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Model evaluation of RIMPUFF within complex terrain using an Ar-41 radiological dataset.
The newly updated atmospheric dispersion model RIMPUFF is evaluated using routine releases of 41Ar from the former HIFAR research reactor located at the Australian Nuclear Science and Technology Organisation (ANSTO) in Sydney, Australia. Predicting radiological dispersion for emergency response at this site proves challenging due to complex topographical conditions including a steep-sided river valley located between the reactor and the nearest residents. A large number of 41Ar measurements from a network of environmental gamma detectors are used to evaluate the model under a range of atmospheric stability conditions. Topographic and meteorological influences that potentially affect a released plume, such as channelling, wind shear, local terrain slope flows and strong inversions are explored. A sensitivity analysis using various combinations of meteorological station data for model input, including vertical wind and temperature profiles, also identifies model strengths and weaknesses within the complex terrain. Various model evaluation tools, such as relevant statistical indices and gamma dose contour plots, are used to evaluate this new version of RIMPUFF for emergency response purposes at ANSTO and for inclusion in the ARGOS Decision Support System
Unsaturated zone hydrology and implications for paleo-climate speleothem reconstructions
Speleothem growth relies on the supply of water which percolates from the surface,
through the unsaturated zone and discharges into cavernous voids. The flow path of
water feeding individual speleothems varies considerably depending on the karst
architecture e.g. micro-fractures, solution pipes, structural voids in the karst, storage
reservoirs, etc., all of which may alter the composition of drip waters over the flow
route. By monitoring drip waters, we can determine: 1) unsaturated zone flow
regimes; 2) connectivity between the surface and cave discharge zone; and 3)
thresholds for groundwater recharge. This information can be used to identify suitable
speleothems in caves for reconstruction of past climatic and hydrologic variability, at
least over the last few thousand years of similar mean climate state.
High-frequency, spatially-dense monitoring was conducted in Harrie Wood Cave,
Yarrangobilly, Snowy Mountains over a 15 month period to characterise the flow
regimes at 14 sites along a depth profile within the cave. Sites were monitored using
acoustic drip loggers (stalagmates®). Discharge rates and response to significant
rainfall events were highly variable between sites. A moderate relationship was found
between decreasing discharge rates and increasing depth (r2 = 0.40). We suggest
unsaturated zone storage and mixing, unrelated to depth, also have a significant
impact on flow regimes. Using a statistical approach, five different drip types, which
often had no spatial commonality, were identified. This information was used to
inform the choice of speleothems for paleo-climate reconstruction, using stalagmites
with differing hydrological regimes feeding growth, of which the preliminary data
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will be presented here. The study highlights the need to understand unsaturated zone
hydrology at the individual drip discharge level, prior to any speleothem study for
paleo-climate, to truly appreciate the drip water signal it is recording. Copyright (C) The Authors
Lower Hunter particle characterisation study Final Report to the NSW Environment Protection Authority
The Lower Hunter Particle Characterisation Study (LHPCS) provides details about the composition and major sources of PM2.5 (fine airborne particles)and PM2.5-10(coarse airborne particles).
Measurements were made for one year from March 2014 to February 2015 at two air quality monitoring stations representative of regional population exposures (Newcastle and Beresfield) and two stations near the Port of Newcastle (Mayfield and Stockton).
Annual average PM2.5 concentrations were very similar at Newcastle, Mayfield and Beresfield (6.4–6.7 μg m-3) but about 40% higher at Stockton (9.1 μg m-3). The higher levels at Stockton were mainly due to both more sea salt and to the primary ammonium nitrate, which was only detected at Stockton. The ammonium nitrate, which contributed on average 19% of the PM2.5 mass (and ~40% in winter), was identified as very likely to be due to primary emissions from Orica’s ammonium nitrate manufacturing facility on Kooragang Island.
