Body Temperature In Captive Long-Beaked Echidnas (Zaglossus Bartoni)

The routine occurrence of both short-term (daily) and long-term torpor (hibernation) in short-beaked echidnas, but not platypus, raises questions about the third monotreme genus, New Guinea's Zaglossus. We measured body temperatures (Tb) with implanted data loggers over three and a half years in two captive Zaglossus bartoni at Taronga Zoo, Sydney. The modal Tb of both long-beaks was 31 degrees C, similar to non-hibernating short-beaked echidnas, Tachyglossus aculeatus, in the wild (30-32 degrees C) and to platypus (32 degrees C), suggesting that this is characteristic of normothermic monotremes. Tb cycled daily, usually over 2-4 degrees C. There were some departures from this pattern to suggest periods of inactivity but nothing to indicate the occurrence of long-term torpor. In contrast, two short-beaked echidnas monitored concurrently in the same pen showed extended periods of low Tb in the cooler months (hibernation) and short periods of torpor at any time of the year, as they do in the wild. Whether torpor or hibernation occurs in Zaglossus in the wild or in juveniles remains unknown. However, given that the environment in this study was conducive to hibernation in short-beaks, which do not easily enter torpor in captivity, and their large size, we think that torpor in wild adult Zaglossus is unlikely

MOLLI T1 mapping versus T2 W-SPAIR at 3T : myocardial area at risk measurements and the influence of microvascular obstruction

Funding Information: This study was supported by a Medical Research Council (UK) grant, as a sub-study of Nitrites in Acute Myocardial Infarction, NCT01388504.Peer reviewe

Pathway profiling of a novel SRC inhibitor, AZD0424, in combination with MEK inhibitors

A more comprehensive understanding of how cells respond to drug intervention, the likely immediate signalling responses and how resistance may develop within different microenvironments will help inform treatment regimes. The nonreceptor tyrosine kinase SRC regulates many cellular signalling processes, and pharmacological inhibition has long been a target of cancer drug discovery projects. Here, we describe the in vitro and in vivo characterisation of the small‐molecule SRC inhibitor AZD0424. We show that AZD0424 potently inhibits the phosphorylation of tyrosine‐419 of SRC (IC50 ~ 100 nm) in many cancer cell lines; however, inhibition of cell viability, via a G1 cell cycle arrest, was observed only in a subset of cancer cell lines in the low (on target) micromolar range. We profiled the changes in intracellular pathway signalling in cancer cells following exposure to AZD0424 and other targeted therapies using reverse‐phase protein array (RPPA) analysis. We demonstrate that SRC is activated in response to treatment of KRAS‐mutant colorectal cell lines with MEK inhibitors (trametinib or AZD6244) and that AZD0424 abrogates this. Cell lines treated with trametinib or AZD6244 in combination with AZD0424 had reduced EGFR, FAK and SRC compensatory activation, and cell viability was synergistically inhibited. In vivo, trametinib treatment of mice‐bearing HCT116 tumours increased phosphorylation of SRC on Tyr419, and, when combined with AZD0424, inhibition of tumour growth was greater than with trametinib alone. We also demonstrate that drug‐induced resistance to trametinib is not re‐sensitised by AZD0424 treatment in vitro, likely as a result of multiple compensatory signalling mechanisms; however, inhibition of SRC remains an effective way to block invasion of trametinib‐resistant tumour cells. These data imply that SRC inhibition may offer a useful addition to MEK inhibitor combination strategies

Reframing assessment research: through a practice perspective

Assessment as a field of investigation has been influenced by a limited number of perspectives. These have focused assessment research in particular ways that have emphasised measurement, or student learning or institutional policies. The aim of this paper is to view the phenomenon of assessment from a practice perspective drawing upon ideas from practice theory. Such a view places assessment practices as central. This perspective is illustrated using data from an empirical study of assessment decision-making and uses as an exemplar the identified practice of ‘bringing a new assessment task into being’. It is suggested that a practice perspective can position assessment as integral to curriculum practices and end separations of assessment from teaching and learning. It enables research on assessment to de-centre measurement and take account of the wider range of people, phenomena and things that constitute it

Exile Vol. XXXV No. 2

Peter Goes Groovy, by Carolyn Bern (cover) I Hate Poetry by Craig Bagno 1 Truancy by Richard Latimer 2 I ate a Star Last Night by Rory Herbster 3 Delivery by Amy Judge 4 Untitled by Sue McLain 5 Road Signs by Richard Latimer 7-8 Haiku for Me to Possess by Shannon J. Salser 9 Patches by Michael Payne 10 Untitled by Laura Johnson 11 He by Kent Lambert 13 At the Corner Grill by Lynn Pendleton 14-15 Black Licorice by Richard Latimer 16-17 Blue Shirt by Michael Payne 18 ...Loves a Clown by Margaret Dawson 21-24 The Surreal Sonnet by Shannon J. Salser 26 Untitled by Mat Benson 27 Swimming Lessons by Richard Latimer 29 Communion by Amy Judge 30 Beth\u27s Last Funny Joke by Ted Gould 31-35 Hope for a Peaceful Coming Around by Shannon J. Salser 36 Untitled by Laura Johnson 37 A Child\u27s Moment by Peter Witonsky 39 Observation by Rosemary Walsh 40 Untitled by Carolyn Burns 41 To My Sister by Amy B. Judge 43 Ideas In Bloom by Randy Casden 44 Untitled by Deb Tily 45 A Child of Mind by Charles Riedinger 47 Ars Poetica by Rory Herbster 48 Untitled by Mat Benson 49 REPRINTS Dancer by Bradford Cover 52 Skin Deep by Eric Whitney 53-55 Sunset by Chris Rynd 56 Editorial decision is shared equally among the Editorial Board Members -cover page The editors of Exile would like to formally apologize to those contributors whose works were misprinted in the Fall issue. We have reprinted a few of the pieces that contained the most errors. -51 NOTE: An uncredited and untitled piece of artwork appears on page 19. NOTE: Carolyn Bern (cover) Burns (41) and Berns (contributor notes) all appear to refer to the same artist

