13 resultados para antagonism

em Deakin Research Online - Australia


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This paper explores the consequences of these discourses for the ways that international students are identified and positioned within school communities. My argument is developed in four sections. The first describes my ongoing exploration into the impact of international student programmes in Australia. The second exemplifies my argument: exploring the day-to-day experiences of vice principals in two Victorian government state secondary schools as they market their schools, and examining the systemic and ontological discourses played out within those conversations. The third interrogates discourses of identity and difference, neo-liberalism and nave cosmopolitanism which I find shape teacher conversations about international student programmes. In the final section, I argue that the impact of the discourse formations implicit in teacher talk about international student programmes has been the objectification of international students and their ambivalent inclusion within the school community.

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Heart failure (HF) is an increasingly recognized complication of diabetes. Cardiac fibrosis is an important causative mechanism of HF associated with diabetes. Recent data indicate that inflammation may be particularly important in the pathogenesis of cardiovascular fibrosis. We sought to determine the mechanism by which cardiac fibrosis develops and to specifically investigate the role of the CXCR4 axis in this process. Animals with type I diabetes (streptozotocin treated mice) or type II diabetes (Israeli Sand-rats) and controls were randomized to treatment with a CXCR4 antagonist, candesartan or vehicle control. Additional groups of mice also underwent bone marrow transplantation (GFP+ donor marrow) to investigate the potential role of bone marrow derived cell mobilization in the pathogenesis of cardiac fibrosis. Both type I and II models of diabetes were accompanied by the development of significant cardiac fibrosis. CXCR4 antagonism markedly reduced cardiac fibrosis in both models of diabetes, similar in magnitude to that seen with candesartan. In contrast to candesartan, the anti-fibrotic actions of CXCR4 antagonism occurred in a blood pressure independent manner. Whilst the induction of diabetes did not increase the overall myocardial burden of GFP+ cells, it was accompanied by an increase in GFP+ cells expressing the fibroblast marker alpha-smooth muscle actin and this was attenuated by CXCR4 antagonism. CXCR4 antagonism was also accompanied by increased levels of circulating regulatory T cells. Taken together the current data indicate that pharmacological inhibition of CXCR4 significantly reduces diabetes induced cardiac fibrosis, providing a potentially important therapeutic approach.

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Contents: Cultural contexts. The light within : the 21st century love songs of Nick Cave / Jillian Burt ; Planting seeds / Clinton Walker ; Nick Cave and the Australian language of laughter / Karen Welberry ; Nick Cave, dance performance and the production of masculinity / Laknath Jayasinghe -- Intersections. An audience for antagonism / Chris Bilton ; And the ass saw the angel : a novel of fragment and excess / Carol Hart ; Red right hand : the cinema and Nick Cave / Adrian Danks ; Grinderman : all stripped down / Angela Jones -- The sacred. From mutiny to calling upon the author : Cave's religion / Robert Eaglestone ; Oedipus wrecks : Cave and the Presley myth / Nathan Wiseman-Trowse ; Fleshed sacred : the carnal theologies of Nick Cave / Lyn McCredden ; The moose and Nick Cave : melancholy, creativity and love songs / Tanya Dalziell.

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South Asia has emerged in the post-Cold War era as a region where ongoing nuclear rivalry has the potential to result in a nuclear exchange between India and Pakistan. The United States, together with the global community, is devoting considerable effort to prevent the further development and deployment of nuclear weapons by India and Pakistan. This thesis analyses the underlying reasons for the ongoing nuclear rivalry between India and Pakistan, details post-Cold War initiatives to end the nuclear rivalry and examines the prospect of United States efforts to cap, reduce and eventually eliminate the nuclear arsenals of India and Pakistan. The thesis finds that historical factors form the basis of the continuing hostility and animosity between the two nations. The two nations have been bitter rivals since the time of partition in 1947 and the disputed territory of Kashmir continues to be the manifestation of deep seated antagonism and hostility. Pakistan's geography leaves it extremely vulnerable to conventional Indian attack and possession of nuclear weapons is seen as a means to redress the imbalance. Strong domestic support together with fervent nationalism and international prestige will continue to drive the nuclear programs of each nation. This thesis concludes that the nuclear rivalry between India and Pakistan is regional in nature and the end of the Cold War has done little to improve the prospects for nuclear disarmament in the region. United States led efforts have failed to persuade India or Pakistan to either accede to the Non-Proliferation Treaty (NPT) or dismantle their nuclear weapons. The thesis also notes that the United States has failed to take account of China as a significant regional power and it's impact on the nuclear programs of India and Pakistan. A fresh approach (to include China) with more emphasis on regional dialogue is suggested as a first step to ending the nuclear rivalry.

