52 research outputs found

    Characterizing Inorganic Scintillation Detectors for Determining Radiation Exposure -11358

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    ABSTRACT A number of buildings at Oak Ridge National Lab (ORNL) and Y-12 National Security Complex have been slated for deactivation and decommissioning (D&D) under the Integrated Facility Disposition Project (IFDP). Virtually all of these buildings were used for developing nuclear and radiochemical technologies. The buildings slated for D&D may be contaminated with unknown quantities of radioactive materials. A survey to determine the location of radioactive material and the extent of contamination needs to be performed in each building before personnel can safely enter the buildings and begin D&D. This paper describes the method and equipment used to correlate gamma ray spectra to dosimetric data and methods employed in identifying the gamma detectors that are most effective for dosimetric conversion. The absolute efficiency of several NaI(Tl) and LaBr 3 (Ce) detectors have been measured as a function of distance from several high-activity radioactive isotopes. Systematic surveys of contaminated sites can locate and identify contaminating isotopes. If the source is identified and the position is known, an absolute efficiency value can be matched to the source, allowing for the activity to be easily calculated. If the activity of the source has been determined, using methods described by the National Council on Radiation Protection and Measurements, the dose to personnel as a function of distance from a source can be determined

    Phase II Clinical Trial of Robotic Stereotactic Body Radiosurgery for Metastatic Gynecologic Malignancies

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    Background: Recurrent gynecologic cancers are often difficult to manage without significant morbidity. We conducted a phase II study to assess the safety and the efficacy of ablative robotic stereotactic body radiosurgery (SBRT) in women with metastatic gynecologic cancers. Methods: A total of 50 patients with recurrent gynecologic cancer who had single or multiple (≤4) metastases underwent robotic-armed Cyberknife SBRT (24Gy/3 daily doses). Toxicities were graded prospectively by common toxicity criteria for adverse events (version 4.0). SBRT target responses were recorded following RECIST criteria (version 1.0). Rates of clinical benefit for SBRT and non-radiosurgical disease relapse were calculated. Disease-free and overall survivals were estimated by the Kaplan–Meier method and the Cox proportional hazards model was used to control for prognostic variables. Findings: SBRT was safely delivered, with 49 (98%) of 50 patients completing three prescribed fractions. The most frequent grade 2 or higher adverse events attributed to SBRT included fatigue (16%), nausea (8%), and diarrhea (4%). One (2%) grade four hyperbilirubinemia occurred. SBRT target response was 96% (48 of 50 patients). A 6-month clinical benefit was recorded in 34 [68% (95% CI, 53.2, 80.1)] patients. No SBRT targeted disease progressed. Non-radiosurgical disease relapse occurred in 31 (62%) patients. Median disease-free survival was 7.8 months (95% CI, 4.0, 11.6). Median overall survival was 20.2 months (95% CI, 10.9, 29.5). Interpretation: SBRT safely controlled metastatic gynecologic cancer targets. Given an observed high rate of non-radiosurgical disease relapse, a phase I trial assessing co-administration of SBRT and cytotoxic chemotherapy is underway. Funding: Case Comprehensive Cancer Center

    A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita

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    © The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio

    Molecules with ALMA at Planet-forming Scales (MAPS). II. CLEAN strategies for synthesizing images of molecular line emission in protoplanetary disks

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    Funding: I.C. was supported by NASA through NASA Hubble Fellowship grant No. HST-HF2-51405.001-A, awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. C.W. acknowledges financial support from the University of Leeds, STFC, and UKRI (grant Nos. ST/R000549/1, ST/T000287/1, MR/T040726/1) J.D.I. acknowledges support from STFC under ST/T000287/1.The Molecules with ALMA at Planet-forming Scales Large Program (MAPS LP) surveyed the chemical structures of five protoplanetary disks across more than 40 different spectral lines at high angular resolution (0"15 and 0"30 beams for Bands 6 and 3, respectively) and sensitivity (spanning 0.3-1.3 mJy beam-1 and 0.4-1.9 mJy beam-1 for Bands 6 and 3, respectively). In this article, we describe the multistage workflow-built around the CASA tclean image deconvolution procedure-that we used to generate the core data product of the MAPS LP: the position-position-velocity image cubes for each spectral line. Owing to the expansive nature of the survey, we encountered a range of imaging challenges: some are familiar to the submillimeter protoplanetary disk community, like the need to use an accurate CLEAN mask, and others are less well known, like the incorrect default flux scaling of the CLEAN residual map first described by Jorsater & van Moorsel (the "JvM effect"). We distill lessons learned into recommended workflows for synthesizing image cubes of molecular emission. In particular, we describe how to produce image cubes with accurate fluxes via "JvM correction," a procedure that is generally applicable to any image synthesized via CLEAN deconvolution but is especially critical for low signal-to-noise ratio (S/N) emission. We further explain how we used visibility tapering to promote a common, fiducial beam size and contextualize the interpretation of S/N when detecting molecular emission from protoplanetary disks. This paper is part of the MAPS special issue of the Astrophysical Journal Supplement.Publisher PDFPeer reviewe

