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.

Novel structured emulsions for delivering of food flavours

Flavour release from food is determined by the binding of flavours to other food ingredients and the partition of flavour molecules among different phases. Food emulsions are used as delivery systems for food flavours, and tailored structuring in emulsions provides novel means to better control flavour release. The current study investigated four structured oil-in-water emulsions with structuring in the oil phase, oil-water interface, and water phase. Oil phase structuring was achieved by the formation of monoglyceride (MG) liquid crystals in the oil droplets (MG structured emulsions). Structured interface was created by the adsorption of a whey protein isolate (WPI)-pectin double layer at the interface (multilayer emulsion). Water phase structured emulsions referred to emulsion filled protein gels (EFP gels), where emulsion droplets were embedded in WPI gel network, and emulsions with maltodextrins (MDs) of different dextrose-equivalent (DE) values. Flavour compounds with different physicochemical properties were added into the emulsions, and flavour release (release rate, headspace concentration and air-emulsion partition coefficient) was described by GC headspace analysis. Emulsion structures, including crystalline structure, particle size, emulsion stability, rheology, texture, and microstructures, were characterized using differential scanning calorimetry and X-ray diffraction, light scattering, multisample analytical centrifuge, rheometry, texture analysis, and confocal laser scanning microscopy, respectively. In MG structured emulsions, MG self-assembled into liquid crystalline structures and stable β-form crystals were formed after 3 days of storage at 25 °C. The inclusion of MG crystals allowed tween 20 stabilized emulsions to present viscoelastic properties, and it made WPI stabilized emulsions more sensitive to the change of pH and NaCl concentrations. Flavour compounds in MG structured emulsions had lower initial headspace concentration and air-emulsion partition coefficients than those in unstructured emulsions. Flavour release can be modulated by changing MG content, oil content and oil type. WPI-pectin multilayer emulsions were stable at pH 5.0, 4.0, and 3.0, but they presented extensive creaming when subjected to salt solutions with NaCl ≥ 150 mM and mixed with artificial salivas. Increase of pH from 5.0 to 7.0 resulted in higher headspace concentration but unchanged release rate, and increase of NaCl concentration led to increased headspace concentration and release rate. The study also showed that salivas could trigger higher release of hydrophobic flavours and lower release of hydrophilic flavours. In EFP gels, increases in protein content and oil content contributed to gels with higher storage modulus and force at breaking. Flavour compounds had significantly reduced release rates and air-emulsion partition coefficients in the gels than the corresponding ungelled emulsions, and the reduction was in line with the increase of protein content. Gels with stronger gel network but lower oil content were prepared, and lower or unaffected release rates of the flavours were observed. In emulsions containing maltodextrins, water was frozen at a much lower temperature, and emulsion stability was greatly improved when subjected to freeze-thawing. Among different MDs, MD DE 6 offered the emulsion the highest stability. Flavours had lower air-emulsion partition coefficients in the emulsions with MDs than those in the emulsion without MD. Moreover, the involvement of MDs in the emulsions allowed most flavours had similar release profiles before and after freeze-thaw treatment. The present study provided information about different structured emulsions as delivery systems for flavour compounds, and on how food structure can be designed to modulate flavour release, which could be helpful in the development of functional foods with improved flavour profile.

Synthesis of 4-substituted-3(2H)-furanones with novel luminescence properties

The objective of this project was to prepare a range of 4-substituted 3-(2H)-furanones, and to investigate the relationship between their molecular structures and photoluminescence properties. The effects of substituents and conjugated linker unit were also investigated. After generation of the key 3(2H)-furanone heterocycle, extension of the conjugated framework at the C-4 position was achieved through Pd(0)-catalysed coupling reactions. Chapter one of the thesis comprises a review of the relavent literature and is split into three sections. These include information about the prevalence of 3-(2H)-furanones as natural products and synthetic routes to 3-(2H)-furanones in general. The synthetic routes are divided according to the synthetic precursor employed. The final section of chapter one outlines the fundamental principles and application of photoluminescence to organic compounds in general. Chapter two contains the results of the research achieved in the course of this work and a discussion of the findings. Two routes were successfully employed to generate 4-unsubstituted 3-(2H)-furanone moieties: (i) base induced cyclisation of hydroxyenones and (ii) isoxazole chemistry. A number of methods which proved ineffective in the production of furanones with the desired substitution pattern are also detailed. The majority of this study was focused on the introduction of substituents at the C-4 position of the 3-(2H)-furanone ring. This was achieved through the use of Sonogashira and Suzuki cross coupling protocols for Pd(0) catalysed C-C bond formation. The further functionalisation of some compounds was performed using transfer hydrogenation and “click chemistry” methodologies. Finally, the photophysical properties of 3-(2H)-furanones prepared in this project are discussed and the effect of substitution patterns in a complementary “push push” and “push pull” manner have also been investigated. All the experimental data and details of the synthetic methods employed, for the compounds prepared during the course of this research is contained in chapter three together with the spectroscopic and analytical properties of the compounds prepared.

