A field programmable gate array based Langmuir probe system for measurement of plasma parameters at 500 kHz in a high-power impulse magnetron sputtering plasma.

By utilizing Field Programmable Gate Arrays in a configuration similar to that of the Mirror Langmuir Probe, it is possible to bias a single probe at three precise voltages in sequence. These voltages can be dynamically adjusted in real-time based on the measured plasma electron temperature to ensure the transition region is always sampled. The first results have been obtained by employing this method and have generated real-time outputs of electron temperature, ion saturation current, and floating potential on a low temperature pulsed-DC magnetron at 500 kHz. These results are in good agreement with the analysis of a conventionally swept Langmuir probe. This probe is designed with the intention of being implemented on MAST-U to aid in the study of exhaust physics and enable further investigation into filamentary behavior.

2D measurements of plasma electron density using coherence imaging with a pixelated phase mask.

In this paper, the pixelated phase mask (PPM) method of interferometry is applied to coherence imaging (CI)-a passive, narrowband spectral imaging technique for diagnosing the edge and divertor regions of fusion plasma experiments. Compared to previous CI designs that use a linear phase mask, the PPM method allows for a higher possible spatial resolution. The PPM method is also observed to give a higher instrument contrast (analogous to a more narrow spectrometer instrument function). A single-delay PPM instrument is introduced as well as a multi-delay system that uses a combination of both pixelated and linear phase masks to encode the coherence of the observed radiation at four different interferometer delays simultaneously. The new methods are demonstrated with measurements of electron density ne, via Stark broadening of the Hγ emission line at 434.0 nm, made on the Magnum-PSI linear plasma experiment. A comparison of the Abel-inverted multi-delay CI measurements with Thomson scattering shows agreement across the 3 × 1019 < ne < 1 × 1021 m-3 range. For the single-delay CI results, agreement is found for ne > 1 × 1020 m-3 only. Accurate and independent interpretation of single-delay CI data at lower ne was not possible due to Doppler broadening and continuum emission.

Development of an 11-channel multi wavelength imaging diagnostic for divertor plasmas in MAST Upgrade.

Divertor detachment and alternative divertor magnetic geometries are predicted to be promising approaches to handle the power exhaust of future fusion devices. In order to understand the detachment process caused by volumetric losses in alternative divertor magnetic geometries, a Multi-Wavelength Imaging (MWI) diagnostic has recently been designed and built for the Mega Amp Spherical Tokamak Upgrade. The MWI diagnostic will simultaneously capture 11 spectrally filtered images of the visible light emitted from divertor plasmas and provide crucial knowledge for the interpretation of observations and modeling efforts. This paper presents the optical design, mechanical design, hardware, and test results of an 11-channel MWI system with a field of view of 40°. The optical design shows better than 5 mm FWHM spatial resolution at the plasma on all 11 channels across the whole field of view. The spread of angle of incidence on the surface of each filter is also analyzed to inform the bandwidth specification of the interference filters. The results of the initial laboratory tests demonstrate that a spatial resolution of better than 5 mm FWHM is achieved for all 11 channels, meeting the specifications required for accurate tomography.

Doppler coherence imaging of scrape-off-layer impurity flows in the HL-2A tokamak.

A new Doppler coherence imaging spectroscopy interferometer has been developed on the HL-2A tokamak for the scrape-off-layer impurity flow measurement. Its spatial resolution is estimated to be up to ∼0.8 mm in the horizontal direction and ∼9 mm in the vertical direction, with a field of view of ∼34°. Its typical temporal resolution is about 1 ms. This salient feature allows for time-resolved 2D measurements in short-time phenomena on HL-2A, such as edge localized modes. Group delay and interference fringe pattern were calibrated with a dedicated calibration system. The robustness of group delay calibration and the feasibility of the extrapolation model for fringe pattern calibration are demonstrated. In this paper, we report the details of the optical instruments, calibration, and the initial experimental results of this Doppler coherence imaging spectroscopy interferometer.

The digital mirror Langmuir probe: Field programmable gate array implementation of real-time Langmuir probe biasing.

