424 research outputs found

    Amortised learning by wake-sleep

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    Models that employ latent variables to capture structure in observed data lie at the heart of many current unsupervised learning algorithms, but exact maximum-likelihood learning for powerful and flexible latent-variable models is almost always intractable. Thus, state-of-the-art approaches either abandon the maximum-likelihood framework entirely, or else rely on a variety of variational approximations to the posterior distribution over the latents. Here, we propose an alternative approach that we call amortised learning. Rather than computing an approximation to the posterior over latents, we use a wake-sleep Monte-Carlo strategy to learn a function that directly estimates the maximum-likelihood parameter updates. Amortised learning is possible whenever samples of latents and observations can be simulated from the generative model, treating the model as a “black box”. We demonstrate its effectiveness on a wide range of complex models, including those with latents that are discrete or supported on non-Euclidean spaces

    Relationship of Glucose Variability and Daily Lifestyle by Continuous Glucose Monitoring (CGM)

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    Authors and collaborators have continued diabetic practice and research on low carbohydrate diet (LCD), continuous glucose monitoring (CGM), and so on. The case is a 64-year-old male with type 2 diabetes mellitus (T2DM) treated with multiple daily insulin injections (MDI). When his HbA1c was 8.2% before, he changed to take tofu instead of rice and bread. HbA1c decreased to 7.1% and 4kg of weight reduction in 2 months. Tofu is a traditional Japanese food made from soybeans, which is a suitable LCD with Protein:Fat:Carbohydrate (PFC) ratio=40:45:15 in this case. His HbA1c is recently unstable, then glucose variability was investigated by CGM using FreeStyle Libre. The glucose pattern was different due to his lifestyle, including working day, off day, playing golf, respectively. The average glucose was 143-167 mg/dL and the estimated HbA1c was 7.1%, whereas HbA1c in outclinic was 8.1%, respectively. This report will hopefully become reference data for future research

    Observation of thundercloud-related gamma rays and neutrons in Tibet

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    During the 2010 rainy season in Yangbajing (4300 m above sea level) in Tibet, China, a long-duration count enhancement associated with thunderclouds was detected by a solar-neutron telescope and neutron monitors installed at the Yangbajing Comic Ray Observatory. The event, lasting for ∼40  min, was observed on July 22, 2010. The solar-neutron telescope detected significant γ-ray signals with energies >40  MeV in the event. Such a prolonged high-energy event has never been observed in association with thunderclouds, clearly suggesting that electron acceleration lasts for 40 min in thunderclouds. In addition, Monte Carlo simulations showed that >10  MeV γ rays largely contribute to the neutron monitor signals, while >1  keV neutrons produced via a photonuclear reaction contribute relatively less to the signals. This result suggests that enhancements of neutron monitors during thunderstorms are not necessarily clear evidence for neutron production, as previously thought

    Usefulness of Microcatheters Inserted Overnight for Additional Injection of Sclerosant after Initial Balloon-Occluded Retrograde Transvenous Obliteration of Gastric Varices

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    In patients with large gastric varices, dose limitation of the sclerosant can cause difficulties in achieving complete thrombosis of varices during a single balloon-occluded retrograde transvenous obliteration (BRTO) procedure. For patients with incomplete variceal thrombosis after the first BRTO, additional sclerosant must be injected in a second BRTO. We report a successful case of BRTO for large gastric varices in whom additional sclerosant was injected through a microcatheter that remained inserted overnight. To achieve complete variceal thrombosis in a patient with incomplete thrombosis of large gastric varices after a first BRTO, a retained microcatheter can be used to inject additional sclerosant in a second BRTO the next day

    An initial event in insect innate immune response: structural and biological studies of interactions between β-1,3-glucan and the N-terminal domain of β-1,3-glucan recognition protein

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    In response to invading microorganisms, insect β-1,3-glucan recognition protein (βGRP), a soluble receptor in the hemolymph, binds to the surfaces of bacteria and fungi and activates serine protease cascades that promote destruction of pathogens by means of melanization or expression of antimicrobial peptides. Here we report on the NMR solution structure of the N-terminal domain of βGRP (N-βGRP) from Indian meal moth (Plodia interpunctella), which is sufficient to activate the prophenoloxidase (proPO) pathway resulting in melanin formation. NMR and isothermal calorimetric titrations of N-βGRP with laminarihexaose, a glucose hexamer containing β-1,3 links, suggest a weak binding of the ligand. However, addition of laminarin, a glucose polysaccharide (~ 6 kDa) containing β-1,3 and β-1,6 links that activates the proPO pathway, to N-βGRP results in the loss of NMR cross-peaks from the backbone 15N-1H groups of the protein, suggesting the formation of a large complex. Analytical ultra centrifugation (AUC) studies of formation of N-βGRP:laminarin complex show that ligand-binding induces sel-fassociation of the protein:carbohydrate complex into a macro structure, likely containing six protein and three laminarin molecules (~ 102 kDa). The macro complex is quite stable, as it does not undergo dissociation upon dilution to sub-micromolar concentrations. The structural model thus derived from the present studies for N-βGRP:laminarin complex in solution differs from the one in which a single N-βGRP molecule has been proposed to bind to a triple helical form of laminarin on the basis of an X-ray crystallographic structure of N-βGRP:laminarihexaose complex [Kanagawa, M., Satoh, T., Ikeda, A., Adachi, Y., Ohno, N., and Yamaguchi, Y. (2011) J. Biol. Chem. 286, 29158-29165]. AUC studies and phenoloxidase activation measurements carried out with the designed mutants of N-βGRP indicate that electrostatic interactions involving Asp45, Arg54, and Asp68 between the ligand-bound protein molecules contribute in part to the stability of N-βGRP:laminarin macro complex and that a decreased stability is accompanied by a reduced activation of the proPO pathway. Increased β-1,6 branching in laminarin also results in destabilization of the macro complex. These novel findings suggest that ligand-induced self-association of βGRP:β-1,3-glucan complex may form a platform on a microbial surface for recruitment of downstream proteases, as a means of amplification of the initial signal of pathogen recognition for the activation of the proPO pathway

