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.

Aspects of the biology of the parasite Bonamia ostreae with a view to gaining a greater understanding of how to alleviate its impact on the European flat oyster, Ostrea edulis.

The parasite Bonamia ostreae has decimated Ostrea edulis stocks throughout Europe. The complete life cycle and means of transmission of the parasite remains unknown. The methods used to diagnose B. ostreae were examined to determine sensitivity and reproducibility. Two methods, with fixed protocols, should be used for the accurate detection of infection within a sample. A 13-month study of two stocks of O. edulis with varying periods of exposure to B. ostreae, was undertaken to determine if varying lengths of exposure would translate into observations of differing susceptibility. Oyster stocks can maintain themselves over extended periods of time in B. ostreae endemic areas. To identify a well performing spat stock, which could be used to repopulate beds within the region, hatchery bred spat from three stocks found in the North sea were placed on a B. ostreae infected bed and screened for growth, mortality and prevalence of infection. Local environmental factors may influence oyster performance, with local stocks better adapted to these conditions. Sediment and macroinvertebrate species were screened to investigate mechanisms by which B. ostreae may be maintaining itself on oyster beds. Mytilus edulis was positive, indicating that B. ostreae may use incidental carriers as a method of maintaining itself. The ability of oyster larvae to pick up infection from the surrounding environment was investigated by collecting larvae from brooding oysters from different areas. Larvae may acquire the pathogen from the water column during the process of filter feeding by the brooding adult, even when the parents themselves are uninfected. A study was undertaken to elucidate the activity of the parasite during the initial stage of infection, when it cannot be detected within the host. A naïve stock screened negative for infection throughout the trial, using heart imprints and PCR yet B. ostreae was detected by in-situ hybridisation.

Challengers to provisional republicanism: the official republican movement, people’s democracy and the Irish republican socialist party, 1968–98

The Provisional IRA and its political wing Sinn Féin have attracted by far the greatest scholarly interest of all the players in the Northern Irish conflict. This emphasis is perfectly legitimate, given the centrality of the Provos to so many turning-points in the conflict, from the collapse of Stormont in the early 1970s to the hunger strikes of the following decade and the ceasefires which were followed by the Belfast Agreement. My project, however, looks at political groups that at one time or another challenged the Provos for leadership of the militant, anti-state constituency in Northern Ireland (chiefly based in the Catholic working class). Although never as large or influential as the Provisional republicans, groups such as the Official IRA and the Irish Republican Socialist Party sometimes had a discernible impact on the course of events which is overlooked by most studies, and often pioneered ideas and tactics that were later adopted by the Provos themselves. The idea that republicans should embrace political action and work in broad campaigning alliances was promoted by the IRSP and socialist groups such as People’s Democracy before it was taken up by Gerry Adams and his allies, while the Official IRA supported the principle of a settlement based on democratization of the Northern Irish state, which was later accepted by Sinn Féin in the form of the Belfast Agreement. The goal of my research is to provide a novel perspective on the conflict in Northern Ireland, while engaging with theoretical debates about its character.

Climate and energy scenarios for Ireland to 2050 using the Irish TIMES energy systems model

