Synthesis and evaluation of novel ligands for quantum dot stabilisation and polymerisation studies

This thesis describes the design and synthesis of a variety of functionalised phosphine oxides and sulfides, based on the structure of trioctylphosphine oxide, synthesised for the purpose of surface modification of quantum dots. The ability of the ligands to modify the surface chemistry via displacement of the original hexadecylamine capping layer of quantum dots was evaluated. Finally the surface modified quantum dots were investigated for enhancement in their inherent properties and improved compatibility with the various applications for which they were initially designed. Upon the commencement of research involving quantum dots it became apparent that more information on their behaviour and interaction with the environment was required. The limits of the inherent stability of hexadecylamine capped quantum dots were investigated by exposure to a number of different environments. The effect upon the stability of the quantum dots was monitored by changes in the photoluminescence ability of their cores. Subtle differences between different batches of quantum dots were observed and the necessity to account for these in future applications noted. Lastly the displacement of the original hexadecylamine coating with the "designer" functionalised ligands was evaluated to produce a set of conditions that would result in the best possible surface modification. A general procedure was elucidated however it was discovered that each displacement still required slight adjustment by consideration of the other factors such as the difference in ligand structure and the individuality of the various batches of quantum dots. This thesis also describes a procedure for the addition of a protective layer to the surface of quantum dots by cross-linking the functionalised ligands bound to the surface via an acyclic diene metathesis polymerisation. A detailed description of the problems encountered in the analysis of these materials combined with the use of novel techniques such as diffusion ordered spectroscopy is provided as a means to overcome the limitations encountered. Finally a demonstration of the superior stability, upon exposure to a range of aggressive environments of these protected materials compared with those before cross-linking provided physical proof of the cross-linking process and the advantages of the cross-linking modification. Finally this thesis includes the presentation of initial work into the production of luminescent nanocrystal encoded resin beads for the specific use in solid phase combinatorial chemistry. Demonstration of the successful covalent incorporation of quantum dots into the polymeric matrices of non-functionalised and functionalised resin beads is described. Finally by preliminary work to address and overcome the possible limitations that may be encountered in the production and general employment of these materials in combinatorial techniques is given.

The design and evaluation of an automated drug partitioning system for thermodynamic studies

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Design, synthesis and evaluation of dipeptides as probes for studies of gastrointestinal tract dipeptide transport system

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Design, synthesis and evaluation of dipeptides as probes for studies of gastro-intestinal tract dipeptide transport

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

The effect of dual -language instruction on academic achievement as measured by the SAT: An evaluation of the "International Studies Program" of Miami -Dade County Public Schools

This study investigated the influence that receiving instruction in two languages, English and Spanish, had on the performance of students enrolled in the International Studies Program (delayed partial immersion model) of Miami Dade County Public Schools on a standardized test in English, the Stanford Achievement Test, eighth edition, for three of its sections, Reading Comprehension, Mathematics Computations, and Mathematics Applications.^ The performance of the selected IS program/Spanish section cohort of students (N = 55) on the SAT Reading Comprehension, Mathematics Computation, and Mathematics Application along four consecutive years was contrasted with that of a control group of comparable students selected within the same feeder pattern where the IS program is implemented (N = 21). The performance of the group was also compared to the cross-sectional achievement patterns of the school's corresponding feeder pattern, region, and district.^ The research model for the study was a variation of the "causal-comparative" or "ex post facto design" sometimes referred to as "prospective". After data were collected from MDCPS, t-tests were performed to compare IS-Spanish students SAT performance for grades 3 to 6 for years 1994 to 1997 to control group, feeder pattern, region and district norms for each year for Reading Comprehension, Mathematics Computation, and Mathematics Applications. Repeated measures ANOVA and Tukey's tests were calculated to compare the mean percentiles of the groups under study and the possible interactions of the different variables. All tests were performed at the 5% significance level.^ From the analyses of the tests it was deduced that the IS group performed significantly better than the control group for all the three measures along the four years. The IS group mean percentiles on the three measures were also significantly higher than those of the feeder pattern, region, and district. The null hypotheses were rejected and it was concluded that receiving instruction in two languages did not negatively affect the performance of IS program students on tests taken in English. It was also concluded that the particular design the IS program enhances the general performance of participant students on Standardized tests.^ The quantitative analyses were coupled with interviews from teachers and administrators of the IS program to gain additional insight about different aspects of the implementation of the program at each particular school. ^

