158 research outputs found

    Multiabsorber Transition-Edge Sensors for X-Ray Astronomy

    Get PDF
    We are developing arrays of position-sensitive microcalorimeters for future x-ray astronomy applications. These position-sensitive devices commonly referred to as hydras consist of multiple x-ray absorbers, each with a different thermal coupling to a single-transition-edge sensor microcalorimeter. Their development is motivated by a desire to achieve very large pixel arrays with some modest compromise in performance. We report on the design, optimization, and first results from devices with small pitch pixels (<75 m) being developed for a high-angular and energy resolution imaging spectrometer for Lynx. The Lynx x-ray space telescope is a flagship mission concept under study for the National Academy of Science 2020 decadal survey. Broadband full-width-half-maximum (FWHM) resolution measurements on a 9-pixel hydra have demonstrated E(FWHM) = 2.23 0.14 eV at Al-K, E(FWHM) = 2.44 0.29 eV at Mn-K, and E(FWHM) = 3.39 0.23 eV at Cu-K. Position discrimination is demonstrated to energies below <1 keV and the device performance is well-described by a finite-element model. Results from a prototype 20-pixel hydra with absorbers on a 50-m pitch have shown E(FWHM) = 3.38 0.20 eV at Cr-K1. We are now optimizing designs specifically for Lynx and extending the number of absorbers up to 25/hydra. Numerical simulation suggests optimized designs could achieve 3 eV while being compatible with the bandwidth requirements of the state-of-the art multiplexed readout schemes, thus making a 100,000 pixel microcalorimeter instrument a realistic goal

    Metabolic Synergy between Human Symbionts \u3ci\u3eBacteroides\u3c/i\u3e and \u3ci\u3eMethanobrevibacter\u3c/i\u3e

    Get PDF
    ABSTRACT Trophic interactions between microbes are postulated to determine whether a host microbiome is healthy or causes predisposition to disease. Two abundant taxa, the Gram-negative heterotrophic bacterium Bacteroides thetaiotaomicron and the methanogenic archaeon Methanobrevibacter smithii, are proposed to have a synergistic metabolic relationship. Both organisms play vital roles in human gut health; B. thetaiotaomicron assists the host by fermenting dietary polysaccharides, whereas M. smithii consumes end-stage fermentation products and is hypothesized to relieve feedback inhibition of upstream microbes such as B. thetaiotaomicron. To study their metabolic interactions, we defined and optimized a coculture system and used software testing techniques to analyze growth under a range of conditions representing the nutrient environment of the host. We verify that B. thetaiotaomicron fermentation products are sufficient for M. smithii growth and that accumulation of fermentation products alters secretion of metabolites by B. thetaiotaomicron to benefit M. smithii. Studies suggest that B. thetaiotaomicron metabolic efficiency is greater in the absence of fermentation products or in the presence of M. smithii. Under certain conditions, B. thetaiotaomicron and M. smithii form interspecies granules consistent with behavior observed for syntrophic partnerships between microbes in soil or sediment enrichments and anaerobic digesters. Furthermore, when vitamin B12, hematin, and hydrogen gas are abundant, coculture growth is greater than the sum of growth observed for monocultures, suggesting that both organisms benefit from a synergistic mutual metabolic relationship. IMPORTANCE The human gut functions through a complex system of interactions between the host human tissue and the microbes which inhabit it. These diverse interactions are difficult to model or examine under controlled laboratory conditions. We studied the interactions between two dominant human gut microbes, B. thetaiotaomicron and M. smithii, using a seven-component culturing approach that allows the systematic examination of the metabolic complexity of this binary microbial system. By combining high-throughput methods with machine learning techniques, we were able to investigate the interactions between two dominant genera of the gut microbiome in a wide variety of environmental conditions. Our approach can be broadly applied to studying microbial interactions and may be extended to evaluate and curate computational metabolic models. The software tools developed for this study are available as user-friendly tutorials in the Department of Energy KBase

    Local, Regional, and Remote Seismo‐Acoustic Observations of the April 2015 VEI 4 Eruption of Calbuco Volcano, Chile

    Get PDF
    The two major explosive phases of the 22–23 April 2015 eruption of Calbuco volcano, Chile, produced powerful seismicity and infrasound. The eruption was recorded on seismo-acoustic stations out to 1,540 km and on ïŹve stations (IS02, IS08, IS09, IS27, and IS49) of the International Monitoring System (IMS) infrasound network at distances from 1,525 to 5,122 km. The remote IMS infrasound stations provide an accurate explosion chronology consistent with the regional and local seismo-acoustic data and with previous studies of lightning and plume observations. We use the IMS network to detect and locate the eruption signals using a brute-force, grid-search, cross-bearings approach. After incorporating azimuth deviation corrections from stratospheric crosswinds using 3-D ray tracing, the estimated source location is 172 km from true. This case study highlights the signiïŹcant capability of the IMS infrasound network to provide automated detection, characterization, and timing estimates of global explosive volcanic activity. Augmenting the IMS with regional seismo-acoustic networks will dramatically enhance volcanic signal detection, reduce latency, and improve discrimination capability