Context-aware real-time assistant architecture for pervasive healthcare

The aging population in many countries brings into focus rising healthcare costs and pressure on conventional healthcare services. Pervasive healthcare has emerged as a viable solution capable of providing a technology-driven approach to alleviate such problems by allowing healthcare to move from the hospital-centred care to self-care, mobile care, and at-home care. The state-of-the-art studies in this field, however, lack a systematic approach for providing comprehensive pervasive healthcare solutions from data collection to data interpretation and from data analysis to data delivery. In this thesis we introduce a Context-aware Real-time Assistant (CARA) architecture that integrates novel approaches with state-of-the-art technology solutions to provide a full-scale pervasive healthcare solution with the emphasis on context awareness to help maintaining the well-being of elderly people. CARA collects information about and around the individual in a home environment, and enables accurately recognition and continuously monitoring activities of daily living. It employs an innovative reasoning engine to provide accurate real-time interpretation of the context and current situation assessment. Being mindful of the use of the system for sensitive personal applications, CARA includes several mechanisms to make the sophisticated intelligent components as transparent and accountable as possible, it also includes a novel cloud-based component for more effective data analysis. To deliver the automated real-time services, CARA supports interactive video and medical sensor based remote consultation. Our proposal has been validated in three application domains that are rich in pervasive contexts and real-time scenarios: (i) Mobile-based Activity Recognition, (ii) Intelligent Healthcare Decision Support Systems and (iii) Home-based Remote Monitoring Systems.

Electromagnetic tracking and steering for catheter navigation

This thesis explores the use of electromagnetics for both steering and tracking of medical instruments in minimally invasive surgeries. The end application is virtual navigation of the lung for biopsy of early stage cancer nodules. Navigation to the peripheral regions of the lung is difficult due to physical dimensions of the bronchi and current methods have low successes rates for accurate diagnosis. Firstly, the potential use of DC magnetic fields for the actuation of catheter devices with permanently magnetised distal attachments is investigated. Catheter models formed from various materials and magnetic tip formations are used to examine the usefulness of relatively low power and compact electromagnets. The force and torque that can be exerted on a small permanent magnet is shown to be extremely limited. Hence, after this initial investigation we turn our attention to electromagnetic tracking, in the development of a novel, low-cost implementation of a GPS-like system for navigating within a patient. A planar magnetic transmitter, formed on a printed circuit board for a low-profile and low cost manufacture, is used to generate a low frequency magnetic field distribution which is detected by a small induction coil sensor. The field transmitter is controlled by a novel closed-loop system that ensures a highly stable magnetic field with reduced interference from one transmitter coil to another. Efficient demodulation schemes are presented which utilise synchronous detection of each magnetic field component experienced by the sensor. The overall tracking accuracy of the system is shown to be less than 2 mm with an orientation error less than 1°. A novel demodulation implementation using a unique undersampling approach allows the use of reduced sample rates to sample the signals of interest without loss of tracking accuracy. This is advantageous for embedded microcontroller implementations of EM tracking systems. The EM tracking system is demonstrated in the pre-clinical environment of a breathing lung phantom. The airways of the phantom are successfully navigated using the system in combination with a 3D computer model rendered from CT data. Registration is achieved using both a landmark rigid registration method and a hybrid fiducial-free approach. The design of a planar magnetic shield structure for blocking the effects of metallic distortion from below the transmitter is presented which successfully blocks the impact of large ferromagnetic objects such as operating tables. A variety of shielding material are analysed with MuMetal and ferrite both providing excellent shieling performance and an increased signal to noise ratio. Finally, the effect of conductive materials and human tissue on magnetic field measurements is presented. Error due to induced eddy currents and capacitive coupling is shown to severely affect EM tracking accuracy at higher frequencies.