High bandwidth, high spatial resolution measurements of electron temperature, density, and plasma potential are valuable for resolving turbulence in the boundary plasma of tokamaks. While conventional Langmuir probes can provide such measurements, either their temporal or spatial resolution is limited: the former by the sweep rate necessary for obtaining I-V characteristics and the latter by the need to use multiple electrodes, as is the case in triple and double probe configurations. The Mirror Langmuir Probe (MLP) bias technique overcomes these limitations by rapidly switching the voltage on a single electrode cycling between three bias states, each dynamically optimized for the local plasma conditions. The MLP system on Alcator C-Mod used analog circuitry to perform this function, measuring Te, VF, and Isat at 1.1 MSPS. Recently, a new prototype digital MLP controller has been implemented on a Red Pitaya Field Programmable Gate Array (FPGA) board which reproduces the functionality of the original controller and performs all data acquisition. There is also the potential to provide the plasma parameters externally for use with feedback control systems. The use of FPGA technology means the system is readily customizable at a fraction of the development time and implementation cost. A second Red Pitaya was used to test the MLP by simulating the current response of a physical probe using C-Mod experimental measurements. This project is available as a git repository to facilitate extensibility (e.g., real-time control outputs and more voltage states) and scalability through collaboration.

Modifications to the synthetic aperture microwave imaging diagnostic.

The synthetic aperture microwave imaging diagnostic has been operating on the MAST experiment since 2011. It has provided the first 2D images of B-X-O mode conversion windows and showed the feasibility of conducting 2D Doppler back-scattering experiments. The diagnostic heavily relies on field programmable gate arrays to conduct its work. Recent successes and newly gained experience with the diagnostic have led us to modify it. The enhancements will enable pitch angle profile measurements, O and X mode separation, and the continuous acquisition of 2D DBS data. The diagnostic has also been installed on the NSTX-U and is acquiring data since May 2016.

Prognostic serum miRNA biomarkers associated with Alzheimer's disease shows concordance with neuropsychological and neuroimaging assessment.

There is no consensus for a blood-based test for the early diagnosis of Alzheimer's disease (AD). Expression profiling of small non-coding RNA's, microRNA (miRNA), has revealed diagnostic potential in human diseases. Circulating miRNA are found in small vesicles known as exosomes within biological fluids such as human serum. The aim of this work was to determine a set of differential exosomal miRNA biomarkers between healthy and AD patients, which may aid in diagnosis. Using next-generation deep sequencing, we profiled exosomal miRNA from serum (N=49) collected from the Australian Imaging, Biomarkers and Lifestyle Flagship Study (AIBL). Sequencing results were validated using quantitative reverse transcription PCR (qRT-PCR; N=60), with predictions performed using the Random Forest method. Additional risk factors collected during the 4.5-year AIBL Study including clinical, medical and cognitive assessments, and amyloid neuroimaging with positron emission tomography were assessed. An AD-specific 16-miRNA signature was selected and adding established risk factors including age, sex and apolipoprotein ɛ4 (APOE ɛ4) allele status to the panel of deregulated miRNA resulted in a sensitivity and specificity of 87% and 77%, respectively, for predicting AD. Furthermore, amyloid neuroimaging information for those healthy control subjects incorrectly classified with AD-suggested progression in these participants towards AD. These data suggest that an exosomal miRNA signature may have potential to be developed as a suitable peripheral screening tool for AD.

Coherence imaging of scrape-off-layer and divertor impurity flows in the Mega Amp Spherical Tokamak (invited).

A new coherence imaging Doppler spectroscopy diagnostic has been deployed on the UK's Mega Amp Spherical Tokamak for scrape-off-layer and divertor impurity flow measurements. The system has successfully obtained 2D images of C III, C II, and He II line-of-sight flows, in both the lower divertor and main scrape-off-layer. Flow imaging has been obtained at frame rates up to 1 kHz, with flow resolution of around 1 km/s and spatial resolution better than 1 cm, over a 40° field of view. C III data have been tomographically inverted to obtain poloidal profiles of the parallel impurity flow in the divertor under various conditions. In this paper we present the details of the instrument design, operation, calibration, and data analysis as well as a selection of flow imaging results which demonstrate the diagnostic's capabilities.

Enhanced visible and near-infrared capabilities of the JET mirror-linked divertor spectroscopy system.

