91 research outputs found

    Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth.

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    Glucose utilization increases in tumors, a metabolic process that is observed clinically by <sup>18</sup> F-fluorodeoxyglucose positron emission tomography ( <sup>18</sup> F-FDG-PET). However, is increased glucose uptake important for tumor cells, and which transporters are implicated in vivo? In a genetically-engineered mouse model of lung adenocarcinoma, we show that the deletion of only one highly expressed glucose transporter, Glut1 or Glut3, in cancer cells does not impair tumor growth, whereas their combined loss diminishes tumor development. <sup>18</sup> F-FDG-PET analyses of tumors demonstrate that Glut1 and Glut3 loss decreases glucose uptake, which is mainly dependent on Glut1. Using <sup>13</sup> C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we also report the presence of lamellar body-like organelles in tumor cells accumulating glucose-derived biomass, depending partially on Glut1. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma, the dual blockade of which could reach therapeutic responses not achieved by individual targeting

    Pharmacological Emergency management of Agitation in Children and Young people: protocol for a randomised controlled trial of intraMuscular medication (PEAChY-M)

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    Introduction: Acute severe behavioural disturbance (ASBD) is a condition seen with increasing frequency in emergency departments (EDs) in adults and young people. Despite the increasing number of presentations and significant associated risks to patients, families and caregivers, there is limited evidence to guide the most effective pharmacological management in children and adolescents. The aim of this study is to determine whether a single dose of intramuscular olanzapine is more effective than intramuscular droperidol at successfully sedating young people with ASBD requiring intramuscular sedation. Methods and analysis: This study is a multicentre, open-label, superiority randomised controlled trial. Young people aged between 9 and 17 years and 364 days presenting to an ED with ASBD who are deemed to require medication for behavioural containment will be recruited to the study. Participants will be randomised in a 1:1 allocation between a single weight-based dose of intramuscular olanzapine and intramuscular droperidol. The primary outcome is the proportion of participants who achieve successful sedation at 1-hour post randomisation without the need for additional sedation. Secondary outcomes will include assessing for adverse events, additional medications provided in the ED, further episodes of ASBD, length of stay in the ED and hospital and satisfaction with management. Effectiveness will be determined using an intention-to-treat analysis, with medication efficacy determined as part of the secondary outcomes using a per-protocol analysis. The primary outcome of successful sedation at 1 hour will be presented as a percentage within each treatment group, with comparisons presented as a risk difference with its 95% CIs. Ethics and dissemination: Ethics approval was received from the Royal Children’s Hospital Human Research Ethics Committee (HREC/69948/RCHM-2021). This incorporated a waiver of informed consent for the study. The findings will be disseminated in a peer-reviewed journal and at academic conferences. Trial registration number: ACTRN12621001238864.Elyssia M Bourke, Meredith L Borland, Amit Kochar, Shane George, Deborah Shellshear, Shefali Jani, Kent Perkins, Doris Tham, Michael Solomon Gordon, Kate Klein, Chidambaram Prakash, Katherine Lee, Andrew Davidson, Jonathan C Knott, Simon Craig, Franz E Babl, On behalf of the Paediatric research in Emergency Departments International Collaborative (PREDICT

    Enhancing Visualization Skills-Improving Options aNd Success (EnViSIONS) of Engineering and Technology Students

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    Spatial visualization skills are vital to many careers and in particular to STEM fields. Materials have been developed at Michigan Technological University and Penn State Erie, The Behrend College to assess and develop spatial skills.  The EnViSIONS (Enhancing Visualization Skills-Improving Options aNd Success) project is combining these materials and testing them with pre-college and college students at  seven institutions: Michigan Tech, Penn State Behrend, Purdue University, University of Iowa, Virginia State University, Virginia Tech, and a “Project Lead the Way” course in south-central Arizona.  By removing a barrier to success for students with low visualization skills, particularly women, the project leaders hope to improve the retention of these students in STEM disciplines and to enhance their success. This paper will give a brief overview of the implementations at the university level and the findings

    Overview of the JET results in support to ITER

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    Nafion-MPMDMS nanocomposite membranes with low methanol permeability

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    In this work Nation nancomposite membranes have been synthesised using a directed sol-gel synthesis technique with (3-mercaptopropyl) methyldimethoxysilane as the silicon alkoxide precursor. The resulting membranes with 16.7 wt% inorganic content showed a 89% reduction in methanol permeability compared to Nafion 117 at 50 degrees C. Small angle X-ray scattering data profiles for the nanocomposite membranes were distinctly different to those of unmodified Nafion 117 and showed a distinct upturn at low q. The slope of the curves was approximately -3.5 over the range 0.01 < q < 0.015, suggesting the presence of scattering objects with a mass fractal structure in the range 40-60 nm. Such objects were directly observed by transmission electron microscopy, and indicate an interpenetrated network of inorganic agglomerates and the host Nafion polymer, which significantly decreases the methanol permeability. The membranes may be suitable candidates for use in direct methanol fuel cells. (c) 2006 Elsevier B.V. All rights reserved

    Physical and electrochemical characterization of nanocomposite membranes of Nafion and functionalized silicon oxide

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    Nafion nanocomposite membranes were prepared from Nafion 117 and a systematic range of organically functionalized silicon alkoxide precursors using an in situ sol gel synthesis technique. The physical structure of the resulting nanocomposite membranes were characterized using small and wide-angle X-ray scattering, small angle neutron scattering, positron annihilation lifetime spectroscopy, and transmission electron microscopy. A structural model is proposed for three typical nanocomposite membranes (Nafion-TEOS, Nafion-MPTMS and Nafion-MPMDMS). The proton and methanol transport properties of the membranes included in the model were evaluated by impedance spectroscopy and pervaporation experiments, respectively, and correlated to their composite microstructure. In particular, this model explains the increased selectivity for transport over protons for nanocomposite membranes produced using (3-mercaptopropyl)methyldimethoxysilane as the silicon alkoxide precursor, which is more than six times higher than that of Nafion 117
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