: Abdominal Aortic Aneurysm (AAA) screening programmes have been carried out worldwide on males between the ages of 65-75 years. The results of such programmes show AAA screening to be beneficial and cost effective. In the Multicentre Aneurysm Screening Study conducted in the United Kingdom, the incidence of AAA was 4.9%. Early diagnoses of AAA’s have reduced AAA related deaths by 42%. This study investigated the incidence of AAA in Irish males between the ages of 55-75 years and incorporated an assessment of cardiovascular risk factors. A younger group of males were screened to see if there was any benefit in screening for AAA and to determine the incidence of cardiovascular risk factors in this younger population. Method: From April 2006 to December 2007, males ages between 55-75 years living in the catchment area of the hospital, were invited to participate in the screening programme. A ultrasound scan of their aortas was preformed and a finger prick blood test was carried out to assess their cardiovascular risk factor status. Results: Nine hundred and four participants were screened. Of these, 17 (1.9%) participants had an undiagnosed AAA, of which 4.2% were aged between 65-75years and 0.6% aged between 55-64 years. The incidence for hypertension, 33% had been previously diagnosed with hypertension, with 165 of these uncontrolled. In the participants with no history of HTN, 31% had an elevated blood pressure reading. The study found, 26% had a previous history of hypercholesterolemia, with 70% of these remaining uncontrolled. Of those with no previous history of hypercholesterolemia, 33% had an elevated reading. The glucose results revealed 3% of the total participants had a raised glucose level with had no previous history of DM. Of those who were being treated for diabetes, 49% showed poor sugar control. Only 63% (573) of all participants agreed to have their body mass index measured. Of these, 16% were found to be morbidly obese and 64% were overweight. Conclusion: The incidence of AAA in males between 65-75 years is similar to other worldwide studies, therefore screening would be beneficial in Ireland. However, screening males of 55-65 years was not proven to be beneficial. Cardiovascular risk factors, such as hypertension, hypercholesterolemia and diabetes are very prevalent in Ireland. In this study 8 the prevalence of cardiovascular risk factors were high. Of those who have been diagnosed with a cardiovascular risk factor, many remain uncontrolled despite treatment. There was also a larger number of the screened population undiagnosed for their risk factors. Therefore screening for cardiovascular risk factors is a necessity and it can easily be incorporated in to other screening programmes.

Macular Pigment: Practical Implications for Optometric Practice in Preventative Health Care and Visual Performance Enhancement

Grainne Scanlon (Thesis) — Mon, 12 Sep 2011 06:17:26 PDT

The macula is a specialised part of the retina responsible for detailed central and colour vision. The carotenoids, lutein, zeaxanthin and meso-zeaxanthin are uniquely concentrated in the inner and central layers of the primate macula, where they are known as macular pigment (MP). It has been shown that MP is entirely of dietary origin and that lutein and zeaxanthin levels in serum, diet and retina correlate. Age-Related Macular Degeneration (AMD) is a disease of the macula and results in loss of central vision. MP, because of its optical filtration and antioxidant properties, may have an important role in the prevention or delay of AMD, and also in the enhancement and preservation of visual performance in healthy individuals.

An Investigation into the Design, Development and Testing of a Tool to Improve the Accessibility of Access Information for People with Disabilities

