1,233 results on '"Brown AJ"'
Search Results
2. Considerations for Embedding Equity in the Energy Transition.
- Author
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Zhang, Emily, Pasternak, Samantha, and Brown, AJ
- Abstract
Decarbonizing our economies represents one of the most significant economic and industrial challenges in modern history. The drive toward decarbonization involves the widespread electrification of vehicles and buildings, adoption at scale of renewable energy resources, and modernization of the electric grid infrastructure. Together, these electrification efforts are projected to cause US electricity consumption to grow by 1.5 percent annually from 2024 to 2026,1 requiring a tripling or quadrupling in electric generation, transmission, and distribution infrastructure to meet future demands.2 While these developments have the potential to create a more sustainable and resilient energy system, they also risk exacerbating existing inequalities. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Democracy and the corruption question: Problems, solutions and future possibilities
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Brown, AJ
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- 2020
4. Protecting whistleblowers: Creating the optimal environment
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Lawrence, Sandra and Brown, AJ
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- 2019
5. An olivine cumulate outcrop on the floor of Jezero crater, Mars
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Liu, Y, Tice, MM, Schmidt, ME, Treiman, AH, Kizovski, TV, Hurowitz, JA, Allwood, AC, Henneke, J, Pedersen, DAK, VanBommel, SJ, Jones, MWM, Knight, AL, Orenstein, BJ, Clark, BC, Elam, WT, Heirwegh, CM, Barber, T, Beegle, LW, Benzerara, K, Bernard, S, Beyssac, O, Bosak, T, Brown, AJ, Cardarelli, EL, Catling, DC, Christian, Cloutis, EA, Cohen, BA, Davidoff, S, Fairén, AG, Farley, KA, Flannery, DT, Galvin, A, Grotzinger, JP, Gupta, S, Hall, J, Herd, CDK, Hickman-Lewis, K, Hodyss, RP, Horgan, BHN, Johnson, Jørgensen, JL, Kah, LC, Maki, JN, Mandon, L, Mangold, N, McCubbin, FM, McLennan, SM, Moore, K, Nachon, M, Nemere, P, Nothdurft, LD, Núñez, JI, O'Neil, L, Quantin-Nataf, CM, Sautter, V, Shuster, DL, Siebach, KL, Simon, JI, Sinclair, KP, Stack, KM, Steele, A, Tarnas, JD, Tosca, NJ, Uckert, K, Udry, A, Wade, LA, Weiss, BP, Wiens, RC, Williford, KH, Zorzano, M-P, Mangold, Nicolas, Cosmochimie [IMPMC] (IMPMC_COSMO), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Planétologie et Géosciences [UMR_C 6112] (LPG), Université d'Angers (UA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement (LGL-TPE), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Liu, Y [0000-0003-0308-0942], Tice, MM [0000-0003-2560-1702], Schmidt, ME [0000-0003-4793-7899], Treiman, AH [0000-0002-8073-2839], Kizovski, TV [0000-0001-8188-9769], Hurowitz, JA [0000-0002-5857-8652], Henneke, J [0000-0002-3195-7417], Pedersen, DAK [0000-0001-7182-8567], VanBommel, SJ [0000-0002-6565-0827], Jones, MWM [0000-0002-0720-8715], Knight, AL [0000-0001-6832-8190], Orenstein, BJ [0000-0002-6586-4227], Clark, BC [0000-0002-5546-8757], Beegle, LW [0000-0002-4944-4353], Benzerara, K [0000-0002-0553-0137], Bernard, S [0000-0001-5576-7020], Beyssac, O [0000-0001-8879-4762], Bosak, T [0000-0001-5179-5323], Brown, AJ [0000-0002-9352-6989], Cardarelli, EL [0000-0001-5451-2309], Catling, DC [0000-0001-5646-120X], Christian, JR [0000-0003-4646-2852], Cloutis, EA [0000-0001-7301-0929], Cohen, BA [0000-0001-5896-5903], Davidoff, S [0000-0002-4417-7268], Fairén, AG [0000-0002-2938-6010], Flannery, DT [0000-0001-8982-496X], Grotzinger, JP [0000-0001-9324-1257], Gupta, S [0000-0001-6415-1332], Hall, J [0000-0003-0884-3777], Herd, CDK [0000-0001-5210-4002], Hickman-Lewis, K [0000-0001-8014-233X], Hodyss, RP [0000-0002-6523-3660], Horgan, BHN [0000-0001-6314-9724], Johnson, JR [0000-0002-5586-4901], Jørgensen, JL [0000-0002-0343-239X], Kah, LC [0000-0001-7172-2033], Maki, JN [0000-0002-7887-0343], Mandon, L [0000-0002-9310-0742], Mangold, N [0000-0002-0022-0631], McCubbin, FM [0000-0002-2101-4431], McLennan, SM [0000-0003-4259-7178], Nachon, M [0000-0003-0417-7076], Nothdurft, LD [0000-0001-9646-9070], Núñez, JI [0000-0003-0930-6674], O'Neil, L [0000-0003-1555-8229], Quantin-Nataf, CM [0000-0002-8313-8595], Shuster, DL [0000-0003-2507-9977], Siebach, KL [0000-0002-6628-6297], Simon, JI [0000-0002-3969-8958], Sinclair, KP [0000-0001-6261-4591], Stack, KM [0000-0003-3444-6695], Steele, A [0000-0001-9643-2841], Tarnas, JD [0000-0002-6256-0826], Tosca, NJ [0000-0003-4415-4231], Uckert, K [0000-0002-0859-5526], Udry, A [0000-0002-0074-8110], Wade, LA [0000-0001-8254-8181], Weiss, BP [0000-0003-3113-3415], Wiens, RC [0000-0002-3409-7344], Zorzano, M-P [0000-0002-4492-9650], and Apollo - University of Cambridge Repository
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[SDU.STU.PL]Sciences of the Universe [physics]/Earth Sciences/Planetology ,Multidisciplinary ,5101 Astronomical Sciences ,37 Earth Sciences ,3705 Geology ,5109 Space Sciences ,[SDU.STU.PL] Sciences of the Universe [physics]/Earth Sciences/Planetology ,51 Physical Sciences ,3703 Geochemistry - Abstract
International audience; The geological units on the floor of Jezero crater, Mars, are part of a wider regional stratigraphy of olivine-rich rocks, which extends well beyond the crater. We investigate the petrology of olivine and carbonate-bearing rocks of the Séítah formation in the floor of Jezero. Using multispectral images and x-ray fluorescence data, acquired by the Perseverance rover, we performed a petrographic analysis of the Bastide and Brac outcrops within this unit. We find that these outcrops are composed of igneous rock, moderately altered by aqueous fluid. The igneous rocks are mainly made of coarse-grained olivine, similar to some Martian meteorites. We interpret them as an olivine cumulate, formed by settling and enrichment of olivine through multi-stage cooling of a thick magma body.
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- 2022
6. A Detailed Look at ‘I Think I CAN’
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Brown, AJ, Andel, TR, McDonald, JT, and Yampolskiy, M
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- 2017
7. Explainer: What is the proposed commonwealth integrity commission and how would it work?
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Brown, AJ
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- 2020
8. Selective Interstitial Hydration Explains Anomalous Structural Distortions and Ionic Conductivity in 6H-Ba4Ta2O9·1/2H2O
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Marlton, FP, Brown, AJ, Sale, M, Maljuk, A, Büchner, B, Lewis, W, Luck, I, Wood, ML, Mole, RA, Ling, CD, Marlton, FP, Brown, AJ, Sale, M, Maljuk, A, Büchner, B, Lewis, W, Luck, I, Wood, ML, Mole, RA, and Ling, CD
- Abstract
The mixed ionic-electronic conductor 6H-Ba4Ta2O9 undergoes an unconventional symmetry-lowering lattice distortion when cooled below 1100 K in the presence of atmospheric water. This temperature corresponds to the onset of hydration, which reaches a maximum value for 6H-Ba4Ta2O9·1/2H2O below ∼500 K. We use a combination of diffraction, ab initio calculations, and spectroscopy to show that both processes are intimately linked. The presence of very large Ba2+ cations in octahedral interstitial sites (B sites of its hexagonal perovskite-type structure) forces the adjacent vacant octahedral interstitial sites also to expand, making room for them to incorporate hydration species with a total stoichiometric H2O in constrained and highly acidic environments, where they show structural and dynamic characteristics intermediate between those of covalent water molecules and discrete protons and hydroxide ions. This in turn destabilizes the structure so that it distorts on cooling in a way that cannot be explained by conventional symmetry-lowering mechanisms. The resulting synergistic hydration-distortion mechanism is, to the best of our knowledge, unique to close-packed ionic compounds.