Polymer and metallodielectric based photonic crystals

The bottom-up colloidal synthesis of photonic crystals has attracted interest over top-down approaches due to their relatively simplicity, the potential to produce large areas, and the low-costs with this approach in fabricating complex 3-dimensional structures. This thesis focuses on the bottom-up approach in the fabrication of polymeric colloidal photonic crystals and their subsequent modification. Poly(methyl methacrylate) sub-micron spheres were used to produce opals, inverse opals and 3D metallodielectric photonic crystal (MDPC) structures. The fabrication of MDPCs with Au nanoparticles attached to the PMMA spheres core–shell particles is described. Various alternative procedures for the fabrication of photonic crystals and MDPCs are described and preliminary results on the use of an Au-based MDPC for surface-enhanced Raman scattering (SERS) are presented. These preliminary results suggest a threefold increase of the Raman signal with the MDPC as compared to PMMA photonic crystals. The fabrication of PMMA-gold and PMMA-nickel MDPC structures via an optimised electrodeposition process is described. This process results in the formation of a continuous dielectric-metal interface throughout a 3D inverted photonic crystal structure, which are shown to possess interesting optical properties. The fabrication of a robust 3D silica inverted structure with embedded Au nanoparticles is described by a novel co-crystallisation method which is capable of creating a SiO2/Au NP composite structure in a single step process. Although this work focuses on the creation of photonic crystals, this co-crystallisation approach has potential for the creation of other functional materials. A method for the fabrication of inverted opals containing silicon nanoparticles using aerosol assisted chemical vapour deposition is described. Silicon is a high dielectric material and nanoparticles of silicon can improve the band gap and absorption properties of the resulting structure, and therefore have the potential to be exploited in photovoltaics.

Transitions: From novice participation to expertise, pre-school 'matters' in an Irish pre-school community

This in depth, qualitative, participant observer study tracks children's transition experiences from novice to experienced membership of their pre-school community. It also considers adult roles in mediating this process in the context of the recent introduction of a universal free-pre-school year for children growing up in Ireland. Participation and the space to negotiate a participatory identity is understood in this study as a key element of positive experiences of early years transitions, within pre-school and beyond. The underlying theoretical framework is socio-cultural. This approach shifts from a scientific positivist view of thinking and learning as an individual inside the head process and asserts the historical, social, cultural as well as the situated context of learning and meaning making All participants, including myself as researcher, are recognised, explored and valued as embedded in the cultural context studied. In a sense, this approach tilts the worlds being observed through participation in them and reflects them in new light. The aim is to interpret and reflect the multiple realities constructed in this context rather than seek a truth out there waiting to be found. Special efforts are made to be invited in to and acknowledge children's expertise in the cultural worlds they negotiate with peers and adults in pre-school. The aim is to better understand what children may find motivating, interesting or problematic as they interpret reproduce and transform meaning within their play and learning worlds. My aim is for an honest rendering of the voices of stakeholders in pre-school communities from teachers, parents, and policy makers to children themselves. It makes visible constraints; potentials and possibilities within everyday Irish pre-school practices in the situated context studied as well as the broader societal, legislative and macro policy influences it reflects. Casting light on the taken for granted opens the possibility of adaptation or transformation. Transition itself can act as a tool to meet the changing needs of children on their developmental pathways across the life cycle

An investigation into reactivity and selectivity in cycloadditions of 1,3-dipoles with formamidines

The objective of this research was to investigate the synthesis of nitrile oxides and to study their reactivity in 1,3-dipolar cycloadditions with formamidines. Chapter one looks at the literature surrounding the 1,3-dipolar cycloaddition reaction. It explores the generation of 1,3-dipoles (mainly nitrile oxides) and dipolarophiles (predominantly amidines). It discusses the potential synthetic uses of the 1,3-dipolar cycloadducts. It examines both and inter- and intra-molecular cycloaddition reactions. It recognises the use of the 1,3-dipolar cycloadditions as a successful method in building natural products and oxadiazolines. The decomposition of oxadiazolines as a route to nitriles is also outlined in this chapter. Chapter two discusses the results of this research candidate. The preparation of nitrile oxide precursors - hydroximoyl halides - is outlined at first. The generation of nitrile oxides is then demonstrated, followed by the preparation of furoxans. Methods for preparing the reference materials (nitriles and ureas), which result from decomposition of oxadiazolines, then follow. The preparation of series of Δ2-1,2,4- oxadiazolines via the 1,3-dipolar cycloaddition reaction is illustrated in this chapter. The selectivity of the addition of nitrile oxides to dipolarophiles was tested by competition reactions, which are also described in this chapter. NMR techniques were used in the study of the kinetics of the 1,3-dipolar cycloadditions used for the preparation of a series of Δ2-1,2,4-oxadiazolines, which is addressed in this chapter. Chapter three charts the experimental procedures followed to gain results which are discussed in chapter two. It also outlines all analytical data produced during the course of this research.