Functional Evaluation of Causal Mutations Identified in Human Genetic Studies

Human genetics has been experiencing a wave of genetic discoveries thanks to the development of several technologies, such as genome-wide association studies (GWAS), whole-exome sequencing, and whole genome sequencing. Despite the massive genetic discoveries of new variants associated with human diseases, several key challenges emerge following the genetic discovery. GWAS is known to be good at identifying the locus associated with the patient phenotype. However, the actually causal variants responsible for the phenotype are often elusive. Another challenge in human genetics is that even the causal mutations are already known, the underlying biological effect might remain largely ambiguous. Functional evaluation plays a key role to solve these key challenges in human genetics both to identify causal variants responsible for the phenotype, and to further develop the biological insights from the disease-causing mutations.

We adopted various methods to characterize the effects of variants identified in human genetic studies, including patient genetic and phenotypic data, RNA chemistry, molecular biology, virology, and multi-electrode array and primary neuronal culture systems. Chapter 1 is a broader introduction for the motivation and challenges for functional evaluation in human genetic studies, and the background of several genetics discoveries, such as hepatitis C treatment response, in which we performed functional characterization.

Chapter 2 focuses on the characterization of causal variants following the GWAS study for hepatitis C treatment response. We characterized a non-coding SNP (rs4803217) of IL28B (IFNL3) in high linkage disequilibrium (LD) with the discovery SNP identified in the GWAS. In this chapter, we used inter-disciplinary approaches to characterize rs4803217 on RNA structure, disease association, and protein translation.

Chapter 3 describes another avenue of functional characterization following GWAS focusing on the novel transcripts and proteins identified near the IL28B (IFNL3) locus. It has been recently speculated that this novel protein, which was named IFNL4, may affect the HCV treatment response and clearance. In this chapter, we used molecular biology, virology, and patient genetic and phenotypic data to further characterize and understand the biology of IFNL4. The efforts in chapter 2 and 3 provided new insights to the candidate causal variant(s) responsible for the GWAS for HCV treatment response, however, more evidence is still required to make claims for the exact causal roles of these variants for the GWAS association.

Chapter 4 aims to characterize a mutation already known to cause a disease (seizure) in a mouse model. We demonstrate the potential use of multi-electrode array (MEA) system for the functional characterization and drug testing on mutations found in neurological diseases, such as seizure. Functional characterization in neurological diseases is relatively challenging and available systematic tools are relatively limited. This chapter shows an exploratory research and example to establish a system for the broader use for functional characterization and translational opportunities for mutations found in neurological diseases.

Overall, this dissertation spans a range of challenges of functional evaluations in human genetics. It is expected that the functional characterization to understand human mutations will become more central in human genetics, because there are still many biological questions remaining to be answered after the explosion of human genetic discoveries. The recent advance in several technologies, including genome editing and pluripotent stem cells, is also expected to make new tools available for functional studies in human diseases.

Increasing the power of genome wide association studies in natural populations using repeated measures : evaluation and implementation

