Chancellery Research - Research Publications

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    Simulated in vivo Electrophysiology Experiments Provide Previously Inaccessible Insights into Visual Physiology.
    Quiroga, M ; Price, NSC ( 2016)
    Lecture content and practical laboratory classes are ideally complementary. However, the types of experiments that have led to our detailed understanding of sensory neuroscience are often not amenable to classroom experimentation as they require expensive equipment, time-consuming surgeries, specialized experimental techniques, and the use of animals. While sometimes feasible in small group teaching, these experiments are not suitable for large cohorts of students. Previous attempts to expose students to sensory neuroscience experiments include: the use of electrophysiology preparations in invertebrates, data-driven simulations that do not replicate the experience of conducting an experiment, or simply observing an experiment in a research laboratory. We developed an online simulation of a visual neuroscience experiment in which extracellular recordings are made from a motion sensitive neuron. Students have control over stimulation parameters (direction and contrast) and can see and hear the action potential responses to stimuli as they are presented. The simulation provides an intuitive way for students to gain insight into neurophysiology, including experimental design, data collection and data analysis. Our simulation allows large cohorts of students to cost-effectively "experience" the results of animal research without ethical concerns, to be exposed to realistic data variability, and to develop their understanding of how sensory neuroscience experiments are conducted.
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    DIALOGUE / COLLABORATION
    Andrew, B ; Walter, T ; Maidment, S ; Ryan, J (National Gallery of Victoria, 2017)
    The text focusses on key moments in Brook Andrew’s 25-year career, and looking at the artist’s fascination with archival materials and strong interest in process that remain central to his practice. A point of focus is Andrew’s interdisciplinary and collaborative approach which encompasses mediums of photography, video, neon, text, collage, printmaking, assemblage, sculpture, painting and installation.
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    'Knowing Whether' in Proper Epistemic Knowledge Bases
    Miller, T ; Felli, P ; Muise, C ; Pearce, AR ; Sonenberg, L (AAAI Press, 2016)
    Proper epistemic knowledge bases (PEKBs) are syntactic knowledge bases that use multi-agent epistemic logic to represent nested multi-agent knowledge and belief. PEKBs have certain syntactic restrictions that lead to desirable computational properties; primarily, a PEKB is a conjunction of modal literals, and therefore contains no disjunction. Sound entailment can be checked in polynomial time, and is complete for a large set of arbitrary formulae in logics Kn and KDn. In this paper, we extend PEKBs to deal with a restricted form of disjunction: 'knowing whether.' An agent i knows whether Q iff agent i knows Q or knows not Q; that is, []Q or []not(Q). In our experience, the ability to represent that an agent knows whether something holds is useful in many multi-agent domains. We represent knowing whether with a modal operator, and present sound polynomial-time entailment algorithms on PEKBs with the knowing whether operator in Kn and KDn, but which are complete for a smaller class of queries than standard PEKBs.
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    Planning for a Single Agent in a Multi-Agent Environment Using FOND
    Muise, C ; Felli, P ; Miller, T ; Pearce, AR ; Sonenberg, L ; Kambhampati, S (AAAI Press, 2016)
    Single-agent planning in a multi-agent environment is challenging because the actions of other agents can affect our ability to achieve a goal. From a given agent's perspective, actions of others can be viewed as non-deterministic outcomes of that agent's actions. While simple conceptually, this interpretation of planning in a multi-agent environment as non-deterministic planning remains challenging, not only due to the non-determinism resulting from others' actions, but because it is not clear how to compactly model the possible actions of others in the environment. In this paper, we cast the problem of planning in a multiagent environment as one of Fully-Observable Non-Deterministic (FOND) planning. We extend a non-deterministic planner to plan in a multi-agent setting, allowing non-deterministic planning technology to solve a new class of planning problems. To improve the efficiency in domains too large for solving optimally, we propose a technique to use the goals and possible actions of other agents to focus the search on a set of plausible actions. We evaluate our approach on existing and new multiagent benchmarks, demonstrating that modelling the other agents' goals improves the quality of the resulting solutions.
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    Social planning for social HRI
    Sonenberg, E ; Miller, T ; Pearce, AR ; Felli, P ; Muise, CJ ; Dignum, F ; Baxter, P ; Trafton, G ; Lemaignan, S (arxiv, 2016)
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    Detection of Toscana virus from an adult traveler returning to Australia with encephalitis.
    Arden, KE ; Heney, C ; Shaban, B ; Nimmo, GR ; Nissen, MD ; Sloots, TP ; Mackay, IM (Wiley, 2017-10)
    Toscana virus (TOSV) is identified in sandflies, animals, and humans around the Mediterranean Sea. TOSV has not been reported in Australia. During investigations of cerebrospinal fluid samples from patients with encephalitis, TOSV genetic sequences were identified in a traveler returning to Australia from Europe. TOSV should be considered, especially during May to October, in travelers to Australia who embarked in countries in and around the Mediterranean Sea and who subsequently present for medical care because of neurological symptoms.
