882 research outputs found

    Programmable Edge-to-Cloud Virtualization for 5G Media Industry: The 5G-MEDIA Approach

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    To ensure high Quality of Experience (QoE) for end users, many media applications require significant quantities of computing and network resources, making their realization challenging in resource constrained environments. In this paper, we present the approach of the 5G-MEDIA project, providing an integrated programmable service platform for the development, design and operations of media applications in 5G networks, facilitating media service management across the service life cycle. The platform offers tools to service developers for efficient development, testing and continuous correction of services. One step further, it provides a service virtualization platform offering horizontal services, such as a Media Service Catalogue and accounting services, as well as optimization mechanisms to flexibly adapt service operations to dynamic conditions with efficient use of infrastructure resources. The paper outlines three use cases where the platform was tested and validated

    Globular Cluster Distance Determinations

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    The present status of the distance scale to Galactic globular clusters is reviewed. Six distance determination techniques which are deemed to be most reliable are discussed in depth. These different techniques are used to calibrate the absolute magnitude of the RR Lyrae stars. The various calibrations fall into three groups. Main sequence fitting using Hipparcos parallaxes, theoretical HB models and the RR Lyrae in the LMC all favor a bright calibration, implying a `long' globular cluster distance scale. White dwarf fitting and the astrometric distances yield a somewhat fainter RR Lyrae calibration, while the statistical parallax solution yields faint RR Lyrae stars implying a `short' distance scale to globular clusters. Various secondary distance indicators discussed all favor the long distance scale. The `long' and `short' distance scales differ by (0.31+/-0.16) mag. Averaging together all of the different distance determinations yields Mv(RR) = (0.23+/-0.04)([Fe/H] + 1.6) + (0.56+/-0.12) mag.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles', A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in pres

    High Affinity Antigen Recognition of the Dual Specific Variants of Herceptin Is Entropy-Driven in Spite of Structural Plasticity

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    The antigen-binding site of Herceptin, an anti-human Epidermal Growth Factor Receptor 2 (HER2) antibody, was engineered to add a second specificity toward Vascular Endothelial Growth Factor (VEGF) to create a high affinity two-in-one antibody bH1. Crystal structures of bH1 in complex with either antigen showed that, in comparison to Herceptin, this antibody exhibited greater conformational variability, also called “structural plasticity”. Here, we analyzed the biophysical and thermodynamic properties of the dual specific variants of Herceptin to understand how a single antibody binds two unrelated protein antigens. We showed that while bH1 and the affinity-improved bH1-44, in particular, maintained many properties of Herceptin including binding affinity, kinetics and the use of residues for antigen recognition, they differed in the binding thermodynamics. The interactions of bH1 and its variants with both antigens were characterized by large favorable entropy changes whereas the Herceptin/HER2 interaction involved a large favorable enthalpy change. By dissecting the total entropy change and the energy barrier for dual interaction, we determined that the significant structural plasticity of the bH1 antibodies demanded by the dual specificity did not translate into the expected increase of entropic penalty relative to Herceptin. Clearly, dual antigen recognition of the Herceptin variants involves divergent antibody conformations of nearly equivalent energetic states. Hence, increasing the structural plasticity of an antigen-binding site without increasing the entropic cost may play a role for antibodies to evolve multi-specificity. Our report represents the first comprehensive biophysical analysis of a high affinity dual specific antibody binding two unrelated protein antigens, furthering our understanding of the thermodynamics that drive the vast antigen recognition capacity of the antibody repertoire

    Viral non-coding RNA inhibits HNF4α expression in HCV associated hepatocellular carcinoma

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    BACKGROUND: Hepatitis C virus (HCV) infection is an established cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC); however, it is unclear if the virus plays a direct role in the development of HCC. Hepatocyte nuclear factor 4α (HNF4α) is critical determinant of epithelial architecture and hepatic development; depletion of HNF4α is correlated with oncogenic transformation. We explored the viral role in the inhibition of HNF4α expression, and consequent induction of tumor-promoting genes in HCV infection-associated HCC. METHODS: Western blot analysis was used to monitor the changes in expression levels of oncogenic proteins in liver tissues from HCV-infected humanized mice. The mechanism of HNF4α depletion was studied in HCV-infected human hepatocyte cultures in vitro. Targeting of HNF4α expression by viral non-coding RNA was examined by inhibition of Luciferase HNF4α 3’-UTR reporter. Modulation of invasive properties of HCV-infected cells was examined by Matrigel cell migration assay. RESULTS: Results show inhibition of HNF4α expression by targeting of HNF4α 3’-UTR by HCV-derived small non-coding RNA, vmr11. Vmr11 enhances the invasive properties of HCV-infected cells. Loss of HNF4α in HCV-infected liver tumors of humanized mice correlates with the induction of epithelial to mesenchymal transition (EMT) genes. CONCLUSIONS: We show depletion of HNF4α in liver tumors of HCV-infected humanized mice by HCV derived small non-coding RNA (vmr11) and resultant induction of EMT genes, which are critical determinants of tumor progression. These results suggest a direct viral role in the development of hepatocellular carcinoma

