Studies in asymmetric and heterocyclic synthesis: I. chiral ketones II. Quinolones III. Trifluoromethylated pyrones

This thesis is split into three sections based on three different areas of research. In the first section, investigations into the α-alkylation of ketones using a novel chiral auxiliary is reported. This chiral auxiliary was synthesised containing a pyrrolidine ring in the chiral arm and was applied in the preparation of α-alkylated ketones which were obtained in up to 92% ee and up to 63% yield over two steps. Both 3-pentanone and propiophenone based ketones were used in the investigation with a variety of both alkyl and benzyl based electrophiles. The novel chiral auxiliary was also successful when applied to Michael and aldol reactions. A diamine precursor en route to the chiral auxiliary was also applied as an organocatalyst in a Michael reaction, with the product obtained in excellent enantioselectivity. In the second section, investigations into potential anti-quorum sensing molecules are reported. The bacteria Pseudomonas aeruginosa is an antibiotic-resistant pathogen that demonstrates cooperative behaviours and communicates using small chemical molecules in a process termed quorum sensing. A variety of C-3 analogues of the quorum sensing molecules used by P. aeruginosa were synthesised. Expanding upon previous research within the group, investigations were carried out into alternative protecting group strategies of 2-heptyl-4-(1H)- quinolone with the aim of improving the yields of products of cross-coupling reactions. In the third section, investigations into fluorination and trifluoromethylation of 2-pyrones, pyridones and quinolones is reported. The incorporation of a fluorine atom or a trifluoromethyl group into a molecule is important in pharmaceutical drug discovery programmes as it can lead to increased lipophilicity and bioavailability, however late-stage incorporation is rarely reported. Both direct fluorination and trifluoromethylation were attempted. Eight trifluoromethylated 2-pyrones, five trifluoromethylated 2-pyridones and a trifluoromethylated 2-quinolone were obtained in a late-stage synthesis from their respective iodinated precursors using methyl fluorosulfonyldifluoroacetate as a trifluoromethylating reagent.

Macro-epibenthic communities, bathymetry and enviromental information at the tip of the Antarctic Peninsula

The Southern Ocean ecosystem at the Antarctic Peninsula has steep natural environmental gradients, e.g. in terms of water masses and ice cover, and experiences regional above global average climate change. An ecological macroepibenthic survey was conducted in three ecoregions in the north-western Weddell Sea, on the continental shelf of the Antarctic Peninsula in the Bransfield Strait and on the shelf of the South Shetland Islands in the Drake Passage, defined by their environmental envelop. The aim was to improve the so far poor knowledge of the structure of this component of the Southern Ocean ecosystem and its ecological driving forces. It can also provide a baseline to assess the impact of ongoing climate change to the benthic diversity, functioning and ecosystem services. Different intermediate-scaled topographic features such as canyon systems including the corresponding topographically defined habitats 'bank', 'upper slope', 'slope' and 'canyon/deep' were sampled. In addition, the physical and biological environmental factors such as sea-ice cover, chlorophyll-a concentration, small-scale bottom topography and water masses were analysed. Catches by Agassiz trawl showed high among-station variability in biomass of 96 higher systematic groups including ecological key taxa. Large-scale patterns separating the three ecoregions from each other could be correlated with the two environmental factors, sea-ice and depth. Attribution to habitats only poorly explained benthic composition, and small-scale bottom topography did not explain such patterns at all. The large-scale factors, sea-ice and depth, might have caused large-scale differences in pelagic benthic coupling, whilst small-scale variability, also affecting larger scales, seemed to be predominantly driven by unknown physical drivers or biological interactions.

Molecular docking and geographical information systems as tools to assess the potential impact of veterinary medicines on non-target organisms and the environment