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    Scriptaid enhances skeletal muscle insulin action and cardiac function in obese mice
    Gaur, V ; Connor, T ; Venardos, K ; Henstridge, DC ; Martin, SD ; Swinton, C ; Morrison, S ; Aston-Mourney, K ; Gehrig, SM ; van Ewijk, R ; Lynch, GS ; Febbraio, MA ; Steinberg, GR ; Hargreaves, M ; Walder, KR ; McGee, SL (WILEY, 2017-07)
    AIM: To determine the effect of Scriptaid, a compound that can replicate aspects of the exercise adaptive response through disruption of the class IIa histone deacetylase (HDAC) corepressor complex, on muscle insulin action in obesity. MATERIALS AND METHODS: Diet-induced obese mice were administered Scriptaid (1 mg/kg) via daily intraperitoneal injection for 4 weeks. Whole-body and skeletal muscle metabolic phenotyping of mice was performed, in addition to echocardiography, to assess cardiac morphology and function. RESULTS: Scriptaid treatment had no effect on body weight or composition, but did increase energy expenditure, supported by increased lipid oxidation, while food intake was also increased. Scriptaid enhanced the expression of oxidative genes and proteins, increased fatty acid oxidation and reduced triglycerides and diacylglycerides in skeletal muscle. Furthermore, ex vivo insulin-stimulated glucose uptake by skeletal muscle was enhanced. Surprisingly, heart weight was reduced in Scriptaid-treated mice and was associated with enhanced expression of genes involved in oxidative metabolism in the heart. Scriptaid also improved indices of both diastolic and systolic cardiac function. CONCLUSION: These data show that pharmacological targeting of the class IIa HDAC corepressor complex with Scriptaid could be used to enhance muscle insulin action and cardiac function in obesity.
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    Topography of Claustrum and Insula Projections to Medial Prefrontal and Anterior Cingulate Cortices of the common marmoset (Callithrix jacchus)
    Reser, DH ; Majka, P ; Snell, S ; Chan, JMH ; Watkins, K ; Worthy, K ; Quiroga, MDM ; Rosa, MGP (WILEY, 2017-04)
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    Pro-inflammatory self-reactive T cells are found within murine TCR-αβ+CD4-CD8-PD-1+ cells
    Rodriguez-Rodriguez, N ; Apostolidis, SA ; Fitzgerald, L ; Meehan, BS ; Corbett, AJ ; Martin-Villa, JM ; McCluskey, J ; Tsokos, GC ; Crispin, JC (WILEY-BLACKWELL, 2016-06)
    TCR-αβ(+) double negative (DN) T cells (CD3(+) TCR-αβ(+) CD4(-) CD8(-) NK1.1(-) CD49b(-) ) represent a minor heterogeneous population in healthy humans and mice. These cells have been ascribed pro-inflammatory and regulatory capacities and are known to expand during the course of several autoimmune diseases. Importantly, previous studies have shown that self-reactive CD8(+) T cells become DN after activation by self-antigens, suggesting that self-reactive T cells may exist within the DN T-cell population. Here, we demonstrate that programmed cell death 1 (PD-1) expression in unmanipulated mice identifies a subset of DN T cells with expression of activation-associated markers and a phenotype that strongly suggests they are derived from self-reactive CD8(+) cells. We also found that, within DN T cells, the PD-1(+) subset generates the majority of pro-inflammatory cytokines. Finally, using a TCR-activation reporter mouse (Nur77-GFP), we confirmed that in the steady-state PD-1(+) DN T cells engage endogenous antigens in healthy mice. In conclusion, we provide evidence that indicates that the PD-1(+) fraction of DN T cells represents self-reactive cells.
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    Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells
    Keller, AN ; Eckle, SBG ; Xu, W ; Liu, L ; Hughes, VA ; Mak, JYW ; Meehan, BS ; Pediongco, T ; Birkinshaw, RW ; Chen, Z ; Wang, H ; D'Souza, C ; Kjer-Nielsen, L ; Gherardin, NA ; Godfrey, DI ; Kostenko, L ; Corbett, AJ ; Purcell, AW ; Fairlie, DP ; McCluskey, J ; Rossjohn, J (NATURE PUBLISHING GROUP, 2017-04)
    The major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists. Crystal structures of a T cell antigen receptor (TCR) from a MAIT cell in complex with MR1 bound to the non-stimulatory and stimulatory compounds showed distinct ligand orientations and contacts within MR1, which highlighted the versatility of the MR1 binding pocket. The findings demonstrated that MR1 was able to capture chemically diverse structures, spanning mono- and bicyclic compounds, that either inhibited or activated MAIT cells. This indicated that drugs and drug-like molecules can modulate MAIT cell function in mammals.