Chemistry and synthesis of 3(2H)-furanones and 4,5-dihydro analogues: mechanistic investigations and stereochemical control

The subject matter of this thesis relates to the chemistry of the five-membered oxygen heterocycles – 3(2H)-furanones and their 4, 5-dihydro analogues. Chapter one of the thesis is a review of the relevant chemistry of the compounds: their synthesis and key transformations. In chapter two, new research on 3(2H)-furanones is outlined in two parts. The first describes an investigation into the cyclisation of α'-trialkylsilyloxyenone adducts with arenesulfenyl and selenenyl chlorides into the corresponding sulfur and selenium substituted 3(2H)-furanones without the involvement of a Lewis acid catalyst. The study, largely involving in situ NMR techniques, identified key features associated with the formation and reaction of the chlorosulfide and chloroselenide intermediates, including operation of the Thorpe-Ingold effect. The knowledge gained in this study was applied (the second part) to the synthesis of vinyl substituted furanone systems from α'-trialkylsilyloxydienones where choice of the reaction conditions and electrophilic reagent was a key feature. An important difference in the behaviour of arenesulfenyl and selenenyl halides towards conjugated dienes emerged from this work. This phase of the research concluded with a new synthesis of geiparvarin, a natural product possessing anti-tumour properties.

Algorithms for indoor localization based on IEEE 802.15.4-2011 UWB and inertial sensors

In this thesis, extensive experiments are firstly conducted to characterize the performance of using the emerging IEEE 802.15.4-2011 ultra wideband (UWB) for indoor localization, and the results demonstrate the accuracy and precision of using time of arrival measurements for ranging applications. A multipath propagation controlling technique is synthesized which considers the relationship between transmit power, transmission range and signal-to-noise ratio. The methodology includes a novel bilateral transmitter output power control algorithm which is demonstrated to be able to stabilize the multipath channel, and enable sub 5cm instant ranging accuracy in line of sight conditions. A fully-coupled architecture is proposed for the localization system using a combination of IEEE 802.15.4-2011 UWB and inertial sensors. This architecture not only implements the position estimation of the object by fusing the UWB and inertial measurements, but enables the nodes in the localization network to mutually share positional and other useful information via the UWB channel. The hybrid system has been demonstrated to be capable of simultaneous local-positioning and remote-tracking of the mobile object. Three fusion algorithms for relative position estimation are proposed, including internal navigation system (INS), INS with UWB ranging correction, and orientation plus ranging. Experimental results show that the INS with UWB correction algorithm achieves an average position accuracy of 0.1883m, and gets 83% and 62% improvements on the accuracy of the INS (1.0994m) and the existing extended Kalman filter tracking algorithm (0.5m), respectively.

The role of transformative thinking and practice in a property entrepreneur's response to the funding crisis since 2008