    NOD × 129.H2g7 Backcross Delineates 129S1/SvImJ-Derived Genomic Regions Modulating Type 1 Diabetes Development in Mice

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    OBJECTIVE: Introduction of genes targeted in 129/Sv embryonic stem (ES) cells into NOD mice brings about linked genes that may modulate type 1 diabetes. Our objective was to identify 129S1/SvJ non-MHC regions contributing type 1 diabetes resistance or susceptibility in backcross to NOD/LtJ. RESEARCH DESIGN AND METHODS: After congenic transfer of the NOD H2(g7) haplotype onto 129S1/Sv, 310 females were produced by NOD x (NOD x 129.H2(g7))F1 backcross (N2). A genome scan for quantitative trait locus (QTL) affecting clinical diabetes, age of diabetes onset, and insulitis severity was performed using subphenotype characteristics to improve power and resolution for detection of diabetes susceptibility loci. RESULTS: Thirty-six of 310 (11.6%) N2 females developed type 1 diabetes between 14 and 40 weeks. Significant evidence of linkage for only a single previously reported Idd complex locus (Idd10/17/18, chromosome [Chr] 3) was indicated for clinical diabetes. The quantitative traits of insulitis either alone or combined with age at type 1 diabetes onset were significantly linked to known Idd regions on Chr 1 (Idd5 region), Chr 4 (Idd9 region), Chr 8 (Idd22), Chr 11 (Idd4.3), and proximal Chr 17 (Idd16 region). Significant 129S1/Sv resistance contributions were identified on Chr 1, 15 (two loci), and 19, with suggestive evidence for additional novel 129/Sv resistance QTL on Chr 5 and 17 and susceptibility on Chr 2. CONCLUSIONS: The 129S1/SvJ genome harbors collections of both known and potentially novel non-MHC Idd loci. Investigators targeting 129/Sv genes mapping within chromosomal regions reported herein or elsewhere in the genome need to exclude potential contributions from linked Idd loci by generating a NOD.129 control strain expressing the nontargeted allele

    Two-Phased Intra-Cluster Medium in the Centaurus Cluster of Galaxies

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    ASCA and ROSAT data of the Centaurus cluster were analyzed. A central excess in the radial brightness profile is found in the hard energy band up to 10keV. This requires a deeper central potential than a King-type one. A double-beta brightness distribution gives a good account of the data. A deprojected energy spectrum within a spherical region of radius 30 kpc at the cluster center indicates that the ICM cannot be isothermal there. Simultaneous fitting of the three (PSPC, GIS, and SIS) energy spectra extracted from the central 3' region showed that a two-temperature model that has temperatures of 1.4keV and 4.4keV and a common metallicity of 1.0 solar with the Galactic absorption gives the best description to the spectra. A cooling-flow spectral model did not give satisfactory fit. A 3-dimensional cluster model incorporating the two-phase picture, the double-beta brightness distribution, and the central metallicity increase reproduced the overall ASCA and ROSAT data successfully. The derived spatial distribution of the dark matter deviates from a King-type profile exhibiting a central excess, which is consistent with the Navvaro-Frenk-White model. The iron is revealed to be more widely spread than stars, which may have been caused by energetic supernovae and the motion of the cD galaxy. Since the derived characteristics of the cool phase including the temperature, angular extent, gas mass, and metallicity, are on a smooth extension of those of inter-stellar medium (ISM) of elliptical galaxies, the cool phase can be regarded as the ISM associated with the cD galaxy. The cool-phase X-ray emission is presumably sustained by energies dissipated by infalling mass to the cD galaxy in the course of cluster evolution.Comment: accepted for publication in Ap

    ALMA Observations of a Gap and a Ring in the Protoplanetary Disk around TW Hya

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    We report the first detection of a gap and a ring in 336 GHz dust continuum emission from the protoplanetary disk around TW Hya, using the Atacama Large Millimeter/Submillimeter Array (ALMA). The gap and ring are located at around 25 and 41 au from the central star, respectively, and are associated with the CO snow line at ∟30 au. The gap has a radial width of less than 15 au and a mass deficit of more than 23%, taking into account that the observations are limited to an angular resolution of ∟15 au. In addition, the 13CO and C18O J=3-2 lines show a decrement in CO line emission throughout the disk, down to ∟10 au, indicating a freeze-out of gas-phase CO onto grain surfaces and possible subsequent surface reactions to form larger molecules. The observed gap could be caused by gravitational interaction between the disk gas and a planet with a mass less than super-Neptune (2{M}{{Neptune}}), or could be the result of the destruction of large dust aggregates due to the sintering of CO ice
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