Other than the ammonium nitrate, PM2.5 composition and sources were found to be fairly similar across the four sites. Key results on the sources and their contributions are: fresh sea salt particles: 24% at Newcastle, decreasing to 13% at Beresfield; pollutant-aged sea salt: ~23% at all sites; this is sea salt reacted with industrial, commercial, road and non-road transport emissions from local and regional sources; wood smoke: 15% at Beresfield, decreasing to 6% at Stockton; secondary ammonium sulfate: ~10% at all sites; soil dust: ~10% at all sites; vehicles: ~10% at three sites, but only 5% at Stockton; industry factors: ~12% at three sites but 24% at Stockton; mixed shipping/industry: ~3% at all sites; nitrate: 19% ammonium nitrate at Stockton and secondary nitrate at other sites (6-11%).
On an annual average basis, there is an approximately 50:50 split between primary and secondary particles at three sites (Newcastle, Beresfield and Mayfield) and a 65:35 split at Stockton because of the significant contribution from the primary ammonium nitrate.
PM2.5-10 composition and sources were only determined at the stations near the Port of Newcastle. The 2½ times higher annual average PM2.5-10 concentration at Stockton (21.5 μg m-3) than at Mayfield (8.3 μg m-3) was found to be mainly due to a much higher contribution by fresh sea salt particles at Stockton.
The PM2.5-10 factors and their contributions were identified as:
fresh sea salt: 13.6 μg m-3 at Stockton, 3.3 μg m-3 at Mayfield
industry plus pollutant-aged sea salt: 2.4 μg m-3 at both sites
light-absorbing carbon: 2.2 μg m-3 at Stockton, 0.9 μg m-3 at Mayfield
soil: 2.3 μg m-3 at Stockton, 1.2 μg m-3 at Mayfield
bioaerosol: 1.1 μg m-3 at Stockton, 0.5 μg m-3 at Mayfield.
Most PM2.5-10 particles are primary particles or physical combinations of primary emissions, but there is evidence of chemical reactions in the pollutant-aged sea salt factor.
Coal particles could contribute up to 10% of PM2.5-10 particles. Further investigations are needed to clarify the contribution of coal
Geological evidence for the destruction of Shinmachi, Hawaii, by the 1946 Aleutian and 1960 Chile Tsunamis?
The Japanese community of Shinmachi, established on low-lying land between downtown Hilo and Waiakea, Hawaii, was obliterated by the 1946 Aleutian tsunami but was rebuilt, only to be destroyed again by the 1960 Chilean tsunami. The aim of this study was to find out if any geological evidence of these well documented events had been preserved in the sedimentary record in Wailoa River State Park, which replaced Shinmachi after the 1960 tsunami. This was achieved by collecting cores in the park and performing sedimentological, chronological and geochemical analyses, the latter also processed by principal component analysis. Sediment transport modelling was carried out for both tsunamis, to infer the source of the sediment and areas of deposition on land. The field survey revealed two distinct units within peat and soil, a thin lower unit composed of weathered basalt fragments within mud (Unit 1) and an upper unit dominated by fine volcanic sand within fine silt exhibiting subtle upward fining and coarsening (Unit 2, consisting of Unit 2A and Unit 2B), although these two anomalous units only occur on the western shore of Waiakea Mill Pond. Analysis with an ITRAX core scanner shows that Unit 1 is characterised by high Mn, Fe, Rb, La and Ce counts, combined with elevated magnetic susceptibility. Based on its chemical and sedimentological characteristics, Unit 1 is attributed to a flood event in Wailoa River that occurred around 1520–1660 CE, most probably as a result of a tropical storm. The sharp lower contact of Unit 2 coincides with the appearance of arsenic, contemporaneous with an increase in Ca, Sr, Si, Ti, K, Zr, Mn, Fe, La and Ce. In this study, As is used as a chronological and source material marker, as it is known to have been released into Wailoa River Estuary and Waiakea Mill Pond by the Canec factory between 1932 and 1963. Thus, not only the chemical and sedimentological evidence but also sediment transport modelling, corroborating the historical record, suggest that Unit 2A was deposited by the 1946 tsunami, and the sediment most likely originated from Wailoa River Estuary, beach and nearshore seafloor. The upper part of this unit, Unit 2B, is believed to have been deposited by the 1960 tsunami, as suggested by sediment transport modelling, although limited accommodation space is likely to have resulted in the thin deposit (3 cm thickness) present at that site. Limited accommodation space on the island of Hawaii has led to only rare locations where tsunami deposits are preserved, despite the repeated occurrence of tsunamis affecting the island. © 2020 Elsevier B.