The mirror-linked divertor spectroscopy diagnostic on JET has been upgraded with a new visible and near-infrared grating and filtered spectroscopy system. New capabilities include extended near-infrared coverage up to 1875 nm, capturing the hydrogen Paschen series, as well as a 2 kHz frame rate filtered imaging camera system for fast measurements of impurity (Be II) and deuterium Dα, Dß, Dγ line emission in the outer divertor. The expanded system provides unique capabilities for studying spatially resolved divertor plasma dynamics at near-ELM resolved timescales as well as a test bed for feasibility assessment of near-infrared spectroscopy.

Packaging of prions into exosomes is associated with a novel pathway of PrP processing.

Prion diseases are fatal, transmissible neurodegenerative disorders associated with conversion of the host-encoded prion protein (PrP(C)) into an abnormal pathogenic isoform (PrP(Sc)). Following exposure to the infectious agent (PrP(Sc)) in acquired disease, infection is propagated in lymphoid tissues prior to neuroinvasion and spread within the central nervous system. The mechanism of prion dissemination is perplexing due to the lack of plausible PrP(Sc)-containing mobile cells that could account for prion spread between infected and uninfected tissues. Evidence exists to demonstrate that the culture media of prion-infected neuronal cells contain PrP(Sc) and infectivity but the nature of the infectivity remains unknown. In this study we have identified PrP(C) and PrP(Sc) in association with endogenously expressing PrP neuronal cell-derived exosomes. The exosomes from our prion-infected neuronal cell line were efficient initiators of prion propagation in uninfected recipient cells and to non-neuronal cells. Moreover, our neuronal cell line was susceptible to infection by non-neuronal cell-derived exosome PrP(Sc). Importantly, these exosomes produced prion disease when inoculated into mice. Exosome-associated PrP is packaged via a novel processing pathway that involves the N-terminal modification of PrP and selection of distinct PrP glycoforms for incorporation into these vesicles. These data extend our understanding of the relationship between PrP and exosomes by showing that exosomes can establish infection in both neighbouring and distant cell types and highlight the potential contribution of differentially processed forms of PrP in disease distribution. These data suggest that exosomes represent a potent pool of prion infectivity and provide a mechanism for studying prion spread and PrP processing in cells endogenously expressing PrP.

Aspartyl protease inhibitor pepstatin binds to the presenilins of Alzheimer's disease.

Mutations in the presenilin genes PS1 and PS2 cause early-onset Alzheimer's disease by altering gamma-secretase cleavage of the amyloid precursor protein, the last step in the generation of Abeta peptide. Ablation of presenilin (PS) genes, or mutation of two critical aspartates, abolishes gamma-secretase cleavage, suggesting that PS may be the gamma-secretases. Independently, inhibition experiments indicate that gamma-secretase is an aspartyl protease. To characterize the putative gamma-secretase activity associated with presenilins, lysates from human neuroblastoma SH-SY5Y and human brain homogenates were incubated with biotin derivatives of pepstatin, followed by immunoprecipitation of PS and associated proteins, and biotin detection by Western blotting. Precipitation with PS1 antibodies, directed to either N-terminal or loop regions, yielded the same 43 kDa band, of apparent molecular mass consistent with that of full-length PS1, although it may represent an aspartyl protease complexed with PS1. Incubation of cell lysates with pepstatin-biotin, followed by streptavidin precipitation and PS1 Western blotting, revealed PS1 fragments and full-length protein, indicating that pepstatin-biotin bound to both cleaved and uncleaved PS1. Binding could be competed by gamma-secretase inhibitor L-685,458 and could not be achieved with a PS1 mutant lacking the two transmembrane aspartates. Pepstatin-biotin was also shown to bind to PS2. PS1 was specifically absorbed to pepstatin-agarose, with an optimal pH of 6. Binding of pepstatin-biotin to PS1 from lymphocytes of a heterozygous carrier of pathologic exon 9 deletion was markedly decreased as compared to control lymphocytes, suggesting that this PS1 mutation altered the pepstatin binding site.

Cryogenic wavefront correction using membrane deformable mirrors.