Susan Codd (Thesis) — Tue, 19 Apr 2011 05:17:27 PDT

Independent access for all to the built environment is one of the most basic of human rights. It provides social inclusion, integration and acceptance in communities. People with disabilities often encounter barriers to such access, barriers that can discriminate and marginalise to the extent that it prohibits independent living. Visiting the built environment becomes a lottery whereby inaccessible features may be present around every corner. People with disabilities deserve more than operating on a system of chance; they require a tool to make an informed decision prior to embarking on a journey. However in order to provide such information three distinct aspects must be considered, the individual, the disability and the built environment. Understanding and building upon each of these aspects holds the solution to the current gap in service provision for people with disabilities.
Considerate investigation into the meaning of disability and the requirement of the individual will help strengthen the credibility of any research undertaken to improve the status of people with disabilities. From this the built environment can then be suitably examined as to where accessibility does and does not exist. Once accessibility or indeed inaccessibility information has been collected a means whereby the information may be communicated to people with disabilities must be developed. This research aims to develop a concept entitled “LADDER” to meet this current gap in services. The use of a regulatory requirement as the access audit standard to collect data and a GIS as a communication tool broadens the application of concept not only to people with disabilities but also to key stakeholders who can advance their status within society. It is only through gaining a broad insight into legislative, structural and emotional requirements for access for people with disabilities can worthwhile research on this area be carried out. A multi-dimensional approach to the design of the research was employed. Preliminary research involved an examination of associated literature and surveys of key stakeholders to gain an insight into the determinants of access. Part one of the “LADDER” concept designed an access audit using the regulatory standard that was then tested on a defined research area to assess both the suitability of the legislation as an auditing tool, and to evaluate the effectiveness of the legislation in providing access. Part two then investigated how to best communicate such information to key stakeholders in a meaningful and useful manner using GIS. The result generated an exciting new tool that may not only reform how stakeholders use data and promote and improve disability access, but also change how a person with a disability plans and lives their life. This research was conducted in close collaboration with people of varying abilities as it is only through consulting with and understanding the needs of people with disabilities can society begin to create an environment that is truly accessible and inclusive to all.

Investigation of Velocity Profiles in Anatomically Realistic Renal Artery Flow Phantoms by Physiological Flow Experimentation

Deepa Chari (Thesis) — Tue, 19 Apr 2011 04:37:36 PDT

Renal Artery stenosis is one of the major causes of curable renovascular hypertension.An early investigation of renal artery stenosis helps in the management of renovascular hypertension by alternative, less-invasive methods such as drug treatments, thereby reducing the risk involved in the surgery. Therefore an early investigation of renal artery stenosis has been always an attractive goal for the physicians. The renal artery stenosis affects the blood velocity profile in the renal artery. These profiles can be investigated by quantitative Doppler Ultrasound measurements obtained by flow experimentations and can be used as a tool for the identification of renal artery stenosis. In the present study, the velocity profiles produced in anatomically realistic renal artery wall-less flow phantoms were investigated by physiological flow experimentations. The renal artery flow phantoms mimic renal vasculature anatomically and acoustically as well as representing symmetrical (30%, 50% and 70%) and asymmetrical (25%, 35% and 45%) stenosis conditions. A physiological flow of velocity between 2 – 40 cms-1 was produced in each renal artery flow phantom. The blood mimicking fluid (BMF) velocity was determined at regular axial and radial intervals of 1mm, using Siemens Antares Ultrasound system with a broadband curvilinear transducer (C5-2). The physiological velocity profiles in each phantom were investigated. By studying the characteristics of the physiological velocity profiles in the
anatomically realistic renal flow phantoms, a greater understanding of renal flow behavior in the normal and diseased conditions can be obtained. These flow characteristics can serve as a basis for identification and quantification of the degree of stenosis. The flow characteristics in the investigated velocity profiles may lead to earlier detection of renal artery stenosis using noninvasive ultrasonic methods. Subcutaneous fat is a well documented limitation of renal imaging. Recent studies have indicated that the subcutaneous fat introduces an error in the maximum velocity estimation and
thereby in the quantification of degree of stenosis. In the present thesis, the effect of a fat mimicking layer on: a) physiological velocity profiles and b) the shape and profile of Spectral Doppler velocity waveforms was studied. The knowledge of how the subcutaneous fat affects the physiological waveforms and thereby the clinical diagnosis is important while using the physiological flow waveforms and the physiological velocity profiles as a criteria for identification of renal artery stenosis.