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- 2023
9. The referendum that wasn't: Constitutional recognition of local government and the Australian federal reform dilemma
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Brown, AJ and Kildea, Paul
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- 2016
10. Entrepreneurship & Business Management N6 SB: TVET FIRST
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BB Brown, AJ Voges & KD Knowles
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- 2015
11. Diabetes mellitus is independently associated with early stent thrombosis in patients undergoing drug eluting stent implantation: Analysis from the Victorian cardiac outcomes registry
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Nogic, J, Nerlekar, N, Soon, K, Freeman, M, Chan, J, Roberts, L, Brenan, A, Diem, D, Lefkovits, J, Brown, AJ, Nogic, J, Nerlekar, N, Soon, K, Freeman, M, Chan, J, Roberts, L, Brenan, A, Diem, D, Lefkovits, J, and Brown, AJ
- Abstract
BACKGROUND: Diabetes mellitus (DM) is a predictor of restenosis and late stent thrombosis (ST) in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting-stents (DES). Real-world data on rates of early ST is lacking. We compared clinical outcomes of patients with and without DM from the Victorian cardiac outcomes registry. METHODS: Consecutive patients undergoing PCI with DES were analyzed with primary outcome being ST at 30-days. Secondary outcomes including major adverse cardiovascular events (MACE) and all-cause mortality. RESULTS: Of 43,209 patients included, 9730 (22.5%) had DM. At 30 days, DM was independently associated with higher rates of early ST (0.7% vs. 0.5%) OR 1.41 (95% confidence interval; 1.05-1.87, p = 0.02), MACE (4.1% vs. 3.5%, p = 0.004) and mortality (1.9% vs. 1.5%, p = 0.01). Increased risk was not simply due to treatment. Patients with DM requiring insulin were equally affected in regard to MACE (4.7% vs. 3.9%, p = 0.069) and mortality (1.9%, vs. 1.8%, p = 0.746). On National Death Index linkage, patients with DM had increased all-cause mortality over five-year follow-up (OR 1.69 CI 1.55-1.83, p = < 0.001). CONCLUSION: In this large real-world-registry, DM was an independent predictor of early ST, MACE and mortality at 30 days. These data suggest additional therapeutic strategies are required to reduce the risk of early complications in patients with DM undergoing PCI with DES.
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- 2022
12. Dominant Kitaev interactions in the honeycomb materials Na3Co2SbO6 and Na2Co2TeO6
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Sanders, AL, Mole, RA, Liu, J, Brown, AJ, Yu, D, Ling, CD, Rachel, S, Sanders, AL, Mole, RA, Liu, J, Brown, AJ, Yu, D, Ling, CD, and Rachel, S
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- 2022
13. COMBED: Rapid non-invasive Cardiac Output Monitoring Baseline assessment in adult Emergency Department patients with haemodynamic instability
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Eyeington, CT, Canet, E, Cutuli, SL, Ancona, P, Brown, AJ, Jenkins, E, Taylor, DM, Eastwood, GM, Bellomo, R, Eyeington, CT, Canet, E, Cutuli, SL, Ancona, P, Brown, AJ, Jenkins, E, Taylor, DM, Eastwood, GM, and Bellomo, R
- Abstract
OBJECTIVE: The application of rapid, non-operator-dependent, non-invasive cardiac output monitoring (COM) may provide early physiological information in ED patients with haemodynamic instability (HI). Our primary objective was to assess the feasibility of measuring pre-intervention (baseline) cardiac index (CI) and associated haemodynamic parameters. METHODS: We performed a prospective observational study of adults shortly after presentation to the ED of a large university hospital with tachycardia or hypotension or both. We applied non-invasive COM for 5 min and recorded CI, mean arterial pressure (MAP), stroke volume index (SVI) and systemic vascular resistance index (SVRI). We assessed for differences between those presenting with hypotension or hypotension and tachycardia with tachycardia alone and between those with or without suspected infection. RESULTS: We obtained haemodynamic parameters in 46 of 49 patients. In patients with hypotension or hypotension and tachycardia (n = 15) rather than tachycardia alone (n = 31), we observed a lower MAP (60.8 vs 87.7, P < 0.0001), CI (2.8 vs 3.9, P = 0.0167) and heart rate (85.5 vs 115.4, P < 0.0001). There was no difference in SVI (33.7 vs 33.4, P = 0.93) or SVRI (1970 vs 2088, P = 0.67). Patients with suspected infection had similar haemodynamic values except for a lower SVRI (1706 vs 2237, P = 0.011). CONCLUSIONS: Rapid, non-operator-dependent, non-invasive COM was possible in >90% of ED patients presenting with HI. Compared with tachycardia alone, patients with hypotension had lower CI, MAP and heart rate, while those with suspected infection had a lower SVRI. This technology provides novel insights into the early state of the circulation in ED patients with HI.
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- 2022
14. Non-hyperaemic assessment of coronary ischaemia: application of machine learning techniques
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Cameron, JN, Comella, A, Sutherland, N, Brown, AJ, Phan, TG, Cameron, JN, Comella, A, Sutherland, N, Brown, AJ, and Phan, TG
- Abstract
AIMS: Hyperaemic and non-hyperaemic pressure ratios (NHPR) are routinely used to identify significant coronary lesions. Machine learning (ML) techniques may help better understand these indices and guide future practice. This study assessed the ability of a purpose-built ML algorithm to classify coronary ischaemia during non-hyperaemia compared with the existing gold-standard technique (fractional flow reserve, FFR). Further, it investigated whether ML could identify components of coronary and aortic pressure cycles indicative of ischaemia. METHODS AND RESULTS: Seventy-seven coronary vessel lesions (39 FFR defined ischaemia, 53 patients) with proximal and distal non-hyperaemic pressure waveforms and FFR values were assessed using supervised and unsupervised learning techniques in combination with principal component analysis (PCA). Fractional flow reserve measurements were obtained from the right coronary artery (13), left anterior descending (46), left circumflex (11), left main (1), obtuse marginal (2), and diagonal (4). The most accurate supervised learning classification utilized whole-cycle aortic with diastolic distal blood pressure waveforms, yielding a classification accuracy of 86.9% (sensitivity 86.8%, specificity 87.2%, positive predictive value 86.8%, negative predictive value 87.2%). Principal component analysis showed subtle variations in coronary pressures at the start of diastole have significant relation to ischaemia, and whole-cycle aortic pressure data are important for determining ischaemia. CONCLUSIONS: Our ML algorithm classifies significant coronary lesions with accuracy similar to previous studies comparing time-domain NHPRs with FFR. Further, it has identified characteristics of pressure waveforms that relate to function. These results provide an application of ML to ischaemia requiring only standard data from non-hyperaemic pressure measurements.
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- 2022
15. The Living Subject: Warts and All
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Brown, AJ
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- 2011
16. A tale of two questions?: An argument for coordinated constitutional reform
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Brown, AJ and Levy, Ron
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- 2011
17. Australian whistleblowing law reform debate hots up
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Brown, AJ
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- 2014
18. In the Shadow of Federalism: Dilemmas of Institutional Design in Australian Rural and Remote Regional Governance
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Brown, AJ and Bellamy, JA
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- 2010
19. When the Whistle Is Blown
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Brown, AJ
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- 2009
20. Thinking Big: Public Opinion and Options for Reform of Australia's Federal System
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Brown, AJ
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- 2009
21. The States We're In
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Brown, AJ
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- 2008
22. Whistleblower Laws: International Best Practice
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Latimer, Paul and Brown, AJ
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- 2008
23. In Pursuit of the 'Genuine Partnership': Local Government and Federal Constitutional Reform in Australia
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Brown, AJ
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- 2008
24. In Whose Interest?: The Need for Consistency in to Whom, and about Whom, Australian Public Interest Whistleblowers Can Make Protected Disclosures
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Latimer, Paul and Brown, AJ
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- 2007
25. When Does Property Become Territory?: Nuclear Waste, Federal Land Acquisition and Constitutional Requirements for State Consent
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Brown, AJ
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- 2007
26. Reshaping Australia's Federation: The Choices for Regional Australia
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Brown, AJ
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- 2007
27. Towards a More Regional Federalism: Rural and Urban Attitudes to Institutions, Governance and Reform in Australia
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Brown, AJ, Gray, Ian, and Giorgas, Dimitria
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- 2006
28. Beyond EIA - Incorporating Environment into the Engineering Design Process
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National Conference on Environmental Engineering (1992 : Gold Coast, Qld.) and Brown, AJ
- Published
- 1992
29. Homebrew reagents for low cost RT-LAMP
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Anibal Arce, Rivera M, Brown Aj, Isaac Núñez, César A. Ramírez-Sarmiento, Paula Blázquez-Sánchez, Tamara Matute, Chiara Gandini, Fernán Federici, Jenny Molloy, and Javiera Reyes
- Subjects
DNA polymerase ,Computer science ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Loop-mediated isothermal amplification ,Economic shortage ,Sensitivity and Specificity ,Article ,Mice ,diagnostics ,Animals ,Humans ,Cold chain ,Molecular Biology ,RT-LAMP ,biology ,SARS-CoV-2 ,COVID-19 ,Articles ,Replication (computing) ,Reverse transcriptase ,Molecular Diagnostic Techniques ,Reagent ,biology.protein ,RNA, Viral ,Indicators and Reagents ,Biochemical engineering ,Nucleic Acid Amplification Techniques - Abstract
RT-LAMP (reverse transcription - Loop-mediated isothermal amplification) has gained popularity for the detection of SARS-CoV-2. The high specificity, sensitivity, simple protocols and potential to deliver results without the use of expensive equipment has made it an attractive alternative to RT-PCR. However, the high cost per reaction, the centralized manufacturing of required reagents and their distribution under cold chain shipping limits RT-LAMP’s applicability in low-income settings. The preparation of assays using homebrew enzymes and buffers has emerged worldwide as a response to these limitations and potential shortages. Here, we describe the production of Moloney murine leukemia virus (M-MLV) Reverse Transcriptase and BstLF DNA polymerase for the local implementation of RT-LAMP reactions at low cost. These reagents compared favorably to commercial kits and optimum concentrations were defined in order to reduce time to threshold, increase ON/OFF range and minimize enzyme quantities per reaction. As a validation, we tested the performance of these reagents in the detection of SARS-CoV-2 from RNA extracted from clinical nasopharyngeal samples, obtaining high agreement between RT-LAMP and RT-PCR clinical results. The in-house preparation of these reactions results in an order of magnitude reduction in costs, and thus we provide protocols and DNA to enable the replication of these tests at other locations. These results contribute to the global effort of developing open and low cost diagnostics that enable technological autonomy and distributed capacities in viral surveillance.
