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Nested partnerships and interdisciplinary science: from the National Medical Cyclotron to the research cyclotron of the National Imaging Facility
Get PDFIn Australia, the routine use of medical isotopes produced by a prototype cyclotron for diagnostic imaging commenced in the early 1990s. Since then, the mainly clinically focused imaging in nuclear medicine has become a broader and more interdisciplinary endeavour. As 'molecular imaging', it has become a field that supports a wide range of basic, translational and clinical research and draws in skills from many areas, including physics, chemistry, engineering, biology and medicine. Such growth has been accompanied by the emergence of scientific collaborations well beyond individual institutions. This paper provides the historical context to the former National Medical Cyclotron (NMC) facility (1992-2009) at Camperdown, Sydney and the subsequent partnerships that led to its refurbishment as the new site of the National Imaging Facility (NIF) Cyclotron, a flagship research facility enabled by the National Collaborative Research Infrastructure Strategy (NCRIS). It is now the centrepiece of a physical research infrastructure as well as a growing network of collaborations that open up access to medical isotopes for research and clinical applications across Australia to new users and applications. It is also a contemporary example of how science has moved from individual scholarly endeavour to highly networked activity. The funding model initiated through NCRIS included shared funding, funding leveraging and in-kind contributions primarily for the establishment of the large instrument and laboratory infrastructure rather than their operational costs. Here, we illustrate how partnership arrangements emerged at institutional, state and national level and how they address the task of providing open access to, and sustainable operation of, a major piece of research infrastructure that spans multiple institutions. © The Royal Society of NSW
Synthesis and biological evaluation of substituted [18F]Imidazo[1,2-a]pyridines and [18F]Pyrazolo[1,5-a]pyrimidines for the study of the peripheral benzodiazepine receptor using positron emission tomography
No full textThe fluoroethoxy and fluoropropoxy substituted 2-(6-chloro-2-phenyl)imidazo[1,2- a]pyridin-3-yl)- N, N-diethylacetamides 8 (PBR102) and 12 (PBR111) and 2-phenyl-5,7-dimethylpyrazolo[1,5- a]pyrimidin-3-yl)- N, N-diethylacetamides 15 (PBR099) and 18 (PBR146) were synthesized and found to have high in vitro affinity and selectivity for the peripheral benzodiazepine receptors (PBRs) when compared with the central benzodiazepine receptors (CBRs). The corresponding radiolabeled compounds [ (18)F] 8 [ (18)F] 12, [ (18)F] 15, and [ (18)F] 18 were prepared from their p-toluenesulfonyl precursors in 50-85% radiochemical yield. In biodistribution studies in rats, the distribution of radioactivity of the [ (18)F]PBR compounds paralleled the known localization of PBRs. In the olfactory bulbs, where the uptake of radioactivity was higher than in the rest of the brain, PK11195 and Ro 5-4864 were able to significantly inhibit [ (18)F] 12, while little or no pharmacological action of these established PBR drugs were observed on the uptake of [ (18)F] 8, [ (18)F] 15, and [ (18)F] 18 compared to control animals. Hence, [ (18)F] 12 appeared to be the best candidate for evaluation as an imaging agent for PBR expression in neurodegenerative disorders. © 2008 American Chemical Societ
Checkpoints to the brain: directing myeloid cell migration to the central nervous system
Get PDFMyeloid cells are a unique subset of leukocytes with a diverse array of functions within the central nervous system during health and disease. Advances in understanding of the unique properties of these cells have inspired interest in their use as delivery vehicles for therapeutic genes, proteins, and drugs, or as “assistants” in the clean-up of aggregated proteins and other molecules when existing drainage systems are no longer adequate. The trafficking of myeloid cells from the periphery to the central nervous system is subject to complex cellular and molecular controls with several ‘checkpoints’ from the blood to their destination in the brain parenchyma. As important components of the neurovascular unit, the functional state changes associated with lineage heterogeneity of myeloid cells are increasingly recognized as important for disease progression. In this review, we discuss some of the cellular elements associated with formation and function of the neurovascular unit, and present an update on the impact of myeloid cells on central nervous system (CNS) diseases in the laboratory and the clinic. We then discuss emerging strategies for harnessing the potential of site-directed myeloid cell homing to the CNS, and identify promising avenues for future research, with particular emphasis on the importance of untangling the functional heterogeneity within existing myeloid subsets. © 2016 MDPI
Holocene ecosystem change in Little Llangothlin Lagoon, Australia: implications for the management of a Ramsar-listed wetland
No full textWe present new chironomid and stable isotope (δ13C and δ15N) data from Little Llangothlin Lagoon, Australia that provides more detail on changes in this wetland since European settlement ca. 1840 AD. We also examine how the updated Holocene paleoecological record provides insights for management of this Ramsar-listed wetland. The current management strategy for Little Llangothlin is to restore the wetland and catchment to its natural state. This strategy is intended to protect the values that allowed it to be listed as a Ramsar wetland; i.e. its role as a drought refuge for waterbirds and to preserve or enhance threatened ecological communities. There are clear conflicts between the Ramsar listing criteria, management objectives and the management strategy in light of information provided by the palaeoecological record. In particular, restoration of terrestrial ecosystems through reforestation may jeopardise the wetlands role as a drought refuge. Some activities, such as artificial raising of the water level in 1989 are intended to restore, but actually introduced a state that did not exist prior to human settlement. We recommend a more integrated management approach that heeds the information provided by the palaeoecological record and focuses more on maintenance or enhancement of ecosystem services and biodiversity. © 2016, Springe
