Quantitative evaluation of electron beam writing in passivated gold nanoclusters

Jenkins, Tudor; Hayton, D.J.; Bedson, T.R.; Palmer, R.E., (2001) 'Quantitative evaluation of electron beam writing in passivated gold nanoclusters', Applied Physics Letters (78) pp.1921-1923 RAE2008

A trait specific model of competition in a spatially structured plant community

John Warren and Chris Topping (2004). A trait specific model of competition in a spatially structured plant community. Ecological Modelling, 180 pp.477-485 RAE2008

Representation, comparison, and interpretation of metabolome fingerprint data for total composition analysis and quality trait investigation in potato cultivars

Manfred Beckmann, David P. Enot, David P. Overy, and John Draper (2007). Representation, comparison, and interpretation of metabolome fingerprint data for total composition analysis and quality trait investigation in potato cultivars. Journal of Agricultural and Food Chemistry, 55 (9) pp.3444-3451 RAE2008

Quantitative Analysis of Single Nucleotide Polymorphisms within Copy Number Variation

Background Single nucleotide polymorphisms (SNPs) have been used extensively in genetics and epidemiology studies. Traditionally, SNPs that did not pass the Hardy-Weinberg equilibrium (HWE) test were excluded from these analyses. Many investigators have addressed possible causes for departure from HWE, including genotyping errors, population admixture and segmental duplication. Recent large-scale surveys have revealed abundant structural variations in the human genome, including copy number variations (CNVs). This suggests that a significant number of SNPs must be within these regions, which may cause deviation from HWE. Results We performed a Bayesian analysis on the potential effect of copy number variation, segmental duplication and genotyping errors on the behavior of SNPs. Our results suggest that copy number variation is a major factor of HWE violation for SNPs with a small minor allele frequency, when the sample size is large and the genotyping error rate is 0~1%. Conclusions Our study provides the posterior probability that a SNP falls in a CNV or a segmental duplication, given the observed allele frequency of the SNP, sample size and the significance level of HWE testing.

Quantitative Particle Characterization by Scattered Ultrasound

The topic of this thesis is an acoustic scattering technique for detennining the compressibility and density of individual particles. The particles, which have diameters on the order of 10 µm, are modeled as fluid spheres. Ultrasonic tone bursts of 2 µsec duration and 30 MHz center frequency scatter from individual particles as they traverse the focal region of two confocally positioned transducers. One transducer acts as a receiver while the other both transmits and receives acoustic signals. The resulting scattered bursts are detected at 90° and at 180° (backscattered). Using either the long wavelength (Rayleigh) or the weak scatterer (Born) approximations, it is possible to detennine the compressibility and density of the particle provided we possess a priori knowledge of the particle size and the host properties. The detected scattered signals are digitized and stored in computer memory. With this information we can compute the mean compressibility and density averaged over a population of particles ( typically 1000 particles) or display histograms of scattered amplitude statistics. An experiment was run first run to assess the feasibility of using polystyrene polymer microspheres to calibrate the instrument. A second study was performed on the buffy coat harvested from whole human blood. Finally, chinese hamster ovary cells which were subject to hyperthermia treatment were studied in order to see if the instrument could detect heat induced membrane blebbing.