- Published
- 2021
30. The integrity branch: a ‘system’, an ‘industry’, or a sensible emerging fourth arm of government?
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Brown, AJ, primary
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- 2014
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31. A structure of human scap bound to insig-2 suggests how their interaction is regulated by sterols
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Yan, R, Cao, P, Song, W, Qian, H, Du, X, Coates, HW, Zhao, X, Li, Y, Gao, S, Gong, X, Liu, X, Sui, J, Lei, J, Yang, H, Brown, AJ, Zhou, Q, Yan, C, Yan, N, Yan, R, Cao, P, Song, W, Qian, H, Du, X, Coates, HW, Zhao, X, Li, Y, Gao, S, Gong, X, Liu, X, Sui, J, Lei, J, Yang, H, Brown, AJ, Zhou, Q, Yan, C, and Yan, N
- Abstract
The sterol regulatory element-binding protein (SREBP) pathway controls cellular homeostasis of sterols. The key players in this pathway, Scap and Insig-1 and-2, are membrane-embedded sterol sensors. The 25-hydroxycholesterol (25HC)-dependent association of Scap and Insig acts as the master switch for the SREBP pathway. Here, we present cryo-electron microscopy analysis of the human Scap and Insig-2 complex in the presence of 25HC, with the transmembrane (TM) domains determined at an average resolution of 3.7 angstrom. The sterol-sensing domain in Scap and all six TMs in Insig-2 were resolved. A 25HC molecule is sandwiched between the S4 to S6 segments in Scap and TMs 3 and 4 in Insig-2 in the luminal leaflet of the membrane. Unwinding of the middle of the Scap-S4 segment is crucial for 25HC binding and Insig association.
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- 2021
32. Translating prefigurative politics: social networks and rhetorical strategies in the alter-globalisation movement
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Brown, AJ
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- 2020
33. A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice
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Montgomery SA, Gralinski LE, Moorman NJ, Gully KL, Sheahan TP, Dinnon KH III, Schäfer A, Baric RS, Scobey T, Sanders W, Okuda K, Leist SR, Edwards CE, West A, Hou YJ, Brown AJ, Fritch EJ, Boucher RC, and Tse LV
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respiratory tract diseases - Abstract
The SARS-CoV-2 pandemic has caused extreme human suffering and economic harm. We generated and characterized a new mouse-adapted SARS-CoV-2 virus that captures multiple aspects of severe COVID-19 disease in standard laboratory mice. This SARS-CoV-2 model exhibits the spectrum of morbidity and mortality of COVID-19 disease as well as aspects of host genetics, age, cellular tropisms, elevated Th1 cytokines, and loss of surfactant expression and pulmonary function linked to pathological features of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This model can rapidly access existing mouse resources to elucidate the role of host genetics, underlying molecular mechanisms governing SARS-CoV-2 pathogenesis, and the protective or pathogenic immune responses related to disease severity. The model promises to provide a robust platform for studies of ALI and ARDS to evaluate vaccine and antiviral drug performance, including in the most vulnerable populations (i.e., the aged) using standard laboratory mice.
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- 2020
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34. When Should the People Decide?: Public Support for Direct Democracy in Australia
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Kildea, P, Brown, AJ, Deem, J, Kildea, P, Brown, AJ, and Deem, J
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This article examines the strength of support for direct democracy among Australian citizens, both in general and, in a world-first, across different specific topics. Analysing data from the Australian Constitutional Values Survey, we investigate whether that support is higher among people who are more educated and politically interested (in line with a ‘cognitive mobilisation’ hypothesis) or those who are dissatisfied with politics, with low levels of political trust (‘political disaffection’). The article finds that Australians widely support the use of direct democracy, but especially with respect to constitutional issues and matters of principle that they feel they can readily engage with, whereas parliaments are still seen as best placed to decide more technical matters. The article also finds that support for direct democracy is strongest among politically disaffected citizens, in ways that suggest greater use of direct democracy may have a role to play in addressing decline in political trust in Australia.
- Published
- 2020
35. Fractional Flow Reserve following Percutaneous Coronary Intervention
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Thakur, U, Khav, N, Comella, A, Michail, M, Ihdayhid, AR, Poon, E, Nicholls, SJ, Ko, B, Brown, AJ, Thakur, U, Khav, N, Comella, A, Michail, M, Ihdayhid, AR, Poon, E, Nicholls, SJ, Ko, B, and Brown, AJ
- Abstract
Fractional flow reserve (FFR) is routinely used to determine lesion severity prior to percutaneous coronary intervention (PCI). However, there is an increasing recognition that FFR may also be useful following PCI to identify mechanisms leading to restenosis and the need for repeat revascularization. Post-PCI FFR is associated with the presence and severity of stent under-expansion and may help identify peri-stent-related complications. FFR pullback may also unmask other functionally significant lesions within the target vessel that were not appreciable on angiography. Recent studies have confirmed the prognostic utility of performing routine post-PCI FFR and suggest possible interventional targets that would improve stent durability. In this review, we detail the theoretical basis underlying post-PCI FFR, provide practical tips to facilitate measurement, and discuss the growing evidence supporting its use.
- Published
- 2020
36. Subsidiarity or subterfuge? Resolving the future of Local Government in the Australian federal system
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Brown, AJ
- Subjects
Australia -- Political aspects ,Federalism -- Comparative analysis ,Political reform -- Planning ,Political reform -- Comparative analysis ,Company business planning ,Government - Abstract
During Australia's centenary of federation (2001), the author, Local Government Association of Queensland and Courier-Mail newspaper surveyed 1,264 Queenslanders for their attitudes to future constitutional change, including a sample of 259 local government opinion leaders from across the state. The results of this pilot suggest ongoing political, functional and theoretical challenges surrounding the position of local government in Australia. Only 22 percent of local government respondents indicated a preference for the federal system to remain the same in another 100 years, against 70+ percent preferring significant structural change (50 percent seeking regional governments that replace the states). This higher-than-expected interest in change suggests that ongoing national reviews of the position of local government will need to reconsider federalism's values and structures from first principles, including engagement by Commonwealth and states alike with the principle of `subsidiarity', if they are to deliver any long-term gains.
- Published
- 2002
37. The effect of ascorbic acid on plasma lipids and oxidisability of LDL in male smokers
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Samman, S, Brown, AJ, Beltran, C, and Singh, S
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- 1997
- Full Text
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38. Anti-nuclear protest in post-Fukushima Tokyo: Power struggles
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Brown, AJ
- Abstract
© 2018 Alexander James Brown. This book explores the politics of anti-nuclear activism in Tokyo after the Fukushima nuclear disaster of March 2011. Analyzing the protests in the context of a longer history of citizen activism in Tokyo, it also situates the movement within the framework of a global struggle for democracy, from the Arab Spring to Occupy Wall Street. By examining the anti-nuclear movement at both urban and transnational scales, the book also reveals the complex geography of today’s globally connected social movements. It emphasizes the contestation of urban space by anti-nuclear activists in Tokyo and the weaving together of urban and cyber space in their praxis. By focusing on the cultural life of the movement-from its characteristic demonstration style to its blogs, zines and pamphlets-this book communicates activists’ voices in their own words. Based on excellent ethnographic research, it concludes that the anti-nuclear protests in Tokyo after the Fukushima disaster have redefined social movement politics for a new era. Providing an analysis of a unique period in Japan’s contemporary urban history from the perspective of eyewitness observations, this book will be useful to students and scholars of Japanese Politics, Sociology and Japanese Studies in general.
