Cardiovascular disease is the most common cause of morbidity and mortality in type 2 diabetes. Short-term studies of glucagon-like peptide-1 (GLP-1)-targeted therapies suggest potential beneficial effects on cardiovascular outcomes. The mechanism behind this unexpectedly rapid effect is not known. In this study, full-length human GLP-1 receptor (GLP-1R) mRNA was cloned and sequenced from a human megakaryocyte cell line. Quantitative RT-PCR results showed that expression levels were comparable to other GLP-1R expressing tissues. Furthermore, incubation with GLP-1 and the GLP-1R agonist exenatide elicited a cAMP response in these cells. As megakaryocytes are the cellular precursors of platelets, the effect of GLP-1 and exenatide were studied in gel-filtered human platelet aggregation, where they were both shown to have an inhibitory effect on thrombin-stimulated platelet aggregation. Platelet inhibition by GLP-1 and GLP-1R agonists presents a potential mechanism for the reduced incidence of atherothrombotic events thought to be associated with GLP-1-targeted therapies.

The molecular conformations, potential energy functions and vibrational spectra of several cyclic molecules have been investigated by ab initio and density functional theory calculations and by infrared and Raman spectroscopy. The ab initio computations of 3-cyclopenten-1-ol predict that its lowest energy conformer has a weak pi-type intramolecular hydrogen bonding. The three other conformers lie 301 to 411 cm^-1 higher in energy. The infrared and Raman spectra of this molecule confirm the presence of the four conformers. The energy difference between the two conformers of lowest energy was also determined from the experimental spectroscopic data and was found to be 435 plus/minus 160 cm^-1, in reasonable agreement with the ab initio computations results. Ab initio calculations for cyclopentane and d1, 1,1-d2, 1,1,2,2,3,3-d6, and d10 isotopomers confirm cyclopentane confirmed that has twist and bent structures and that these differ in energy by less than 10 cm^-1. The bending angle is 41.5 degrees and the twisting angle is 43.2 degrees. A complete vibrational assignment for each of the isotopomers was achieved. Ab initio calculations were also carried out for methylcyclopropane, cyclopropylsilane, cylopropylgermane, cyclopropylamine, cyclopropanethiol and cyclopropanol. The structure and the potential energy function for internal rotation was calculated for each and compared to available experimental results determined from infrared and Raman spectra. The calculated barriers to internal rotation agree very well with the experimental data. The structures, relative energies, and frequencies for the lowest energy vibrations of the twisted, bent, and planar forms of cyclohexene and four of its oxygen analogs were calculated and compared to experimental results. The calculated structural data agree very well with that from the microwave work, but the computed barriers are somewhat lower than those based on far-infrared data. 4-Silaspiro-(3,3)-heptane possesses two four-membered rings, each puckered with and angle of 34 degrees. The molecule possesses a two-dimensional ring-puckering potential energy surface with four equivalent minima. The ab initio calculations predict a barrier to planarity of each ring of 582 cm^-1 while the energy of the structure with both rings planar is 1220 cm^-1 higher. The calculated infrared and Raman spectra were compared to those previously published, and the agreement is excellent.

Introduction - India is beginning to resemble the western worlds’ way of living and that leads to an increased risk of chronic diseases such as diabetes. Due to its very large population India has the world second largest number of people with diabetes; 61, 3 million people. Studies have shown that the awareness of diabetes is poor, especially in rural areas. Aim - To investigate nurses’ experience of applying professional competence in patient education with focus on diabetes type II in an Indian rural hospital. Method – Data was gathered through twelve qualitative interviews. The interviews were tape recorded, transcribed verbatim and then analyzed through content analysis. Result – Three main categories were identified; Acquired competence to meet the patients, Helping the patients manage their disease and Nurses’ ideas for quality improvements regarding diabetes care. Conclusion - This study identified different obstacles that could have a negative effect on the care and treatment of patients with diabetes type II. The nurses had many ideas for quality improvements which could raise the awareness of the disease among patients, improve clinical outcomes and the work environment for the nurses. The nurses are willing to get more education about the disease and implement quality improvements if the resources and equipment are provided by the hospital.

C-type Natriuretic Peptide (CNP), a relatively new member of the natriuretic peptide family, is found throughout the central nervous system. Circumstantial evidence associates CNP with learning and memory, as its expression is highest in brain regions known to be involved in memory and associated with hippocampal physiology. Here, the first study housed rats in an enriched environment, regarded as providing an 'informal' learning experience, for either 14 or 28 days of housing in enrichment in six regions of interest, which was attributed to changes in the degradation of CNP. The second study examined a group of rats trained on object -recognition task – the bow-tie maze. A difference was found in CNP production in the limbic medial prefrontal cortex over repeated exposures to novel objects relative to controls that received 'yoked learning' an exposure only to the test room. CNP concentrations also tended to be lower in rats with better levels of discrimination between familiar objects. Together, these studies provide some initial evidence that CNP influences learning –induced plasticity in the intact brain.