Veterinary medicines (VMs) from agricultural industry can enter the environment in a number of ways. This includes direct exposure through aquaculture, accidental spillage and disposal, and indirect entry by leaching from manure or runoff after treatment. Many compounds used in animal treatments have ecotoxic properties that may have chronic or sometimes lethal effects when they come into contact with non-target organisms. VMs enter the environment in mixtures, potentially having additive effects. Traditional ecotoxicology tests are used to determine the lethal and sometimes reproductive effects on freshwater and terrestrial organisms. However, organisms used in ecotoxicology tests can be unrepresentative of the populations that are likely to be exposed to the compound in the environment. Most often the tests are on single compound toxicity but mixture effects may be significant and should be included in ecotoxicology testing. This work investigates the use, measured environmental concentrations (MECs) and potential impact of sea lice treatments on salmon farms in Scotland. Alternative methods for ecotoxicology testing including mixture toxicity, and the use of in silico techniques to predict the chronic impact of VMs on different species of aquatic organisms were also investigated. The Scottish Environmental Protection Agency (SEPA) provided information on the use of five sea lice treatments from 2008-2011 on Scottish salmon farms. This information was combined with the recently available data on sediment MECs for the years 2009-2012 provided by SEPA using ArcGIS 10.1. In depth analysis of this data showed that from a total of 55 sites, 30 sites had a MEC higher than the maximum allowable concentration (MAC) as set out by SEPA for emamectin benzoate and 7 sites had a higher MEC than MAC for teflubenzuron. A number of sites that were up to 16 km away from the nearest salmon farm reported as using either emamectin benzoate or teflubenzuron measured positive for the two treatments. There was no relationship between current direction and the distribution of the sea lice treatments, nor was there any evidence for alternative sources of the compounds e.g. land treatments. The sites that had MECs higher than the MAC could pose a risk to non-target organisms and disrupt the species dynamics of the area. There was evidence that some marine protected sites might be at risk of exposure to these compounds. To complement this work, effects on acute mixture toxicity of the 5 sea lice treatments, plus one major metabolite 3-phenoxybenzoic acid (3PBA), were measured using an assay using the bioluminescent bacteria Aliivibrio fischeri. When exposed to the 5 sea lice treatments and 3PBA A. fischeri showed a response to 3PBA, emamectin benzoate and azamethiphos as well as combinations of the three. In order to establish any additive effect of the sea lice treatments, the efficacy of two mixture prediction equations, concentration addition (CA) and independent action ii(IA) were tested using the results from single compound dose response curves. In this instance IA was the more effective prediction method with a linear regression confidence interval of 82.6% compared with 22.6% of CA. In silico molecular docking was carried out to predict the chronic effects of 15 VMs (including the five used as sea lice control). Molecular docking has been proposed as an alternative screening method for the chronic effects of large animal treatments on non-target organisms. Oestrogen receptor alpha (ERα) of 7 non-target bony fish and the African clawed frog Xenopus laevis were modelled using SwissModel. These models were then ‘docked’ to oestradiol, the synthetic oestrogen ethinylestradiol, two known xenoestrogens dichlorodiphenyltrichloroethane (DDT) and bisphenol A (BPA), the antioestrogen breast cancer treatment tamoxifen and 15 VMs using Auto Dock 4. Based on the results of this work, four VMs were identified as being possible xenoestrogens or anti-oestrogens; these were cypermethrin, deltamethrin, fenbendazole and teflubenzuron. Further investigation, using in vitro assays, into these four VMs has been suggested as future work. A modified recombinant yeast oestrogen screen (YES) was attempted using the cDNA of the ERα of the zebrafish Danio rerio and the rainbow trout Oncorhynchus mykiss. Due to time and difficulties in cloning protocols this work was unable to be completed. Use of such in vitro assays would allow for further investigation of the highlighted VMs into their oestrogenic potential. In conclusion, VMs used as sea lice treatments, such as teflubenzuron and emamectin benzoate may be more persistent and have a wider range in the environment than previously thought. Mixtures of sea lice treatments have been found to persist together in the environment, and effects of these mixtures on the bacteria A. fischeri can be predicted using the IA equation. Finally, molecular docking may be a suitable tool to predict chronic endocrine disrupting effects and identify varying degrees of impact on the ERα of nine species of aquatic organisms.

Capitalising on the conceptual divide: access to public and private justice in children's proceedings

This article argues that the concept of a public/private divide is inappropriate in the context of children's proceedings in Northern Ireland. It highlights the problem by examining policy proposals in respect of legal aid/services, which have been structured and validated by the concept. A spectral model for understanding children's proceedings is proffered by way of a proposed replacement.

Caring for You and Your Information - Consultation Response Document (MS Word 105KB)