Synthesis and in vitro evaluation of tetrahydroisoquinolines with pendent aromatics as sigma-2 (σ2) selective ligands
Abstract5-Bromo-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-butyl)]-2,3-dimethoxybenzamide 1 is a potent and selective σ2 receptor ligand suitable for further development. A series of new analogues, incorporating a variety of isoquinoline and carboxylic acid moieties, linked together with either a linear or cyclic amine spacer have been synthesised and assessed for their σ1/σ2 binding affinity and selectivity. Compounds with a rigid piperidine spacer gave Ki values for the σ2 receptor between 8.7–845 nM. Changing the configuration of the methoxy groups on the isoquinoline moiety resulted in molecules with σ2Ki values of 4.4–133 nM whereas varying the length and flexibility of the carbon spaces gave σ2Ki values 0.88–15.0 nM, some of the most active, selective σ2 ligands to date. Thus, the flexibility and length of the carbon linker and the carboxylic acid moiety are confirmed to be key to the exceptional binding affinity and selectivity for this active series. Additionally, the incorporation of a halogen on selected carboxylic acid moieties provided a convenient strategy for the introduction of a radiohalogen for applications in pharmacological and imaging studies. © 2014 The Royal Society of Chemistr
Preclinical in vivo and in vitro comparison of the translocator protein PET ligands [18F]PBR102 and [18F]PBR111
Purpose
To determine the metabolic profiles of the translocator protein ligands PBR102 and PBR111 in rat and human microsomes and compare their in vivo binding and metabolite uptake in the brain of non-human primates (Papio hamadryas) using PET-CT.
Methods
In vitro metabolic profiles of PBR102 and PBR111 in rat and human liver microsomes were assessed by liquid chromatography–tandem mass spectrometry. [18F]PBR102 and [18F]PBR111 were prepared by nucleophilic substitution of their corresponding p-toluenesulfonyl precursors with [18F]fluoride. List mode PET-CT brain imaging with arterial blood sampling was performed in non-human primates. Blood plasma measurements and metabolite analysis, using solid-phase extraction, provided the metabolite profile and metabolite-corrected input functions for kinetic model fitting. Blocking and displacement PET-CT scans, using PK11195, were performed.
Results
Microsomal analyses identified the O-de-alkylated, hydroxylated and N-de-ethyl derivatives of PBR102 and PBR111 as the main metabolites. The O-de-alkylated compounds were the major metabolites in both species; human liver microsomes were less active than those from rat. Metabolic profiles in vivo in non-human primates and previously published rat experiments were consistent with the microsomal results. PET-CT studies showed that K1 was similar for baseline and blocking studies for both radiotracers; VT was reduced during the blocking study, suggesting low non-specific binding and lack of appreciable metabolite uptake in the brain.
