186 research outputs found

    Detecting small low emission radiating sources

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    The article addresses the possibility of robust detection of geometrically small, low emission sources on a significantly stronger background. This problem is important for homeland security. A technique of detecting such sources using Compton type cameras is developed, which is shown on numerical examples to have high sensitivity and specificity and also allows to assign confidence probabilities of the detection. 2D case is considered in detail

    Stress-inducible phosphoprotein 1 (HOP/STI1/STIP1) regulates the accumulation and toxicity of α-synuclein in vivo

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    The predominantly pre-synaptic intrinsically disordered protein α-synuclein is prone to misfolding and aggregation in synucleinopathies, such as Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB). Molecular chaperones play important roles in protein misfolding diseases and members of the chaperone machinery are often deposited in Lewy bodies. Here, we show that the Hsp90 co-chaperone STI1 co-immunoprecipitated α-synuclein, and co-deposited with Hsp90 and Hsp70 in insoluble protein fractions in two mouse models of α-synuclein misfolding. STI1 and Hsp90 also co-localized extensively with filamentous S129 phosphorylated α-synuclein in ubiquitin-positive inclusions. In PD human brains, STI1 transcripts were increased, and in neurologically healthy brains, STI1 and α-synuclein transcripts correlated. Nuclear Magnetic Resonance (NMR) analyses revealed direct interaction of α-synuclein with STI1 and indicated that the STI1 TPR2A, but not TPR1 or TPR2B domains, interacted with the C-terminal domain of α-synuclein. In vitro, the STI1 TPR2A domain facilitated S129 phosphorylation by Polo-like kinase 3. Moreover, mice over-expressing STI1 and Hsp90ß presented elevated α-synuclein S129 phosphorylation accompanied by inclusions when injected with α-synuclein pre-formed fibrils. In contrast, reduced STI1 function decreased protein inclusion formation, S129 α-synuclein phosphorylation, while mitigating motor and cognitive deficits as well as mesoscopic brain atrophy in α-synuclein-over-expressing mice. Our findings reveal a vicious cycle in which STI1 facilitates the generation and accumulation of toxic α-synuclein conformers, while α-synuclein-induced proteostatic stress increased insoluble STI1 and Hsp90

    Determination of nitric oxide metabolites, nitrate and nitrite, in Anopheles culicifacies mosquito midgut and haemolymph by anion exchange high-performance liquid chromatography: plausible mechanism of refractoriness

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    <p>Abstract</p> <p>Background</p> <p>The diverse physiological and pathological role of nitric oxide in innate immune defenses against many intra and extracellular pathogens, have led to the development of various methods for determining nitric oxide (NO) synthesis. NO metabolites, nitrite (NO<sub>2</sub><sup>-</sup>) and nitrate (NO<sub>3</sub><sup>-</sup>) are produced by the action of an inducible <it>Anopheles culicifacies </it>NO synthase (AcNOS) in mosquito mid-guts and may be central to anti-parasitic arsenal of these mosquitoes.</p> <p>Method</p> <p>While exploring a plausible mechanism of refractoriness based on nitric oxide synthase physiology among the sibling species of <it>An. culicifacies</it>, a sensitive, specific and cost effective high performance liquid chromatography (HPLC) method was developed, which is not influenced by the presence of biogenic amines, for the determination of NO<sub>2</sub><sup>- </sup>and NO<sub>3</sub><sup>- </sup>from mosquito mid-guts and haemolymph.</p> <p>Results</p> <p>This method is based on extraction, efficiency, assay reproducibility and contaminant minimization. It entails de-proteinization by centrifugal ultra filtration through ultracel 3 K filter and analysis by high performance anion exchange liquid chromatography (Sphereclone, 5 μ SAX column) with UV detection at 214 nm. The lower detection limit of the assay procedure is 50 pmoles in all midgut and haemolymph samples. Retention times for NO<sub>2</sub><sup>- </sup>and NO<sub>3</sub><sup>- </sup>in standards and in mid-gut samples were 3.42 and 4.53 min. respectively. Assay linearity for standards ranged between 50 n<it>M </it>and 1 m<it>M</it>. Recoveries of NO<sub>2</sub><sup>- </sup>and NO<sub>3</sub><sup>- </sup>from spiked samples (1–100 μ<it>M</it>) and from the extracted standards (1–100 μ<it>M</it>) were calculated to be 100%. Intra-assay and inter assay variations and relative standard deviations (RSDs) for NO<sub>2</sub><sup>- </sup>and NO<sub>3</sub><sup>- </sup>in spiked and un-spiked midgut samples were 5.7% or less. Increased levels NO<sub>2</sub><sup>- </sup>and NO<sub>3</sub><sup>- </sup>in midguts and haemolymph of <it>An. culicifacies </it>sibling species B in comparison to species A reflect towards a mechanism of refractoriness based on AcNOS physiology.</p> <p>Conclusion</p> <p>HPLC is a sensitive and accurate technique for identification and quantifying pmole levels of NO metabolites in mosquito midguts and haemolymph samples that can be useful for clinical investigations of NO biochemistry, physiology and pharmacology in various biological samples.</p