Department's response to public consultation

The gender wage gap in the public and private sectors in Bangladesh

The gender wage gap is well studied in developed countries; however, recently it has generated much interest in developing countries. This thesis addresses three issues regarding the gender wage gap in Bangladesh. Firstly, it explores the wage determinants for formal public and private sector employees in Bangladesh and examines the gender pay gap. This is the first time different decomposition methods have been used to compare the sources of the gender wage gap as well as any potential discrimination effect in the formal sector of the Bangladeshi labour market. These decomposition methods are: the original Oaxaca (1973) and Blinder (1973) decomposition methods, the Neumark (1988), Cotton (1988), and Reimers (1983) methods, and the extended Oaxaca method including both the employment selection and the double selection correction in the wage equation. In addition to mentioned methods, to quantify the gender wage gap in monetary terms, a recently developed ‘simulated change’ approach by Olsen and Walby (2004) is also applied for the first time to the Bangladeshi data. By using the Labour Force Survey 2005-06, BBS (LFS 2005-06) data results show formal sector female employees earn about 32.1 per cent less than their male counterparts. Without considering the selection correction, a large range of human capital, demographic and labour market related variables are explained less than half of the total gender wage gap (21 to 46 per cent of the total wage gap) and the major part of the wage gap is unexplained (54 to 79 per cent of the total wage gap). This could partly be attributed to discrimination. Using the double selection correction method, the decomposition results changed where a small part of the wage gap was explained by the measured characteristics (only nine per cent of the total wage gap) and a major part is attributed to the discrimination and selection effect. The selection effect also reveals that exclusion of the double selection correction might lead to an overestimation of the gender wage gap in the formal sector of Bangladesh. In addition, results based on the Olsen and Walby (2004) simulation method show that, if the other characteristics of male and female employees were similar, ‘being female’ is sufficient, to generate significantly lower wages than males in the formal sector. If females in the workplace are treated as males, without considering any other endowment increases, females could increase their earnings by 4095.3 Taka1 per year. Results also indicate that not only endowment differences in human capital and work experience related variables were important, but discrimination appears to play a significant role in the total wage gap throughout the formal sector of the Bangladeshi labour market. Secondly, the study investigates whether public sector employees enjoyed a wage premium or not, compared to the private sector and whether the gender wage gap is greater in the public sector. In addition, the research considered whether there was an impact from the inclusion of the different selection correction terms in the wage equation. In Bangladesh, public sector employees have, on average, a 60 per cent wage premium over the private sector. Using both the original Oaxaca and the extended Oaxaca methods, where selection effect is partly captured by both explained and unexplained components, and using the public sector wage structure as the basis of the non-discriminatory wage structure, these methods revealed a considerably larger portion of explained (72 - 93 per cent of the total wage gap) and a smaller portion of unexplained part of the wage gap. However, if the selection correction is considered as another component of the decomposition outcome then the major portion of the total public and private sectors wage gap is justified (explained) by the effect of the selection correction and unexplained factors. Furthermore, a large part of the wage premium exists in favour of public sector female employees compared to males and the gender wage gap is lower in the public sector than the private sector. Finally, this study compares the gender wage gap of five different occupations. The gender wage gap is associated with labour market rigidities where one of the important factors is occupational segregation where females are disproportionately distributed in occupations resulting in lower earnings. The largest gender wage gap was found in agriculture, forestry, fisheries, production and transport labour jobs (56.4 per cent) and the lowest in the professional, technical administrative and managerial jobs (22.1 per cent). Substantial differences are found in the size of the endowment gap across occupations and larger variations occurred in the adjusted wage gap which varied from 21.4 per cent in sales and service occupations, to 100 per cent in professional and technical jobs (the highest). This too can be partly explained by discrimination. A reduction in the gender wage gap is expected not only to increase national income, but also to reduce poverty and lead to better outcomes for future generations. National policy should aim to reduce the gender wage gap and achieve gender wage equality in the formal sector; for example through a targeted program to remove the gender differences in education and to reduce the skill difference, with a better child care policy to encourage labour force retention and increased labour market experience for female employees, with anti-discriminatory policies and the enforcement of existing antidiscrimination policies, and a more equal distribution of males and females across occupations.

Map of New York, places of interest and general information concerning the city /

Shows subways, elevated lines, and streetcar lines in Manhattan south of 120th Street.

Managing and utilizing information flow for new products’ periodic account sales process

The goal was to understand, document and module how information is currently flown internally in the largest dairy organization in Finland. The organization has undergone radical changes in the past years due to economic sanctions between European Union and Russia. Therefore, organization’s ultimate goal would be to continue its growth through managing its sales process more efficiently. The thesis consists of a literature review and an empirical part. The literature review consists of knowledge management and process modeling theories. First, the knowledge management discusses how data, information and knowledge are exchanged in the process. Knowledge management models and processes are describing how knowledge is created, exchanged and can be managed in an organization. Secondly, the process modeling is responsible for visualizing information flow through discussion of modeling approaches and presenting different methods and techniques. Finally, process’ documentation procedure was presented. In the end, a constructive research approach was used in order to identify process’ related problems and bottlenecks. Therefore, possible solutions were presented based on this approach. The empirical part of the study is based on 37 interviews, organization’s internal data sources and theoretical framework. The acquired data and information were used to document and to module the sales process in question with a flowchart diagram. Results are conducted through construction of the flowchart diagram and analysis of the documentation. In fact, answers to research questions are derived from empirical and theoretical parts. In the end, 14 problems and two bottlenecks were identified in the process. The most important problems are related to approach and/or standardization for information sharing, insufficient information technology tool utilization and lack of systematization of documentation. The bottlenecks are caused by the alarming amount of changes to files after their deadlines.

Work performed for the Course "The Reader and their information needs"

During "The reader and their information needs" students tried to implement the theory discussed in class. To this end, organized into sub-groups and worked in different types of libraries. The following paper covers the practice that the students: Jenssy Arguedas Salazar Hernández Sandoval Lidiette Oses and Olga Corrales held in the Library "Sister Onorina Leporati" Help Ma College of Alajuela.

Information brokers and the use of budgetary and financial information by politicians: the case of Portugal

This paper analyses the intermediary role of the technical bodies that support the use of budgetary and financial information by central government politicians in Portugal. The main findings show that information brokers are playing a central role in preparing this information in a credible, simple and understandable way. However, even if not intentionally, the information they present can be biased. Politicians need to be aware that the information brokers they rely on may not be giving them ‘neutral’ information.