Conclusions
[18F]PBR102 and [18F]PBR111 have distinct metabolic profiles in rat and non-human primates. Radiometabolites contributed to non-specific binding and confounded in vivo brain analysis of [18F]PBR102 in rodents; the impact in primates was less pronounced. Both [18F]PBR102 and [18F]PBR111 are suitable for PET imaging of TSPO in vivo. In vitro metabolite studies can be used to predict in vivo radioligand metabolism and can assist in the design and development of better radioligands. © 2016 Springer-Verla
Synthesis and stability of S-(2-[18F]fluoroethyl)-L-homocysteine for potential tumour imaging
inThe F-18 labelled methionine derivative S-(2-[18F]fluoroethyl)-L-homocysteine ([18F]FEHCys) was prepared by a one-pot two-step synthesis via the protected S-(2-bromoethyl)-L-homocysteine 1 and S-(2-chloroethyl)-L-homocysteine 2 precursors. The bromoethyl derivative 1 gave higher radiochemical yields (40% at 5 min) at 100°C compared with the chloro-analogue (22% at 100°C in 30 min). However, [18F]FEHCys was found to be unstable in aqueous systems being transformed to the corresponding hydroxyl derivative within 20 min. © 2008 John Wiley & Sons, Ltd
Simultaneous scanning of two mice in a small-animal PET scanner: a simulation-based assessment of the signal degradation
In PET imaging, research groups have recently proposed different experimental set ups allowing multiple animals to be simultaneously imaged in a scanner in order to reduce the costs and increase the throughput. In those studies, the technical feasibility was demonstrated and the signal degradation caused by additional mice in the FOV characterized, however, the impact of the signal degradation on the outcome of a PET study has not yet been studied. Here we thoroughly investigated, using Monte Carlo simulated [18F]FDG and [11C]Raclopride PET studies, different experimental designs for whole-body and brain acquisitions of two mice and assessed the actual impact on the detection of biological variations as compared to a single-mouse setting. First, we extended the validation of the PET-SORTEO Monte Carlo simulation platform for the simultaneous simulation of two animals. Then, we designed [18F]FDG and [11C]Raclopride input mouse models for the simulation of realistic whole-body and brain PET studies. Simulated studies allowed us to accurately estimate the differences in detection between single- and dual-mode acquisition settings that are purely the result of having two animals in the FOV. Validation results showed that PET-SORTEO accurately reproduced the spatial resolution and noise degradations that were observed with actual dual phantom experiments. The simulated [18F]FDG whole-body study showed that the resolution loss due to the off-center positioning of the mice was the biggest contributing factor in signal degradation at the pixel level and a minimal inter-animal distance as well as the use of reconstruction methods with resolution modeling should be preferred. Dual mode acquisition did not have a major impact on ROI-based analysis except in situations where uptake values in organs from the same subject were compared. The simulated [11C]Raclopride study however showed that dual-mice imaging strongly reduced the sensitivity to variations when mice were positioned side-by-side while no sensitivity reduction was observed when they were facing each other. This is the first study showing the impact of different experimental designs for whole-body and brain acquisitions of two mice on the quality of the results using Monte Carlo simulated [18F]FDG and [11C]Raclopride PET studies. © 2016 Institute of Physics and Engineering in Medicin
Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats
The acute effects of the party drug 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) in humans include feelings of love, closeness towards other people and an increased acceptance of others views and feelings. Some evidence suggests that regular MDMA users develop a subsensitivity to the positive effects of the drug and escalate their intake of the drug over time as a result. The current study investigated whether brief exposure to relatively high doses of MDMA in rats produces a subsequent attenuation in the ability of MDMA to enhance social interaction. Male Wistar rats were exposed to either MDMA (4 × 5 mg/kg over 4 h) or vehicle on two consecutive days. Twelve weeks later, MDMA pre-exposed rats displayed a significantly shorter period of time spent in social interaction than controls when tested in the drug-free state. MDMA pre-exposed rats also showed a blunted prosocial response to MDMA (2.5 mg/kg) relative to controls. This difference was overcome by increasing the MDMA dose to 5 mg/kg. The 5-HT1A agonist 8-OH-DPAT (250 µg/kg but not 125 µg/kg) increased social interaction and this effect did not differ in MDMA and vehicle pre-exposed rats. HPLC analysis showed a small but significant depletion of prefrontal 5-HT and 5-HIAA in MDMA pre-exposed rats. Prefrontal 5-HIAA concentrations were also reduced in the subset of vehicle and MDMA pre-exposed rats that received additional testing with MDMA. These results indicate that treatment with MDMA not only causes lasting reductions in social interaction in rats but causes an attenuation of the prosocial effects of subsequent MDMA administration. The lack of a differential response to 8-OH-DPAT agrees with other findings that the 5-HT1A receptor system remains functionally intact following MDMA pre-exposure and suggests that other neuroadaptations may underlie the lasting social deficits caused by MDMA. © 2008 Elsevier Inc