Due to growing concerns regarding the anthropogenic interference with the climate system, countries across the world are being challenged to develop effective strategies to mitigate climate change by reducing or preventing greenhouse gas (GHG) emissions. The European Union (EU) is committed to contribute to this challenge by setting a number of climate and energy targets for the years 2020, 2030 and 2050 and then agreeing effort sharing amongst Member States. This thesis focus on one Member State, Ireland, which faces specific challenges and is not on track to meet the targets agreed to date. Before this work commenced, there were no projections of energy demand or supply for Ireland beyond 2020. This thesis uses techno-economic energy modelling instruments to address this knowledge gap. It builds and compares robust, comprehensive policy scenarios, providing a means of assessing the implications of different future energy and emissions pathways for the Irish economy, Ireland’s energy mix and the environment. A central focus of this thesis is to explore the dynamics of the energy system moving towards a low carbon economy. This thesis develops an energy systems model (the Irish TIMES model) to assess the implications of a range of energy and climate policy targets and target years. The thesis also compares the results generated from the least cost scenarios with official projections and target pathways and provides useful metrics and indications to identify key drivers and to support both policy makers and stakeholder in identifying cost optimal strategies. The thesis also extends the functionality of energy system modelling by developing and applying new methodologies to provide additional insights with a focus on particular issues that emerge from the scenario analysis carried out. Firstly, the thesis develops a methodology for soft-linking an energy systems model (Irish TIMES) with a power systems model (PLEXOS) to improve the interpretation of the electricity sector results in the energy system model. The soft-linking enables higher temporal resolution and improved characterisation of power plants and power system operation Secondly, the thesis develops a methodology for the integration of agriculture and energy systems modelling to enable coherent economy wide climate mitigation scenario analysis. This provides a very useful starting point for considering the trade-offs between the energy system and agriculture in the context of a low carbon economy and for enabling analysis of land-use competition. Three specific time scale perspectives are examined in this thesis (2020, 2030, 2050), aligning with key policy target time horizons. The results indicate that Ireland’s short term mandatory emissions reduction target will not be achieved without a significant reassessment of renewable energy policy and that the current dominant policy focus on wind-generated electricity is misplaced. In the medium to long term, the results suggest that energy efficiency is the first cost effective measure to deliver emissions reduction; biomass and biofuels are likely to be the most significant fuel source for Ireland in the context of a low carbon future prompting the need for a detailed assessment of possible implications for sustainability and competition with the agri-food sectors; significant changes are required in infrastructure to deliver deep emissions reductions (to enable the electrification of heat and transport, to accommodate carbon capture and storage facilities (CCS) and for biofuels); competition between energy and agriculture for land-use will become a key issue. The purpose of this thesis is to increase the evidence-based underpinning energy and climate policy decisions in Ireland. The methodology is replicable in other Member States.

Studies on factors relating to the development of defects in commercial cheese

Defects in commercial cheese result in a downgrading of the final cheese and a consequential economic loss to the cheese producer. Developments of defects in cheese are often not fully understood and therefore not controllable by the producer. This research investigated the underlying factors in the development of split and secondary fermentation defect and of pinking defects in commercial Irish cheeses. Split defect in Swiss-type cheese is a common defect associated with eye formation and manifests as slits and cracks visible in the cut cheese loaf (Reinbold, 1972; Daly et al., 2010). No consensus exists as to the definitive causes of the defect and possible factors which may contribute to the defect were reviewed. Models were derived to describe the relationship between moisture, pH, and salt levels and the distance from sample location to the closest external block surface during cheese ripening. Significant gradients within the cheese blocks were observed for all measured parameters in cheeses at 7 day post/after manufacture. No significant pH gradient was found within the blocks on exit from hot-room ripening and at three months post exit from the hot-room. Moisture content reached equilibrium within the blocks between exit from hot-room and 3 months after exit from hot-room while salt and salt-to-moisture levels had not reached equilibrium within the cheese blocks even at three months after exit from hot-room ripening. A characterisation of Swiss-type cheeses produced from a seasonal milk supply was undertaken. Cheeses were sampled on two days per month of the production year, at three different times during the manufacturing day, at internal and external regions of the cheese block and at four ripening time points (7 days post manufacture, post hot-room, 14 days post hot-room and 3 months in a cold room after exit from hot-room). Compositional, biochemical and microbial indices were determined, and the results were analysed as a splitplot with a factorial arrangement of treatments (season, time of day, area) on the main plot and ripening time on the sub-plot. Season (and interactions) had a significant effect on pH and salt-in-moisture levels (SM), mean viable counts of L. helveticus, propionic acid and non-starter lactic acid bacteria, levels of primary and secondary proteolysis and cheese firmness. Levels of proteolysis increased significantly during hot-room ripening but also during cold room storage, signifying continued development of cheese ripening during cold storage (> 8°C). Rheological parameters (e.g. springiness and cohesiveness) were significantly affected by interactions between ripening and location within cheese blocks. Time of day of manufacture significantly affected mean cheese calcium levels at 7 days post manufacture and mean levels of arginine and mean viable counts of NSLAB. Cheeses produced during the middle of the production day had the best grading scores and were more consistent compared to cheeses produced early or late during day of manufacture. Cheeses with low levels of S/M and low values of resilience were associated with poor grades at 7 days post manufacture. Chesses which had high elastic index values and low values of springiness in the external areas after exit from hot-room ripening also obtained good commercial grades. Development of a pink colour defect is an intermittent defect in ripened cheese which may or may not contain an added colourant, e.g., annatto. Factors associated with the defect were reviewed. Attempts at extraction and identification of the pink discolouration were unsuccessful. The pink colour partitioned with the water insoluble protein fraction. No significant difference was observed between ripened control and defect cheese for oxygen levels and redox potential or for the results of elemental analysis. A possible relationship between starter activity and defect development was established in cheeses with added coulourant, as lower levels of residual galactose and lactose were observed in defective cheese compared to control cheese free of the defect. Swiss-type cheese without added colourant had significantly higher levels of arginine and significantly lower lactate levels. Flow cell cytometry indicated that levels of bacterial cell viability and metabolic state differed between control and defect cheeses (without added colourant). Pyrosequencing analysis of cheese samples with and without the defect detected the previously unreported bacteria in cheese, Deinococcus thermus (a potential carotenoid producer). Defective Swiss-type cheeses had elevated levels of Deinococcus thermus compared to control cheeses, however the direct cause of pink was not linked to this bacterium alone. Overall, research was undertaken on underlying factors associated with the development of specific defects in commercial cheese, but also characterised the dynamic changes in key microbial and physicochemical parameters during cheese ripening and storage. This will enable the development of processing technologies to enable seasonal manipulation of manufacture protocols to minimise compositional and biochemical variability and to reduce and inhibit the occurrence of specific quality defects.