    Probing Cellular Dynamics with a Chemical Signal Generator

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    Observations of material and cellular systems in response to time-varying chemical stimuli can aid the analysis of dynamic processes. We describe a microfluidic “chemical signal generator,” a technique to apply continuously varying chemical concentration waveforms to arbitrary locations in a microfluidic channel through feedback control of the interface between parallel laminar (co-flowing) streams. As the flow rates of the streams are adjusted, the channel walls are exposed to a chemical environment that shifts between the individual streams. This approach can be used to probe the dynamic behavior of objects or substances adherent to the interior of the channel. To demonstrate the technique, we exposed live fibroblast cells to ionomycin, a membrane-permeable calcium ionophore, while assaying cytosolic calcium concentration. Through the manipulation of the laminar flow interface, we exposed the cells' endogenous calcium handling machinery to spatially-contained discrete and oscillatory intracellular disturbances, which were observed to elicit a regulatory response. The spatiotemporal precision of the generated signals opens avenues to previously unapproachable areas for potential investigation of cell signaling and material behavior

    Mirizzi syndrome type IV associated with cholecystocolic fistula: a very rare condition- report of a case

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    <p>Abstract</p> <p>Background</p> <p>Mirizzi syndrome is a rare complication of prolonged cholelithiasis with presence of large, impacted gallstone into the Hartman's pouch, causing chronic extrinsic compression of common bile duct (CBD). Fistula formation between the CBD and the gallbladder may represent an outcome of that condition. According to Mirizzi's classification and Csendes's subclassification, Mirizzi syndrome type IV represents the most uncommon type (4%).</p> <p>Spontaneous biliary-enteric fistulas have also been rarely reported (1.2–5%) in a large series of cholecystectomies. Cholecystocolic fistula is the most infrequent biliary enteric fistula, causing significant morbidity and representing a diagnostic challenge.</p> <p>Case presentation</p> <p>We describe a very rare, to our knowledge, combination of Mirizzi syndrome type IV and cholecystocolic fistula. A 52 year old male, presented to our clinic complaining of episodic diarrhea (monthly episodes lasting 16 days), high temperature (38°C–39°C), right upper quadrant pain without jaundice. The definitive diagnosis was made intraoperatively. Magnetic Resonance Imaging (MRI) and Endoscopic Retrograde Cholangiopancreatography (ERCP) demonstrated the presence of Mirizzi syndrome with cholecystocolic fistula formation. The patient was operated upon, and cholecystectomy, cholecystocolic fistula excision and Roux-en-Y biliary-enteric anastomosis were undertaken with excellent post-operative course.</p> <p>Conclusion</p> <p>Appropriate biliary tree imaging with ERCP and MRI/MRCP is essential for the diagnosis of Mirizzi syndrome and its complications. Cholecystectomy, fistula excision and biliary-enteric anastomosis with Roux-en-Y loop appears to be the most appropriate surgical intervention in order to avoid damage to Calot's triangle anatomic elements. Particularly in our case, ERCP was a valuable diagnostic tool that Mirizzi syndrome type IV and cholecystocolic fistula.</p

    The Presence–Absence Situation and Its Impact on the Assemblage Structure and Interspecific Relations of Pronophilina Butterflies in the Venezuelan Andes (Lepidoptera: Nymphalidae)

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    Assemblage structure and altitudinal patterns of Pronophilina, a species-rich group of Andean butterflies, are compared in El Baho and Monte Zerpa, two closely situated and ecologically similar Andean localities. Their faunas differ only by the absence of Pedaliodes ornata Grose-Smith in El Baho. There are, however, important structural differences between the two Pronophilina assemblages. Whereas there are five co-dominant species in Monte Zerpa, including P. ornata, Pedaliodes minabilis Pyrcz is the only dominant with more than half of all the individuals in the sample in El Baho. The absence of P. ornata in El Baho is investigated from historical, geographic, and ecological perspectives exploring the factors responsible for its possible extinction including climate change, mass dying out of host plants, and competitive exclusion. Although competitive exclusion between P. ornata and P. minabilis is a plausible mechanism, considered that their ecological niches overlap, which suggests a limiting influence on each other’s populations, the object of competition was not identified, and the reason of the absence of P. ornata in El Baho could not be established. The role of spatial interference related to imperfect sexual behavioral isolation is evaluated in maintaining the parapatric altitudinal distributions of three pairs of phenotypically similar and related species of Pedaliodes, Corades, and Lymanopoda

    Observation of associated near-side and away-side long-range correlations in √sNN=5.02  TeV proton-lead collisions with the ATLAS detector

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    Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  Όb-1 of data as a function of transverse momentum (pT) and the transverse energy (ÎŁETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∌0) correlation that grows rapidly with increasing ÎŁETPb. A long-range “away-side” (Δϕ∌π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ÎŁETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ÎŁETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁥2Δϕ modulation for all ÎŁETPb ranges and particle pT
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