Exile Vol. XXXV No. 1

ARTWORK Untitled by Eric Whitney (cover) Untitled by Rory Herbster 7 Little Boy by Eric Whitney 45 FICTION Through the Window Pane by Jennifer Read 4 to whom i may concern by Chris Campi 19 For Lack of Sleep by Amy Judge 26 Jonathan by Jim Cox 39 Skin Deep by Eric Whitney 51 NON-FICTION A Theopoetic by Robert Marshall 11 POETRY Clay Pot by Christopher Collette 1 Ars Poetica by Mans Agantyr 2 Bible Thumber by Chris Rynd 6 Play by Amy Judge 9 Satellites by Andrew C. Carinston 10 Music - Love? by Shammon J. Salser 15 Allusion by Rosemary Walsh 17 Self Portrait by Margaret Dawson 18 On Our Way by Lynn Pendleton 21 They called her Mitzi... by Jen Miller 22 Storms of Illusion by Kevin Merriman 23 Beauty by Andrew C. Carington 24 Thoughts of a Husband by Kent Lambert 25 The Music of the Sum by Zach Smith 31 Don\u27t Think by Mary Forsythe 32 Aspiration by Tim Emrick 33 Where We Go Together by Man Angantyr 35 Sunset by Chris Byrd 36 The Child of my Fatalism by Jennifer Peterson 37 Untitled by Kent Lambert 38 Terribly close to being... by Michael Payne 44 Anne Frank\u27s House by Mary Forsythe 47 Invitation by Kevin Merriman 48 Height Protest by Jen Miller 49 Dancer by Bradford Cover 50 Ars Poetica by Amy Judge 55 Editorial decision is shared equally among the Editorial Board members -title page NOTE: The author of the poem Satellites is listed as Andrew C. Carinston in the published table of contents. This is likely a misspelling as there are four instances of an Andrew C. Carington elsewhere in this edition, including the attribution on the page where Satellites is published. NOTE: The author of the poem Where We Go Together is listed as Man Angantyr in the published table of contents. This is likely a misspelling as there are four instances of an Mans Angantyr elsewhere in this edition, including the attribution on the pages where Where We Go Together is published. NOTE: Chris Byrd is listed as the author of the poem Sunset in the published version. However a note in the received version indicates that the author is actually Chris Rynd, whose poem Bible Thumper is also published in this issue. No Chris Byrd is listed among the contributors to this issue. NOTE: The author of the poem Music = Love? is listed as Shammon J. Salser in the published table of contents. This is likely a misspelling. Where Music = Love? appears the author is listed as Shannon J. Salser. The same is true of the contributors section. NOTE: Though the published table of contents is followed here, the poem by Zach Smith that is published on page 31 is listed as The Music of the Sun on page 31

A Conformation Selective Mode of Inhibiting SRC Improves Drug Efficacy and Tolerability

43 p.-5 fig.Despite the approval of several multikinase inhibitors that target SRC and the overwhelming evidence of the role of SRC in the progression and resistance mechanisms of many solid malignancies, inhibition of its kinase activity has thus far failed to improve patient outcomes. Here we report the small molecule eCF506 locks SRC in its native inactive conformation, thereby inhibiting both enzymatic and scaffolding functions that prevent phosphorylation and complex formation with its partner FAK. This unprecedented mechanism of action resulted in highly potent and selective pathway inhibition, in culture and in vivo. Treatment with eCF506 resulted in increased antitumor efficacy and tolerability in syngeneic murine cancer models, demonstrating significant therapeutic advantages over existing SRC/ABL inhibitors. Therefore, this novel mode of inhibiting SRC could lead to improved treatment of SRC-associated disorders.C.T. thanks the CMVM of the University of Edinburgh (Principal's scholarship). D.L. acknowledges support from the Spanish Ministry of Science, Innovation and Universities for the Spanish State Research Agency Retos Grant RTI2018-099318-B-I00, cofunded by the European Regional Development Fund (FEDER). E.R.W., J.C.D. and K.G.M. are funded by CRUK. J.R.L.O. acknowledges support from the Molecular Interactions Facility funds at the CIB-CSIC. T.V. is funded by H2020-MSCA-IF-2016-749299. RCM thanks the support from the Vice Rectorate for Research of the University of Granada. X.-F.L. and B.-Z.Q. are funded by a CRUK Career Development Fellowship (C49791/A17367). B.-Z.Q. also acknowledges support from an ERC Starting Grant (716379). C.S, M.C.F. and V.G.B are funded by CRUK Programme Grant C157/A15703. N.O.C. and A.U.B are grateful to the CMVM of the University of Edinburgh and Wellcome Trust for financial support (ISSF3).Peer reviewe

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research

Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community