653 research outputs found

    Zoom-in-Net: Deep Mining Lesions for Diabetic Retinopathy Detection

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    We propose a convolution neural network based algorithm for simultaneously diagnosing diabetic retinopathy and highlighting suspicious regions. Our contributions are two folds: 1) a network termed Zoom-in-Net which mimics the zoom-in process of a clinician to examine the retinal images. Trained with only image-level supervisions, Zoomin-Net can generate attention maps which highlight suspicious regions, and predicts the disease level accurately based on both the whole image and its high resolution suspicious patches. 2) Only four bounding boxes generated from the automatically learned attention maps are enough to cover 80% of the lesions labeled by an experienced ophthalmologist, which shows good localization ability of the attention maps. By clustering features at high response locations on the attention maps, we discover meaningful clusters which contain potential lesions in diabetic retinopathy. Experiments show that our algorithm outperform the state-of-the-art methods on two datasets, EyePACS and Messidor.Comment: accepted by MICCAI 201

    Biochemical and structural investigations clarify the substrate selectivity of the 2-oxoglutarate oxygenase JMJD6.

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    JmjC domain-containing protein 6 (JMJD6) is a 2-oxoglutarate (2OG)-dependent oxygenase linked to various cellular processes, including splicing regulation, histone modification, transcriptional pause release, hypoxia sensing, and cancer. JMJD6 is reported to catalyze hydroxylation of lysine residue(s) of histones, the tumor-suppressor protein p53, and splicing regulatory proteins, including u2 small nuclear ribonucleoprotein auxiliary factor 65-kDa subunit (U2AF65). JMJD6 is also reported to catalyze N-demethylation of N-methylated (both mono- and di-methylated) arginine residues of histones and other proteins, including HSP70 (heat-shock protein 70), estrogen receptor α, and RNA helicase A. Here, we report MS- and NMR-based kinetic assays employing purified JMJD6 and multiple substrate fragment sequences, the results of which support the assignment of purified JMJD6 as a lysyl hydroxylase. By contrast, we did not observe N-methyl arginyl N-demethylation with purified JMJD6. Biophysical analyses, including crystallographic analyses of JMJD6Δ344-403 in complex with iron and 2OG, supported its assignment as a lysyl hydroxylase rather than an N-methyl arginyl-demethylase. The screening results supported some, but not all, of the assigned JMJD6 substrates and identified other potential JMJD6 substrates. We envision these results will be useful in cellular and biological work on the substrates and functions of JMJD6 and in the development of selective inhibitors of human 2OG oxygenases.Commonwealth Scholarship Commission, U

    Imaging high-dimensional spatial entanglement with a camera

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    The light produced by parametric down-conversion shows strong spatial entanglement that leads to violations of EPR criteria for separability. Historically, such studies have been performed by scanning a single-element, single-photon detector across a detection plane. Here we show that modern electron-multiplying charge-coupled device cameras can measure correlations in both position and momentum across a multi-pixel field of view. This capability allows us to observe entanglement of around 2,500 spatial states and demonstrate Einstein-Podolsky-Rosen type correlations by more than two orders of magnitude. More generally, our work shows that cameras can lead to important new capabilities in quantum optics and quantum information science.Comment: 5 pages, 4 figure

    Fuzzy-TOPSIS based Cluster Head selection in mobile sensor networks

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    One of the critical parameters of Wireless Sensor Networks (WSNs) is node lifetime. There are various methods to increase WSN node lifetime, the clustering technique is being one of them. In clustering, selection of a desired percentage of Cluster Heads (CHs) is performed among the sensor nodes (SNs). Selected CHs are responsible for collecting data from their member nodes, aggregating the data and finally sending it to the sink. In this paper, we propose a Fuzzy-TOPSIS technique, based on multi criteria decision making, to choose CH efficiently and effectively to maximize the WSN lifetime. We will consider several criteria including: residual energy; node energy consumption rate; number of neighbor nodes; average distance between neighboring nodes; and distance from the sink. A threshold based intra-cluster and inter-cluster multi-hop communication mechanism is used to decrease energy consumption. We have also analyzed the impact of node density and different types of mobility strategies in order to investigate impact over WSN lifetime. In order to maximize the load distribution in the WSN, a predictable mobility with octagonal trajectory is proposed. This results in improvement of overall network lifetime and latency. Results shows that the proposed scheme improves the network lifetime by 60%, conserve energy by 80%, a significant reduction of frequent Cluster Head (CH) per round selection by 25% is achieved as compared to the conventional Fuzzy and LEACH protocols

    Seropositivity for Coxiella burnetii in Wild Boar (Sus scrofa) and Red Deer (Cervus elaphus) in Portugal

