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    Finding communities in sparse networks

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    Spectral algorithms based on matrix representations of networks are often used to detect communities, but classic spectral methods based on the adjacency matrix and its variants fail in sparse networks. New spectral methods based on non-backtracking random walks have recently been introduced that successfully detect communities in many sparse networks. However, the spectrum of non-backtracking random walks ignores hanging trees in networks that can contain information about their community structure. We introduce the reluctant backtracking operators that explicitly account for hanging trees as they admit a small probability of returning to the immediately previous node, unlike the non-backtracking operators that forbid an immediate return. We show that the reluctant backtracking operators can detect communities in certain sparse networks where the non-backtracking operators cannot, while performing comparably on benchmark stochastic block model networks and real world networks. We also show that the spectrum of the reluctant backtracking operator approximately optimises the standard modularity function. Interestingly, for this family of non- and reluctant-backtracking operators the main determinant of performance on real-world networks is whether or not they are normalised to conserve probability at each node

    Entry mechanisms of herpes simplex virus 1 into murine epidermis: involvement of nectin-1 and herpesvirus entry mediator as cellular receptors.

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    UNLABELLED: Skin keratinocytes represent a primary entry site for herpes simplex virus 1 (HSV-1) in vivo. The cellular proteins nectin-1 and herpesvirus entry mediator (HVEM) act as efficient receptors for both serotypes of HSV and are sufficient for disease development mediated by HSV-2 in mice. How HSV-1 enters skin and whether both nectin-1 and HVEM are involved are not known. We addressed the impact of nectin-1 during entry of HSV-1 into murine epidermis and investigated the putative contribution of HVEM. Using ex vivo infection of murine epidermis, we showed that HSV-1 entered the basal keratinocytes of the epidermis very efficiently. In nectin-1-deficient epidermis, entry was strongly reduced. Almost no entry was observed, however, in nectin-1-deficient keratinocytes grown in culture. This observation correlated with the presence of HVEM on the keratinocyte surface in epidermis and with the lack of HVEM expression in nectin-1-deficient primary keratinocytes. Our results suggest that nectin-1 is the primary receptor in epidermis, while HVEM has a more limited role. For primary murine keratinocytes, on which nectin-1 acts as a single receptor, electron microscopy suggested that HSV-1 can enter both by direct fusion with the plasma membrane and via endocytic vesicles. Thus, we concluded that nectin-1 directs internalization into keratinocytes via alternative pathways. In summary, HSV-1 entry into epidermis was shown to strongly depend on the presence of nectin-1, but the restricted presence of HVEM can potentially replace nectin-1 as a receptor, illustrating the flexibility employed by HSV-1 to efficiently invade tissue in vivo. IMPORTANCE: Herpes simplex virus (HSV) can cause a range of diseases in humans, from uncomplicated mucocutaneous lesions to life-threatening infections. The skin is one target tissue of HSV, and the question of how the virus overcomes the protective skin barrier and penetrates into the tissue to reach its receptors is still open. Previous studies analyzing entry into cells grown in vitro revealed nectin-1 and HVEM as HSV receptors. To explore the contributions of nectin-1 and HVEM to entry into a natural target tissue, we established an ex vivo infection model. Using nectin-1- or HVEM-deficient mice, we demonstrated the distinct involvement of nectin-1 and HVEM for HSV-1 entry into epidermis and characterized the internalization pathways. Such advances in understanding the involvement of receptors in tissue are essential preconditions for unraveling HSV invasion of skin, which in turn will allow the development of antiviral reagents

    The Herschel Virgo Cluster Survey. XVIII. Star-forming dwarf galaxies in a cluster environment

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    To assess the effects of the cluster environment on the different components of the interstellar medium, we analyse the far-infrared (FIR) and submillimetre (submm) properties of a sample of star-forming dwarf galaxies detected by the Herschel Virgo Cluster Survey (HeViCS). We determine dust masses and dust temperatures by fitting a modified black body function to the spectral energy distributions (SEDs). Stellar and gas masses, star formation rates (SFRs), and metallicities are obtained from the analysis of a set of ancillary data. Dust is detected in 49 out of a total 140 optically identified dwarfs covered by the HeViCS field; considering only dwarfs brighter than mB = 18 mag, this gives a detection rate of 43%. After evaluating different emissivity indices, we find that the FIR-submm SEDs are best-fit by β = 1.5, with a median dust temperature Td = 22.4 K. Assuming β = 1.5, 67% of the 23 galaxies detected in all five Herschel bands show emission at 500 μm in excess of the modified black-body model. The fraction of galaxies with a submillimetre excess decreases for lower values of β, while a similarly high fraction (54%) is found if a β-free SED modelling is applied. The excess is inversely correlated with SFR and stellar masses. To study the variations in the global properties of our sample that come from environmental effects, we compare the Virgo dwarfs to other Herschel surveys,such as the Key Insights into Nearby Galaxies: Far-Infrared Survey with Herschel (KINGFISH), the Dwarf Galaxy Survey (DGS), and the HeViCS Bright Galaxy Catalogue (BGC). We explore the relations between stellar mass and Hi fraction, specific star formation rate, dust fraction, gas-to-dust ratio over a wide range of stellar masses (from 107 to 1011 M⊙) for both dwarfs and spirals. Highly Hi-deficient Virgo dwarf galaxies are mostly characterised by quenched star formation activity and lower dust fractions giving hints for dust stripping in cluster dwarfs. However, to explain the large dust-to-gas mass ratios observed in these systems, we find that the fraction of dust removed has to be less than that of the Hi component. The cluster environment seems to mostly affect the gas component and star formation activity of the dwarfs. Since the Virgo star-forming dwarfs are likely to be crossing the cluster for the first time, a longer timescale might be necessary to strip the more centrally concentrated dust distribution