QUANTITATIVE THREE DIMENSIONAL ELASTICITY IMAGING

Neoplastic tissue is typically highly vascularized, contains abnormal concentrations of extracellular proteins (e.g. collagen, proteoglycans) and has a high interstitial fluid pres- sure compared to most normal tissues. These changes result in an overall stiffening typical of most solid tumors. Elasticity Imaging (EI) is a technique which uses imaging systems to measure relative tissue deformation and thus noninvasively infer its mechanical stiffness. Stiffness is recovered from measured deformation by using an appropriate mathematical model and solving an inverse problem. The integration of EI with existing imaging modal- ities can improve their diagnostic and research capabilities. The aim of this work is to develop and evaluate techniques to image and quantify the mechanical properties of soft tissues in three dimensions (3D). To that end, this thesis presents and validates a method by which three dimensional ultrasound images can be used to image and quantify the shear modulus distribution of tissue mimicking phantoms. This work is presented to motivate and justify the use of this elasticity imaging technique in a clinical breast cancer screening study. The imaging methodologies discussed are intended to improve the specificity of mammography practices in general. During the development of these techniques, several issues concerning the accuracy and uniqueness of the result were elucidated. Two new algorithms for 3D EI are designed and characterized in this thesis. The first provides three dimensional motion estimates from ultrasound images of the deforming ma- terial. The novel features include finite element interpolation of the displacement field, inclusion of prior information and the ability to enforce physical constraints. The roles of regularization, mesh resolution and an incompressibility constraint on the accuracy of the measured deformation is quantified. The estimated signal to noise ratio of the measured displacement fields are approximately 1800, 21 and 41 for the axial, lateral and eleva- tional components, respectively. The second algorithm recovers the shear elastic modulus distribution of the deforming material by efficiently solving the three dimensional inverse problem as an optimization problem. This method utilizes finite element interpolations, the adjoint method to evaluate the gradient and a quasi-Newton BFGS method for optimiza- tion. Its novel features include the use of the adjoint method and TVD regularization with piece-wise constant interpolation. A source of non-uniqueness in this inverse problem is identified theoretically, demonstrated computationally, explained physically and overcome practically. Both algorithms were test on ultrasound data of independently characterized tissue mimicking phantoms. The recovered elastic modulus was in all cases within 35% of the reference elastic contrast. Finally, the preliminary application of these techniques to tomosynthesis images showed the feasiblity of imaging an elastic inclusion.

A Quantitative Evaluation of the AVITEWRITE Model of Handwriting Learning

Much sensory-motor behavior develops through imitation, as during the learning of handwriting by children. Such complex sequential acts are broken down into distinct motor control synergies, or muscle groups, whose activities overlap in time to generate continuous, curved movements that obey an intense relation between curvature and speed. The Adaptive Vector Integration to Endpoint (AVITEWRITE) model of Grossberg and Paine (2000) proposed how such complex movements may be learned through attentive imitation. The model suggest how frontal, parietal, and motor cortical mechanisms, such as difference vector encoding, under volitional control from the basal ganglia, interact with adaptively-timed, predictive cerebellar learning during movement imitation and predictive performance. Key psycophysical and neural data about learning to make curved movements were simulated, including a decrease in writing time as learning progresses; generation of unimodal, bell-shaped velocity profiles for each movement synergy; size scaling with isochrony, and speed scaling with preservation of the letter shape and the shapes of the velocity profiles; an inverse relation between curvature and tangential velocity; and a Two-Thirds Power Law relation between angular velocity and curvature. However, the model learned from letter trajectories of only one subject, and only qualitative kinematic comparisons were made with previously published human data. The present work describes a quantitative test of AVITEWRITE through direct comparison of a corpus of human handwriting data with the model's performance when it learns by tracing human trajectories. The results show that model performance was variable across subjects, with an average correlation between the model and human data of 89+/-10%. The present data from simulations using the AVITEWRITE model highlight some of its strengths while focusing attention on areas, such as novel shape learning in children, where all models of handwriting and learning of other complex sensory-motor skills would benefit from further research.

Mapping the gene for autosomal dominant restless legs syndrome in an Irish family