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    Q fever is caused by the pathogen Coxiella burnetii and is a zoonosis that naturally infects goats, sheep, and cats, but can also infect humans, birds, reptiles, or arthropods. A survey was conducted for the detection of antibodies against C. burnetii in a sample of 617 free-ranging wild ruminants, 358 wild boar (Sus scrofa) and 259 red deer (Cervus elaphus), in east-central Portugal during the 2016-2022 hunting seasons. Only adult animals were sampled in this study. Antibodies specific to C. burnetii were detected using a commercial enzyme-linked immunosorbent assay (ELISA; IDVet(R), Montpellier, France) according to the manufacturer's instructions. The seroprevalence of C. burnetii infection was 1.5% (n = 9; 95% confidence interval [CI]: 0.7-2.8%). Antibodies against C. burnetii were detected in 4/358 wild boar (1.1%; 95% CI: CI: 0.3-2.8%) and 5/259 red deer (1.9%; 0.6-4.5%). Results of the present study indicate that antibodies against C. burnetii were present in wild boar and red deer in Portugal. These findings can help local health authorities to focus on the problem of C. burnetii in wildlife and facilitate the application of a One Health approach to its prevention and control

    Exchange bias in Fe/EuTe(111) bilayers

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    We report on the investigation of the exchange bias effect in Fe layers on EuTe(111), an antiferromagnetic semiconductor. For this ferromagnet (FM)/semiconducting antiferromagnet (AFM) exchange bias system, we have found positive and negative exchange bias effect (EB). Fresh samples exhibit positive EB, independently of the applied cooling field, indicating antiferromagnetic coupling between the FM and the AFM layers at the Fe/EuTe(111) interface. The change in EB with time, from positive EB for fresh samples to negative EB after short time,is attributed to aging effects at the Fe/EuTe interface. (c) 2007 American Institute of Physics.102

    The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module

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    The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Herein, we present the crystal structure of the C-terminal hydrophilic domain of the ethambutol-sensitive Araf transferase M. tuberculosis EmbC, which is essential for LAM synthesis. The structure of the C-terminal domain of EmbC (EmbCCT) encompasses two sub-domains of different folds, of which subdomain II shows distinct similarity to lectin-like carbohydrate-binding modules (CBM). Co-crystallisation with a cell wall-derived di-arabinoside acceptor analogue and structural comparison with ligand-bound CBMs suggest that EmbCCT contains two separate carbohydrate binding sites, associated with subdomains I and II, respectively. Single-residue substitution of conserved tryptophan residues (Trp868, Trp985) at these respective sites inhibited EmbC-catalysed extension of LAM. The same substitutions differentially abrogated binding of di- and penta-arabinofuranoside acceptor analogues to EmbCCT, linking the loss of activity to compromised acceptor substrate binding, indicating the presence of two separate carbohydrate binding sites, and demonstrating that subdomain II indeed functions as a carbohydrate-binding module. This work provides the first step towards unravelling the structure and function of a GT-C-type glycosyltransferase that is essential in M. tuberculosis. Author Summary Top Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis, burdens large swaths of the world population. Treatment of active TB typically requires administration of an antibiotic cocktail over several months that includes the drug ethambutol. This front line compound inhibits a set of arabinosyltransferase enzymes, called EmbA, EmbB and EmbC, which are critical for the synthesis of arabinan, a vital polysaccharide in the pathogen's unique cell envelope. How precisely ethambutol inhibits arabinosyltransferase activity is not clear, in part because structural information of its pharmacological targets has been elusive. Here, we report the high-resolution structure of the C-terminal domain of the ethambutol-target EmbC, a 390-amino acid fragment responsible for acceptor substrate recognition. Combining the X-ray crystallographic analysis with structural comparisons, site-directed mutagenesis, activity and ligand binding assays, we identified two regions in the C-terminal domain of EmbC that are capable of binding acceptor substrate mimics and are critical for activity of the full-length enzyme. Our results begin to define structure-function relationships in a family of structurally uncharacterised membrane-embedded glycosyltransferases, which are an important target for tuberculosis therapy

    Frequency, course and correlates of alcohol use from adolescence to young adulthood in a Swiss community survey

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    BACKGROUND: Few studies have analyzed the frequency of alcohol use across time from adolescence to young adulthood and its outcome in young adulthood. A Swiss longitudinal multilevel assessment project using various measures of psychopathology and psychosocial variables allowed for the study of the frequency and correlates of alcohol use so that this developmental trajectory may be better understood. METHOD: Alcohol use was studied by a questionnaire in a cohort of N = 593 subjects who had been assessed at three times between adolescence and young adulthood within the Zurich Psychology and Psychopathology Study (ZAPPS). Other assessment included questionnaire data measuring emotional and behavioural problems, life events, coping style, self-related cognitions, perceived parenting style and school environment, and size and efficiency of the social network. RESULTS: The increase of alcohol use from early adolescence to young adulthood showed only a few sex-specific differences in terms of the amount of alcohol consumption and the motives to drink. In late adolescence and young adulthood, males had a higher amount of alcohol consumption and were more frequently looking for drunkenness and feeling high. Males also experienced more negative consequences of alcohol use. A subgroup of heavy or problem drinkers showed a large range of emotional and behavioural problems and further indicators of impaired psychosocial functioning both in late adolescence and young adulthood. CONCLUSION: This Swiss community survey documents that alcohol use is problematic in a sizeable proportion of youth and goes hand in hand with a large number of psychosocial problems
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