Simulation of light C4+ ion irradiation and its enhancement to the critical current density in BaFe1.9Ni0.1As2 single crystals
No full textIn this work, we analyse the influence of C4+ irradiation with ion flounce of 3 × 1012 up to 2.3 × 1015 ion·cm−2 on significant enhancement of the critical current density, Jc , in BaFe1.9Ni0.1As2 single crystals. Jc was increased from 0.61 × 105 up to 0.94 × 105 A/cm2 at T = 10 K and H = 0.5 T. BaFe1.9Ni0.1As2 single crystals with and without the C4+-irradiation were characterized by magneto-transport and magnetic measurements up to 13 T over a wide range of temperatures below and above the superconducting critical temperature, Tc . It is found that the C4+-irradiation causes little change in Tc , but it can greatly enhance the in-field critical current density by a factor of up to 1.5. Higher dose of C4+ ions, causes further Jc enhancement at T=10 K. furthermore, flux jumping completely disappeared at T=2 K after second C4+-irradiation. Our Monte Carlo simulation results show that all the C4+ ions end up in a well defined layer, causing extended defects and vacancies at the layer, but few defects elsewhere on the irradiation paths. Furthermore, the normal state resistivity is enhanced by the light C4+ irradiation, while the upper critical field, H c2, the irreversibility field, H irr, and Tc were affected very little. © 2014 American Scientific Publishe
XPS and TEM study of deposited and Ru–Si solid state reaction grown ruthenium silicides on silicon
No full textRu2Si3 silicide was prepared in two different ways: (i) through a deposition (D) from a Ru2Si3 sputtering target and (ii) via a solid state reaction (SSR) of ruthenium thin film with silicon to form a rectifying structure silicide/silicon. Both types of silicides were treated at 700 °C in nitrogen ambient for 5 min in order to facilitate crystallization and solid state reaction, respectively. Transmission electron microcopy (TEM), x-ray photoelectron spectroscopy (XPS) and Raman spectroscopy were applied to study structural, compositional and chemical properties of the two types of silicides. © 2015 Elsevier Ltd
A large spin-crossover [Fe4L4]8+ tetrahedral cage
No full textAbstractA large discrete face-capped tetranuclear iron(II) cage, [Fe4L4](BF4)8·n(solvent), was synthesised via metal-ion directed self-assembly. The cage is formed from a rigid tritopic ligand that incorporates chelating imidazole-imine functional groups. The cage displays temperature induced spin-crossover and LIESST effects and is amongst the largest iron(II) tetrahedral cages with such properties reported. The synthesis, structure and magnetic properties of this new metallo-cage are presented. © 2015 The Royal Society of Chemistr
Preparation of Y2Ti2O7 pyrochlore glass-ceramics as potential waste forms for actinides: the effects of processing conditions
No full textGlass-Y2Ti2O7 pyrochlore was fabricated by sintering the mixture of glass precursor powder and (YTi)-composite which was prepared by a soft chemistry route. X-ray diffraction and Raman spectroscopy confirmed that the phase pure pyrochlore was crystallized in-situ in amorphous glass matrix at 1200 °C with dwelling time over 1 h. Pyrochlore was formed in glass matrix with cooling rate ∼0.1–40 °C/min, and independent of addition of alkali/alkaline earth fluorides. Glass matrix was able to accommodate/dissolve small amounts of impurities and the mean pyrochlore particle size was between 1 and 2 μm in glass observed by scanning electron microscopy. © 2017 Elsevier B.V
Skeletal arsenic of the pre-Columbian population of Caleta Vitor, northern Chile
No full textExposure to toxic arsenic has severe health consequences for past and present societies. This research resolves changes in a pre-Industrial population's exposure to the toxin within an arsenic-endemic area of the Atacama Desert of northern Chile over long timescales. Inductively coupled plasma mass spectrometry (ICP-MS) trace element analysis of human bone and tooth samples from 21 burials at Caleta Vitor on the Pacific coast of northern Chile has established that the pre-Columbian inhabitants were exposed to elevated levels of arsenic where one third of the sample population had accumulated levels in their skeletal system indicative of chronic poisoning. Coupled with new accelerator mass spectrometry (AMS) radiocarbon ages for the skeletal samples, spanning c. 3867 to 474 cal BP and encompassing all major cultural periods of the region, these results demonstrate the continual risk of arsenic poisoning over several millennia of occupation at one site.
Numerous factors may have partially contributed to the population's inferred poisoning, due to the complex interaction of various environmental sources of arsenic and human behaviours. Increased exposure to arsenic could relate to climatic variability influencing sources of drinking water or anthropogenic activities such as mining and metallurgy or dietary changes associated with agriculture. Assessment of these potential sources of arsenic toxication, including evaluation of modern environmental data from the region, suggests contaminated drinking water was the most likely cause of arseniasis. © 2015 Elsevier Ltd
Derivatives of imidazotriazine and pyrrolotriazine C-nucleosides as potential new anti-HCV agents
No full textPrevious investigations identified 2′-C-Me-branched ribo-C-nucleoside adenosine analogues, 1, which contains a pyrrolo[2,1-f][1,2,4]triazin-4-amine heterocyclic base, and 2, which contains an imidazo[2,1-f][1,2,4]triazin-4-amine heterocyclic base as two compounds with promising anti-HCV in vitro activity. This Letter describes the synthesis and evaluation of a series of novel analogues of these compounds substituted at the 2-, 7-, and 8-positions of the heterocyclic bases. A number of active new HCV inhibitors were identified but most compounds also demonstrated unacceptable cytotoxicity. However, the 7-fluoro analogue of 1 displayed good potency with a promising cytotherapeutic margin. © 2014 Elsevier Ltd