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    Radiation effects on microstructure and hardness of a titanium aluminide alloy irradiated by helium ions at room and elevated temperatures

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    A 45XD TiAl alloy possessing a lamellar microstructure was irradiated using 5MeV helium ions to a fluence of 5×1021ionm−2 (5000appm) with a dose of about 1dpa (displacements per atom). A uniform helium ion stopping damage region about 17μm deep from the target surface was achieved by applying an energy degrading wheel. Radiation damage defects including helium-vacancy clusters and small helium bubbles were found in the microstructure of the samples irradiated at room temperature. With increasing irradiation temperature to 300°C and 500°C helium bubbles were clearly observed in both the α2 and γ phases of the irradiated microstructure. By means of nanoindentation significant irradiation hardening was measured. For the samples irradiated at room temperature the hardness increased from 5.6GPa to 8.5GPa and the irradiation-hardening effect reduced to approximately 8.0GPa for the samples irradiated at 300°C and 500°C. © 2015 Elsevier B.V

    Alternative approaches for PET radiotracer development in Alzheimer's disease: imaging beyond plaque

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    Alzheimer's disease (AD) and related dementias show increasing clinical prevalence, yet our understanding of the etiology and pathobiology of disease-related neurodegeneration remains limited. In this regard, noninvasive imaging with radiotracers for positron emission tomography (PET) presents a unique tool for quantifying spatial and temporal changes in characteristic biological markers of brain disease and for assessing potential drug efficacy. PET radiotracers targeting different protein markers are being developed to address questions pertaining to the molecular and/or genetic heterogeneity of AD and related dementias. For example, radiotracers including [11C]-PiB and [18F]-AV-45 (Florbetapir) are being used to measure the density of Aβ-plaques in AD patients and to interrogate the biological mechanisms of disease initiation and progression. Our focus is on the development of novel PET imaging agents, targeting proteins beyond Aβ-plaques, which can be used to investigate the broader mechanism of AD pathogenesis. Here, we present the chemical basis of various radiotracers which show promise in preclinical or clinical studies for use in evaluating the phenotypic or biochemical characteristics of AD. Radiotracers for PET imaging neuroinflammation, metal ion association with Aβ-plaques, tau protein, cholinergic and cannabinoid receptors, and enzymes including glycogen-synthase kinase-3β and monoamine oxidase B amongst others, and their connection to AD are highlighted. Copyright © 2013 John Wiley & Sons, Ltd

    Using X-ray tomography, PALS and Raman spectroscopy for characterization of inhibitors in epoxy coatings

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    Model paint materials were generated by adding a range of inorganic materials into an epoxy. The inorganic materials included inhibitors (Zn3(PO4)2 and SrCrO4) and a filler (rutile TiO2).The SrCrO4 system was characterized using SEM, TEM, PALS and Raman spectroscopy and found to have an even distribution of inhibitor in the polymer matrix. X-ray tomography was performed on the mixed SrCrO4/TiO2 and Zn3(PO4)2/TiO2 systems. A new technique called data constrained modelling was combined with the tomographic technique to produce a 3D distribution of the inorganic phases within the polymer matrix. © 2011 Elsevier B.V

    Prenatal poly I:C age-dependently alters cannabinoid type 1 receptors in offspring: a longitudinal small animal PET study using [18F]MK-9470

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    Evidence suggests that there is a link between the endocannabinoid system (ECS) and neuropsychiatric illnesses, including schizophrenia. Whilst the ECS has been shown to be involved in immune system regulation in various ways, it is known that infections during pregnancy can modulate the immune system of the mother and increase the risk for schizophrenia in offspring. In animal studies, maternal immune activation following administration of viral or bacterial mimics has been shown to reproduce many key structural, behavioural, and pharmacological abnormalities in offspring that resemble schizophrenia. In the present study, we used Positron Emission Tomography (PET) and [18F]MK-9470, a selective high-affinity inverse agonist radioligand for cannabinoid type 1 receptors (CB1R), to longitudinally assess CB1R expression in the progeny of female rats exposed to the viral mimic polyriboinosinic–polyribocytidilic acid (poly I:C) (4 mg/kg i.v.) or vehicle at gestational day 15 (GD 15). PET scans were performed in offspring at postnatal days (PND) 32–42 (adolescence) and in the same animals again at PNDs 75–79 (adulthood). Sixteen regions of interest were assessed, encompassing the whole rat brain. At adolescence, offspring exposed prenatally to poly I:C had significantly lower CB1R relative Standard Uptake Values (rSUV) compared to controls in the globus pallidus (p = 0.046). In adulthood, however, poly I:C exposed offspring had higher levels of CB1R rSUV in sensory cortex (p = 0.034) and hypothalamus (p = 0.032) compared to controls. Our results suggest that prenatal poly I:C leads to long term alterations in the integrity of the ECS that are age and region-specific. The increased CB1R expression in adulthood following poly I:C mirrors the increased CB1R observed in patients with schizophrenia in post-mortem and in vivo PET studies. © Elsevie