- Published
- 2018
39. IMPROVING RESIDENT PHYSICIAN COMPLIANCE WITH PREVENTIVE HEALTH CARE RECOMMENDATIONS THROUGH QUALITY IMPROVEMENT
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Brown, AJ, Parker, DL, Montgomery, KA, and Domenici, LJ
- Published
- 1996
40. Utility of photoplethysmography for heart rate estimation among inpatients
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Koshy, AN, Sajeev, JK, Nerlekar, N, Brown, AJ, Rajakariar, K, Zureik, M, Wong, MC, Roberts, L, Street, M, Cooker, J, Teh, AW, Koshy, AN, Sajeev, JK, Nerlekar, N, Brown, AJ, Rajakariar, K, Zureik, M, Wong, MC, Roberts, L, Street, M, Cooker, J, and Teh, AW
- Abstract
The accuracy of photoplethysmography (PPG) for heart rate (HR) estimation in cardiac arrhythmia is unknown. PPG-HR was evaluated in 112 hospitalised inpatients (cardiac arrhythmias (n = 60), sinus rhythm (n = 52)) using a continuous electrocardiogram monitoring as a reference standard. Strong agreement was observed in sinus rhythm HR < 100 and atrial flutter (bias 1 beat), modest agreement in sinus tachycardia (bias 24 beats) and complete heart block (bias -6 beats) and weak agreement with significant HR underestimation was seen in atrial fibrillation (bias 23 beats). Routine utilisation of PPG for HR estimation may delay early recognition of clinical deterioration in certain arrhythmias and sinus tachycardia.
- Published
- 2018
41. Association of Volumetric Epicardial Adipose Tissue Quantification and Cardiac Structure and Function
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Nerlekar, N, Muthalaly, RG, Wong, N, Thakur, U, Wong, DTL, Brown, AJ, Marwick, TH, Nerlekar, N, Muthalaly, RG, Wong, N, Thakur, U, Wong, DTL, Brown, AJ, and Marwick, TH
- Abstract
Background Epicardial adipose tissue ( EAT ) is in immediate apposition to the underlying myocardium and, therefore, has the potential to influence myocardial systolic and diastolic function or myocardial geometry, through paracrine or compressive mechanical effects. We aimed to review the association between volumetric EAT and markers of myocardial function and geometry. Methods and Results PubMed, Medline, and Embase were searched from inception to May 2018. Studies were included only if complete EAT volume or mass was reported and related to a measure of myocardial function and/or geometry. Meta-analysis and meta-regression were used to evaluate the weighted mean difference of EAT in patients with and without diastolic dysfunction. Heterogeneity of data reporting precluded meta-analysis for systolic and geometric associations. In the 22 studies included in the analysis, there was a significant correlation with increasing EAT and presence of diastolic dysfunction and mean e' (average mitral annular tissue Doppler velocity) and E/e' (early inflow / annular velocity ratio) but not E/A (ratio of peak early (E) and late (A) transmitral inflow velocities), independent of adiposity measures. There was a greater EAT in patients with diastolic dysfunction (weighted mean difference, 24.43 mL; 95% confidence interval, 18.5-30.4 mL; P<0.001), and meta-regression confirmed the association of increasing EAT with diastolic dysfunction ( P=0.001). Reported associations of increasing EAT with increasing left ventricular mass and the inverse correlation of EAT with left ventricular ejection fraction were inconsistent, and not independent from other adiposity measures. Conclusions EAT is associated with diastolic function, independent of other influential variables. EAT is an effect modifier for chamber size but not systolic function.
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- 2018
42. From symbols to systems: progress in the reform of Australia’s private sector whistleblowing laws
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Hall, Kath, Brown, AJ, Hall, Kath, and Brown, AJ
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- 2018
43. A conserved degron containing an amphipathic helix regulates the cholesterol-mediated turnover of human squalene monooxygenase, a rate-limiting enzyme in cholesterol synthesis
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Chua, NK, Howe, V, Jatana, N, Thukral, L, Brown, AJ, Chua, NK, Howe, V, Jatana, N, Thukral, L, and Brown, AJ
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Cholesterol biosynthesis in the endoplasmic reticulum (ER) is tightly controlled by multiple mechanisms to regulate cellular cholesterol levels. Squalene monooxygenase (SM) is the second rate-limiting enzyme in cholesterol biosynthesis and is regulated both transcriptionally and post-translationally.SMundergoes cholesterol-dependent proteasomal degradation when cholesterol is in excess. The first 100 amino acids of SM (designated SM N100) are necessary for this degradative process and represent the shortest cholesterol-regulated degron identified to date. However, the fundamental intrinsic characteristics of this degron remain unknown. In this study, we performed a series of deletions, point mutations, and domain swaps to identify a 12-residue region (residues Gln-62-Leu-73), required for SM cholesterol-mediated turnover. Molecular dynamics and circular dichroism revealed an amphipathic helix within this 12-residue region. Moreover, 70% of the variation in cholesterol regulation was dependent on the hydrophobicity of this region. Of note, the earliest known Doa10 yeast degron, Deg1, also contains an amphipathic helix and exhibits 42% amino acid similarity with SM N100. Mutating SM residues Phe-35/Ser-37/Leu- 65/Ile-69 into alanine, based on the key residues in Deg1, bluntedSMcholesterol-mediated turnover. Taken together, our results support a model whereby the amphipathic helix in SM N100 attaches reversibly to the ER membrane depending on cholesterol levels; with excess, the helix is ejected and unravels, exposing a hydrophobic patch, which then serves as a degradation signal. Our findings shed new light on the regulation of a key cholesterol synthesis enzyme, highlighting the conservation of critical degron features from yeast to humans.
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- 2017
44. Above and Below the Streets: A Musical Geography of Anti-nuclear Protest in Tokyo
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Brown, AJ
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1601 Anthropology, 1608 Sociology, 2002 Cultural Studies - Abstract
© 2016 Elsevier Ltd Affects such as anger, fear and love have compelled Tokyoites to take to the streets in protest in the wake of the Fukushima nuclear disaster of March 2011. One of the characteristic forms these protests have taken has been the anti-nuclear “sound demonstrations” in which bands, DJs and rappers perform from the backs of trucks that lead demonstrators through the streets. Projecting their emotive music through urban space with the aid of powerful sound systems, these demonstrations disrupt the everyday noises of the neoliberal city and create a public space for the vocalisation of dissent. After the demonstrations, these same artists and demonstrators move to the underground live houses and social centres that constitute a subterranean backbone to the visible demonstrations in the street. Expressing emotions through musical protest is a powerful motor for what Stevphen Shukatitis has called affective composition, the process via which collective political subjectivities are formed through the expression of shared emotions. This paper outlines the emotional geography of anti-nuclear music in post-Fukushima Tokyo. It examines the dynamic interplay between aboveground political protest and the city's subterranean network of musical performance spaces.
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- 2016
45. The Global Hiroba: Transnational Spaces in Tokyo’s Anti-nuclear Movement
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Brown, AJ and Bender, CT
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Following the emphasis on emotion and praxis in the anarchist geography literature (Clough 2012, 2014; Routledge 2011), this chapter is an attempt to capture the ‘anarchist geographies’ of transnational space we have experienced and convey some of the excitement and feeling of freedom we felt at that time as similar forms of struggle emerged across a variety of issues in Australia, the United States and Japan. In the words of Iwasaburō (Sabu) Kohso (2009, 198), we write ‘together with the “anti-authoritarian global revolutionary movement” and aim to construct thoughts/words while walking together’.2 In order to further elucidate the theoretical concerns which underpin our analysis in this chapter, we begin with a discussion of the way anarchist geographies might be conceptualized in the context of recent social movements.
