224 research outputs found

    Condenser capacity and hyperbolic diameter

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    Given a compact connected set EE in the unit disk B2\mathbb{B}^{2}, we give a new upper bound for the conformal capacity of the condenser (B2,E)(\mathbb{B}^{2}, E) in terms of the hyperbolic diameter tt of EE. Moreover, for t>0t>0, we construct a set of hyperbolic diameter tt and apply novel numerical methods to show that it has larger capacity than a hyperbolic disk with the same diameter. The set we construct is called a Reuleaux triangle in hyperbolic geometry and it has constant hyperbolic width equal to tt.Comment: 15 pages, 5 figure

    Image augmentation with conformal mappings for a convolutional neural network

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    For augmentation of the square-shaped image data of a convolutional neural network (CNN), we introduce a new method, in which the original images are mapped onto a disk with a conformal mapping, rotated around the center of this disk and mapped under such a M\"obius transformation that preserves the disk, and then mapped back onto their original square shape. This process does not result the loss of information caused by removing areas from near the edges of the original images unlike the typical transformations used in the data augmentation for a CNN. We offer here the formulas of all the mappings needed together with detailed instructions how to write a code for transforming the images. The new method is also tested with simulated data and, according the results, using this method to augment the training data of 10 images into 40 images decreases the amount of the error in the predictions by a CNN for a test set of 160 images in a statistically significant way (p-value=0.0360).Comment: 13 pages, 3 figure

    Pim-1 Kinase Expression Predicts Radiation Response in Squamocellular Carcinoma of Head and Neck and Is under the Control of Epidermal Growth Factor Receptor

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    Pim-1 is an oncogenic serine/threonine kinase with poorly defined function in epithelial cancers. In this study, we determined 1) associations of Pim-1 expression with clinicopathological parameters including responsiveness to irradiation in squamocellular cancers of head and neck and 2) how Pim-1 expression is controlled subsequent to irradiation. Moderate to high expression of Pim-1 correlated to poor response to radiation therapy (P = .003). It is also associated to the expression of epidermal growth factor receptor (EGFR, P < .0001), which has been shown to be activated by irradiation. In radioresistant tumors, irradiation promoted nuclear translocation of Pim-1 (P < .005). When directly testing EGFR dependence of Pim-1 expression, up-regulation and nuclear translocation of Pim-1 could be induced through stimulation of EGFR with its ligands EGF or transforming growth factor a. Both ligand- and irradiation-induced changes in Pim-1 expression and localization could be inhibited by the monoclonal anti-EGFR antibody cetuximab and by the tyrosine kinase inhibitor gefitinib also targeting EGFR. These results suggest that irradiation-induced activation of EGFR upregulates Pim-1, and Pim-1 may be used as a novel predictive marker of radiation response in patients with squamocellular cancers of head and neck.</p

    Pim-selective inhibitor DHPCC-9 reveals Pim kinases as potent stimulators of cancer cell migration and invasion

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    <p>Abstract</p> <p>Background</p> <p>Pim family kinases are small constitutively active serine/threonine-specific kinases, elevated levels of which have been detected in human hematopoietic malignancies as well as in solid tumours. While we and others have previously shown that the oncogenic Pim kinases stimulate survival of hematopoietic cells, we now examined their putative role in regulating motility of adherent cancer cells. For this purpose, we inhibited Pim kinase activity using a small molecule compound, 1,10-dihydropyrrolo[2,3-<it>a</it>]carbazole-3-carbaldehyde (DHPCC-9), which we had recently identified as a potent and selective inhibitor for all Pim family members.</p> <p>Results</p> <p>We now demonstrate that the Pim kinase inhibitor DHPCC-9 is very effective also in cell-based assays. DHPCC-9 impairs the anti-apoptotic effects of Pim-1 in cytokine-deprived myeloid cells and inhibits intracellular phosphorylation of Pim substrates such as Bad. Moreover, DHPCC-9 slows down migration and invasion of cancer cells derived from either prostate cancer or squamocellular carcinoma patients. Silencing of Pim expression reduces cell motility, while Pim overexpression enhances it, strongly suggesting that the observed effects of DHPCC-9 are dependent on Pim kinase activity. Interestingly, DHPCC-9 also abrogates NFATc-dependent migration of cancer cells, implying that NFATc factors mediate at least part of the pro-migratory effects of Pim kinases.</p> <p>Conclusions</p> <p>Altogether, our data indicate that DHPCC-9 is not only a powerful tool to investigate physiological effects of the oncogenic Pim family kinases, but also an attractive molecule for drug development to inhibit invasiveness of Pim-overexpressing cancer cells.</p

