Wire tomography in the H-1NF heliac for investigation of fine structure of magnetic islands

Electron beam wire tomography in the H-1NF heliac enables high resolution mapping of vacuum flux surfaces with minimal disruption of the plasma operations schedule. Recent experimental results have proven this technique to be a highly accurate and high resolution method for mapping vacuum magnetic islands. Islands of width as small as delta approximately 8 mm have been measured, providing estimates of the internal rotational transform of the island. Point-to-point comparison of the mapping results with computer tracing, in conjunction with an image warping technique, enables systematic exploration of magnetic islands and surfaces of interest. Recent development of a fast mapping technique significantly reduced the mapping time and made this technique suitable for mapping at higher magnetic fields. This article presents recent experimental results and associated techniques.with support from the Australian Research Council Grant No. DP0344361

Core magnetic islands and plasma confinement in the H-1NF heliac

Plasma confinement in the vicinity of vacuum magnetic islands near the magnetic axis in the H-1NF heliac [S. M. Hamberger et al., Fusion Technol.17, 123 (1990)] has been experimentally studied in a low temperature argon plasma. Experimental results indicate that, under favorable conditions, these low order (m=2)islands near the core of the plasma serve as “pockets” of higher electron density. This results in significant profile modifications including enhancement of the core radial electric field to a large positive value, possibly through an electron-root ambipolar condition. The characteristics of islands are found to be dependent on the plasma collisionality and island width.This research was supported in part by the Australian Research Council Grant No. DP0344361 and the U.S. Department of Energy under Contract No. DE-AC05- 00OR22725 with UT-Battelle, LLC

Three view electronically scanned interferometer for plasma electron density measurements on the H-1 heliac

We report the development of a three view electronically scanned millimeter-wave interferometer for plasma electron density profile measurement on the H-1 heliac. The system utilizes an electronically tunable backward-wave oscillator whose output is incident on a fixed blazed diffraction grating such that sweeping the source frequency effects a spatial scan of the plasma cross section. Two diagonal views essentially span most of the plasma cross section, while the horizontal arm views the lower half of the plasma. The diffracted beams traverse the plasma in <1ms with a spatial resolution ∼20mm. A study of the density projection dependence on magnetic configuration shows that the presence of low-order rational surfaces in the plasma gives rise to sharp density gradients in the vicinity of the surface

Virtual screening leads to the discovery of novel non-nucleotide P2Y1 receptor antagonists

The P2Y1 receptor (P2Y1R) is a G protein-coupled receptor naturally activated by extracellular ADP. Its stimulation is an essential requirement of ADP-induced platelet aggregation, thus making antagonists highly sought compounds for the development of antithrombotic agents. Here, through a virtual screening campaign based on a pharmacophoric representation of the common characteristics of known P2Y1R ligands and the putative shape and size of the receptor binding pocket, we have identified novel antagonist hits of µM affinity derived from a N,N’-bis-arylurea chemotype. Unlike the vast majority of known P2Y1R antagonists, these drug-like compounds do not have a nucleotidic scaffold or highly negatively charged phosphate groups. Hence, our compounds may provide a direction for the development of receptor probes with altered physicochemical properties

Synthesis and P2Y₂ receptor agonist activities of uridine 5'-phosphonate analogues

We explored the influence of modifications of uridine 5’-methylenephosphonate on biological activity at the human P2Y(2) receptor. Key steps in the synthesis of a series of 5-substituted uridine 5’-methylenephosphonates were the reaction of a suitably protected uridine 5’-aldehyde with [(diethoxyphosphinyl)methylidene]triphenylphosphorane, C-5 bromination and a Suzuki–Miyaura coupling. These analogues behaved as selective agonists at the P2Y(2) receptor, with three analogues exhibiting potencies in the submicromolar range. Although maximal activities observed with the phosphonate analogues were much less than observed with UTP, high concentrations of the phosphonates had no effect on the stimulatory effect of UTP. These results suggest that these phosphonates bind to an allosteric site of the P2Y(2) receptor

Dopamine D2 receptor-mediated modulation of adenosine A2A receptor agonist binding within the A2AR/D2R oligomer framework