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- 2016
46. Re-vaccination with an adjuvanted pandemic influenza H1N1 vaccine provides early protection in healthcare workers
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Azzi, Alberta, Corcioli, Fabiana, Arvia, Rosaria, Clausi, Valeria, Giannecchini, Simone, Puzelli, Simona, Donatelli, Isabella, Bredholt, Geir, Pathirana, Rishi, Pedersen, Gabriel, Akselsen, Per Espen, Sjursen, Haakon, Cox, Rebecca, Chaudhry, Mamoona, Rashid, Hamad Bin, Hussain, Manzoor, Thrusfield, Michael, Rashid, Haroon, Welburn, Sue, Eisler, Mark, Cheng, Xiao-wen, Lu, Jian-hua, Zhang, Shun-xiang, He, Jian-fan, Wu, Xiao-min, Lu, Xing, Fang, Shi-song, Wu, Chun-li, Chui, Cecilia, Li, Chris, Wilkinson, Tom, Gilbert, Anthony, Zhou, Jian-Fang, Shu, Yue-Long, Oxford, John, McMichael, Andrew, Xu, Xiaoning, Germundsson, A, Gjerset, B, Hjulsager, C, Larsen, LE, Er, C, Hungnes, O, Lium, B, Mbewana, Sandiswa, Mortimer, Elizabeth, Maclean, James, Tanzer, Fiona, Hitzeroth, Inga, Rybicki, Edward, Iorio, Anna Maria, Bistoni, Onelia, Galdiero, Massimiliano, Lepri, Enrica, Camilloni, Barbara, Russano, Anna Maria, Neri, Mariella, Basileo, Michela, Spinozzi, Fabrizio, Wang, Xin, Wang, Dong-li, Fang, Shi-song., Zhang, Renli, Cheng, Jinquan, Lycett, SJ, Bhatt, S, Pybus, OG, Baillie, G, Coulter, E, Kellam, P, Wood, JL, Brown, IH, consortium, COSI, Brown, AJ, Nazir, Jawad, Haumacher, Renate, Abbas, Maha D, Marschang, Rachel E, Robertson, James, Stech, J, Stech, O, Veits, J, Weber, S, Bogs, J, Gohrbandt, S, Hundt, J, Breithaupt, A, Teifke, JC, Mettenleiter, TC, Svindland, Signe C, Jul-Larsen, Åsne, Andersen, Solveig, Madhun, Abdullah, Montomoli, Emanuele, Gill, Inder, Cox, Rebecca J, Uchida, Yuko, Watanabe, Chiaki, Takemae, Nobuhiro, Hayashi, Tsuyoshi, Ito, Toshihiro, and Saito, Takehiko
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Conference Proceedings - Abstract
21-23 September 2010, St Hilda's College, Oxford, United Kingdom, Since the first appearance of the pandemic (H1N1) 2009 virus many efforts have been made to monitor the changes of the virus at molecular level with the aim to early detect mutations which could alter its pathogenicity. Some mutations have been observed more frequently in viruses that caused severe or fatal infections than in viruses involved in mild infections. Among these, the most common seems to be the amino acid substitution D222G (or D222E or D222N) in the HA1 sequence. However, to better assess the association of such mutation with pandemic virus pathogenicity a large set of data is required, in addition to other experimental studies. In our laboratory, as regional reference laboratory in Tuscany, 2350 respiratory specimens have been analysed for pandemic virus detection from May 2009 to May 2010 and 552 out of them showed positive by a real time RT-PCR. Here we report the results of the sequencing of a small region of the HA1 gene, 180 nucleotide long, performed to detect the previously reported mutation in two small groups of our positive samples. Thirteen out of 18 isolates (72%) from patients with severe disease had the D222E mutation in the HA1 in comparison with 7 out of 26 isolates (27%) from patients with mild disease. In this last group 7 children coming back from a school trip in England were included. Five of them shed a virus with the D222E substitution, suggesting that the mutated virus had been transmitted from a shared source. By cloning the PCR products of some samples from severe case of influenza, the presence of “quasispecies” was observed. Altogether, the 20 isolates with the D222E mutation were obtained from July to November 2009. Our observation confirm that the mutation is more frequently detectable in association with severe forms of influenza and that the mutated virus was easy transmissible. Keywords: pandemic influenza 2009, pathogenicity marker, haemagglutinin, Healthcare workers were prioritized for pandemic vaccination in the majority of countries to maintain the integrity of the healthcare system. In October 2009, we conducted a clinical trial in 250 frontline healthcare workers vaccinated with a low dose split pandemic H1N1 virus (X179a A/California/7/2009) vaccine adjuvanted with AS03. Vaccination induced a protective level of haemagglutination inhibition (HI) antibodies by 6-7 days post-vaccination, however in 10% of volunteers vaccination failed to induce and maintain a protective HI antibody response at 3 months post-vaccination. These non-responders were offered re-vaccination with the X179a H1N1 vaccine and here we report the kinetics of serum B- and T-cellular response to re-vaccination. Twelve healthcare workers (8 females and 4 males, average age 40.3 ± 12.7 years) were re-vaccinated with one dose of AS03 adjuvanted pandemic vaccine (3.75 μg haemagglutinin). The serum antibody response to homologous vaccine strain (X179a) and cross-reactivity to 3 other H1N1 strains (A/Brisbane/59/2007, A/New Caledonia/20/99 and A/Texas/36/91) was evaluated by HI assay. The frequency of antigen-specific antibody secreting cells and memory B-cell responses were detected by ELISPOT assays. The percentage of antigen-specific CD4+ T-cells secreting one or more Th1 cytokine (TNF alpha, IFN gamma or IL-2) was analysed by intracellular staining and multiparametric flow cytometry. There was a significant (p, Avian influenza type A and Newcastle Disease viruses cause significant economic losses to commercial poultry in Pakistan and are endemic in this area. Rural poultry contributes 56% of total egg production and 25% of poultry meat in Pakistan. Almost all rural, and 20% of urban, households keep backyard flocks, which are affected by common circulating viruses of poultry. A serological survey was designed to determine the prevalence of these viruses among the backyard flocks in Lahore district during July-August 2009. Two-stage cluster sampling was undertaken. In the first stage, 35 out of a total of 308 villages in Lahore district were selected on the basis of probability proportional to size (PPS) as clusters. In the second stage, six chickens of >2 months were selected as elementary units. A total of 210 serum samples were collected and examined by the haemagglutination inhibition test for specific antibodies against avian influenza virus (AIV) subtype H9, AIV subtype H5 and ND viruses. The seroprevalence of AIV subtype H9 was 63.8% (95% CI: 55-72%), that of AIV subtype H5 was 18.1% (95% CI: 12-24%) and of Newcastle Disease virus 41.9% (95% CI: 33-50%). The study therefore confirmed the exposure of backyard flocks to these viruses and indicated that AIV subtypes H9 and H5 and Newcastle Disease virus are circulating in backyard poultry. AIV potentially poses a zoonotic risk to human beings, interacting daily with these birds. The spread of these viruses could be due to low biosecurity at farm level or due to mixing of wild and migratory birds with backyard poultry. To control the further spread of AIV and ND, improvement in biosecurity of backyard flocks and ongoing monitoring of their disease status is recommended. Keywords: Avian influenza type A, seroprevalence, Newcastle disease, haemagglutination Inhibition, backyard flock, AIV H5, AIV H9, cluster sampling, This study was conducted to understand the knowledge, attitudes and practices of human H5N1 avian influenza (AI) in the Shen Zhen general population. Using a cross-sectional, Proportional Probability Sampling (PPS), face-to-face survey, 2073 Chinese people in Shen Zhen were interviewed anonymously in August of 2007. 90.4% of respondents had heard of avian influenza. The knowledge, attitudes and practices of human H5N1 avian influenza were significantly different among sex, age, education and occupation. 40.5% of respondents who heard of avian influenza had gone to the living chicken market AOR=2.31 (1.61∼3.32), and do not touch the cage AOR=0.35 (0.12∼0.98). Related AI information primarily came from public newspaper and television. Thus, the AI risk perception is high level, but the level of self-efficacy is low in Shen Zhen. Attention to risk communication and how to increase the self-efficacy should be paid. Timely dissemination of update information is greatly warranted. Keywords: Human H5N1 avian Influenza, knowledge, attitudes, practices, Influenza virus causes morbidity and mortality worldwide. Neutralizing antibodies are the major correlates of protection against influenza infection and the magnitude of their induction is widely used to evaluate the effectiveness of an influenza vaccine. Despite substantial evidence in animal models which suggest critical roles of T cells in the viral clearance, the role of cellular immunity in humans remained poorly understood. This project aims to determine cellular immune responses in sero-negative human volunteers following nasal challenge with a live virus, and to identify the role of pre-existing T cell responses in the virus shedding and disease severity in the absence of antibody. I have found that pre-existing memory T cells persist in most individuals and predominantly are specific against internal proteins such as nucleoprotein and matrix proteins. The challenge studies identified over 50 peptides and revealed the T cell response to be predominantly CD4-dependent. Seven days after challenge infection, these influenza-specific CD4 cells have greatly expanded (about 10 times) in both breadth and magnitude, and were able to kill antigen-loaded autologous B cell lines in vitro by chromium release assay. These acutely expanded T cells were shown to be highly activated (CD38+) and proliferative (Ki-67+). In a separate pandemic H1N1 vaccine trial where 150 healthy volunteers were vaccinated with an inactivated unadjuvanted split virion pandemic H1N1 vaccine, a modest response of influenza-specific T cells could be induced. Responses to both surface (HA and NA) and internal proteins were induced, and specific response measured by HA and NA peptide pools were also found to be strongly CD4+ dependent. Sixteen peptides were identified in this vaccine cohort. Activated proliferating cells induced during vaccination are of a central memory phenotype. As immune memory forms the basis of protection through natural infection or vaccination, the project will carry on to dissect how these memory CD4+ T cells function and differentiate in an acute infection. Due to the cross-reactive nature of T cell recognition and high degree of homology of different influenza subtypes, it is intriguing to explore the heterotypic immunity of T cell responses in acute influenza infection. This work should provide an insight on how cellular immunity can be targeted in conferring broad protection against different subtypes of influenza A viruses. Keywords: human seasonal influenza, experimental infection, T cell immunity, influenza inactivated vaccine, pandemic H1N1, In March-April 2009, a novel pandemic influenza A (H1N1) virus (pH1N1-09v) emerged in the human population. The first case of pH1N1v infection in pigs was reported from Canada in May 2009. In Norway, pH1N1v infection was recorded in a swine herd on the 10th of October of 2009. Here, we report results from the investigation performed during the outbreak and the follow up surveillance performed in the Norwegian pig population. Nasal swabs were collected from herds i) where pigs had been exposed to persons with verified pH1N1-09v infection or with influenza-like