Development of strategies to increase commercial production of mohair and cashmere in Australia

We aimed to identify impediments to investing into mohair and cashmere production and to suggest programs and strategies to attract investors. Targeted interviews of people focussed on attributes of an investment opportunity. Analysis differentiated views of small and large-scale producers and those not involved in these industries. Potential investors into mohair and cashmere make decisions based on the compatibility of the enterprise to their farm system, the technical, financial and market feasibility of the enterprise and its comparative advantage with other possible courses of action. They are sceptical of information coming from within these industries that is not sufficiently supported by fact. There are many implications from these findings including the need for the industries to: understand the investment decision process; provide objective financial and benchmarking data; make information more accessible; overcome resistance to these industries; and increase the visibility of the industries.<br /

Depletion of the phosphatase inhibitor, PPP1R1A, may contribute to beta-cell loss in Type 1 diabetes

Increasing evidence implicates a persistent enteroviral infection of β-cells as a potential trigger for the development of Type 1 diabetes (T1D). In support of this, findings presented in this thesis demonstrate that interferon-stimulated genes are upregulated in pancreas samples from T1D donors, but absent from donors without T1D, despite evidence of viral protein in their islets. The reasons for this exaggerated response are unclear but may be related to altered regulation of the viral recognition protein, MDA5. Protein phosphatase 1, regulatory, inhibitory, subunit 1A (PPP1R1A) is a largely unstudied molecule and has a restricted tissue distribution, but is highly expressed in β-cells. PPP1R1A specifically regulates protein phosphatase 1 (PP1) which has a central role in coordinating MDA5 activity. Findings presented in this thesis demonstrate that PPP1R1A is depleted from β-cells in T1D. To explore the impact of PPP1R1A on β-cell function, clonal lines of tetracycline inducible β-cells were developed using the PPP1R1A-deficient 1.1B4 cells as a host line for the Flp-In T-REx system. Two cell lines were generated which express either wild-type (WT) PPP1R1A or a phosphorylation-null (T35A) mutant form, upon addition of tetracycline. During the development of these Flp-In T-REx lines, I made the discovery that the parental 1.1B4 line was contaminated with an unidentified rat cell line. Data are presented on how this contamination was discovered and the steps taken to re-derive and characterise new human 1.1B4 cells lines. These findings have resulted in the withdrawal of 1.1B4 (and other related cell lines) from the European Collection of Authenticated Cell Cultures (ECACC) and a change in international practice for the authentication of cell lines. Despite these difficulties, the Flp-In T-REx PPP1R1A cell lines and other human cell lines available, were used to explore (1) the role of PPP1R1A in cell cycle progression and (2) the role of PPP1R1A in regulation of secretion from β-cells. Cell cycle progression was found to be reliant upon the timing of sequential PPP1R1A phosphorylation and dephosphorylation. Phosphorylation of PPP1R1A is critical for successful completion of the cell cycle and sustained phosphorylation of PPP1R1A resulted in apoptosis. Previous studies had identified PPP1R1A as a critical component necessary for insulin secretion. The studies reported in this thesis demonstrate that PPP1R1A could also play a previously unrecognised role in regulating constitutive secretion of molecules from cells.Diabetes U

Molecular pharmacological characterisation of recombinant and native NR2B- and NR3B- containing NMDA receptors

NMDA receptors are ionotropic, glutamate receptors which mediate fast excitatory transmissions within the central nervous system. They form tetrameric or pentameric heterologous complexes from seven NMDA receptor subunits NRl, NR2A-D and NR3A-B which each convey distinct expression patterns, functional and pharmacological properties to the receptor complex. Due to its involvement in excitatory transmission, over-excitation of the NMDA receptor, particularly the NR2B subunit, has been the focus of pharmaceutical therapeutic targeting for neurodegenerative conditions and chronic pain. This thesis discusses the potential importance and clinical effectiveness of targeting NMDA receptors and the difficulties in drag development arising from the receptor's heteromeric nature. The work herein focuses on the pharmacological characterisation of two novel NR2B-selective antagonists Compound A and Compound B， the physiological and pharmacological effects of NR3 subunit inclusion in the NMDA receptor complex, and the modifications of NMDA receptor physiology and subunit expression during chronic pain states. This research provides novel evidence to suggest that Compound A and Compound В bind with a high selectivity and affinity towards NR1/NR2B containing receptors. It provides novel evidence for a differential cytoprotective effect of the NR3 subunits showing significant cytoprotection in NR1/NR2B, but not NR1/NR2A, receptors and shows that NR3B inclusion in the receptor can differentially modulate the binding affinities ofNR2B-selective antagonists. This study also shows evidence for increased activity of spinal and supra-spinal NR2B-containmg receptors indicating NMDA receptor modulation and involvement in a chronic pain model

Identification of immunostimulatory adjuvant(s) that will promote a Th17-type of immune response