The aim of the study was to explore the role of autonomy in participants’ self-management of exercise behaviours and the transfer of responsibility throughout adolescence. The design of this study used qualitative description with information collected and presented using a case study approach. Participants were five emerging adults (aged 18–24) with Type 1 diabetes for a minimum of one year who lived in Canterbury. Data was gathered through three sources: a semi-structured interview seeking self-reported exercise throughout adolescence, a set of questionnaires based on four instruments, and physical activity performed over a week as recorded by an activity monitor. All participants achieved autonomy for exercise, however participants achieved autonomy at different ages. Participants’ diabetes self-management and physical activity levels varied according to their stage of life and lifestyle. They received varying advice about exercise from health professionals. Participants sought to determine their own exercise choices during adolescence, leading them to obtain a driver licence to be independent of parental transport. Three of the five met current guidelines for physical activity levels, and another met recommendations by her clinician. Policy implications regarding healthcare advice and barriers to exercise for young people are discussed, as are limitations of the research and future avenues for research.

This dissertation investigates the growth of high quality GaN and InN thin films by plasma assisted molecular beam epitaxy (PAMBE). It also explores the growth of self-seeded GaN branching nanowires and p-type doping of InN, two topics of particular interest at present. The growth of high quality III-Nitride semiconductor thin films have been shown to be dependent on the group-III (metal) to nitrogen ratio. A metal-rich growth environment enhances the diffusion of the group-III adatoms through the formation of a group-III adlayer. By using a metal-rich growth environment, determined by growth rate studies using laser reflection interferometry or RHEED analysis of the surface, both GaN and InN films have been grown with a smooth surface morphology. Additionally the smooth surface morphology has beneficial effects on the electrical and optical properties of both materials. However, with the growth using a metal-rich environment, group-III droplets are present on all film surfaces, which can be an issue for device fabrication, as they produce facets in the crystal structure due to enhanced growth rates. MBE growth of GaN nanowires via the vapour liquid solid (VLS) and vapour solid (VS) growth techniques have so far been based on the N-rich growth regime. However, we have shown that the Ga-rich growth regime can be used to grow self-seeded one dimensional and hierarchical GaN nanowires. 7 µm long hierarchical GaN nanowires with at least three branches were grown and shown to have a high crystalline quality. The suggested growth mechanism is a self-seeding VLS process driven by liquid phase epitaxy at the nanoscale, while the branching growth was nucleated due to the Ga-rich growth regime by excess Ga droplets forming on the trunk during growth. The growth of vertical GaN nanowires has also been achieved using the same self-seeding process and the critical parameter seems to be the Ga to N ratio. Also, the growth rate of the Ga-rich grown GaN nanowires can supersede the growth rates reported from N-rich grown GaN nanowires by at least a factor of two. The fabrication of vertical and planar GaN nanowire devices has been demonstrated in this study. Two point and three point contacts were fabricated to the branching GaN nanowires in the planar direction with resistive measurements ranging from 200 - 900 kΩ, similar to chemical vapour deposition and MBE grown GaN nanowires. The nonlinear current-voltage characteristics from the three point contacts may lead to unique nano-devices. The planar nanowires have also shown to have potential as UV detectors. Schottky diodes were fabricated on the vertical nanowires, with values for the barrier heights consistent with bulk diodes. Mg and Zn doping studies of InN were also performed. Both InN:Mg and InN:Zn have strong photoluminescence only at low doping concentrations. However, the InN:Mg films have reduced mobilities with increased Mg content, whereas the mobility determined from the InN:Zn films is independent of Zn. When the InN:Zn film quality was improved by growing under the In-rich growth regime, electrochemical capacitance-voltage results suggest n{type conductivity, and strong photoluminescence was obtained from all of the films with four features seen at 0.719 eV, 0.668 eV, 0.602 eV and 0.547 eV. The features at 0.719 eV and 0.668 eV are possibly due to a near band edge to valence band or shallow acceptor transition, while the 0.547 eV has an activation energy of 60 meV suggesting a deep level acceptor.