illness (ILI); ii) where pigs showed clinical signs or iii) with a history of close contact with or close proximity to infected herds. In addition, blood samples were collected from nucleus and multiplier breeding herds. Detection of pH1N1-09v was initially performed using a real-time RT-PCR targeted to detect influenza A virus. Positive samples were tested by a pH1N1-09v specific real-time RT-PCR. Blood samples were tested for presence of antibodies against influenza A virus by ELISA (IDVET) and positive samples in the ELISA were tested by haemagglutinin inhibition test using A/California/07/09 as antigen. From the onset of the outbreak and until 31st of December 2009, the pH1N1-09v was detected in nasal swabs from 54 of 114 herds investigated tested, while 55 of 140 herds tested positive for antibodies against pH1N1-09v. No herd has been tested positive for pH1N1-09v since early January 2010, however, results of the Norwegian surveillance and control programme for specific swine herds for 2010 so far indicates that 40 % of the swine herds (154 herds) are positive for antibodies against pH1N1-09. Serological evaluation of swine herds and detailed back tracking of the outbreak indicated that the virus was introduced in September 2009. The Norwegian swine population has, until the outbreak of pH1N1-09v, been considered free from influenza A virus infection as documented through serological surveillance program running since 1997. Virus isolated from one of the herds positive for pH1N1-09v was fully identical across the full genome to virus isolated from a confirmed human case at the farm. The majority of the positive herds had a history of contact with humans that were diagnosed with pandemic influenza or with ILI. This suggests that infected humans are the most likely source for introduction of pH1N1-09v to the Norwegian pig herds, especially in the early phase of the outbreak. Keywords: influenza A, pH1N1-09v, pigs, humans, Influenza A viruses are responsible for causing annual outbreaks in humans, and the latest pandemic H1N1 virus is an example of the potential for these viruses to recombine. The highly pathogenic avian influenza type H5N1 is the most virulent influenza virus, reported thus far. Currently Africa does not have the capacity to produce influenza vaccines, thus relies on the goodwill of the developed countries for vaccine stocks. Our aim is to develop a stable and cheap candidate vaccine against H5N1 for Africa by producing it in plants. Recombinant plant expression allows for the production of easy, rapid, inexpensive and infinitely scalable vaccines. We focused on producing two variants of the HA protein derived from the A/Viet/1194/ 2004 sequence: these were a full-length (H5) and truncated form (H5tr) with the membrane insertion domain removed. These variants were expressed in plants from genes that were optimised for human codon use. We also cloned the HA variant genes into a DNA vaccine vector. For plant expression, the HA genes (H5 and H5tr) were cloned into four binary plant expression vectors which target recombinant protein into the different subcellular compartments of the host plant cells. These are the cytoplasm, endoplasmic reticulum (ER), the chloroplast and the apoplast. Gene expression was tested by stable transformation of Nicotiana tabacum and transient expression in N. benthamiana via Agrobacterium tumefaciens mediated gene transfer. Western blots of plant extract indicated that both protein variants were successfully expressed in plants. These proteins were purified by diafiltration and His-tag purification via nickel-bound resin. HA protein was produced in plants in high amounts in the ER (H5tr) and apoplast (H5) compared to the other plant compartments. Haemagglutination (HA) and haemagglutination inhibition assays (HI) confirmed that the conformation of both proteins was correct. For the DNA vaccine, the H5 and H5tr genes were cloned into a mammalian expression vector pTH and both were successfully expressed in HEK293 cells as detected by western blotting. A mouse immunisation trial was conducted followed by immunological analysis. The presence of H5 specific antibodies was detected in the mouse sera by western blotting. To conclude, the HPAI H5N1 influenza HA variants (H5 and H5tr) were successfully produced in plants. Highest amounts of H5tr were produced in the ER while H5 was best expressed in the apoplast. Mice inoculated with the H5 and H5tr candidate DNA vaccines showed a positive antibody response to both vaccines. These results indicate that vaccines using HA-derived H5 and H5tr are immunologically effective and that production can be made cheaper as they are expressed successfully in plants. Keywords: Avian influenza H5N1, plant expression, DNA vaccine, Africa, The generally mild illness induced by the recent pH1N1 virus and the higher incidence of illness in people younger than 65 years suggested the possible influence of pre-existing cross-reactive immunity against the new virus in the oldest people and probably in people previously vaccinated with seasonal influenza vaccines [1,2]. This study evaluated humoral and ex vivo cellular immune responses in 12 healthy adult subjects vaccinated with the 2007/2008 MF59-adjuvanted trivalent (A/Wisconsin/67/05 (H3N2), A/Solomon Islands/3/06 (H1N1), B/Malaysia/2506/04) subunit vaccine (FLUAD, Novartis). Peripheral blood mononuclear cells (PBMCs) and serum samples, obtained before and respectively 7 and 30 days after vaccination, were frozen and successively used. Cellular responses were evaluated determining antigen-specific activation of T lymphocytes by FACS enumeration of CD69+ CD3+ or CD69+ CD8+ T lymphocytes and by measuring antigen-induced IFN-gamma release by ELISPOT. PBMCs were stimulated in vitro with the influenza vaccine antigens, the new pH1N1 virus and a haemagglutinin-(HA)-peptide317-341, corresponding to a highly conserved sequence of the HA stalk region containing the fusion peptide, a possible candidate for a universal influenza vaccine [3]. After vaccination there was an increase, in most instances significative, in the numbers of activated (CD69+) total T lymphocytes, as well as CD8+ cells and in T lymphocytes IFN-gamma production, following stimulation not only with vaccine antigens, but also with the new pH1N1 virus and with the HA-peptide317-341. Humoral responses were studied determining haemagglutination inhibiting (HI) antibody titres against the vaccine antigens and the new pH1N1 virus in 11 of the 12 volunteers. Nine (82%) volunteers seroconverted at least against one vaccine antigens, whereas only one against pH1N1. After vaccination the percentages of seroprotected (HI titre =40) people against the vaccine antigens ranged between 64 and 91%, whereas only one volunteer showed protection against pH1N1. Overall, these data raised the possibility that, although annual influenza vaccines are primarily aimed to stimulate the generation of anti-HA antibodies, which confer protection against homologous strains, they can induce also some level of cross-reactive immunity, especially cellular immunity. The finding, after 2007/2008 influenza vaccination, of induction of cellular cross-reactivity against pH1N1virus is consistent with epidemiological studies suggesting effectiveness against pandemic H1N1-associated illness deriving from seasonal vaccination [1,2] and the induction of reactivity against the highly conserved HA- peptide317-341 support the possibility of a universal influenza vaccine [3]. This research was supported by PRIN (2007CCW84J), Ministero Università Ricerca, Italy Keywords: Influenza vaccination, cellular and humoral immunity, cross-reactive responses, Since April 2009, the pandemic (H1N1) 2009 caused by a new strain of H1N1 influenza virus has spread all over the world. Massive vaccination is anticipated to have an important role for controlling the transmission. Shenzhen, located in southern China's Guangdong province, is situated immediately north of Hong Kong. Due to its geographical location and massive immigration, Shenzhen became one of the cities dispensing free H1N1 vaccines produced by a domestic company. In this study, we surveyed antibody response in serum samples obtained from children before and after the vaccination. A total of 286 children without history of a recent respiratory infection were given in a single shot in December 2009. Two serum samples were collected from every child, which were obtained at the time of the vaccination, and two weeks after the vaccination, respectively. Hemagglutination-inhibition (HI) tests were conducted to determine the antibody levels. The seropositive rate (SPR, the percentage with HI titer = 1:40 post-vaccination) to pandemic (H1N1) 2009 virus and the geometric mean titer (GMT) were calculated. Meanwhile, paired-Samples T test was used to comparatively analyze antibody response before and after the vaccination. The mean ages of the children were 11.3±2.7 years. Among 286 individuals, 71 were seropositive with a cut-off antibody titer of 1:10, and 20 presented a protecting antibody titer of at least 1:40 before the vaccination. The results indicate that some people might have contracted the H1N1 2009 infection. The SPR of antibodies to pandemic (H1N1) 2009 virus was 62.6%. There was significant difference in GMT antibodies to pandemic (H1N1) 2009 virus between serums collected before and after the vaccination (19.4 vs. 62.4, P=0.00). In this survey, the antibody level in children to pandemic (H1N1) 2009 virus rapidly rose after a single shot with the vaccine made in China. In addition to vaccination, some people were found to be seropositive after the first wave of the pandemic (H1N1) 2009. Along with the community transmission of H1N1 influenza virus and the campaign of vaccination, more and more people will present with protecting serum antibodies. Keywords: H1N1 vaccination, Antibodies, Shenzhen, The natural reservoir hosts for influenza viruses are thought to be wild waterfowl. Nevertheless transmissions to mammals occur and some lineages have become established in swine and humans. The aim of this work is to investigate mutations in influenza A viruses which are directly associated with adaptation to swine and humans, and distinguish them from mutations that are compensatory. In this study we focus on zoonotic transmissions in subtypes H1N1 - H3N2 and H5N1, and analyse complete genome sequences from the NCBI database. To gain a better understanding of the diversity and evolution of the pandemic (H1N1) 2009 precursor strains we undertook complete genome sequencing of archived European swine isolates using an Illumina platform. From over 600 archived isolates available, an initial selection of approximately 100 was made to include one isolate per subtype per country per year, prioritising H1N1 sequences from 1990 onwards. The evolutionary histories of the viral segments in the swine ‘flu lineages were investigated using time resolved phylogenetic trees (inferred using BEAST) and rates of evolution were calculated in different lineages. The detailed associations between mutations at amino acid sites and avian, swine and human host changes were inferred using Bayesian Graphical Models (BGMs). A BGM represents the direct conditional dependencies between variables as edges in a network, so distinguishes between direct and indirect interactions. To investigate the effect