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8-Cyclopentyl-3-(3-(4-fluorosulfonylbenzoyl)oxy)propyl-propylxanthine (44, FSCPX) has been reported to exhibit potent and selective irreversible antagonism of the A1 adenosine receptor when using in vitro biological preparations. However, FSCPX (44) suffers from cleavage of the ester linkage separating the reactive 4-(fluorosulfonyl)phenyl moiety from the xanthine pharmacophore when used in in vivo biological preparations or preparations containing significant enzyme activity, presumably by esterases. Cleavage of the ester linkage renders FSCPX (44) inactive in terms of irreversible receptor binding. In order to obtain an irreversible A1 adenosine receptor antagonist with improved stability, and to further elucidate the effects of linker structure on pharmacological characteristics, several FSCPX (44) analogues incorporating the chemoreactive 4-(fluorosulfonyl)phenyl moiety were targeted, where the labile ester linkage has been replaced by more stable functionalites. In particular, ether, alkyl, amide and ketone linkers were targeted, where the length of the alkyl chain was varied from between one to five atoms. Synthesis of the target compounds was achieved via direct attachment of the N-3 substituent to the xanthine. These compounds were then tested for their biological activity at the A1 adenosine receptor via their ability to irreversibly antagonise the binding of [3H]-8-cyclopentyl-1,3-dipropylxanthine ([3H]DPCPX, ( 9) to the A1 adenosine receptor of DDT1 MF-2 cells. For comparison, the xanthines were also tested for their ability to inhibit the binding of [3H]-4-(2-[7-amino-2-{furyl} {1,2,4}- triazolo{2,3-a} {1,3,5}triazin-5-ylamino-ethyl)]phenol ([3H]ZM241385, 36) to the A2A adenosine receptor of PC-12 cells. The results suggest that the length and chemical composition of the linker separating the reactive 4-(fluorosulfonyl)phenyl moiety from the xanthine ring contribute to the potency and efficacy of the irreversible A1 adenosine receptor ligands. Like FSCPX (44, IC50 A1 = 11.8 nM), all derivatives possessed IC50 values in the low nM range under in vitro conditions. Compounds 94 (IC50 A1 = 165 nM), 95 (IC50 A1 = 112 nM) and 96 (IC50 A1 = 101 nM) possessing one, three and five methylene spacers within the linkage respectively, exhibited potent and selective binding to the A1 adenosine receptor versus the A2A adenosine receptor. Compound 94 did not exhibit any irreversible binding at A1 adenosine receptors, while 95 and 96 exhibit only weak irreversible binding at A1 adenosine receptors. Those compounds containing a benzylic carbonyl separating the 4-(fluorosulfonyl)phenyl moiety from the xanthine ring in the form of an amide (119, IC50 A1 = 24.9 nM, and 120, IC50 A1 = 21 nM) or ketone (151, IC50 A1 = 14 nM) proved to be the most potent, with compound 120 exhibiting the highest selectivity of 132-fold for the A receptor over the A2A receptor. compounds 119, 120 and 151 also strongly inhibited the binding of [3H]DPCPX irreversibly (82%, 83% and 78% loss of [3H]DPCPX binding at 100 nM respectively). compounds 120 and 151 are currently being evaluated for use in in vivo studies. Structure-activity studies suggest that altering the 8-cycloalkyl group of A1 selective xanthines for a 3-substituted or 2,3-disubstituted styryl, combined with N-7 methyl substitution will produce a compound with high affinity and selectivity for the A2A adenosine receptor over the A1 adenosine receptor. Compound 167 (IC50 A2A = 264 nM) possessing 8-(m-chloro)styryl substitution and the reactive 4-(fluorosulfonyl)phenyl moiety separated from the xanthine ring via an amide linker in the 3-position (as for 119 and 120), exhibited relatively potent binding to the A2A adenosine receptor of PC-12 cells, with a 16-fold selectivity for that receptor over the A1 adenosine receptor. However, compound 167 exhibited only very weak irreversible binding at A2A adenosine receptors. Overall, at this stage of biological testing, compound 120 appears to possess the most advantageous characteristics as an irreversible antagonist for the A1 adenosine receptor. This can be attributed to its high selectivity for the A1 adenosine receptor as compared to the A2A adenosine receptor. It also has relatively high potency for the A1 adenosine receptor, a concentration-dependent and selective inactivation of A1 adenosine receptors, and unbound ligand is easily removed (washed out) from biological membranes. These characteristics mean compound 151 has the potential to be a useful tool for the further study of the structure and function of the A1 adenosine receptor.