Restless Legs Syndrome (RLS) is a common neurological disorder affecting nearly 15% of the general population. Ironically, RLS can be described as the most common condition one has never heard of. It is usually characterised by uncomfortable, unpleasant sensations in the lower limbs inducing an uncontrollable desire to move the legs. RLS exhibits a circadian pattern with symptoms present predominantly in the evening or at night, thus leading to sleep disruption and daytime somnolence. RLS is generally classified into primary (idiopathic) and secondary (symptomatic) forms. Primary RLS includes sporadic and familial cases of which the age of onset is usually less than 45 years and progresses slowly with a female to male ratio of 2:1. Secondary forms often occur as a complication of another health condition, such as iron deficiency or thyroid dysfunction. The age of onset is usually over 45 years, with an equal male to female ratio and more rapid progression. Ekbom described the familial component of the disorder in 1945 and since then many studies have been published on the familial forms of the disorder. Molecular genetic studies have so far identified ten loci (5q, 12q, 14p, 9p, 20p, 16p, 19p, 4q, 17p). No specific gene within these loci has been identified thus far. Association mapping has highlighted a further five areas of interest. RLS6 has been found to be associated with SNPs in the BTBD9 gene. Four other variants were found within intronic and intergenic regions of MEIS1, MAP2K5/LBXCOR1, PTPRD and NOS1. The pathophysiology of RLS is complex and remains to be fully elucidated. Conditions associated with secondary RLS, such as pregnancy or end-stage renal disease, are characterised by iron deficiency, which suggests that disturbed iron homeostasis plays a role. Dopaminergic dysfunction in subcortical systems also appears to play a central role. An ongoing study within the Department of Pathology (University College Cork) is investigating the genetic characteristics of RLS in Irish families. A three generation RLS pedigree RLS3002 consisting of 11 affected and 7 unaffected living family members was recruited. The family had been examined for four of the known loci (5q, 12q, 14p and 9p) (Abdulrahim 2008). The aim of this study was to continue examining this Irish RLS pedigree for possible linkage to the previously described loci and associated regions. Using informative microsatellite markers linkage was excluded to the loci on 5q, 12q, 14p, 9p, 20p, 16p, 19p, 4q, 17p and also within the regions reported to be associated with RLS. This suggested the presence of a new unidentified locus. A genome-wide scan was performed using two microsatellite marker screening sets (Research Genetics Inc. Mapping set and the Applied Biosystems Linkage mapping set version 2.5). Linkage analysis was conducted under an autosomal dominant model with a penetrance of 95% and an allele frequency of 0.01. A maximum LOD score of 3.59 at θ=0.00 for marker D19S878 indicated significant linkage on chromosome 19p. Haplotype analysis defined a genetic region of 6.57 cM on chromosome 19p13.3, corresponding to 2.5 Mb. There are approximately 100 genes annotated within the critical region. Sequencing of two candidate genes, KLF16 and GAMT, selected on the assumed pathophysiology of RLS, did not identify any sequence variant. This study provides evidence of a novel RLS locus in an Irish pedigree, thus supporting the picture of RLS as a genetically heterogeneous trait.

Issues in the prescribing of psychotropic and psychoactive medication for persons with learning disability: quantitative and qualitative perspectives

The administration of psychotropic and psychoactive medication for persons with learning disability and accompanying mental illness and/or challenging behaviour has undergone much critical review over the past two decades. Assessment and diagnosis of mental illness in this population continues to be psychopharmacological treatment include polypharmacy, irrational prescription procedures and frequent over-prescription. It is clear that all forms of treatment including non-pharmacological interventions need to be driven by accurate and appropriate diagnoses. Where a psychiatric diagnosis has been identified, it greatly aides the selection of appropriate medication, although a specific medication for each diagnosis, as was once hoped, is simply no longer a reality in practice. Part one of the present thesis seeks to address many of the current issues in mental health problems and pharmacological treatment to date. The author undertook a drug prevalence study within both residential and community facilities for persons with learning disability within the Mid-West region of Ireland in order to ascertain the current level of prescribing of psychotropic and psychoactive medications for this population. While many attempts have been made to account for the variation in prescribing, little systematic and empirical research has been undertaken to investigate the factors thought to influence such prescribing. While studies investigating the prescribing behaviours of General Practitioners (GP's) have illustrated the complex nature of the decision making process in the context of general practice, no similar efforts have yet been directed at examining the prescribing behaviours of Consultant Psychiatrists. Using The Critical Incident Technique, the author interviewed Consultant Psychiatrists in the Republic of Ireland to gather information relating not only to their patterns of prescribing for learning disabled populations, but also to examine reasons influencing their prescribing in addition to several related factors. Part two of this thesis presents the findings from this study and a number of issues are raised, not only in relation to attempting to account for the findings from part one of the thesis, but also with respect to implications for improved management and clinical practice.