    Installation of a pilot experimental trench at the Little Forest legacy site

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    During 2017, a pilot experimental trench was constructed at the Little Forest Legacy Site (LFLS). The objective of installing this trench was to facilitate experimental field-work aimed at further characterising the site, in particular the hydrology of the excavated trenches and of the near-surface layers in which the trenches are located. The test trench is of similar depth to the waste disposal trenches at the legacy site (3 metres) and extends 6 m in length. However, unlike the disposal trenches, the experimental trench contains no waste materials of any kind. Instead, the trench contains a number of sampling points and other instrumentation, and is back filled with river gravel to provide a uniform composition and maintain structural stability. It is intended that the pilot trench will be followed by other trenches with specific experimental objectives. The purposes of this report are to discuss the background, rationale for, and implementation of the facility; to provide a detailed description of the pilot trench; and to compile information and photographs documenting the excavation process. Although some preliminary hydrological data and comparisons with the legacy trenches are presented, the scientific data will be fully discussed and interpreted in future scientific reports

    Rhenium and technetium tricarbonyl complexes of N-Heterocyclic carbene ligands

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    A strategy for the conjugation of N-heterocyclic carbene (NHC) ligands to biomolecules via amide bond formation is described. Both 1-(2-pyridyl)imidazolium or 1-(2-pyridyl)benzimidazolium salts functionalized with a pendant carboxylic acid group were prepared and coupled to glycine benzyl ester using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide. A series of 10 rhenium(I) tricarbonyl complexes of the form [ReX(CO)3(ĈN)] (ĈN is a bidentate NHC ligand, and X is a monodentate anionic ligand: Cl–, RCO2–) were synthesized via a Ag2O transmetalation protocol from the Re(I) precursor compound Re(CO)5Cl. The synthesized azolium salts and Re(I) complexes were characterized by elemental analysis and by 1H and 13C NMR spectroscopy, and the molecular structures for one imidazolium salt and seven Re(I) complexes were determined by single-crystal X-ray diffraction. 1H NMR and mass spectrometry studies for an acetonitrile-d3 solution of [ReCl(CO)3(1-(2-pyridyl)-3-methylimidazolylidene)] show that the monodentate chloride ligand is labile and exchanges with this solvent yielding a cationic acetonitrile adduct. For the first time the labeling of an NHC ligand with technetium-99m is reported. Rapid Tc-99m labeling was achieved by heating the imidazolium salt 1-(2-pyridyl)-3-methylimidazolium iodide and Ag2O in methanol, followed by the addition of fac-[99mTc(OH2)3(CO)3]+. To confirm the structure of the 99mTc-labeled complex, the equivalent 99Tc complex was prepared, and mass spectrometric studies showed that the formed Tc complexes are of the form [99m/99Tc(CH3CN)(CO)3(1-(2-pyridyl)-3-methylimidazolylidene)]+ with an acetonitrile molecule coordinated to the metal center. © 2014 American Chemical Societ

    [18F]Fluorination optimisation and the fully automated production of [18F]MEL050 using a microfluidic system

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    The [18F]radiolabelling of the melanin-targeting positron-emission tomography radiotracer [18F]MEL050 was rapidly optimised using a commercial continuous-flow microfluidic system. The optimal [18F]fluorination incorporation conditions were then translated to production-scale experiments (35–150 GBq) suitable for preclinical imaging, complete with automated HPLC–solid phase extraction purification and formulation. [18F]MEL050 was obtained in 43 ± 10 % radiochemical yield in ~50 min. © 2015 CSIRO Publishing

    Meeting the challenges of global nuclear medicine technologist training in the 21st century: the IAEA Distance Assisted Training (DAT) program