Micro-machined membrane deformable mirrors (MMDMs) are being evaluated for their suitability as wavefront correctors at cryogenic temperatures. Presented here are experimental results for the change in the initial mirror figure of 37-channel MMDMs from OKO Technologies upon cooling to T=78K. The changes in the influence functions are also explored. Of the sample of 3 mirrors tested, one was found to have sufficiently small initial static aberrations to be useful as a wavefront corrector at this temperature. The influence functions at T=78K were found to be similar in shape to both those at room temperature and theoretical predictions of the MMDMs surface shape. The magnitude of the surface deflection at T=78K was reduced by around 20% compared with room temperature values.

Adriamycin-induced inhibition of mitochondrial-encoded polypeptides as a model system for the identification of hotspots for DNA-damaging agents.

It has recently been shown that the anti-cancer drug Adriamycin forms drug-DNA adducts which function as 'virtual' interstrand cross-links in cells, and these cross-links are specific for GpC sequences. The objective of this work was to determine whether all GpC sites are equally susceptible to the formation of Adriamycin-DNA adducts in the mitochondrial genome or whether any 'hotspots' exist whereby lesions are formed preferentially at particular GpC-containing sequences. The mitochondrial genome was used as a model system as it provides a series of contiguous genes, all of which lack introns and in which transcription is driven from a single promoter. With the absence of nucleotide excision repair, this provides an excellent system with which to observe Adriamycin-induced DNA damage since such lesions are reflected as an inhibition of mitochondrial protein synthesis. HeLa cells were treated with Adriamycin and the extent to which synthesis of individual mitochondrial-encoded proteins was inhibited was quantitated. Mitochondrial protein synthesis was found to be inhibited in a discontinuous manner, corresponding to regions rich in 5'-GpC sequences. These results therefore indicate that Adriamycin-DNA adducts do not form randomly with GpC sites throughout the mitochondrial genome, but instead appear to form preferentially at regions of high GpC content. This selective inhibition of mitochondrial-encoded proteins demonstrates the potential of this method for the in situ detection of localized regions of binding by DNA-acting drugs.

Presenilin 2 expression in neuronal cells: induction during differentiation of embryonic carcinoma cells.

Mutations in the presenilin 1 and 2 (PS1 and PS2) genes cause most cases of early onset Alzheimer's disease. The genes encode two homologous multipass membrane proteins. Since the endogenous expression of PS2 has been poorly analyzed to date, we studied PS2 expression and localization in cultured human neuroblastoma cells and mouse neuronal cells. PS2 was mainly detected as a full-length protein of about 52 kDa in these cells and in brain, in contrast to PS1 that is mainly detected as endoproteolytic N-terminal and C-terminal fragments. Using immunofluorescence we found that like PS1, PS2 colocalized with markers of the endoplasmic reticulum-Golgi intermediate compartment, ERGIC-53 and beta-COP. Double labeling for PS1 and PS2 indicated that both proteins are colocalized in neuroblastoma SH-SY5Y cells. To study PS2 expression during differentiation, mouse embryonic carcinoma P19 cells were treated with retinoic acid. We found minimal PS2 expression in undifferentiated cells, an increase from day 2, and a maximum at day 8 after treatment. PS1 expression remained constant during this period. The differential expression of PS1 and PS2 within the P19 cells following retinoic acid treatment indicates different utilization or temporal requirements for these proteins during neuronal differentiation.

Dual-conjugate wavefront generation for adaptive optics.

We present results of the isoplanatic performance of an astronomical adaptive optics system in the laboratory, by using a dual layer turbulence simulator. We describe how the performance of adaptive correction degrades with off--axis angle. These experiments demonstrate that it is now possible to produce quantifiable multi-layer turbulence in the laboratory as a precursor to constructing multi-conjugate adaptive optics.

Binary adaptive optics: atmospheric wave-front correction with a half-wave phase shifter.

We describe a binary approach to adaptive wave-front correction, especially suitable for narrow band applications, which would be simpler than conventional adaptive technology. Appropriate parts of the aberrant wave front are phase retarded by half a wavelength to ensure that none of the image-forming rays add together destructively. Simulations for monochromatic light show that the residual wave-front errors, in the absence of other errors, would result in Strehl ratios of ~40% with diffraction-limited widths at visible wavelengths. We simulate the imaging performance of such a system and describe a possible implementation that uses a ferroelectric liquid-crystal spatial light modulator.