The psychology of immersion and development of a quantitative measure of immersive response in games

This study sets out to investigate the psychology of immersion and the immersive response of individuals in relation to video and computer games. Initially, an exhaustive review of literature is presented, including research into games, player demographics, personality and identity. Play in traditional psychology is also reviewed, as well as previous research into immersion and attempts to define and measure this construct. An online qualitative study was carried out (N=38), and data was analysed using content analysis. A definition of immersion emerged, as well as a classification of two separate types of immersion, namely, vicarious immersion and visceral immersion. A survey study (N=217) verified the discrete nature of these categories and rejected the null hypothesis that there was no difference between individuals' interpretations of vicarious and visceral immersion. The primary aim of this research was to create a quantitative instrument which measures the immersive response as experienced by the player in a single game session. The IMX Questionnaire was developed using data from the initial qualitative study and quantitative survey. Exploratory Factor Analysis was carried out on data from 300 participants for the IMX Version 1, and Confirmatory Factor Analysis was conducted on data from 380 participants on the IMX Version 2. IMX Version 3 was developed from the results of these analyses. This questionnaire was found to have high internal consistency reliability and validity.

An examination of the underlying trait structure of psychopathy: applications for screening and measurement

This thesis seeks to clarify the faceted organisation of psychopathy with a view to developing a comprehensive protocol for the assessment of core psychopathic personality traits. The framework developed will, as best as possible, be free of sample bias. The Self-and Informant-report Deviant Personality Screen (DPS) is introduced and a series of empirical studies are conducted to examine the psychometric properties and construct validity of these measures in general and offender populations. Findings from these studies provide strong support for the utility of the DPS scales for the appraisal of psychopathy across diverse population samples. In addition to this, the utility of cognitive based performance measures for the assessment of emotional deficits in psychopathy is evaluated. Results from this study suggest limited correspondence between these measurement techniques and self-report psychopathy measures. Finally, research conducted on offenders suggests that information obtained from DPS reports may be useful within a broad framework of risk assessment. Further empirical and theoretical implications of the research are discussed.

Functional metagenomic analysis of the human gut microbiome to identify novel salt tolerance genes

The ability to adapt to and respond to increases in external osmolarity is an important characteristic that enables bacteria to survive and proliferate in different environmental niches. When challenged with increased osmolarity, due to sodium chloride (NaCl) for example, bacteria elicit a phased response; firstly via uptake of potassium (K+), which is known as the primary response. This primary response is followed by the secondary response which is characterised by the synthesis or uptake of compatible solutes (osmoprotectants). The overall osmotic stress response is much broader however, involving many diverse cellular systems and processes. These ancillary mechanisms are arguably more interesting and give a more complete view of the osmotic stress response. The aim of this thesis was to identify novel genetic loci from the human gut microbiota that confer increased tolerance to osmotic stress using a functional metagenomic approach. Functional metagenomics is a powerful tool that enables the identification of novel genes from as yet uncultured bacteria from diverse environments through cloning, heterologous expression and phenotypic identification of a desired trait. Functional metagenomics does not rely on any previous sequence information to known genes and can therefore enable the discovery of completely novel genes and assign functions to new or known genes. Using a functional metagenomic approach, we have assigned a novel function to previously annotated genes; murB, mazG and galE, as well as a putative brp/blh family beta-carotene 15,15’-monooxygenase. Finally, we report the identification of a completely novel salt tolerance determinant with no current known homologues in the databases. Overall the genes identified originate from diverse taxonomic and phylogenetic groups commonly found in the human gastrointestinal (GI) tract, such as Collinsella and Eggerthella, Akkermansia and Bacteroides from the phyla Actinobacteria, Verrucomicrobia and Bacteroidetes, respectively. In addition, a number of the genes appear to have been acquired via lateral gene transfer and/or encoded on a prophage. To our knowledge, this thesis represents the first investigation to identify novel genes from the human gut microbiota involved in the bacterial osmotic stress response.

