175 research outputs found

    An Optically-Discovered Outburst from XTE J1859+226

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    Using the Zwicky Transient Facility, in 2021 February we identified the first known outburst of the Black Hole X-ray Transient XTE J1859+226 since its discovery in 1999. The outburst was visible at X-ray, UV, and optical wavelengths for less than 20 days, substantially shorter than its 320-day full outburst in 1999, and the observed peak luminosity was two orders of magnitude lower. Its peak bolometric luminosity was only 2×10352\times 10^{35} erg s−1^{-1}, implying an Eddington fraction of about 3×10−43\times10^{-4}. The source remained in the hard spectral state throughout the outburst. From optical spectroscopy measurements we estimate an outer disk radius of 1011^{11} cm. The low observed X-ray luminosity is not sufficient to irradiate the entire disk, but we observe a surprising exponential decline in the X-ray lightcurve. These observations highlight the potential of optical and infrared (O/IR) synoptic surveys to discover low-luminosity activity from X-ray transients.Comment: 12 pages, 6 figures, accepted for publication in Ap

    Nanopore-based kinetics analysis of individual antibody-channel and antibody-antigen interactions

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    <p>Abstract</p> <p>Background</p> <p>The UNO/RIC Nanopore Detector provides a new way to study the binding and conformational changes of individual antibodies. Many critical questions regarding antibody function are still unresolved, questions that can be approached in a new way with the nanopore detector.</p> <p>Results</p> <p>We present evidence that different forms of channel blockade can be associated with the same antibody, we associate these different blockades with different orientations of "capture" of an antibody in the detector's nanometer-scale channel. We directly detect the presence of antibodies via reductions in channel current. Changes to blockade patterns upon addition of antigen suggest indirect detection of antibody/antigen binding. Similarly, DNA-hairpin anchored antibodies have been studied, where the DNA linkage is to the carboxy-terminus at the base of the antibody's Fc region, with significantly fewer types of (lengthy) capture blockades than was observed for free (un-bound) IgG antibody. The introduction of chaotropic agents and its effects on protein-protein interactions have also been observed.</p> <p>Conclusion</p> <p>Nanopore-based approaches may eventually provide a direct analysis of the complex conformational "negotiations" that occur upon binding between proteins.</p

    Proteomic Biomarkers for the Prediction of Transition to Psychosis in Individuals at Clinical High Risk: A Multi-cohort Model Development Study

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    Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% (n = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution

    Loss of Nuclear Activity of the FBXO7 Protein in Patients with Parkinsonian-Pyramidal Syndrome (PARK15)

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    Mutations in the F-box only protein 7 gene (FBXO7) cause PARK15, an autosomal recessive neurodegenerative disease presenting with severe levodopa-responsive parkinsonism and pyramidal disturbances. Understanding the PARK15 pathogenesis might thus provide clues on the mechanisms of maintenance of brain dopaminergic neurons, the same which are lost in Parkinson's disease. The protein(s) encoded by FBXO7 remain very poorly characterized. Here, we show that two protein isoforms are expressed from the FBXO7 gene in normal human cells. The isoform 1 is more abundant, particularly in primary skin fibroblasts. Both isoforms are undetectable in cell lines from the PARK15 patient of an Italian family; the isoform 1 is undetectable and the isoform 2 is severely decreased in the patients from a Dutch PARK15 family. In human cell lines and mouse primary neurons, the endogenous or over-expressed, wild type FBXO7 isoform 1 displays mostly a diffuse nuclear localization. An intact N-terminus is needed for the nuclear FBXO7 localization, as N-terminal modification by PARK15-linked missense mutation, or N-terminus tag leads to cytoplasmic mislocalization. Furthermore, the N-terminus of wild type FBXO7 (but not of mutant FBXO7) is able to confer nuclear localization to profilin (a cytoplasmic protein). Our data also suggest that overexpressed mutant FBXO7 proteins (T22M, R378G and R498X) have decreased stability compared to their wild type counterpart. In human brain, FBXO7 immunoreactivity was highest in the nuclei of neurons throughout the cerebral cortex, intermediate in the globus pallidum and the substantia nigra, and lowest in the hippocampus and cerebellum. In conclusion, the common cellular abnormality found in the PARK15 patients from the Dutch and Italian families is the depletion of the FBXO7 isoform 1, which normally localizes in the cell nucleus. The activity of FBXO7 in the nucleus appears therefore crucial for the maintenance of brain neurons and the pathogenesis of PARK15

    An X-ray Census of Young Stars in the Massive Southern Star-Forming Complex NGC 6357

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    We present the first high spatial resolution X-ray study of the massive star forming region NGC 6357, obtained in a 38 ks Chandra/ACIS observation. Inside the brightest constituent of this large HII region complex is the massive open cluster Pismis 24. It contains two of the brightest and bluest stars known, yet remains poorly studied; only a handful of optically bright stellar members have been identified. We investigate the cluster extent and Initial Mass Function and detect ~800 X-ray sources with a limiting sensitivity of 10^{30} ergs s^{-1}; this provides the first reliable probe of the rich intermediate-mass and low-mass population of this massive cluster, increasing the number of known members from optical study by a factor of ~50. The high luminosity end (log L_h[2-8 keV]\ge 30.3 ergs s^{-1}) of the observed X-ray luminosity function in NGC 6357 is clearly consistent with a power law relation as seen in the Orion Nebula Cluster and Cepheus B, yielding the first estimate of NGC 6357's total cluster population, a few times the known Orion population. We investigate the structure of the cluster, finding small-scale substructures superposed on a spherical cluster with 6 pc extent, and discuss its relationship to the nebular morphology. The long-standing Lx - 10^{-7}L_{bol} correlation for O stars is confirmed. Twenty-four candidate O stars and one possible new obscured massive YSO or Wolf-Rayet star are presented. Many cluster members are estimated to be intermediate-mass stars from available infrared photometry (assuming an age of 1 Myr), but only a few exhibit K-band excess. We report the first detection of X-ray emission from an Evaporating Gaseous Globule at the tip of a molecular pillar; this source is likely a B0-B2 protostar.Comment: 64 pages (double columns), 9 table, 17 figures (reduced resolution), ApJ accepted. Please contact J. Wang for full table

    Application of 3D Printing for Smart Objects with Embedded Electronic Sensors and Systems

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    Applications of a 3D printing process are presented. This process integrates liquid-state printed components and interconnects with IC chips in all three dimensions, various orientations, and multiple printing layers to deliver personalized system-level functionalities. As an example application, a form-fitting glove is demonstrated with embedded programmable heater, temperature sensor, and the associated control electronics for thermotherapeutic treatment
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