    Palaeomagnetism of the Early Permian Mount Leyshon Intrusive Complex and Tuckers Igneous Complex, North Queensland, Australia

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    This study provides reliable, precisely defined and well-dated Early Permian (286 ± 6 Ma) palaeomagnetic poles for Australia from the Mount Leyshon Intrusive Complex (MLIC) and the Tuckers Igneous Complex (TIC). Both complexes are associated with prominent negative magnetic anomalies, indicating the presence of rocks carrying stable remanence of reverse polarity, with a Koenigsberger ratio greater than unity. The characteristic remanence carried by the intrusive phases and by locally remagnetized, contact-metamorphosed host rocks is always of reverse polarity, consistent with acquisition during the Permo-Carboniferous (Kiaman) Reverse Superchron. The corresponding palaeopoles confirm that Australia occupied high latitudes in the Early Permian. The pole positions are: MLIC: lat. = 43.2 °S, long. = 137.3 °E; dp=6.0°, dm=6.4°; Q =6; TIC: lat.=47.5 °S, long.=143.0 °E, dp=6.0°, dm=6.6°; Q = 6. Permian palaeomagnetic overprinting is detectable at considerable distances from the MLIC (2–3 km), well beyond the zone of visible alteration. The primary nature of the Early Permian palaeomagnetic signature is established by full baked contact/aureole tests at both localities. Other newdata from Australia are consistent with the poles reported here. Comparison of the Australian, African and South American Apparent Polar Wander Paths (APWP) suggests that mean Permian and Triassic poles fromWest Gondwana, particularly from South America, are biased by remagnetization in the Jurassic–Cretaceous and that the Late Palaeozoic–Mesozoic APWP for Gondwana is best defined by Australian data. The Australian APWP exhibits substantial movement through the Mesozoic. Provided only that the time-averaged palaeofield was zonal, the Early Triassic palaeomagnetic data from Australia provide an important palaeogeographic constraint that the south geographic pole was within, or very close to, SE Australia around 240 Ma. The new Early Permian poles are apparently more consistent with Pangaea B-type reconstructions of Gondwana and Laurussia than with the Pangaea A2 configuration. This may be partly an artefact of reconstruction problems within Gondwana, as systematic differences between approximately coeval, apparently reliable, Permo-Carboniferous poles from Africa, South America and Australia are evident in standard Gondwana reconstructions. These discordances require a tighter fit of the southern continents, suggesting that some attenuation of continental margins, not accounted for in the reconstructions, has occurred during breakup of Gondwana, or that the fit between East and West Gondwana needs to be substantially modified. If stretching of continental margins during breakup of supercontinents is a general phenomenon, it may help to ameliorate, but not solve, the long-standing controversy regarding Pangaea reconstructions. Although alternative Pangaea reconstructions, such as Pangaea B, may reconcile poles from Laurussia with Australian poles in the Late Carboniferous–Early Permian, no plausible reconstruction can bring the Early Triassic poles into agreement. This suggests that persistent departures from a pure dipole field may have been present in the Early Triassic. Lesser, but still significant, non-dipole effects may also have been present during the Late Carboniferous and Permian, and may help resolve the Pangaea A versus B controversy, without requiring substantial attenuation of continental margins or intracontinental deformation. We suggest that the most parsimonious interpretation of the palaeomagnetic and geological information is that Laurussia and Gondwana remained in a Pangaea A2-type configuration through the Permian and Triassic. Discordance between the APWPs for these two supercontinents is attributable mainly to persistent non-dipole components of the geomagnetic field, which were most important in the Early Triassic.25 page(s