Towards the enantioselective synthesis of Plakortide P and its application to the development of drugs for the treatment of Chagas disease

The primary focus of this thesis was the asymmetric peroxidation of α,β-unsaturated aldehydes and the development of this methodology to include the synthesis of bioactive chiral 1,2-dioxane and 1,2-dioxalane rings. In Chapter 1 a review detailing the new and improved methods for the acyclic introduction of peroxide functionality to substrates over the last decade was discussed. These include a detailed examination of metal-mediated transformations, chiral peroxidation using organocatalytic means and the improvements in methodology of well-established peroxidation pathways. The second chapter discusses the method by which peroxidation of our various substrates was attempted and the optimisation studies associated with these reactions. The method by which the enantioselectivity of our β-peroxyaldehydes was determined is also reviewed. Chapters 3 and 4 focus on improving the enantioselectivity associated with our asymmetric peroxidation reaction. A comprehensive analysis exploring the effect of solvent, concentration and temperature on enantioselectivity was examined. The effect that different catalytic systems have on enantioselectivity and reactivity was also investigated in depth. Chapter 5 details the various transformations that β-peroxyaldehydes can undergo and the manipulation of these transformations towards the establishment of several routes for the formation of chiral 1,2-dioxane and 1,2-dioxalane rings. Chapter 6 details the full experimental procedures, including spectroscopic and analytical data for the compounds prepared during this research.

Design and evaluation of novel microencapsulation technologies to enhance delivery of Ciclosporin

Drug delivery systems influence the various processes of release, absorption, distribution and elimination of drug. Conventional delivery methods administer drug through the mouth, the skin, transmucosal areas, inhalation or injection. However, one of the current challenges is the lack of effective and targeted oral drug administration. Development of sophisticated strategies, such as micro- and nanotechnology that can integrate the design and synthesis of drug delivery systems in a one-step, scalable process is fundamental in advancing the limitations of conventional processing techniques. Thus, the objective of this thesis is to evaluate novel microencapsulation technologies in the production of size-specific and target-specific drug-loaded particles. The first part of this thesis describes the utility of PDMS and silicon microfluidic flow focusing devices (MFFDs) to produce PLGA-based microparticles. The formation of uniform droplets was dependent on the surface of PDMS remaining hydrophilic. However, the durability of PDMS was limited to no more than 1 hour before wetting of the microchannel walls with dichloromethane and subsequent swelling occurred. Critically, silicon MFFDs revealed very good solvent compatibility and was sufficiently robust to withstand elevated fluid flow rates. Silicon MFFDs facilitated experiments to run over days with continuous use and re-use of the device with a narrower microparticle size distribution, relative to conventional production techniques. The second part of this thesis demonstrates an alternative microencapsulation technology, SmPill® minispheres, to target CsA delivery to the colon. Characterisation of CsA release in vitro and in vivo was performed. By modulating the ethylcellulose:pectin coating thickness, release of CsA in-vivo was more effectively controlled compared to current commercial CsA formulations and demonstrated a linear in-vitro in-vivo relationship. Coated minispheres were shown to limit CsA release in the upper small intestine and enhance localised CsA delivery to the colon.