Immunostimulatory adjuvants are substances added to vaccines to promote and direct a robust Th1, Th2, or Th17 immune response. Murine Th17 cells are produced and differentiated from naïve T cells in the presence of transforming growth factor (TGF)-β and interleukin (IL)-6 and once differentiated, Th17 cells produce cytokines IL-17A, IL-17F, IL-21 and IL-22. We investigated how immunostimulatory molecules such as poly[di(sodium carboxylatoethylphenoxy)-phosphazene (PCEP), Alum, CpG oligodeoxynucleotide (CpG ODN), Curdlan, Leptin and Lipopolysaccharide (LPS), alone or in combination influenced differentiation and/or activation of Th17 type immune cells in mice. In vitro studies showed that murine splenocytes stimulated with CpG showed significantly induced production of IL-12, a cytokine important for induction of Th1 type immune cells and IL-12 is known to be inhibitory for differentiation of Th17-type immune cells. Curdlan + Leptin +/- PCEP and PCEP + Curdlan induced significant expression of TGF-β. No immunostimulant combination induced both IL-6 and TGF-β, which we anticipated would be required for Th17 cell differentiation. When we investigated the cytokines induced by the immunostimulants 48 hours after injection in muscle tissue, we determined that Curdlan + Leptin significantly induced production of IL-17, likely from activation of already differentiated T cells. TGF-β was significantly induced in response to Curdlan and Leptin, alone and in combination but they were poor inducers of IL-6. PCEP+/- CpG or LPS significantly induced expression of IL-6 but not TGF-β. Finally, we immunized mice via intramuscular (i.m.) route with OVA in the presence of the immunostimulatory adjuvants and assessed cytokine production from OVA-restimulated splenocytes 5 weeks later. ELISA results indicated that OVA-specific IL-17 production was significantly induced in splenocytes from mice immunized with PCEP + OVA relative to the mice immunized with Curdlan + OVA, although it was insignificant with respect to the OVA immunization group presumably due to the highly variable responses. Using flow cytometric analysis, we observed that vaccination with PCEP + OVA and Curdlan + Leptin + OVA significantly induced the frequency of OVA-specific splenic CD4+IL-17+ cells. Curdlan + Leptin also significantly induced the frequency of OVA-specific CD4+Foxp3+ cells and CD4+IL-17+Foxp3+ double positive cells. Thus, we conclude that in vitro studies are poorly predictive of the type of adaptive response that may be induced when immunostimulatory adjuvants were used in a vaccine. Furthermore, vaccines formulated with PCEP and Curdlan + Leptin adjuvants promote Th17 cell differentiation and should be investigated as a combinational adjuvant for bacteria or fungal based immunizations

Structure/function relationships in the graminaceous leaf

Aspects of the structure/function relationships in leaves of Lolium temulentum L. were examined during their growth, ageing and senescence. The first part of the thesis deals with the blade and sheath and demonstrates the presence of interactions within leaves (between blade and sheath) and between leaves during their extension growth. ' A short biddhemical study of aspects; of blade and sheath ageing and. senescence of attached 4th leaves examined changes in fresh and dry weight, total chlorophyll, soluble protein, and nucleic acids (both quantitative and qualitative by polyacrylamide gel electrophoresis). The overall patterns of change were similar to those previously described for artificially' induced grass leaf senescence but differences were found between the two organs. It was concluded that the blade was not a good model for sheath or leaf senescence. A study of the vasculature of the leaf - with particular reference to metabolite trans port during ageing and senescence - revealed the presence of tyloses in the protoxylem vessels/lacunae at the blade/sheath junction of senescing leaves. The second part of the thesis deals with the membranous ligules of L. temulentum, L. perenne L., L. multiflorum Lam., L. x hybridum Hausskn., and Festuca pratensis Huds. The structure and ultrastructure of all appeared to be the same and had the appearance of a glandular organ. Using a number of cytochemical procedures in L. temulentum, catalase, cytochrome c oxidase and succinate dehydrogenase activities were identified, along with the apparent secretion of a glycoprotein- like material by the cells of the adaxial epidermis. Aspects of the endomembrane system of cells of the latter tissue and initiation and early development of the ligule of L. temulentum were also studied. The structure/function relationships within these ligules are discussed in terms of a possible function of the membranous grass ligule. Aspects of ligule and root cap biology in L. temulentum were compared

Reduced DC circuit breaker requirement on mixed converter HVDC networks

© 2015 IEEE.Recently proposed meshed HVDC networks include both converters and DC circuit breakers, and the fault currents experienced and therefore the capacity requirement of circuit breakers are dependent on the topology of converters used on the network. This paper analyses the difference in fault currents seen in various network configurations utilising fault-feeding and fault-blocking converters. Results are presented showing the reduced fault currents seen in the regions of the DC network where fault current limiting converters have been implemented, which could have an impact on the topology, current rating and therefore size and cost of the circuit breaker

Performing at the Block: Scripting Early Modern Executions

This thesis explores the executions of noble men and women in Tudor and early Jacobean England and the theatrical representations of executions that mirrored real life spectacles of deadly punishment. Historical scaffold confessions followed a formulaic pattern and condemned traitors performed their final moments before a crowd of witnesses with the power to judge the quality of the actor’s deportment, costuming and words. As a public stage, the scaffold allowed the traitor a chance to assert and define his or her own individuality in the face of death and formulaic requirements, which I outline in the first chapter. Dramatic representations of executions both reflected and subverted the depictions of real life performances at the block. Playwrights employed the scaffold confession in a variety of ways. Execution spectacles within plays could—depending on the intention of the author—uphold the power of a just monarch, defy conventions and reveal societal ills, or show the agency of the individual characters facing execution

Monotone one-port circuits

Maximal monotonicity is explored as a generalization of the linear theory of passivity, aiming at an algorithmic input/output analysis of physical models. The theory is developed for maximal monotone one-port circuits, formed by the series and parallel interconnection of basic elements. An algorithmic method is presented for solving the periodic output of a periodically driven circuit using a maximal monotone splitting algorithm, which allows computation to be separated for each circuit component. A new splitting algorithm is presented, which applies to any monotone circuit defined as a port interconnection of monotone elements