This portfolio of exploration explores the role of transformative thinking and practice in a property entrepreneur’s response to the financial crisis which swept over Ireland from 2008. The complexity of this challenge and the mental capacity to meet its demands is at the core of the exploration. This inquiry emerged from the challenges the financial crisis presented to my values, beliefs, assumptions, and theories, i.e. the interpretive lens through which I make meaning of my experiences. Given the issue identified, this inquiry is grounded in aspects of theories of constructive developmental psychology, applied developmental science, and philosophy. Integrating and linking these elements to business practice is the applied element of the Portfolio. As the 2008 crisis unfolded I realised I was at the limits of my way of knowing. I came to understand that the underlying structure of a way of knowing is the ‘subject-object relationship’ i.e. what a way of knowing can reflect upon, look at, have perspective on, in other words, make object, as against what is it embedded in, attached to, identified within, or subject to. My goal became enhancing my awareness of how I made meaning and how new insights, which would transform a way of knowing, are created. The focus was on enhancing my practice. This Portfolio is structured into three essays. Essay One reported on my self-reflection and external evaluation out of which emerged my developmental goals. In Essay Two I undertake a reading for change programme in which different meaning making systems were confronted in order to challenge me as a meaning maker. Essay Three reported on my experiment which concerned the question whether it was possible for me as a property entrepreneur, and for others alike, to retain bank finance in the face of the overwhelming objective of the bank to deleverage their balance sheet of property loans. The output of my research can be grouped into General Developmental and Specific Business Implications. Firstly I address those who are interested in a transformational-based response to the challenges of operating in the property sector in Ireland during a crisis. I outline the apparatus of thought that I used to create insight, and thus transform how I thought, these are Awareness, Subject-object separation, Exploring other’s perspectives from the position of incompleteness, Dialectical thinking and Collingwood’s Questioning activity. Secondly I set out my learnings from the crisis and their impact on entrepreneurial behaviour and the business of property development. I identify ten key insights that have emerged from leading a property company through the crisis. Many of these are grounded in common sense, however, in my experience these were, to borrow Shakespeare’s words, “More honor'd in the breach than the observance” in pre Crisis Ireland. Finally I set out a four-step approach for forging a strategy. This requires my peer practitioners to identify (i) what they are subject to, (ii) Assess the Opportunity or challenge in a Systemic Context, (iii) Explore Multiple Perspectives on the opportunity or Challenge with an Orientation to change how you know and (iv) Using the Questioning Activity to create Knowledge. Based on my experience I conclude that transformative thinking and practice is a key enabler for a property entrepreneur, in responding to a major collapse of traditional (bank debt) funding.

Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis.

The attachment of a sugar to a hydrophobic polyisoprenyl carrier is the first step for all extracellular glycosylation processes. The enzymes that perform these reactions, polyisoprenyl-glycosyltransferases (PI-GTs) include dolichol phosphate mannose synthase (DPMS), which generates the mannose donor for glycosylation in the endoplasmic reticulum. Here we report the 3.0 Å resolution crystal structure of GtrB, a glucose-specific PI-GT from Synechocystis, showing a tetramer in which each protomer contributes two helices to a membrane-spanning bundle. The active site is 15 Å from the membrane, raising the question of how water-soluble and membrane-embedded substrates are brought into apposition for catalysis. A conserved juxtamembrane domain harbours disease mutations, which compromised activity in GtrB in vitro and in human DPM1 tested in zebrafish. We hypothesize a role of this domain in shielding the polyisoprenyl-phosphate for transport to the active site. Our results reveal the basis of PI-GT function, and provide a potential molecular explanation for DPM1-related disease.

Sports programs of the Spanish radio in the social network Facebook: compared study (2010-2015)

Social networks have increasingly become a showcase where the media can be promoted. Like many other media, radio stations have made use of social networks to promote themselves in a better way and, sometimes, to keep more feedback with their listeners. But not all programs make the same use and not all of them have managed to reach in the same way his followers. This article discusses the consolidation in the social networks of the major radio sports programs in Spain. Through a comparative analysis between 2010 and 2015, throughout the text, the authors have tried to observe the evolution of the programs and, at the same time, to establish comparisons between the followers that these programs have on social networks and the number of listeners as EGM.

Analysis of audiovisual production and music scene in Extremadura through YouTube channels

A study on Extremenian music and audiovisual production has been carried out through YouTube media. The purpose of this study is to analyze all audiovisual products and also assessing what broadcasting processes are conducted by creators to publicize their musical and audiovisual works. A quantitative and qualitative study of audiovisual materials of Extremadura bands was done to find out which processes are most suitable to increase the number of viewers for videos.

La existencia de necesidades de información y comportamiento informativo en los entrenadores en deportes de combate

Este trabajo tiene como propósito esencial, realizar un acercamiento para detectar e identificar las necesidades de información y el comportamiento informativo de entrenadores en deportes de combate. Para ello se aplicó un cuestionario a instructores de aikido, boxeo, esgrima, judo, karate, kendo, lima lama, lucha y taekwondo seleccionados mediante un muestreo no probabilístico por causalidad. En general encontramos que los principales temas de interés entre los instructores son: los programas de entrenamiento, nutrición y dietas de entrenamiento. Por otra parte, los entrenadores son más propensos a utilizar su experiencia, internet y cursos para obtener información. En contraste se nota que la biblioteca y los libros son poco usados.