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BACKGROUND: Survivin is a member of the inhibitor-of-apoptosis (IAP) family which is widely expressed by many different cancers. Overexpression of survivin is associated with drug resistance in cancer cells, and reduced patient survival after chemotherapy and radiotherapy. Agents that antagonize the function of survivin hold promise for treating many forms of cancer. The purpose of this study was to investigate whether a cell-permeable dominant-negative survivin protein would demonstrate bioactivity against prostate and cervical cancer cells grown in three dimensional culture.

RESULTS: A dominant-negative survivin (C84A) protein fused to the cell penetrating peptide poly-arginine (R9) was expressed in E. coli and purified by affinity chromatography. Western blot analysis revealed that dNSurR9-C84A penetrated into 3D-cultured HeLa and DU145 cancer cells, and a cell viability assay revealed it induced cancer cell death. It increased the activities of caspase-9 and caspase-3, and rendered DU145 cells sensitive to TNF-α via by a mechanism involving activation of caspase-8.

CONCLUSIONS: The results demonstrate that antagonism of survivin function triggers the apoptosis of prostate and cervical cancer cells grown in 3D culture. It renders cancer cells sensitive to the proapoptotic affects of TNF-α, suggesting that survivin blocks the extrinsic pathway of apoptosis. Combination of the biologically active dNSurR9-C84A protein or other survivin antagonists with TNF-α therapy warrants consideration as an approach to cancer therapy.

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Australia is one of the world’s most urbanised nations, with 74.92% of the population living in 17 major cities of 100,000 people or more. To improve the productivity, liveability and sustainability of Australia’s cities, there is an increasing emphasis in urban management policies on democratic stakeholder participation. In order to obtain a full picture of stakeholders’ concerns efficiently, and manage antagonism, prejudice and conflicts between stakeholders effectively, it is important for participatory decision-making in urban development to be able to select and integrate stakeholder analysis and engagement methods. This paper investigates the characteristics of stakeholder participation approaches in urban development, and proposes criteria for approach selection and integration. The outcome is a multi-criteria mechanism for selecting and integrating approaches to stakeholder participation. This could enable effective, efficient and democratic participation in decision-making process of urban development. Meanwhile, the capacity of Australian state, territory and local governments can be largely enhanced to understand and unpack the complex challenges of urban-ecological conditions, and generate a compromise solution that best represents the preferences of stakeholders.

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An increase in the concentration of serotonin in the brain has been shown to cause fatigue during exercise in humans and experimental animals. This type of fatigue is referred to as central fatigue and is likely to be mediated by the concentration of serotonin as well as serotonin receptor sensitivity. Serotonin (5-HT) receptor antagonism in humans and experimental animals has been shown to improve endurance performance. A previous report has shown decreased receptor sensitivity in athletes compared to sedentary controls. It is unclear whether this is due to a training adaptation or if individuals are predisposed to enhanced athletic performance due to their inherent decreased receptor sensitivity. The present study investigated changes in 5-HT receptor sensitivity in response to aerobic exercise. Subjects completed 3 × 30 min of stationary cycling at 70% of their peak aerobic power (V̇O2,peak) for 9 weeks. Serotonin receptor sensitivity was assessed indirectly by measuring the neuroendocrine response following administration of a serotonin agonist (buspirone hydrochloride). The neuroendocrine response following administration of a placebo was also investigated in a blind crossover design. A group of sedentary control subjects was also recruited to control for seasonal variations in central receptor sensitivity. The training caused a significant increase in V̇O2,peak (3.1 ± 0.16 to 3.6 ± 0.15 l min−1, P < 0.05) and endurance capacity (93 ± 8 to 168 ± 11 min, P < 0.05), but there was no change (P > 0.05) in the neuroendocrine response in the presence of a serotonin agonist. However, one-quarter of the subjects in the training group demonstrated decreases in receptor sensitivity. These results suggest that despite increases in V̇O2,peak and endurance performance, there was no measurable change in 5-HT receptor sensitivity in the presence of a serotonin agonist. In addition, it is possible that changes in receptor sensitivity may take longer to occur, that the training stimulus used in the present investigation was inadequate and/or that changes occurred in receptor subtypes that were not probed by the agonist used in the present investigation.