The cloud personal assistant for providing services to mobile clients

This paper introduces the original concept of a cloud personal assistant, a cloud service that manages the access of mobile clients to cloud services. The cloud personal assistant works in the cloud on behalf of its owner: it discovers services, invokes them, stores the results and history, and delivers the results to the mobile user immediately or when the user requests them. Preliminary experimental results that demonstrate the concept are included.

Ironworking in late medieval Ireland, c. AD. 1200 to 1600

The landscape of late medieval Ireland, like most places in Europe, was characterized by intensified agricultural exploitation, the growth and founding of towns and cities and the construction of large stone edifices, such as castles and monasteries. None of these could have taken place without iron. Axes were needed for clearing woodland, ploughs for turning the soil, saws for wooden buildings and hammers and chisels for the stone ones, all of which could not realistically have been made from any other material. The many battles, waged with ever increasingly sophisticated weaponry, needed a steady supply of iron and steel. During the same period, the European iron industry itself underwent its most fundamental transformation since its inception; at the beginning of the period it was almost exclusively based on small furnaces producing solid blooms and by the turn of the seventeenth century it was largely based on liquid-iron production in blast-furnaces the size of a house. One of the great advantages of studying the archaeology of ironworking is that its main residue, slag, is often produced in copious amounts both during smelting and smithing, is virtually indestructible and has very little secondary use. This means that most sites where ironworking was carried out are readily recognizable as such by the occurrence of this slag. Moreover, visual examination can distinguish between various types of slag, which are often characteristic for the activity from which they derive. The ubiquity of ironworking in the period under study further means that we have large amounts of residues available for study, allowing us to distinguish patterns both inside assemblages and between sites. Disadvantages of the nature of the remains related to ironworking include the poor preservation of the installations used, especially the furnaces, which were often built out of clay and located above ground. Added to this are the many parameters contributing to the formation of the above-mentioned slag, making its composition difficult to connect to a certain technology or activity. Ironworking technology in late medieval Ireland has thus far not been studied in detail. Much of the archaeological literature on the subject is still tainted by the erroneous attribution of the main type of slag, bun-shaped cakes, to smelting activities. The large-scale infrastructure works of the first decade of the twenty-first century have led to an exponential increase in the amount of sites available for study. At the same time, much of the material related to metalworking recovered during these boom-years was subjected to specialist analysis. This has led to a near-complete overhaul of our knowledge of early ironworking in Ireland. Although many of these new insights are quickly seeping into the general literature, no concise overviews on the current understanding of the early Irish ironworking technology have been published to date. The above then presented a unique opportunity to apply these new insights to the extensive body of archaeological data we now possess. The resulting archaeological information was supplemented with, and compared to, that contained in the historical sources relating to Ireland for the same period. This added insights into aspects of the industry often difficult to grasp solely through the archaeological sources, such as the people involved and the trade in iron. Additionally, overviews on several other topics, such as a new distribution map of Irish iron ores and a first analysis of the information on iron smelting and smithing in late medieval western Europe, were compiled to allow this new knowledge on late medieval Irish ironworking to be put into a wider context. Contrary to current views, it appears that it is not smelting technology which differentiates Irish ironworking from the rest of Europe in the late medieval period, but its smithing technology and organisation. The Irish iron-smelting furnaces are generally of the slag-tapping variety, like their other European counterparts. Smithing, on the other hand, is carried out at ground-level until at least the sixteenth century in Ireland, whereas waist-level hearths become the norm further afield from the fourteenth century onwards. Ceramic tuyeres continue to be used as bellows protectors, whereas these are unknown elsewhere on the continent. Moreover, the lack of market centres at different times in late medieval Ireland, led to the appearance of isolated rural forges, a type of site unencountered in other European countries during that period. When these market centres are present, they appear to be the settings where bloom smithing is carried out. In summary, the research below not only offered us the opportunity to give late medieval ironworking the place it deserves in the broader knowledge of Ireland's past, but it also provided both a base for future research within the discipline, as well as a research model applicable to different time periods, geographical areas and, perhaps, different industries..