Two studies were conducted to compare nitrogen (N) and glutamate metabolism in Polypay and percentage White Dorper lambs.First, a two-phase digestion/N metabolism trial was conducted with 18 wether lambs of three genetic types: Polypay (PP), 1/2 White Dorper 1/2 Polypay (1/2 D), and 3/4 White Dorper 1/4 Polypay (3/4 D). Six lambs of each genetic type were fed a high roughage diet (HR; Phase 1) or high concentrate diet (HC; Phase 2). DM and N digestion was higher for 1/2 D than PP or 3/4 D fed HC. N retention was highest for 1/2 D regardless of diet.The second study analyzed the effect of genetic type on glutamate transporter and metabolizing enzyme expression in liver, kidney, longissimus dorsi muscle (LD muscle), and subcutaneous fat (Sub Q Fat) tissue of 18 wether lambs of three genetic types: PP, 1/2 D, and 15 /16 White Dorper 1/16 Polypay (15 /16 D). Tissue samples were analyzed for protein and mRNA content of GS, GDH, ALT, EAAC1, and GLT-1. Glutamate transport and metabolism capacity was lowest for the heavier muscled 15 /16 D lambs.The results suggest genetic type has an effect on N metabolism due to differential expression of glutamate transporters and metabolizing enzymes.

Organic electronics have received significant development in the last few decades. p- Type materials are much more in availability than n-type now. There are only a few examples of air-stable n-type materials. The design and synthesis of novel air-stable ntype materials is still a focus of research. Herein is described a study to evaluate the effectiveness of a novel electron-withdrawing group, composed of three electronwithdrawing groups connected in series, to impart material properties known to be favorable for obtaining air-stable n-types. The smaller acenes, naphthalene and anthracene, carrying these electron-withdrawing groups were prepared and studied by UV-Vis absorption spectroscopy and solution electrochemical measurements to estimate changes in frontier molecular orbital energies and single crystal X-ray diffraction to determine packing motif. These measurements suggest that the new materials could be promising as n-type semiconductors in organic field effect transistor (OFET) and as acceptors for organic photovoltaic (OPV) cells. The reasons are based on: (1) the close intermolecular contacts seen in X-ray crystal structures, some of them showing 3D faceto- face stack. (2) Electrochemical measurements indicate LUMO energy levels suitable for air-stable n-type materials.

La traduction d'une séquence nucléotidique d'ARNm dans plus d'un cadre de lecture est un phénomène découvert chez les virus vers la fin des années 1970. Depuis, quelques exemples de ce phénomène de traduction alternative ont été découverts chez l'humain dans les gènes INK4a, GNAS1, XBP1, et PRNP. La protéine alternative du gène GNAS , nommée ALEX, interagit et régule la protéine de référence et une mutation dans la protéine alternative peut engendrer certains phénotypes pathologiques. Plusieurs groupes de recherche ont effectué des analyses bio-informatiques sur le génome humain et ont suggéré que la traduction alternative de gènes pourrait être beaucoup plus importante que les quelques exemples connus à ce jour. Nous avons créé une base de données dans le but de prédire ces protéines alternatives à partir du transcriptome humain. Le gène ATXN1 semblait un candidat très intéressant à valider puisque la protéine de référence du gène, l'ATXN1, est impliquée dans une maladie neurodégénérative importante: l'ataxie spinocérébelleuse de type 1 (SCA1). Cette pathologie est causée par l'expansion d'une région CAG dans l'ADN qui est traduite en région polyglutamique. La protéine pathologique tend à agréger dans des inclusions nucléaires, ce qui induit l'altération de nombreux interacteurs de l'ATXN1 et pourrait interférer avec la fonction normale de ATXN1. Nous avons observé la présence de deux sites d'initiation alternatifs dans la séquence codante du gène ATXN1, situés dans le cadre de lecture +3. Expérimentalement, nous avons montré l'existence de deux isoformes de la protéine alternative nommée Alt-ATXN1, l'isoforme long étant fortement majoritaire. Alt-ATXN1, qui se localise dans le noyau, interagit de façon directe avec l'ATXN1 et coagrège avec celle-ci dans les inclusions nucléaires caractéristiques de la SCA1. Cette caractéristique intéressante suggère que la fonction biologique d'Alt-ATXN1 pourrait être altérée dans les cas de pathologie due à l'agrégation de l'ATXN1. Nous démontrons qu'Alt-ATXN1 lie les ARNm et possède une localisation nucléaire dépendante de la transcription, ce qui est caractéristique des protéines impliquées dans le processing de l'ARNm. L'existence d'Alt-ATXN1 a été confirmée in vivo dans une lignée neuronale humaine et dans des extraits de cervelets humains. Suite à ces découvertes, la fonction approfondie ainsi que la détermination du rôle d'Alt-ATXN1 dans la SCA1 demeurent sous investigation.

Emerging evidence has shown that an abnormal postprandial accumulation of dietary tat IS atherogenic. The aim of this study is to measure triacylglycerol (TAG) kinetics in endogenous and exogenous lipoproteins in both fed and fasted states using stable isotopes.