    Autistic people’s perspectives on stereotypes: An interpretative phenomenological analysis

    Get PDF
    Autism stereotypes can often portray autistic people in a negative way. However, few studies have looked at how autistic people think they are perceived by others, and none have specifically asked autistic people what they think the autistic stereotypes are. Semi-structured interviews with twelve autistic adults (aged between 20-63 years) were conducted. Using Interpretative Phenomenological Analysis, three main themes emerged from the data. These were: (1) primary stereotype is that autistic people are ‘weird’; (2) autistic stereotypes have negative effects and consequences; (3) autistic people are heterogeneous. This study makes an important and novel contribution to understanding the experience of being autistic in several ways by exploring how autistic people feel they are perceived by others and identifying some of the ways in which negative stereotypes are believed to have negative consequences for autistic people

    Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

    Get PDF
    When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than (1.65±0.02)×109 M⊙(1.65\pm0.02) \times 10^9~{M_\odot} using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

    Activation of the integrated stress response (ISR) pathways in response to Ref-1 inhibition in human pancreatic cancer and its tumor microenvironment

    Get PDF
    Pancreatic cancer or pancreatic ductal adenocarcinoma (PDAC) is characterized by a profound inflammatory tumor microenvironment (TME) with high heterogeneity, metastatic propensity, and extreme hypoxia. The integrated stress response (ISR) pathway features a family of protein kinases that phosphorylate eukaryotic initiation factor 2 (eIF2) and regulate translation in response to diverse stress conditions, including hypoxia. We previously demonstrated that eIF2 signaling pathways were profoundly affected in response to Redox factor-1 (Ref-1) knockdown in human PDAC cells. Ref-1 is a dual function enzyme with activities of DNA repair and redox signaling, responds to cellular stress, and regulates survival pathways. The redox function of Ref-1 directly regulates multiple transcription factors including HIF-1α, STAT3, and NF-ÎșB, which are highly active in the PDAC TME. However, the mechanistic details of the crosstalk between Ref-1 redox signaling and activation of ISR pathways are unclear. Following Ref-1 knockdown, induction of ISR was observed under normoxic conditions, while hypoxic conditions were sufficient to activate ISR irrespective of Ref-1 levels. Inhibition of Ref-1 redox activity increased expression of p-eIF2 and ATF4 transcriptional activity in a concentration-dependent manner in multiple human PDAC cell lines, and the effect on eIF2 phosphorylation was PERK-dependent. Treatment with PERK inhibitor, AMG-44 at high concentrations resulted in activation of the alternative ISR kinase, GCN2 and induced levels of p-eIF2 and ATF4 in both tumor cells and cancer-associated fibroblasts (CAFs). Combination treatment with inhibitors of Ref-1 and PERK enhanced cell killing effects in both human pancreatic cancer lines and CAFs in 3D co-culture, but only at high doses of PERK inhibitors. This effect was completely abrogated when Ref-1 inhibitors were used in combination with GCN2 inhibitor, GCN2iB. We demonstrate that targeting of Ref-1 redox signaling activates the ISR in multiple PDAC lines and that this activation of ISR is critical for inhibition of the growth of co-culture spheroids. Combination effects were only observed in physiologically relevant 3D co-cultures, suggesting that the model system utilized can greatly affect the outcome of these targeted agents. Inhibition of Ref-1 signaling induces cell death through ISR signaling pathways, and combination of Ref-1 redox signaling blockade with ISR activation could be a novel therapeutic strategy for PDAC treatment

    Year 1 of the Legacy Survey of Space and Time (LSST): Recommendations for Template Production to Enable Solar System Small Body Transient and Time Domain Science

    Get PDF
    The Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) will discover ~6 million solar system planetesimals, providing in total over a billion photometric and astrometric measurements in 6 broad-band filters. Rubin Observatory's automated data reduction pipelines will employ difference imaging; templates representing the static sky will be subtracted from the nightly LSST observations in order to identify transient sources, including solar system moving objects. These templates are expected to be generated by coadding high quality images of the same pointing from the previous year's survey observations. The first year of LSST operations will require a different method for generating templates, if solar system discoveries are to be reported daily like Year 2 and beyond. We make recommendations for template production in the LSST's first year and present the opportunities for solar system small body transient and time domain science enhanced by this change
    • 

    corecore