Physical function, psychosocial adaptation, and hardiness post stroke

Introduction: Stroke is a chronic condition that significantly impacts on morbidity and mortality (Balanda et al. 2010). Globally, the complexity of stroke is well documented and more recently, in Ireland, as part of the National Survey of Stroke Survivors (Horgan et al. 2014). There are a number of factors that are known to influence adaptation post stroke. However, there is a lack of research to explain the variability in how survivors adapt post stroke. Hardiness is a broad personality trait that leads to better outcome. This study investigated the influence of hardiness and physical function on psychosocial adaptation post stroke. Methods: A quantitative cross-sectional, correlational, exploratory study was conducted between April and November 2013. The sample consisted of stroke survivors (n=100) who were recruited from three hospital outpatient departments and completed a questionnaire package. Results: The mean age of participants was 76 years (range 70-80), over half (56%) of the participants achieved the maximum score of 20 on the Barthel Index indicating independence in activities of daily living. The median number of days since stroke onset was 91 days (range 74-128). The total mean score and standard deviation for hardiness was 1.89 (0.4) as measured by the Dispositional Resilience Scale, indicating medium hardiness (possible range 0-3). Psychosocial adaptation was measured using the Psychosocial Adjustment to Illness Scale, the total weighted mean and standard deviation was 0.54 (0.3) indicating a satisfactory level of psychosocial adaptation (possible range 0-3). A hierarchical multiple linear regression was performed which contained 6 independent variables (hardiness, living arrangement, and length of hospital stay, number of days since stroke onset, physical function and self-rated recovery). Findings demonstrated that physical function (p<0.001) and hardiness (p=0.008) were significantly related to psychosocial adaptation. Altogether, 65% of the variation in psychosocial adaptation can be explained by the combined effect of the independent variables. Physical functioning had the highest unique contribution (11%) to explain the variance in psychosocial adaptation while self-rated recovery, hardiness, and living arrangements contributed 3% each. Conclusion: This research provides important information regarding factors that influence psychosocial adaptation post stroke at 3 months. Physical function significantly contributed to psychosocial adaptation post stroke. The personality trait of hardiness provides insight into how behaviour influenced adaptation post stroke. While hardiness also had a strong relationship with psychosocial adaptation, further research is necessary to fully comprehend this process.

Quantitative analysis of the effect of derivatisation of [Ru(BPY) phen] with a quinoline moiety on the interaction with DNA

The bifunctional Ru(II) complex [Ru(BPY)2POQ-Nmet]2+ (1), in which the metallic unit is tethered by an aliphatic chain to an organic DNA binder, was designed in order to increase the affinity toward nucleic acids. The interaction of 1 with DNA was characterised from luminescence and absorption data and compared with the binding of its monofunctional metallic and organic analogues, [Ru(BPY)2(ac)phen]2+ (2) and Nmet-quinoline (3). The bifunctional complex has a binding affinity one order of magnitude higher than that of each of its separated moieties. Absorption changes induced upon addition of DNA at different pH indicate protonation of the organic sub-unit upon interaction with DNA under neutral conditions. The combination of the luminescence data under steady-state and time-resolved conditions shows that the attachment of the organic unit in 1 induces modifications of the association modes of the metallic unit, owing to the presence of the aliphatic chain which probably hinders the metallic moiety binding. The salt dependence of the binding constants was analysed in order to compare the thermodynamic parameters describing the association with DNA for each complex. This study demonstrates the interest of the derivatisation of a Ru(II) complex with an organic moiety (ia the bifunctional ligand POQ-Nmet) for the development of high affinity DNA probes or photoreactive agents.

Quantitative model of the phase behavior of recombinant pH-responsive elastin-like polypeptides.

Quantitative models are required to engineer biomaterials with environmentally responsive properties. With this goal in mind, we developed a model that describes the pH-dependent phase behavior of a class of stimulus responsive elastin-like polypeptides (ELPs) that undergo reversible phase separation in response to their solution environment. Under isothermal conditions, charged ELPs can undergo phase separation when their charge is neutralized. Optimization of this behavior has been challenging because the pH at which they phase separate, pHt, depends on their composition, molecular weight, concentration, and temperature. To address this problem, we developed a quantitative model to describe the phase behavior of charged ELPs that uses the Henderson-Hasselbalch relationship to describe the effect of side-chain ionization on the phase-transition temperature of an ELP. The model was validated with pH-responsive ELPs that contained either acidic (Glu) or basic (His) residues. The phase separation of both ELPs fit this model across a range of pH. These results have important implications for applications of pH-responsive ELPs because they provide a quantitative model for the rational design of pH-responsive polypeptides whose transition can be triggered at a specified pH.