1. Genomewide association studies (GWAS) enable detailed dissections of the genetic basis for organisms' ability to adapt to a changing environment. In long-term studies of natural populations, individuals are often marked at one point in their life and then repeatedly recaptured. It is therefore essential that a method for GWAS includes the process of repeated sampling. In a GWAS, the effects of thousands of single-nucleotide polymorphisms (SNPs) need to be fitted and any model development is constrained by the computational requirements. A method is therefore required that can fit a highly hierarchical model and at the same time is computationally fast enough to be useful. 2. Our method fits fixed SNP effects in a linear mixed model that can include both random polygenic effects and permanent environmental effects. In this way, the model can correct for population structure and model repeated measures. The covariance structure of the linear mixed model is first estimated and subsequently used in a generalized least squares setting to fit the SNP effects. The method was evaluated in a simulation study based on observed genotypes from a long-term study of collared flycatchers in Sweden. 3. The method we present here was successful in estimating permanent environmental effects from simulated repeated measures data. Additionally, we found that especially for variable phenotypes having large variation between years, the repeated measurements model has a substantial increase in power compared to a model using average phenotypes as a response. 4. The method is available in the R package RepeatABEL. It increases the power in GWAS having repeated measures, especially for long-term studies of natural populations, and the R implementation is expected to facilitate modelling of longitudinal data for studies of both animal and human populations.

Nonparametric Evaluation of Quantitative Traits in Population-Based Association Studies when the Genetic Model is Unknown

Statistical association between a single nucleotide polymorphism (SNP) genotype and a quantitative trait in genome-wide association studies is usually assessed using a linear regression model, or, in the case of non-normally distributed trait values, using the Kruskal-Wallis test. While linear regression models assume an additive mode of inheritance via equi-distant genotype scores, Kruskal-Wallis test merely tests global differences in trait values associated with the three genotype groups. Both approaches thus exhibit suboptimal power when the underlying inheritance mode is dominant or recessive. Furthermore, these tests do not perform well in the common situations when only a few trait values are available in a rare genotype category (disbalance), or when the values associated with the three genotype categories exhibit unequal variance (variance heterogeneity). We propose a maximum test based on Marcus-type multiple contrast test for relative effect sizes. This test allows model-specific testing of either dominant, additive or recessive mode of inheritance, and it is robust against variance heterogeneity. We show how to obtain mode-specific simultaneous confidence intervals for the relative effect sizes to aid in interpreting the biological relevance of the results. Further, we discuss the use of a related all-pairwise comparisons contrast test with range preserving confidence intervals as an alternative to Kruskal-Wallis heterogeneity test. We applied the proposed maximum test to the Bogalusa Heart Study dataset, and gained a remarkable increase in the power to detect association, particularly for rare genotypes. Our simulation study also demonstrated that the proposed non-parametric tests control family-wise error rate in the presence of non-normality and variance heterogeneity contrary to the standard parametric approaches. We provide a publicly available R library nparcomp that can be used to estimate simultaneous confidence intervals or compatible multiplicity-adjusted p-values associated with the proposed maximum test.

External school evaluation : teachers’ perspectives : two case studies from Northern Portugal

The external evaluation of non-higher education schools in Portugal has been developed by the General Inspectorate of Education since 2006. A first cycle of evaluation was completed, covering all educational units in continental Portugal up to 2011. The model of evaluation has since been subject to alterations, and a second cycle of evaluation is now coming to an end. The current model of evaluation is based on documental analysis, analysis of students’ results, and panel interviews with a variety of representatives of the school community, and addresses three domains: results, provision of educational service and management. This paper is part of an ongoing research project, developed by 6 universities and supported by the Portuguese Foundation for Science and Technology (PTDC/CPE-CED/116674/2010) which intends to analyse the impacts and effects this process of external evaluation has had on Portuguese schools. This project includes a variety of perspectives and methodologies. In particular, we will focus on two case studies undertaken in two schools from the northern region of Portugal, and more specifically on the perspectives expressed by the teachers of those schools. These particular schools were chosen because they have been evaluated twice and represent different educational levels (basic and secondary), contexts and results. These case studies included the analysis of documental data, interviews to key informants and a questionnaire directed to teachers (n = 141) – the latter will be the main focus of this paper. Teachers are essential elements of the school community when considering the impacts of external evaluation, as any changes directed at teaching practices, student evaluation, among others are only possible through their direct action and implication. Therefore, their perceptions on the process and its impacts are crucial to the understanding of what does and does not change in schools as a consequence of external evaluation. Although teachers’ opinions are not homogenous and each school reveals a number of differences when it comes to teachers’ perceptions of School Evaluation, it was possible to stress some areas as the most and as the least consensual. Teachers in both schools agree External School Evaluation (ESE) is useful for the identification of the schools’ strengths and weaknesses, values students’ external evaluation results, imposes a model for schools internal evaluation (and in fact contributes to the very existence of internal evaluation practices), and contributes to schools improvement. However teachers in both schools do not believe ESE contributes to teachers’ autonomy produces changes in how curriculum is managed, or leads to innovative teaching practices. These results point to a greater emphasis on change at the levels of school management, self-evaluation and particularly internal evaluation, but little impact on the teaching practices. We believe the classroom is at the core of school practices and teaching processes are essential to any measure of school quality and to their impacts on student learning.