Human intestinal microbiota and metabolites they produce in relation to host health

The aim of this thesis was to identify selected potential probiotic characteristics of Bifidobacterium longum strains isolated from human sources, and to examine these characteristics in detail using genomic and phenotypic techniques. One strain in particular Bifidobacterium longum DPC 6315 was the main focus of the thesis and this strain was used in both the manufacture of yoghurt and an animal study. In total, 38 B. longum strains, obtained from infants and adults, were assessed in vitro for the selected probiotic traits using a combined phenotypic and molecular approach. Differentiation of the 38 strains using amplified ribosomal DNA restriction analysis (ARDRA) into subspecies indicated that of the 38 bifidobacterial strains tested, 34 were designated B. longum subsp. longum and four B. longum subsp. infantis.

High speed optical communication systems: From modulation formats to radically new fibres

High volumes of data traffic along with bandwidth hungry applications, such as cloud computing and video on demand, is driving the core optical communication links closer and closer to their maximum capacity. The research community has clearly identifying the coming approach of the nonlinear Shannon limit for standard single mode fibre [1,2]. It is in this context that the work on modulation formats, contained in Chapter 3 of this thesis, was undertaken. The work investigates the proposed energy-efficient four-dimensional modulation formats. The work begins by studying a new visualisation technique for four dimensional modulation formats, akin to constellation diagrams. The work then carries out one of the first implementations of one such modulation format, polarisation-switched quadrature phase-shift keying (PS-QPSK). This thesis also studies two potential next-generation fibres, few-mode and hollow-core photonic band-gap fibre. Chapter 4 studies ways to experimentally quantify the nonlinearities in few-mode fibre and assess the potential benefits and limitations of such fibres. It carries out detailed experiments to measure the effects of stimulated Brillouin scattering, self-phase modulation and four-wave mixing and compares the results to numerical models, along with capacity limit calculations. Chapter 5 investigates hollow-core photonic band-gap fibre, where such fibres are predicted to have a low-loss minima at a wavelength of 2μm. To benefit from this potential low loss window requires the development of telecoms grade subsystems and components. The chapter will outline some of the development and characterisation of these components. The world's first wavelength division multiplexed (WDM) subsystem directly implemented at 2μm is presented along with WDM transmission over hollow-core photonic band-gap fibre at 2μm. References: [1]P. P. Mitra, J. B. Stark, Nature, 411, 1027-1030, 2001 [2] A. D. Ellis et al., JLT, 28, 423-433, 2010.

The use of fault detection and diagnostics to reduce air handling unit energy consumption

The contribution of buildings towards total worldwide energy consumption in developed countries is between 20% and 40%. Heating Ventilation and Air Conditioning (HVAC), and more specifically Air Handling Units (AHUs) energy consumption accounts on average for 40% of a typical medical device manufacturing or pharmaceutical facility’s energy consumption. Studies have indicated that 20 – 30% energy savings are achievable by recommissioning HVAC systems, and more specifically AHU operations, to rectify faulty operation. Automated Fault Detection and Diagnosis (AFDD) is a process concerned with potentially partially or fully automating the commissioning process through the detection of faults. An expert system is a knowledge-based system, which employs Artificial Intelligence (AI) methods to replicate the knowledge of a human subject matter expert, in a particular field, such as engineering, medicine, finance and marketing, to name a few. This thesis details the research and development work undertaken in the development and testing of a new AFDD expert system for AHUs which can be installed in minimal set up time on a large cross section of AHU types in a building management system vendor neutral manner. Both simulated and extensive field testing was undertaken against a widely available and industry known expert set of rules known as the Air Handling Unit Performance Assessment Rules (APAR) (and a later more developed version known as APAR_extended) in order to prove its effectiveness. Specifically, in tests against a dataset of 52 simulated faults, this new AFDD expert system identified all 52 derived issues whereas the APAR ruleset identified just 10. In tests using actual field data from 5 operating AHUs in 4 manufacturing facilities, the newly developed AFDD expert system for AHUs was shown to identify four individual fault case categories that the APAR method did not, as well as showing improvements made in the area of fault diagnosis.