Investigation of a Metal Complexing Route to Arene trans-Dihydrodiols

Crystal O'Connor (Thesis) — Tue, 19 Apr 2011 03:38:32 PDT

Pleiotrophin and its Role in Regulating Haemopoietic Stem Cell Regeneration

Rebecca Smith (Thesis) — Tue, 19 Apr 2011 03:38:30 PDT

HSCs are cells that have the capacity to self renew, proliferate and differentiate, providing cells of the mature blood system throughout a lifetime. The concept of such a cell was first considered in 1961 subsequent to the injection of healthy marrow into a lethally irradiated recipient mouse which mediated the reconstitution of mature blood cells in the irradiated host
(Till and Mc Culloch, 1961). This finding provided preliminary experimental evidence that all of the blood cells were derived from a single type of progenitor cell, also known as HSC. The majority of mature blood cells have a limited life span, red blood cells survive for 120 days and some white cells just hours, thus requiring their continuous replacement to sustain life. Replenishment of the mature blood cells does not occur as a direct single step but is in fact achieved through the production of progenitor cells that display diminished self-renewal capabilities with increased maturity and the assembly of HSC hierarchy. HSCs differentiate to multi-potent progenitors (Allen.D, 1984). These multi-potent progenitors have the ability to differentiate into either myeloid or lymphoid progenitor cells. Lymphoid progenitor cells
give rise to T, B and Natural Killer (NK) cells while the myeloid progenitor cell gives rise to neutrophils, basophils, eosinophils, red cells, platelets and monocytes/macrophages (figure 1) all of which require constant replenishment to keep circulating blood levels constant. This method of mature blood cell production allows a large number of mature cells to be derived
from a small population of HSCs. (Lajtha, 1979)

Safety Performance on 20 Construction Sites in Dublin

Paul McEvoy (Thesis) — Wed, 02 Mar 2011 02:30:18 PST

Abstract The aim of this research was to assess factors affecting safety performance on twenty apartment construction sites in Dublin using qualitative and quantitative risk assessment techniques. The quantitative techniques involved observing compliance with recommended safety procedures. The qualitative techniques involved an assessment of site safety management documentation and semi structured interviews with site management regarding site safety procedures. The field work was carried out between November 2003 and October 2004. The results showed that five sites out of twenty had high standards of safety and prevented all possible falls from heights. The five best performing sites were characterised by size of company in that that the largest construction companies were found to be the best performing. What was also found was that when a site performed well in terms of safety, it performed well across all safety categories. Evidence showing that the presence on site of a safety representative improved safety relevant to other sites was also found. The five best performing sites all had a safety representative, whilst the remaining 15 sites had a lesser number of safety representatives. However the overall number of safety representatives was too low to prove statistical significance, Interviews with site management regarding safety standards in the construction sector over the last five years found the following. The majority of site management stated there has been large improvement in safety. However, interviewees also stated that there has been no improvement in relation to buildings being any safer to build and hence no design improvements. Furthermore the clients influence on safety as required by legislation has not improved and in some cases has lessened. In terms of extrapolating the results against the literature the following can be stated. There has been a modest but nevertheless welcome improvement in site safety behaviour when comparing this research to comparable and previous Irish site safety research carried out in 2002.

Mig-6 and Its Role in Regulating Adult Lung Epithelium

Sandra Bennett (Thesis) — Wed, 02 Mar 2011 02:30:15 PST

Through the use of developmental and knock out studies Mig-6 has been shown to have a role in development. It has also been shown to be a tumour suppressor gene. Little work has been done as yet looking at its role in the adult. This study examined the role of Mig-6 in the lung with the ultimate goal being to determine if the pulmonary phenotype due to Mig-6 ablation is due to a developmental programming or loss of function in the adult. This was investigated in two ways. 1. To investigate if knocking out Mig-6 in adult lung has an effect on lung function
2. Investigate the role of Mig-6 in lung epithelial cells by RNAi (Investigation of the Role of Mig-6 in Pulmonary Epithelial Cells and Vascular Cells In Vitro).
Knocking out Mig-6 in the adult mice showed no difference in epithelial markers and after staining morphology and airway size were found to be normal. This would seem to indicate that the Mig-6 phenotype is due to altered development of the lungs during the neonatal period and not due to a loss of function in the adult. From the cell work we observed differences in the effect on epithelial cells vs. endothelial
cells when Mig-6 was knocked out. The epithelial cells showed an increased number of viable cells present after knocking out Mig-6 while the number of viable cells was decreased in the endothelial cells. This would indicate that knocking out Mig-6 in epithelial cells causes increased proliferation but in endothelial cells causes apoptosis. Conclusions: Ablation of Mig-6 leads to increased proliferation in epithelial cells (and
apoptosis in endothelial cells) but knocking it out in the adult stage has a mild effect on lung
phenotype