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The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the body's metabolism to high-energy consuming processes such as reproduction and immune responses. We here provide genetic and biochemical evidence that the metabolic and immune functions of leptin can be uncoupled at the receptor level. First, homozygous mutant fatt/fatt mice carry a spontaneous splice mutation causing deletion of the leptin receptor (LR) immunoglobulin-like domain (IGD) in all LR isoforms. These mice are hyperphagic and morbidly obese, but display only minimal changes in size and cellularity of the thymus, and cellular immune responses are unaffected. These animals also displayed liver damage in response to concavalin A comparable to wild-type and heterozygous littermates. Second, treatment of healthy mice with a neutralizing nanobody targeting IGD induced weight gain and hyperinsulinaemia, but completely failed to block development of experimentally induced autoimmune diseases. These data indicate that leptin receptor deficiency or antagonism profoundly affects metabolism, with little concomitant effects on immune functions.

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Many atypical antipsychotics show antagonism at both serotonergic and dopaminergic neurones and show fewer extrapyramidal side effects (EPS). Nefazodone blocks postsynaptic 5HT2A receptors and weakly inhibits serotonin reuptake. This study aimed to elucidate the role of nefazodone in the treatment of antipsychotic-induced EPS. The trial was a double-blind, randomised, placebo-controlled trial of patients requiring antipsychotic treatment with haloperidol 10mg daily; from which a subgroup of patients who developed EPS were selected for the study. Patients were randomised to add-on therapy with either placebo (n=24) or nefazodone (n=25) 100mg bd. EPS were measured on days 0, 3 and 7 using the Simpson Angus, Barnes akathisia, abnormal involuntary movement and Chouinard scales. Nefazodone significantly reduced EPS as measured by both the Simpson Angus scale and CGI (p=0.007 and 0.0247, respectively). Akathisia and tardive dyskinesia did not differ between the two groups (p=0.601; p=0.507, respectively). These results suggest the role of 5HT2 antagonism in the mechanism of action of atypical antipsychotics with respect to lowering rates of drug-induced EPS. In addition, a therapeutic role for nefazodone is suggested in the treatment of antipsychotic-induced EPS.

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The comparison between the Position Statements of the latest two Venice Biennale of Architecture, Fundamentals, directed by Rem Koolhaas in 2014 and Reporting from the front that Alejandro Aravena prepares for 2016, is an evident sign of the internal stress that architectural practice has been suffering during the last decade. Koolhaas intensively focused on the immediate past whilst Aravena presents a Biennalle strongly decided to explore possible alternatives for the future of Architecture. The first one tried to define the core, theessence, the most elemental particles that utterly compose Architecture. The second looks at the boundaries, the periphery, the outskirts, the limits of the discipline. Fundamentals was theoretical, personal, abstract, compact and aesthetic. Reporting from the front will be practical, collective, concrete, permeable and ethical. This fertile antagonism or counterpoint between both approaches is too frequently understood as incompatible. However, as a matter of fact the coexistence of these two different perspectives within architectural practice is the mostdistinctive feature of the complex contemporary architectural landscape. The insertion of the analysis of both position statements within the historical evolution of the Venice Bienale since 1980, allows a reinterpretation of the antagonism between the two exhibitions and evidences some lines of thought and action in the architectural world. Following the war industry terminology that Report from the front has chosen, Aravena identifies with precision the theatre of operations; the space and time that is requesting an urgent response from architecture.Previously Koolhaas had defined the armament that Architecture has available to undertake this crucial mission: to define the role and relevance of Architecture in the immediate future. Until now, battles in the front have been a guerrilla warfare. More reactive than proactive. Battles for survival more than for experience. Necessary but, at the same time, insufficient. Valuable actions in radical contexts; heroic acts in extreme situations; occasional infiltrations that find their final reason for being in their own audacity. Time has come for these counterattackarchitectures to evolve from protests to proposals.

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This book provides insight into the long process of decolonisation within the Methodist Overseas Missions of Australasia, a colonial institution that operated in the British colony of Fiji. The mission was a site of work for Europeans, Fijians and Indo-Fijians, but each community operated separately, as the mission was divided along ethnic lines in 1901. This book outlines the colonial concepts of race and culture, as well as antagonism over land and labour, that were used to justify this separation. Recounting the stories told by the mission’s leadership, including missionaries and ministers, to its grassroots membership, this book draws on archival and ethnographic research to reveal the emergence of ethno-nationalisms in Fiji, the legacies of which are still being managed in the post-colonial state today.