    Molecules with ALMA at Planet-forming Scales (MAPS). I. Program overview and highlights

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    Funding: I.C. was supported by NASA through the NASA Hubble Fellowship grant HST-HF2-51405.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. C.W. acknowledges financial support from the University of Leeds, Science and Technology Facilities Council of the United Kingdom (STFC), and UKRI (grant Nos. ST/R000549/1, ST/T000287/1, MR/T040726/1).Planets form and obtain their compositions in dust- and gas-rich disks around young stars, and the outcome of this process is intimately linked to the disk chemical properties. The distributions of molecules across disks regulate the elemental compositions of planets, including C/N/O/S ratios and metallicity (O/H and C/H), as well as access to water and prebiotically relevant organics. Emission from molecules also encodes information on disk ionization levels, temperature structures, kinematics, and gas surface densities, which are all key ingredients of disk evolution and planet formation models. The Molecules with ALMA at Planet-forming Scales (MAPS) ALMA Large Program was designed to expand our understanding of the chemistry of planet formation by exploring disk chemical structures down to 10 au scales. The MAPS program focuses on five disks-around IM Lup, GM Aur, AS 209, HD 163296, and MWC 480-in which dust substructures are detected and planet formation appears to be ongoing. We observed these disks in four spectral setups, which together cover ~50 lines from over 20 different species. This paper introduces the Astrophysical Journal Supplement's MAPS Special Issue by presenting an overview of the program motivation, disk sample, observational details, and calibration strategy. We also highlight key results, including discoveries of links between dust, gas, and chemical substructures, large reservoirs of nitriles and other organics in the inner disk regions, and elevated C/O ratios across most disks. We discuss how this collection of results is reshaping our view of the chemistry of planet formation.Publisher PDFPeer reviewe

    Association and interaction of PPAR-complex gene variants with latent traits of left ventricular diastolic function

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    <p>Abstract</p> <p>Background</p> <p>Abnormalities in myocardial metabolism and/or regulatory genes have been implicated in left ventricular systolic dysfunction. However, the extent to which these modulate left ventricular diastolic function (LVDF) is uncertain.</p> <p>Methods</p> <p>Independent component analysis was applied to extract latent LVDF traits from 14 measured echocardiography-derived endophenotypes of LVDF in 403 Caucasians. Genetic association was assessed between measured and latent LVDF traits and 64 single nucleotide polymorphisms (SNPs) in three peroxisome proliferator-activated receptor <it>(PPAR)</it>-complex genes involved in the transcriptional regulation of fatty acid metabolism.</p> <p>Results</p> <p>By linear regression analysis, 7 SNPs (4 in <it>PPARA</it>, 2 in <it>PPARGC1A</it>, 1 in <it>PPARG</it>) were significantly associated with the latent LVDF trait, whereas a range of 0-4 SNPs were associated with each of the 14 measured echocardiography-derived endophenotypes. Frequency distribution of <it>P </it>values showed a greater proportion of significant associations with the latent LVDF trait than for the measured endophenotypes, suggesting that analyses of the latent trait improved detection of the genetic underpinnings of LVDF. Ridge regression was applied to investigate within-gene and gene-gene interactions. In the within-gene analysis, there were five significant pair-wise interactions in <it>PPARGC1A </it>and none in <it>PPARA </it>or <it>PPARG</it>. In the gene-gene analysis, significant interactions were found between rs4253655 in <it>PPARA </it>and rs1873532 (p = 0.02) and rs7672915 (p = 0.02), both in <it>PPARGC1A</it>, and between rs1151996 in <it>PPARG </it>and rs4697046 in <it>PPARGC1A </it>(p = 0.01).</p> <p>Conclusions</p> <p>Myocardial metabolism <it>PPAR</it>-complex genes, including within and between genes interactions, may play an important role modulating left ventricular diastolic function.</p

    AI is a viable alternative to high throughput screening: a 318-target study

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    : High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
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