906 research outputs found

    MacuSIM: an in-vitro model of the outer retina as an experimental platform for macular disease and therapeutic trials

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    Purpose : the lack of an anatomical macula in widely utilised animal models led us to design an in-vitro system of the macula in a dish (MacuSIM). When fully developed, this will include salient elements of the outer retina including the RPE monolayer, Bruch’s membrane and a vascular network with features of the choriocapillaris. Similarly, it incorporates a central avascular region to mimic physiological tension in macula RPE cells to model elements of cellular stress. Here, we test the hypothesis that MacuSIM recapitulates some key characteristics of the human macula and presents an improved platform for studying disease pathways linked with age-related macular degeneration (AMD).Methods : computer aided design was used to optimise models for manufacture using FDM 3D printing (PLA) and CNC machining (polycarbonate). CES EduPack evaluated fabrication substrate durability and biocompatibility in combination with LDH assays. Microvascular elements were produced by high-precision laser machining 2D 5-140μm channel networks into glass coverslips or CNC milling of PC, with surface finish and cell growth visualised by SEM. The co-culture/morphology of ARPE-19 transwells and HUVECs within channels was assessed by microCT and CD31, VWF, CD62E, VEGFR2, ZO-1, RPE-65 and Na+/K+ATPase immunofluorescence compared to control monocultures.Results : MacuSIM was manufactured to the design in Figure 1, with PC and PLA identified as optimal substrates. These displayed normal cell growth, low LDH activity and cytotoxicity with HUVEC (p=0.89, 3.7%) and ARPE-19 (p=0.01, 7.4%). Similarly, ZO1 and CD31/VWF expression remained unaffected (p=0.17, p=0.8, p=0.22). SEM of precision-etched microvascular channels confirmed cell growth and morphology along with staining for endothelial markers. Assessment of co-cultures by microCT demonstrated the seamless juxtaposition of all elements within the in-vitro model.Conclusions : using precision engineering techniques we developed an accessible in-vitro model that mimics features of macular physiology. Our approach enables reproducibility, standardised scalability and the set-up of identical systems elsewhere, which are amenable to studies and exploitation by the pharmaceuticals sector. This may be an attractive alternative to rodent models and could accelerate trials through rapid screening of anti-AMD compounds

    “If I were a community leader”: knowing the world by changing it

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    Education Queensland teachers Gael Wilson and Tracey Herslet, and the principal of Waterford West State School, Di Carter, were proud as they watched the screening of their year five students’ movies at the national Building Child Friendly Communities Conference, held in Logan, Queensland in November 2011

    Father‘s first car

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    Episodes 1-3 of 'Father‘s first car' by Hugh Tracey, read by the author from the book published by Routledge & Kegan PaulThe book is based on extracts from the motoring diary of Hugh Tracey's father, Dr Eugene Tracey, who owned the first motor car in their village of Willand near Cullompton, Devon, in 1907For further details refer to the ILAM Document Collection: Hugh Tracey Broadcast

    JobPlan --- a new integrated representation and planner for batch job workflow automation

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    This dissertation presents a new representation and action logic for integrated planning, scheduling, execution monitoring and sensing. These features were motivated by the problem of computer batch job management but are applicable to any domain entailing these forms of reasoning. The existing planning literature has primarily focussed on providing highly efficient representations and algorithms which address specific aspects of planning and sensing. However no single planning framework currently combines the requisite integrated abilities of managing durative triggered actions in an open world environment. The dissertation's contributions are a multi-purpose planning and sensing representation and an associated partial order action logic to support these features. Plans and beliefs are represented as a workflow state machine governed by a clearly defined dynamics. Time based goals are handled by treating time as a fluent. The implementation and evaluation of a prototype planner ``JobPlan" on key domain scenarios illustrating these features is presented.Ph.D.Includes bibliographical referencesIncludes vitaby Tracey D. Lal

    Academic Integrity: A Global Community of Scholars

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    Slides from a keynote presentation at Canadian Symposium on Academic Integrity, held at the University of Calgary, April 17-18, 2019. In this session, Dr. Tracey Bretag examined how academic integrity research, policy and advocacy work is undertaken around the world, discussion the implications for Canadian educational contexts. These slides have been submitted by Sarah Elaine Eaton, Co-Chair of the symposium, with the permission of the author, Dr. Tracey Bretag