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    Many countries have made significant investments in nuclear medicine (NM) technology with the acquisition of modern equipment and establishment of facilities, however, often appropriate training is not considered as part of these investments. Training for NM professionals is continually evolving, with a need to meet changing requirements in the workforce. Even places where established higher education courses are available, these do not necessarily cater to the practical component of training and the ever-changing technology that is central to medical imaging. The continuing advances in NM technology and growth of applications in quantitative clinical assessment place increases the pressure on technologists to learn and practice new techniques. Not only is training to understand new concepts limited but often there is inadequate training in the basics of NM and this can be a major constraint to the effective use of the evolving technology. Developing appropriate training programs for the broader international NM community is one of the goals of the International Atomic Energy Agency (IAEA). A particularly successful and relevant development has been the program on ‘distance assisted training (DAT) for NM professionals’. The development of DAT was initiated in the 1990s through Australian Government funding, administered under auspices of the IAEA through its Regional Cooperative Agreement, involving most countries in Asia that are Member States of the IAEA. The project has resulted in the development of a set of training modules which are designed for use under direct supervision in the workplace, delivered through means of distance-learning. The program has undergone several revisions and peer reviews with the current version providing a comprehensive training package that is now available online. DAT has been utilized widely in Asia or the Pacific region, Latin America, and parts of Africa and Europe. Currently there are approximately 1000 registered participants, including persons providing student support, in the program. © 2013 Elsevier B.V

    A data driven method for estimation of Bavail and appKD using a single injection protocol with [11C]raclopride in the mouse

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    Purpose The partial saturation approach (PSA) is a simple, single injection experimental protocol that will estimate both Bavail and appKD without the use of blood sampling. This makes it ideal for use in longitudinal studies of neurodegenerative diseases in the rodent. The aim of this study was to increase the range and applicability of the PSA by developing a data driven strategy for determining reliable regional estimates of receptor density (Bavail) and in vivo affinity (1/appKD), and validate the strategy using a simulation model. Methods The data driven method uses a time window guided by the dynamic equilibrium state of the system as opposed to using a static time window. To test the method, simulations of partial saturation experiments were generated and validated against experimental data. The experimental conditions simulated included a range of receptor occupancy levels and three different Bavail and appKD values to mimic diseases states. Also the effect of using a reference region and typical PET noise on the stability and accuracy of the estimates was investigated. Results The investigations showed that the parameter estimates in a simulated healthy mouse, using the data driven method were within 10±30% of the simulated input for the range of occupancy levels simulated. Throughout all experimental conditions simulated, the accuracy and robustness of the estimates using the data driven method were much improved upon the typical method of using a static time window, especially at low receptor occupancy levels. Introducing a reference region caused a bias of approximately 10% over the range of occupancy levels. Conclusions Based on extensive simulated experimental conditions, it was shown the data driven method provides accurate and precise estimates of Bavail and appKD for a broader range of conditions compared to the original method. © 2014 Elsevier Inc

    Glutathione relates to neuropsychological functioning in mild cognitive impairment

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    Background Mild cognitive impairment (MCI) represents an at-risk state for Alzheimer's disease in which underlying pathophysiological mechanisms could be delineated. Oxidative stress has been implicated in Alzheimer's disease and can be measured by levels of the antioxidant glutathione. This study aims to assess in vivo levels of glutathione via proton magnetic resonance spectroscopy in patients with MCI and to determine how glutathione relates to cognitive decline. Methods Fifty-four patients with MCI and 41 healthy control subjects underwent proton magnetic resonance spectroscopy in conjunction with medical, psychiatric, and neuropsychological assessments. The concentration of glutathione was measured in the anterior and posterior cingulate, and ratios of glutathione were calculated relative to creatine. Neuropsychological performance was assessed across the domains of processing speed, learning, memory, and executive functions. Results In comparison with control subjects, patients with MCI had significantly elevated ratios of glutathione in the anterior (t = −2.2, P = .03) and posterior (t = −2.9, P = .005) cingulate. Higher levels of anterior cingulate glutathione were related to neuropsychological decrements on tests of executive functions. Elevated posterior cingulate glutathione was associated with poorer memory consolidation. Conclusion This study has shown for the first time that MCI is associated with increased glutathione in the cingulate, which in turn relates to neuropsychological performance. This finding may be indicative of an early compensatory or neuroprotective response, and the role of glial cells and glutathione enzymes requires delineation. Longitudinal studies examining the utility of glutathione as a marker for cognitive decline are now required. © 2014 The Alzheimer's Associatio

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