    Restoration of Vision with Ectopic Expression of Human Rod Opsin

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    Many retinal dystrophies result in photoreceptor loss, but the inner retinal neurons can survive, making them potentially amenable to emerging optogenetic therapies. Here, we show that ectopically expressed human rod opsin, driven by either a non-selective or ON-bipolar cell-specific promoter, can function outside native photoreceptors and restore visual function in a mouse model of advanced retinal degeneration. Electrophysiological recordings from retinal explants and the visual thalamus revealed changes in firing (increases and decreases) induced by simple light pulses, luminance increases, and naturalistic movies in treated mice. These responses could be elicited at light intensities within the physiological range and substantially below those required by other optogenetic strategies. Mice with rod opsin expression driven by the ON-bipolar specific promoter displayed behavioral responses to increases in luminance, flicker, coarse spatial patterns, and elements of a natural movie at levels of contrast and illuminance (≈50–100 lux) typical of natural indoor environments. These data reveal that virally mediated ectopic expression of human rod opsin can restore vision under natural viewing conditions and at moderate light intensities. Given the inherent advantages in employing a human protein, the simplicity of this intervention, and the quality of vision restored, we suggest that rod opsin merits consideration as an optogenetic actuator for treating patients with advanced retinal degeneration

    The End of the Beginning: Virgil's Aeneid and Ovid, Amores 1.2

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    Robust spectrometer-based methods for characterizing radiant exitance of dental LED light curing units

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    Objectives Firstly, to assess light output, from a representative range of dental light curing units (LCUs), using a new portable spectrometer based instrument (checkMARC™) compared with a “gold standard” method. Secondly, to assess possible inconsistency between light output measurements using three different laboratory-grade thermopile instruments. Methods The output of four blue-dental LCUs and four polywave blue-and-violet-LCUs was measured with two spectrometer-based systems: a portable spectrometer instrument and a benchtop Integrating Sphere fiber-coupled spectrometer system. Power output was also recorded with three thermopiles according to ISO 10650-2. Beam profile images were recorded of LCU output to assess for spatial and spectral beam uniformity. Results Power recorded with the portable spectrometer instrument closely matched the ‘gold standard’ Integrating Sphere apparatus calibrated according to International Standards. Radiant exitance for the eight LCUs differed significantly between the three thermopiles. Light source to thermopile sensor distance influenced recorded power significantly (p <0.05), indicating the severe limitations of thermopiles for absolute measurements. Polywave LCU beam profiles demonstrated output spectral heterogeneity. Significance Spectrometer-based methods are capable of overcoming the limitations inherent with thermopile-based measurement techniques. Spectrometer based measurements can fulfill the intention of ISO 10650

    Impact of daily anatomical changes on EPID-based in vivo dosimetry of VMAT treatments of head-and-neck cancer.

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    BACKGROUND AND PURPOSE: Target dose verification for VMAT treatments of head-and-neck (H&N) cancer using 3D in vivo EPID dosimetry is expected to be affected by daily anatomical changes. By including these anatomical changes through cone-beam CT (CBCT) information, the magnitude of this effect is investigated. MATERIALS AND METHODS: For 20 VMAT-treated H&N cancer patients, all plan-CTs (pCTs), 633 CBCTs and 1266 EPID movies were used to compare four dose distributions per fraction: treatment planning system (TPS) calculated dose and EPID reconstructed in vivo dose, both determined using the pCT and using the CBCT. D2, D50 and D98 of the planning target volume (PTV) were determined per dose distribution. RESULTS: When including daily anatomical information, D2, D50 and D98 of the PTV change on average by 0.0±0.4% according to TPS calculations; the standard deviation of the difference between EPID and TPS target dose changes from 2.5% (pCT) to 2.1% (CBCT). Small time trends are seen for both TPS and EPID dose distributions when using the pCT, which disappear when including CBCT information. CONCLUSIONS: Daily anatomical changes hardly influence the target dose distribution for H&N VMAT treatments according to TPS recalculations. Including CBCT information in EPID dose reconstructions slightly improves the agreement with TPS calculations

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