191 research outputs found

    Faraday Cup Designs for High Efficiency Determination of Energy- and Angular-Resolved Charged Particle Fluxes

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    Faraday cups provide a simple and efficient apparatus to measure the absolute magnitude of charge particle fluxes, and with the addition of a retarding field analyzer and defining apertures the capability to determine the energy and angular distributions of the fluxes. Through careful design of the electron optics, a Faraday cup can be tailored to meet specific requirements for detector size, minimum detectable flux, collection efficiency, absolute accuracy, energy discrimination, and angular resolution. This project explores optimal design concepts through electric field and charged particle trajectory simulations, theoretical analysis, and evaluation of experimental prototypes to develop compact, high efficiency Faraday cups capable of a range of energy and angular resolutions. The designs rely on high capture-efficiency Faraday cups, coupled with grid-free Einzel lens energy analyzers for nearly energy-independent determination of absolute fluxes. The project will also develop specific designs for applications of these Faraday cup detectors to electron emission and transport studies, spacecraft charging applications, and electron beam characterization measurements done in conjunction with various projects conducted by the Materials Physics Group

    Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours

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    BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of γ-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of γ-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent γ-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and γ-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0534-2) contains supplementary material, which is available to authorized users

    Caregiver perceptions of children who have complex communication needs following a home-based intervention using augmentative and alternative communication in rural Kenya: an intervention note:Home-based intervention using AAC in rural Kenya

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    A high level of unmet communication need exists amongst children with developmental disabilities in sub-Saharan Africa. This study investigated preliminary evidence of the impact associated with a home-based, caregiver-implemented intervention employing AAC methods, with nine children in rural Kenya who have complex communication needs. The intervention used mainly locally-sourced low-tech materials, and was designed to make use of the child's strengths and the caregiver's natural expertise. A pretest-posttest design was used in the study. Data were gathered using an adapted version of the Communication Profile, which was based on the International Classification of Functioning, Disability, and Health (ICF) framework. The non-parametric Wilcoxon signed-rank test was applied to data from the first two sections of the Communication Profile-Adapted. Qualitative analysis was conducted on the final section. The data provided evidence of statistically significant positive changes in caregiver perceptions of communication at the levels of Body Structure and Function, and Activities for Communication. Also, analysis of the Participation for Communication section revealed some expansion to the children's social activities. The potential impact of the home-based intervention would benefit from investigation on a larger scale. Limitations of the study are discussed

    Wide-field lensing mass maps from Dark Energy Survey science verification data: methodology and detailed analysis

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    Weak gravitational lensing allows one to reconstruct the spatial distribution of the projected mass density across the sky. These "mass maps" provide a powerful tool for studying cosmology as they probe both luminous and dark matter. In this paper, we present a weak lensing mass map reconstructed from shear measurements in a 139 deg2 area from the Dark Energy Survey (DES) science verification data. We compare the distribution of mass with that of the foreground distribution of galaxies and clusters. The overdensities in the reconstructed map correlate well with the distribution of optically detected clusters. We demonstrate that candidate superclusters and voids along the line of sight can be identified, exploiting the tight scatter of the cluster photometric redshifts. We cross-correlate the mass map with a foreground magnitude-limited galaxy sample from the same data. Our measurement gives results consistent with mock catalogs from N -body simulations that include the primary sources of statistical uncertainties in the galaxy, lensing, and photo-z catalogs. The statistical significance of the cross-correlation is at the 6.8 sigma level with 20 arcminute smoothing. We find that the contribution of systematics to the lensing mass maps is generally within measurement uncertainties. In this work, we analyze less than 3% of the final area that will be mapped by the DES; the tools and analysis techniques developed in this paper can be applied to forthcoming larger data sets from the survey

    Wide-field lensing mass maps from Dark Energy Survey science verification data

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    We present a mass map reconstructed from weak gravitational lensing shear measurements over 139 deg2 from the Dark Energy Survey science verification data. The mass map probes both luminous and dark matter, thus providing a tool for studying cosmology. We find good agreement between the mass map and the distribution of massive galaxy clusters identified using a red-sequence cluster finder. Potential candidates for superclusters and voids are identified using these maps. We measure the cross-correlation between the mass map and a magnitude-limited foreground galaxy sample and find a detection at the 6.8 sigma level with 20 arc min smoothing. These measurements are consistent with simulated galaxy catalogs based on N -body simulations from a cold dark matter model with a cosmological constant. This suggests low systematics uncertainties in the map. We summarize our key findings in this Letter; the detailed methodology and tests for systematics are presented in a companion paper

    Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2

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    Joining a function-enhanced Fc-portion of human IgG to the SARS-CoV-2 entry receptor ACE2 produces an antiviral decoy with strain transcending virus neutralizing activity. SARS-CoV-2 neutralization and Fc-effector functions of ACE2-Fc decoy proteins, formatted with or without the ACE2 collectrin domain, were optimized by Fc-modification. The different Fc-modifications resulted in distinct effects on neutralization and effector functions. H429Y, a point mutation outside the binding sites for FcγRs or complement caused non-covalent oligomerization of the ACE2-Fc decoy proteins, abrogated FcγR interaction and enhanced SARS-CoV-2 neutralization. Another Fc mutation, H429F did not improve virus neutralization but resulted in increased C5b-C9 fixation and transformed ACE2-Fc to a potent mediator of complement-dependent cytotoxicity (CDC) against SARS-CoV-2 spike (S) expressing cells. Furthermore, modification of the Fc-glycan enhanced cell activation via FcγRIIIa. These different immune profiles demonstrate the capacity of Fc-based agents to be engineered to optimize different mechanisms of protection for SARS-CoV-2 and potentially other viral pathogens

    The electromagnetic counterpart of the binary neutron star merger LIGO/Virgo GW170817. I. discovery of the optical counterpart using the Dark Energy Camera

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    We present the Dark Energy Camera (DECam) discovery of the optical counterpart of the first binary neutron star merger detected through gravitational-wave emission, GW170817. Our observations commenced 10.5 hr post-merger, as soon as the localization region became accessible from Chile. We imaged 70 deg2 in the i and z bands, covering 93% of the initial integrated localization probability, to a depth necessary to identify likely optical counterparts (e.g., a kilonova). At 11.4 hr post-merger we detected a bright optical transient located 10.6 from the nucleus of NGC 4993 at redshift z=0.0098, consistent (for H0 = 70 km s−1 Mpc−1) with the distance of 40±8 Mpc reported by the LIGO Scientific Collaboration and the Virgo Collaboration (LVC). At detection the transient had magnitudes of i = 17.3 and z = 17.4, and thus an absolute magnitude of Mi = -15.7, in the luminosity range expected for a kilonova. We identified 1500 potential transient candidates. Applying simple selection criteria aimed at rejecting background events such as supernovae, we find the transient associated with NGC 4993 as the only remaining plausible counterpart, and reject chance coincidence at the 99.5% confidence level. We therefore conclude that the optical counterpart we have identified near NGC 4993 is associated with GW170817. This discovery ushers in the era of multi-messenger astronomy with gravitational waves and demonstrates the power of DECam to identify the optical counterparts of gravitational-wave sources

    The Dark Energy Survey Data Release 2

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    We present the second public data release of the Dark Energy Survey, DES DR2, based on optical/near-infrared imaging by the Dark Energy Camera mounted on the 4 m Blanco telescope at Cerro Tololo Inter-American Observatory in Chile. DES DR2 consists of reduced single-epoch and coadded images, a source catalog derived from coadded images, and associated data products assembled from 6 yr of DES science operations. This release includes data from the DES wide-area survey covering ∼5000 deg2 of the southern Galactic cap in five broad photometric bands, grizY. DES DR2 has a median delivered point-spread function FWHM of g = 1.11′′, r = 0.95′′, i = 0.88′′, z = 0.83′′, and Y = 0.′′90, photometric uniformity with a standard deviation of < 3 mmag with respect to Gaia DR2 G band, a photometric accuracy of ∼11 mmag, and a median internal astrometric precision of ∼27 mas. The median coadded catalog depth for a 1.′′95 diameter aperture at signal-to-noise ratio = 10 is g = 24.7, r = 24.4, i = 23.8, z = 23.1, and Y = 21.7 mag. DES DR2 includes ∼691 million distinct astronomical objects detected in 10,169 coadded image tiles of size 0.534 deg2 produced from 76,217 single-epoch images. After a basic quality selection, benchmark galaxy and stellar samples contain 543 million and 145 million objects, respectively. These data are accessible through several interfaces, including interactive image visualization tools, web-based query clients, image cutout servers, and Jupyter notebooks. DES DR2 constitutes the largest photometric data set to date at the achieved depth and photometric precision
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