The molecular interaction between adenosine A(2A) and dopamine D-2 receptors (A(2A)Rs and D(2)Rs, respectively) within an oligomeric complex has been postulated to play a pivotal role in the adenosine-dopamine interplay in the central nervous system, in both normal and pathological conditions (e.g. Parkinson's disease). While the effects of A(2A)R challenge on D2R functioning have been largely studied, the reverse condition is still unexplored, a fact that might have impact in therapeutics. Here, we aimed to examine in a real-time mode the D2R-mediated allosteric modulation of A(2A)R binding when an A(2A)R/D2R oligomer is established. Thus, we synthesized fluorescent A(2A)R agonists and evaluated, by means of a flow cytometry homogeneous no-wash assay and a real-time fluorescence resonance energy transfer (FRET)-based approach, the effects on A(2A)R binding of distinct antiparkinsonian drugs in current clinical use (i.e. pramipexole, rotigotine and apomorphine). Our results provided evidence for the existence of a differential D2R-mediated negative allosteric modulation on A(2A)R agonist binding that was oligomer-formation dependent, and with apomorphine being the best antiparkinsonian drug attenuating A(2A)R agonist binding. Overall, the here-developed methods were found valid to explore the ability of drugs acting on D(2)Rs to modulate A(2A)R binding, thus serving to facilitate the preliminary selection of D2R-like candidate drugs in the management of Parkinson's disease. (c) 2013 Elsevier Ltd. All rights reserved

Synthesis and P2Y2 receptor agonist activities of uridine 5′-phosphonate analogues

We explored the influence of modifications of uridine 5’-methylenephosphonate on biological activity at the human P2Y2 receptor. Key steps in the synthesis of a series of 5-substituted uridine 5’-methylenephosphonates were the reaction of a suitably protected uridine 5’-aldehyde with [(diethoxyphosphinyl)methylidene]triphenylphosphorane, C-5 bromination and a Suzuki–Miyaura coupling. These analogues behaved as selective agonists at the P2Y2 receptor, with three analogues exhibiting potencies in the submicromolar range. Although maximal activities observed with the phosphonate analogues were much less than observed with UTP, high concentrations of the phosphonates had no effect on the stimulatory effect of UTP. These results suggest that these phosphonates bind to an allosteric site of the P2Y2 receptor

Speech delays and behavioral problems are the predominant features in individuals with developmental delays and 16p11.2 microdeletions and microduplications

Microdeletions and microduplications encompassing a ~593-kb region of 16p11.2 have been implicated as one of the most common genetic causes of susceptibility to autism/autism spectrum disorder (ASD). We report 45 microdeletions and 32 microduplications of 16p11.2, representing 0.78% of 9,773 individuals referred to our laboratory for microarray-based comparative genomic hybridization (aCGH) testing for neurodevelopmental and congenital anomalies. The microdeletion was de novo in 17 individuals and maternally inherited in five individuals for whom parental testing was available. Detailed histories of 18 individuals with 16p11.2 microdeletions were reviewed; all had developmental delays with below-average intelligence, and a majority had speech or language problems or delays and various behavioral problems. Of the 16 individuals old enough to be evaluated for autism, the speech/behavior profiles of seven did not suggest the need for ASD evaluation. Of the remaining nine individuals who had speech/behavior profiles that aroused clinical suspicion of ASD, five had formal evaluations, and three had PDD-NOS. Of the 19 microduplications with parental testing, five were de novo, nine were maternally inherited, and five were paternally inherited. A majority with the microduplication had delayed development and/or specific deficits in speech or language, though these features were not as consistent as seen with the microdeletions. This study, which is the largest cohort of individuals with 16p11.2 alterations reported to date, suggests that 16p11.2 microdeletions and microduplications are associated with a high frequency of cognitive, developmental, and speech delay and behavior abnormalities. Furthermore, although features associated with these alterations can be found in individuals with ASD, additional factors are likely required to lead to the development of ASD

Modulation of Sn concentration in ZnO nanorod array: intensification on the conductivity and humidity sensing properties

Tin (Sn)-doped zinc oxide (ZnO) nanorod arrays (TZO) were synthesized onto aluminum-doped ZnO-coated glass substrate via a facile sonicated sol–gel immersion method for humidity sensor applications. These nanorod arrays were grown at different Sn concentrations ranging from 0.6 to 3 at.%. X-ray diffraction patterns showed that the deposited TZO arrays exhibited a wurtzite structure. The stress/strain condition of the ZnO film metamorphosed from tensile strain/compressive stress to compressive strain/tensile stress when the Sn concentrations increased. Results indicated that 1 at.% Sn doping of TZO, which has the lowest tensile stress of 0.14 GPa, generated the highest conductivity of 1.31 S cm− 1. In addition, 1 at.% Sn doping of TZO possessed superior sensitivity to a humidity of 3.36. These results revealed that the optimum performance of a humidity-sensing device can be obtained mainly by controlling the amount of extrinsic element in a ZnO film