    Academic Integrity and Embracing Diversity

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    Slides from the Pre-conference for the Canadian Symposium on Academic Integrity, held at the University of Calgary, April 17-18, 2019. In this session, Dr. Tracey Bretag examined the issue of academic integrity and diversity, focusing specifically on international students and those who speak languages other than English (LOTE). These slides have been submitted by Sarah Elaine Eaton, Co-Chair of the symposium, with the permission of the author, Dr. Tracey Bretag

    Anthropologists witnessing and reshaping the neoliberal academy

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    This Forum continues the discussions opened up in a previous Anuac Forum (vol. 5, n. 1, June 2016) about the changing nature of higher education under neoliberalism and its implications for the future of anthropology. We hope that these additional commentaries and exchanges will inspire university students, scholars and staff to move together towards a transnational coalition in favour of new visions of the university. The Forum features contributions by Virginia R. Dominguez, Sam Beck, Carl A. Maida, Martin A. Mills, Berardino Palumbo, Alan Smart, Ger Duijzings, Alexis M. Jordan & Shaheen M. Christie, Boone W. Shear, Alexander Koensler & Cristina Papa, and the Reclaiming Our University Movement

    Review of \u3ci\u3eGuerrilla Gardening: A Manualfesto\u3c/i\u3e, by David Tracey

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    [First paragraph] David Tracey, author of Guerrilla Gardening: A Manualfesto, summarizes the philosophy of guerrilla gardening in a simple statement: Every plant is political (32)

    An upper bound on the Chebotarev invariant of a finite group

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    A subset {g1,.., gd} of a finite group G invariably generates {g1x1,..,gdxd} generates G for every choice of xi ∈ G. The Chebotarev invariant C(G) of G is the expected value of the random variable n that is minimal subject to the requirement that n randomly chosen elements of G invariably generate G. The first author recently showed that C(G)≤β|G| for some absolute constant β. In this paper we show that, when G is soluble, then β is at most 5/3. We also show that this is best possible. Furthermore, we show that, in general, for each ε > 0 there exists a constant cε such that C(G)≤(1+∈)|G|+c

    Brain-Derived Neurotrophic Factor-Induced Gene Expression Reveals Novel Actions of VGF in Hippocampal Synaptic Plasticity

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    Synaptic strengthening induced by brain-derived neurotrophic factor (BDNF) is associated with learning and is coupled to transcriptional activation. However, identification of the spectrum of genes associated with BDNF-induced synaptic plasticity and the correlation of expression with learning paradigms in vivo has not yet been studied. Transcriptional analysis of BDNF-induced synaptic strengthening in cultured hippocampal neurons revealed increased expression of the immediate early genes (IEGs), c-fos, early growth response gene 1 (EGR1), activity-regulated cytoskeletal-associated protein (Arc) at 20 min, and the secreted peptide VGF (non-acronymic) protein precursor at 3 hr. The induced genes served as prototypes to decipher mechanisms of both BDNF-induced transcription and plasticity. BDNF-mediated gene expression was tyrosine kinase B and mitogen-activated protein kinase-dependent, as demonstrated by pharmacological studies. Single-cell transcriptional analysis of Arc after whole-cell patch-clamp recordings indicated that increased gene expression correlated with enhancement of synaptic transmission by BDNF. Increased expression in vitro predicted elevations in vivo: VGF and the IEGs increased after trace eyeblink conditioning, a hippocampal-dependent learning paradigm. VGF protein was also upregulated by BDNF treatment and was expressed in a punctate manner in dissociated hippocampal neurons. Collectively, these findings suggested that the VGF neuropeptides may regulate synaptic function. We found a novel function for VGF by applying VGF peptides to neurons. C-terminal VGF peptides acutely increased synaptic charge in a dose-dependent manner, whereas N-terminal peptide had no effect. These observations indicate that gene profiling in vitro can reveal new mechanisms of synaptic strengthening associated with learning and memory.Peer reviewe
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