of host change on the appearance of mutations, and account for founder effects and shared ancestry, we use the mutational histories of the sites as variables. The mutational histories were inferred by using codon models (or host change model) fitted to phylogenetic trees. Our initial results show that mutations in the receptor binding site in Hemagglutinin are associated with host change (as expected) and also other changes in HA antigenic sites. Several sites in the polymerase complex were found to co-mutate with each other, and there were 7, 4 and 3 sites directly associated with host change in PB2, PB1 and PA respectively (including PB2-627 and PB2-701). For the NS1 protein, we found 4 sites directly related to host change including sites in SH3, RNA and CPSF30 binding domains. The results suggest that some key mutations are needed to adapt avian influenza viruses for mammalian epidemics, and that several compensatory mutations can occur to enable the virus to increase its fitness in its new environment. Keywords: Adaptation, mutations, modelling, Bayesian, swine influenza, Avian influenza viruses (AIVs) have been shown to persist for extended periods of time in water under laboratory conditions. However, estimation of viral persistence in the environment is a difficult task since viruses are mostly associated with particulate matter which has a major effect on their survival. A germ carrier technique was adapted for use with influenza viruses in moist environments. The technique was employed to measure the persistence of 3 low pathogenic AIVs (H4N6, H5N1 and H6N8), one human influenza virus (H1N1) and two model viruses (NDV and ECBO) in lake water at five different temperatures (30, 20, 10, 0 and -10 °C). Persistence of all of the viruses was highest at 0 °C. Lower T-90 values at -10 °C than 0 °C were possibly due to deleterious effect of freeze thawing on infectivity of filter bound viruses leaving the germ carrier technique inappropriate for use at freezing temperatures. Generally, influenza viruses persisted shorter than model viruses while ECBO has the highest survival time in lake water. Individual influenza viruses were inconsistent in their tenacity at all temperatures. A comparison of tenacity of influenza viruses in suspension in lake water and adsorbed to germ carriers showed that the viruses persisted longer adsorbed to germ carriers at all temperatures except –10 °C. This may be important for the actual behavior of the viruses in the environment, as virus shed in fecal and respiratory material may persist longer than free virus. These findings suggest that AIVs can remain infectious in lake water for extended periods of time at low temperatures, allowing persistence of the viruses in the aquatic habitat over winter and possibly over years., Upon the realisation of a pandemic threat in April 2009 from a newly emerged H1N1 influenza virus, a global network of laboratories began the development of candidate vaccine viruses, viruses required by the vaccine industry for efficient vaccine manufacture. By the end of May 2009 several candidates were available, well before the WHO declared a pandemic on June 11. During the ensuing months further improvements were made to these viruses in order to increase the yield of vaccine antigen that could be derived. The above activities were established and practiced well before 2009 as part of pandemic preparedness; further activities in preparedness include the ongoing development of a ‘library’ of potential pandemic vaccine viruses and research into improving the yield of viral antigen so that the maximum number of doses of vaccine can be produced in the shortest time., Highly pathogenic avian influenza viruses (HPAIV) differ from all other strains by a polybasic cleavage site in their hemagglutinin (HA) and carry an HA with serotypes H5 or H7 only. In our investigations, we studied the ability of three low-pathogenic avian strains with the subtypes H3N8, H5N1 or H9N2 to transform into HPAIV after introduction of a polybasic HA cleavage site. As HPAIV originate from LPAIV, low-pathogenic H5N1 strains have to be considered potential precursors. Furthermore, the H9N2 strains are also of particular relevance because they became wide-spread across several countries and have been transmitted to humans. In contrast to their parent viruses, all polybasic cleavage HA site mutants were able to form plaques and replicate in cell-culture in the absence of trypsin. Therefore, in-vitro they resemble an HPAIV. However in chicken, they did not display high virulence. The H3 cleavage site mutants led only to few temporary clinical symptoms in some chickens accompanied with cloacal shedding whereas the H5 and H9 cleavage site mutants caused temporary non-lethal disease in all animals inoculated. However, a reassortants, derived from LPAIV H5N1 carrying the HA gene of an HPAIV, displayed a lethality of 30% and, furthermore, a reassortant consisting of seven HPAIV genes and the LPAIV HA with engineered cleavage site, exhibited the highest lethality of 80% resembling an authentic HPAIV. Remarkably, a reassortant expressing the H9 HA with engineered polybasic cleavage site and all the other genes from an H5N1 HPAIV is also highly pathogenic in chicken and, with an intravenous pathogenicity index of 1.23, meets the definition of an HPAIV. Overall, these results demonstrate that acquisition of a polybasic HA cleavage site is only one essential step for evolution of low-pathogenic strains into HPAIV. However, the H5N1 low-pathogenic strains may already have cryptic virulence potential. Beyond the polybasic cleavage site, H5N1 HPAIV carry additional virulence determinants which are located within the HA itself and in the other viral proteins. Furthermore, the finding that an artificial H9 polybasic cleavage site mutant displays the phenotype of an HPAIV, highlights that the H5 and H7 HA have the unique ability to gain a polybasic motif at their cleavage sites., Development of influenza vaccines that induce mucosal immunity has been highlighted by the World Health Organisation as a priority. An influenza vaccine's ability to induce mucosal immunity is important as it is correlated to early protection and protection against drifted influenza strains. The intranasal influenza vaccine mimics the course of a natural influenza infection thus providing the first line of defence. An intranasal vaccine offers a good strategy for efficient mass vaccination as it can be self administered. An efficient mass vaccination regime and dose-sparing strategies will be paramount to reduce morbidity and mortality of a future H5N1 pandemic. This study has investigated the immune response and the dose sparing potential of a chitosan adjuvanted intranasal H5N1 (RG-14) subunit (SU) vaccine. Groups of mice were intranasally vaccinated with one or two doses of a chitosan (5mg/ml) adjuvanted SU vaccine (7.5, 15 or 30μg haemagglutinin (HA)) or with a non-adjuvanted SU vaccine (30μg HA). Another group of mice were intranasally vaccinated with a whole H5N1 (RG-14) virus (WV) vaccine (15μg HA). We found that chitosan (ChiSys®), which is Archimedes' Proprietary intranasal delivery system, increased the number of double producing CD4+ cells and influenza specific antibody secreting cells. Local IgA was boosted by the second vaccine dose and two doses of chitosan adjuvanted vaccine enhanced the serum IgA and IgG response. The production of serum antibodies and the haemagglutination inhibition (HI) response against both the homologous vaccine strain and two heterologous H5N1 strains were also adjuvanted by chitosan. The quality of the B and T cellular response improved with higher doses of adjuvanted vaccine and chitosan showed dose sparing potential down to 7.5μg HA. The WV vaccine elicited the highest frequencies of multifunctional T helper cells (INFγ+, IL2+, INFα+). The cross strain serum reactivity, improved B and T cell responses and dose sparing potential of chitosan shows that a chitosan adjuvanted intranasal influenza vaccine is a strong candidate vaccine to induce a strong and broad protection at lower doses also in humans. Keywords: Chitosan, dose, H5N1, influenza, intranasal, vaccine, Pathogenicity of H5 subtype influenza virus in chickens is correlated with the amino acid sequence at the cleavage site of hemagglutinin (HA) protein. It is thought that other factors are involved to viral pathogenicity in chicken as well. Understanding of genetic traits of the pathogenicity would provide a target for prevention and/or control of influenza virus infection in poultries. Aim of our study is to elucidate gene constellations that confer the pathogenicity in chickens and host gene responses against the infection. Reverse genetic engineered recombinant viruses possessing the HA and NA genes from a highly pathogenic avian influenza virus, A/chicken/Yamaguchi/7/2004 (Yam; H5N1) were generated. Three of them, designated RGY, YY and YS, had all of internal gene segments derived from Yam, A/chicken/Yokohama/aq55/2001 (Yok; H9N2) or A/whistling swan/Shimane/580/2002 (Shi; H5N3), respectively. Others contained one or two internal gene segments (X) exchanged ones from YY to YS or vice versa (S_X/YY or Y_X/YS). Survival rate and period of the group of chickens infected by reassortants were subjected to the survival analysis. Gene expression in lung collected at 24 hrs pi was investigated by the microarray analysis. Relation between survival period and gene response in lung was analyzed among group of inoculated chickens that were different significantly in the survival analysis. By the survival analysis among the group of the chickens inoculated with reassorted viruses, they were categorized into three groups with statistical significance. Mean of survival period of YY and YS was 3.87 dpi and 3.33 dpi, and survival rate was 6.67% and 0% respectively. Survival period and rate of chickens inoculated with S_PA/YY and Y_MNS/YS were statistically longer (9.25-10 dpi) and higher (50-100%) than those of YY and YS. All of the chickens inoculated with S_MNS/YY, Y_PB1/YS and RGY died earlier (2-2.25 dpi) than YY and YS. Micro array analysis revealed that expression of 483 genes out of 38681 genes examined was correlated with survival time of the chickens. Gene ontology analysis demonstrated that most of these genes were categorized in either recognition of dsRNA or response to inflammation. These results suggested different constellation of internal gene segments would affect survival period and gene expression of the infected host. Keywords: Avian influenza, HPAI, pathogenicity, reverse genetics, chicken, gene constellation, microarray analysis
- Published
- 2010
47. Remembering Hiroshima and the Lucky Dragon in ChimPom’s Level 7 feat. 'Myth of Tomorrow'
- Author
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Brown, AJ
- Abstract
In May 2011, just one month after the 3/11 triple-disaster, the Chim↑Pom artist collective conducted an unauthorised installation of a panel depicting the crippled nuclear reactors at the Fukushima Daiichi nuclear power plant next to Okamoto Tarō's large-scale mural Myth of Tomorrow in Shibuya railway station. In this paper I read the installation as a commentary on the history of nuclear power and anti-nuclear art in post-war Japan. This commentary reconnects the historical issue of nuclear weapons with contemporary debates about nuclear power.