Evaluation of dry protonated calcium alginate beads for biosorption applications and studies of lead uptake

Alginate polysaccharide is a promising biosorbent for metal uptake. Dry protonated calcium alginate beads for biosorption applications were prepared, briefly characterized and tested for lead uptake. Several advantages of this biosorbent are reported and discussed in comparison with other alginate-based sorbents. The alginate beads contained 4.7 mmol/g of COOH groups, which suffered hydrolysis near pH 4. The Weber and Morris model, applied to kinetic results of lead uptake, showed that intraparticle diffusion was the rate-controlling step in lead sorption by dry alginate beads. Equilibrium experiments were performed and the data were fitted with different isotherm models. The Langmuir equation was the most adequate to model lead sorption. The maximum uptake capacity (qmax) was estimated as 339 mg/g and the Langmuir constant (b) as 0.84 l/mg. These values were compared with that of other sorbents found in the literature, indicating that dry protonated calcium alginate beads are among the best biosorbents for the treatment and recovery of heavy metals from aqueous streams.

Evaluation of dry protonated calcium alginate beads for biosorption applications and studies of lead uptake

Alginate polysaccharide is a promising biosorbent for metal uptake. Dry protonated calcium alginate beads for biosorption applications were prepared, briefly characterized and tested for lead uptake. Several advantages of this biosorbent are reported and discussed in comparison with other alginate-based sorbents. The alginate beads contained 4.7 mmol/g of COOH groups, which suffered hydrolysis near pH 4. The Weber and Morris model, applied to kinetic results of lead uptake, showed that intraparticle diffusion was the rate-controlling step in lead sorption by dry alginate beads. Equilibrium experiments were performed and the data were fitted with different isotherm models. The Langmuir equation was the most adequate to model lead sorption. The maximum uptake capacity (qmax) was estimated as 339 mg/g and the Langmuir constant (b) as 0.84 l/mg. These values were compared with that of other sorbents found in the literature, indicating that dry protonated calcium alginate beads are among the best biosorbents for the treatment and recovery of heavy metals from aqueous streams.

Property cash flow studies : focusing on model consistency and data accuracy

The high degree of variability and inconsistency in cash flow study usage by property professionals demands improvement in knowledge and processes. Until recently limited research was being undertaken on the use of cash flow studies in property valuations but the growing acceptance of this approach for major investment valuations has resulted in renewed interest in this topic. Studies on valuation variations identify data accuracy, model consistency and bias as major concerns. In cash flow studies there are practical problems with the input data and the consistency of the models. This study will refer to the recent literature and identify the major factors in model inconsistency and data selection. A detailed case study will be used to examine the effects of changes in structure and inputs. The key variable inputs will be identified and proposals developed to improve the selection process for these key variables. The variables will be selected with the aid of sensitivity studies and alternative ways of quantifying the key variables explained. The paper recommends, with reservations, the use of probability profiles of the variables and the incorporation of this data in simulation exercises. The use of Monte Carlo simulation is demonstrated and the factors influencing the structure of the probability distributions of the key variables are outline. This study relates to ongoing research into functional performance of commercial property within an Australian Cooperative Research Centre.