Human interfaces to structured documents

This research investigates some of the reasons for the reported difficulties experienced by writers when using editing software designed for structured documents. The overall objective was to determine if there are aspects of the software interfaces which militate against optimal document construction by writers who are not computer experts, and to suggest possible remedies. Studies were undertaken to explore the nature and extent of the difficulties, and to identify which components of the software interfaces are involved. A model of a revised user interface was tested, and some possible adaptations to the interface are proposed which may help overcome the difficulties. The methodology comprised: 1. identification and description of the nature of a ‘structured document’ and what distinguishes it from other types of document used on computers; 2. isolation of the requirements of users of such documents, and the construction a set of personas which describe them; 3. evaluation of other work on the interaction between humans and computers, specifically in software for creating and editing structured documents; 4. estimation of the levels of adoption of the available software for editing structured documents and the reactions of existing users to it, with specific reference to difficulties encountered in using it; 5. examination of the software and identification of any mismatches between the expectations of users and the facilities provided by the software; 6. assessment of any physical or psychological factors in the reported difficulties experienced, and to determine what (if any) changes to the software might affect these. The conclusions are that seven of the twelve modifications tested could contribute to an improvement in usability, effectiveness, and efficiency when writing structured text (new document selection; adding new sections and new lists; identifying key information typographically; the creation of cross-references and bibliographic references; and the inclusion of parts of other documents). The remaining five were seen as more applicable to editing existing material than authoring new text (adding new elements; splitting and joining elements [before and after]; and moving block text).

Access to modified geiparvarins using Pd(0)-mediated C-C bond forming reactions

Geiparvarin is a natural product which contains both a 3(2H)-furanone and a coumarin moiety in its structure. The aim of this project was to investigate the use of Pd(0)-mediated C–C bondforming reactions to produce structurally modified geiparvarins. Chapter 1 consists of a review of the relevant literature, including that pertaining to the syntheses of selected naturally occurring 3(2H)-furanones. The known syntheses of geiparvarin and closely related analogues are examined, along with the documented biological activity of these compounds. The synthetic routes which allow access to 4-substituted-3(2H)-furanones are also described. Chapter 2 describes in detail the synthesis of a variety of novel structurally modified geiparvarins by two complementary routes, both approaches utilising Pd(0)-mediated crosscoupling reactions, and discusses the characterisation of these compounds. The preparation of 5-ethyl-3(2H)-furanones is described, as is their incorporation into geiparvarin and the corresponding 5″-alkylgeiparvarin analogues via formation and dehydration of intermediate alcohols. Halogenation of 5-ethyl-3(2H)-furanones and the corresponding geiparvarin derivatives is discussed, along with further reactions of the resulting halides. Preparation of 3″-arylgeiparvarins involving both Suzuki–Miyura and Stille reactions, using the appropriate intermediate iodides and bromides, is described. The application of Stille and Heck conditions to give 3″-ethenylgeiparvarin analogues and Sonogashira conditions to produce 3″-ethynylgeiparvarin analogues, using the relevant intermediate iodides, is also extensively outlined. Chapter 3 contains all of the experimental data and details of the synthetic methods employed for the compounds prepared during the course of this research. All novel compounds prepared were fully characterised using NMR spectroscopy, IR spectroscopy, mass spectrometry and elemental analysis; the details of which are included.

Formatting information: A beginner's introduction to typesetting with LATEX

This book originally accompanied a 2-day course on using the LATEX typesetting system. It has been extensively revised and updated and can now be used or self-study or in the classroom. It is aimed at users of Linux, Macintosh, or Microsoft Windows but it can be used with LATEX systems on any platform, including other Unix workstations, mainframes, and even your Personal Digital Assistant (PDA).