    Pim kinases are upregulated during Epstein-Barr virus infection and enhance EBNA2 activity

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    Latent Epstein-Barr virus (EBV) infection is strongly associated with B-cell proliferative diseases such as Burkitt's lymphoma. Here we show that the oncogenic serine/threonine kinases Pim-1 and Pim-2 enhance the activity of the viral transcriptional activator EBNA2. During EBV infection of primary B-lymphocytes, the mRNA expression levels of pint genes, especially of pim-2, are upregulated and remain elevated in latently infected B-cell lines. Thus, EBV-induced upregulation of Pim kinases and Pim-stimulated EBNA2 transcriptional activity may contribute to the ability of EBV to immortalize B-cells and predispose them to malignant growth. (C) 2005 Elsevier Inc. All rights reserved

    An Unusual Digestive Foreign Body

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    Foreign digestive bodies present unusual circumstances because they are associated with various degrees of local trauma and may lead to direct perforation or delayed local injury. Patients with foreign bodies should be evaluated upon admission for signs of impaction and perforation. While all objects impacted in the esophagus require urgent treatment, rectal foreign bodies are usually removable through the anus. The current case illustrates successful endoscopic retrieval of a proximally located foreign body in a particular legal situation where physicians had to work closely with police officers and court members

    Bird Feces as Indicators of Metal Pollution: Pitfalls and Solutions

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    Bird feces are commonly used as a proxy for measuring dietary metal exposure levels in wild populations. Our study aims to improve the reliability and repeatability of fecal metal measurements and gives some recommendations for sampling. First, we studied levels of variation in metallic element (arsenic, calcium, cadmium, cobalt, copper, nickel, lead) concentrations: temporal variation within an individual, among siblings in a brood and among-brood/spatial variation. Second, we explored the variation caused by dual composition (urate vs. feces) of bird droppings. Two sets of fresh fecal samples were collected from pied flycatcher (Ficedula hypoleuca) nestlings living in a metal polluted area in summers 2017 (dataset 1) and 2018 (dataset 2). We found a great deal of temporal intra-individual variation in metal levels, suggesting that dietary exposure varied markedly in a short time scale (within a day). A sample from only one nestling per brood did not well describe the brood mean value, and we recommend that at least four siblings should be sampled. Brood level samples give relatively good temporal repeatability for most metals. For all the metals, the levels in the fecal portion were more than double to those in the urate portion. Since the mass proportion of urate in the bird droppings varied a great deal among samples, standardizing sampling, e.g., by collecting only the fecal part, would markedly reduce the variation due to composition. Alternatively, urate portion could be used for biomonitoring of internally circulated bioavailable metal. View Full-TextKeywords: bird feces; calcium; heavy metals; measurement error; pied flycatcher; repeatability; uric acid</div

    KSHV Reactivation from Latency Requires Pim-1 and Pim-3 Kinases to Inactivate the Latency-Associated Nuclear Antigen LANA

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    Host signal-transduction pathways are intimately involved in the switch between latency and productive infection of herpes viruses. As with other herpes viruses, infection by Kaposi's sarcoma herpesvirus (KSHV) displays these two phases. During latency only few viral genes are expressed, while in the productive infection the virus is reactivated with initiation of extensive viral DNA replication and gene expression, resulting in production of new viral particles. Viral reactivation is crucial for KSHV pathogenesis and contributes to the progression of KS. We have recently identified Pim-1 as a kinase reactivating KSHV upon over-expression. Here we show that another Pim family kinase, Pim-3, also induces viral reactivation. We demonstrate that expression of both Pim-1 and Pim-3 is induced in response to physiological and chemical reactivation in naturally KSHV-infected cells, and we show that they are required for KSHV reactivation under these conditions. Furthermore, our data indicate that Pim-1 and Pim-3 contribute to viral reactivation by phosphorylating the KSHV latency-associated nuclear antigen (LANA) on serine residues 205 and 206. This counteracts the LANA-mediated repression of the KSHV lytic gene transcription. The identification of Pim family kinases as novel cellular regulators of the gammaherpesvirus life cycle facilitates a deeper understanding of virus-host interactions during reactivation and may represent potential novel targets for therapeutic intervention
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