    Upper crustal structure of the Tamworth Belt, New South Wales : constraints from new gravity data

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    New gravity data along five profiles across the western side of the southern New England Fold Belt and the adjoining Gunnedah Basin show the Namoi Gravity High over the Tamworth Belt and the Meandarra Gravity Ridge over the Gunnedah Basin. Forward modelling of gravity anomalies, combined with previous geological mapping and a seismic-reflection transect acquired by Geoscience Australia, has led to iterative testing of models of the crustal structure of the southern New England Fold Belt, which indicates that the gravity anomalies can generally be explained using the densities of the presently exposed rock units. The Namoi Gravity High over the Tamworth Belt results from the high density of the rocks of this belt that reflects the mafic volcanic source of the older sedimentary rocks in the Tamworth Belt, the burial metamorphism of the pre-Permian units and the presence of some mafic volcanic units. Modelling shows that the Woolomin Association, present immediately east of the Peel Fault and constituting the most western part of the Tablelands Complex, also has a relatively high density of 2.72 - 2.75 t/m³, and this unit also contributes to the Namoi Gravity High. The Tamworth Belt can be modelled with a configuration where the Tablelands Complex has been thrust over the Tamworth Belt along the Peel Fault that dips steeply to the east. The Tamworth Belt is thrust westward over the Sydney - Gunnedah Basin for 15 - 30 km on the Mooki Fault, which has a shallow dip (∼25°) to the east. The Meandarra Gravity Ridge in the Gunnedah Basin was modelled as a high-density volcanic rock unit with a density contrast of 0.25 t/m³ relative to the underlying rocks of the Lachlan Fold Belt. The modelled volcanic rock unit has a steep western margin, a gently tapering eastern margin and a thickness range of 4.5 - 6 km. These volcanic rocks are assumed to be Lower Permian and to be the western extension of the Permian Werrie Basalts that outcrop on the western edge of the Tamworth Belt and which have been argued to have formed in an extensional basin. Blind granitic plutons are inferred to occur near the Peel Fault along the central and the southern profiles.15 page(s

    Geophysical characterisation of a blind I-type pluton emplaced within the Bundarra Suite S-type granites of the New England Batholith

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    Geophysical data are presented that characterise a blind pluton, the Mountain Home Pluton (MHP), which intrudes the southern portion of the Bundarra Suite (BS), 30 km northeast of Bendemeer, New South Wales. A positive magnetic anomaly within the non-magnetic granites of the BS (Banalasta and Pringles Monzogranites) was previously identified as a sub-surface intrusion. Interpretation of new gravity data and analysis of aeromagnetic data are used to infer the depth, size, density, magnetic susceptibility and likely petrology of the pluton. The best-fit model indicates that the MHP is very similar to the Looanga Monzogranite, a felsic member of the Moonbi Suite of the New England Batholith (NEB) that intrudes the BS 5-7 km southeast of the MHP. The top of the MHP is inferred to lie about 1 km beneath the surface and the pluton extends to a depth of at least 6 km. Our model furthermore suggests that the southwestern margin of the MHP is subvertical, whereas a shallower dip (<45°) towards the north is proposed for the northeastern surface of the pluton. A north-trending dyke swarm, identified on the basis of linear positive magnetic anomalies, may be related to the MHP. This swarm of more than 20 relatively magnetic dykes extends out to about 10 km north from the pluton. Magnetic modelling of the dykes indicates that susceptibility values of the dykes are probably very similar to the range of the MHP, and also suggests the width of individual dykes (also not known to be exposed at the surface) to be at most a few tens of metres. A petrographic examination of the intruded BS granites at the surface suggests that metamorphic zoning as seen in mineralogical characteristics may be related to the underlying pluton.12 page(s
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