- Published
- 2015
48. Mevalonate kinase deficiency leads to decreased prenylation of Rab GTPases
- Author
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Jurczyluk, J, Munoz, MA, Skinner, OP, Chai, RC, Ali, N, Palendira, U, Quinn, JMW, Preston, A, Tangye, SG, Brown, AJ, Argent, E, Ziegler, JB, Mehr, S, Rogers, MJ, Jurczyluk, J, Munoz, MA, Skinner, OP, Chai, RC, Ali, N, Palendira, U, Quinn, JMW, Preston, A, Tangye, SG, Brown, AJ, Argent, E, Ziegler, JB, Mehr, S, and Rogers, MJ
- Abstract
Mevalonate kinase deficiency (MKD) is caused by mutations in a key enzyme of the mevalonate-cholesterol biosynthesis pathway, leading to recurrent autoinflammatory disease characterised by enhanced release of interleukin-1β (IL-1β). It is currently believed that the inflammatory phenotype of MKD is triggered by temperature-sensitive loss of mevalonate kinase activity and reduced biosynthesis of isoprenoid lipids required for the prenylation of small GTPase proteins. However, previous studies have not clearly shown any change in protein prenylation in patient cells under normal conditions. With lymphoblast cell lines from two compound heterozygous MKD patients, we used a highly sensitive in vitro prenylation assay, together with quantitative mass spectrometry, to reveal a subtle accumulation of unprenylated Rab GTPases in cells cultured for 3 days or more at 40 °C compared with 37 °C. This included a 200% increase in unprenylated Rab7A, Rab14 and Rab1A. Inhibition of sterol regulatory element-binding protein (SREBP) activation by fatostatin led to more pronounced accumulation of unprenylated Rab proteins in MKD cells but not parent cells, suggesting that cultured MKD cells may partially overcome the loss of isoprenoid lipids by SREBP-mediated upregulation of enzymes required for isoprenoid biosynthesis. Furthermore, while inhibition of Rho/Rac/Rap prenylation promoted the release of IL-1β, specific inhibition of Rab prenylation by NE10790 had no effect in human peripheral blood mononuclear cells or human THP-1 monocytic cells. These studies demonstrate for the first time that mutations in mevalonate kinase can lead to a mild, temperature-induced defect in the prenylation of small GTPases, but that loss of prenylated Rab GTPases is not the cause of enhanced IL-1β release in MKD.
- Published
- 2016
49. The Referendum That Wasn’t: Constitutional Recognition of Local Government and the Australian Federal Reform Dilemma
- Author
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Kildea, PJ, Brown, AJ, Kildea, PJ, and Brown, AJ
- Abstract
In 2010, the Commonwealth government proposed Australia’s third attempt to give federal constitutional recognition to local government. In 2013, the government secured the passage through Parliament of a Constitution Alteration but, due to political events, and amid much controversy, the proposed amendment was not put to the people. This paper examines the merits and prospects for success of the proposed reform, with an eye to lessons for the future of local government’s place in the federal system. It argues that the legal and constitutional cases for the alteration were strong, but limited, and poorly contextualised, theorised and articulated. We use public opinion evidence to conclude that had it proceeded, the referendum result would probably have been a third failure. These lessons are important for ongoing debate over sub-constitutional and constitutional reform to Australian intergovernmental relations, including questions of federal financial redistribution at the core of the proposal. Overall, the events of 2013 reinforce arguments that reforms to the position of local government, while important, should only be pursued as part of a holistic package of federal reform and renovation; and that more robust deliberative processes and principles must be adhered to before again attempting any constitutional reform.
- Published
- 2016
50. A pilot ASKAP survey of radio transient events in the region around the intermittent pulsar PSR J1107-5907
- Author
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Hobbs, G, Heywood, I, Bell, ME, Kerr, M, Rowlinson, A, Johnston, S, Shannon, RM, Voronkov, MA, Ward, C, Banyer, J, Hancock, PJ, Murphy, T, Allison, JR, Amy, SW, Ball, L, Bannister, K, Bock, DCJ, Brodrick, D, Brothers, M, Brown, AJ, Bunton, JD, Chapman, J, Chippendale, AP, Chung, Y, DeBoer, D, Diamond, P, Edwards, PG, Ekers, R, Ferris, RH, Forsyth, R, Gough, R, Grancea, A, Gupta, N, Harvey-Smith, L, Hay, S, Hayman, DB, Hotan, AW, Hoyle, S, Humphreys, B, Indermuehle, B, Jacka, CE, Jackson, CA, Jackson, S, Jeganathan, K, Joseph, J, Kendall, R, Kiraly, D, Koribalski, B, Leach, M, Lenc, E, MacLeod, A, Mader, S, Marquarding, M, Marvil, J, McClure-Griffiths, N, McConnell, D, Mirtschin, P, Neuhold, S, Ng, A, Norris, RP, O'Sullivan, J, Pearce, S, Phillips, CJ, Popping, A, Qiao, RY, Reynolds, JE, Roberts, P, Sault, RJ, Schinckel, AET, Serra, P, Shaw, R, Shimwell, TW, Storey, M, Sweetnam, AW, Tzioumis, A, Westmeier, T, Whiting, M, Wilson, CD, Hobbs, G, Heywood, I, Bell, ME, Kerr, M, Rowlinson, A, Johnston, S, Shannon, RM, Voronkov, MA, Ward, C, Banyer, J, Hancock, PJ, Murphy, T, Allison, JR, Amy, SW, Ball, L, Bannister, K, Bock, DCJ, Brodrick, D, Brothers, M, Brown, AJ, Bunton, JD, Chapman, J, Chippendale, AP, Chung, Y, DeBoer, D, Diamond, P, Edwards, PG, Ekers, R, Ferris, RH, Forsyth, R, Gough, R, Grancea, A, Gupta, N, Harvey-Smith, L, Hay, S, Hayman, DB, Hotan, AW, Hoyle, S, Humphreys, B, Indermuehle, B, Jacka, CE, Jackson, CA, Jackson, S, Jeganathan, K, Joseph, J, Kendall, R, Kiraly, D, Koribalski, B, Leach, M, Lenc, E, MacLeod, A, Mader, S, Marquarding, M, Marvil, J, McClure-Griffiths, N, McConnell, D, Mirtschin, P, Neuhold, S, Ng, A, Norris, RP, O'Sullivan, J, Pearce, S, Phillips, CJ, Popping, A, Qiao, RY, Reynolds, JE, Roberts, P, Sault, RJ, Schinckel, AET, Serra, P, Shaw, R, Shimwell, TW, Storey, M, Sweetnam, AW, Tzioumis, A, Westmeier, T, Whiting, M, and Wilson, CD
- Abstract
© 2016 The Authors. We use observations from the Boolardy Engineering Test Array (BETA) of the Australian Square Kilometre Array Pathfinder (ASKAP) telescope to search for transient radio sources in the field around the intermittent pulsar PSR J1107-5907. The pulsar is thought to switch between an 'off' state in which no emission is detectable, a weak state and a strong state. We ran three independent transient detection pipelines on two-minute snapshot images from a 13 h BETA observation in order to (1) study the emission from the pulsar, (2) search for other transient emission from elsewhere in the image and (3) to compare the results from the different transient detection pipelines. The pulsar was easily detected as a transient source and, over the course of the observations, it switched into the strong state three times giving a typical time-scale between the strong emission states of 3.7 h. After the first switch it remained in the strong state for almost 40 min. The other strong states lasted less than 4 min. The second state change was confirmed using observations with the Parkes radio telescope. No other transient events were found and we place constraints on the surface density of such events on these time-scales. The high sensitivity Parkes observations enabled us to detect individual bright pulses during the weak state and to study the strong state over a wide observing band. We conclude by showing that future transient surveys with ASKAP will have the potential to probe the intermittent pulsar population.
- Published
- 2016
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