72 research outputs found

    The Distance Between:An Algorithmic Approach to Comparing Stochastic Models to Time-Series Data

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    While mean-field models of cellular operations have identified dominant processes at the macroscopic scale, stochastic models may provide further insight into mechanisms at the molecular scale. In order to identify plausible stochastic models, quantitative comparisons between the models and the experimental data are required. The data for these systems have small sample sizes and time-evolving distributions. The aim of this study is to identify appropriate distance metrics for the quantitative comparison of stochastic model outputs and time-evolving stochastic measurements of a system. We identify distance metrics with features suitable for driving parameter inference, model comparison, and model validation, constrained by data from multiple experimental protocols. In this study, stochastic model outputs are compared to synthetic data across three scales: that of the data at the points the system is sampled during the time course of each type of experiment; a combined distance across the time course of each experiment; and a combined distance across all the experiments. Two broad categories of comparators at each point were considered, based on the empirical cumulative distribution function (ECDF) of the data and of the model outputs: discrete based measures such as the Kolmogorov–Smirnov distance, and integrated measures such as the Wasserstein-1 distance between the ECDFs. It was found that the discrete based measures were highly sensitive to parameter changes near the synthetic data parameters, but were largely insensitive otherwise, whereas the integrated distances had smoother transitions as the parameters approached the true values. The integrated measures were also found to be robust to noise added to the synthetic data, replicating experimental error. The characteristics of the identified distances provides the basis for the design of an algorithm suitable for fitting stochastic models to real world stochastic data.</p

    Hybrid in silico/in vitro target fishing to assign function to “orphan” compounds of food origin – The case of the fungal metabolite atromentin

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    Many small molecules of food origin may effect human health but lack an adequate description of their biological activity. To fill this knowledge gap, a first-line workflow is needed to assign putative functions, rank the endpoints for testing and guide wet-lab experiments. In this framework, the identification of potential biological targets can be used to probe the activity of orphan compounds using a so-called “target fishing” approach. Here, we present a proof of concept study using an in silico/in vitro target fishing approach on the fungal secondary metabolite atromentin. The procedure relies on a computational screening for activity identification coupled with experimental trials for dose-response characterization. Computational results identified estrogen receptors and 17-β-hydroxysteroid dehydrogenase as potential targets. Experiments confirmed a weak estrogenic activity, supporting the reliability of the procedure. Despite limited estrogenicity of atromentin, the proposed inhibition of 17-β-hydroxysteroid dehydrogenase should be considered as a source for endocrine disruptive effects

    The response of phytoplankton, zooplankton and macrozoobenthos communities to change in the water supply from surface to groundwater in aquaculture ponds

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    Investigating forces driving the structure of aquatic communities has long been an important issue in ecology. In the present study, we focused on the effects of changed water supply for aquaculture ponds on phytoplankton, zooplankton and macrozoobenthos communities during two seasons of rearing common carp. We compared these communities between two types of inflow water: surface sources of water a reservoir pond, two open wells and a small stream and groundwater deep tube well. Significant changes were observed in environmental variables after the introduction of the groundwater source: oxygen concentration and water hardness decreased, while conductivity, phosphorus and un-ionized ammonia increased. Results revealed that all investigated groups, except Mollusca (macrozoobenthos), decreased in species richness, abundance and biomass due to changed water chemistry, but differed in the level of susceptibility. Rotifera and Cladocera were the most affected showing a sharp decline in density and number of species since 66% of species disappeared from the ponds. The abundance of Copepoda was relatively high although significantly lower under new conditions, with adults being more tolerant to changed inflow water than nauplii larvae. Phytoplankton had the highest potential to replace previous species with newcomers more adapted to changed water chemistry, providing 36 immigrant species, whereas 49 became extinct. Although mainly influenced by fish predation, Chironomidae (macrozoobenthos) were undoubtedly affected by changed water chemistry. These results suggest profound changes in three key ecological groups produced by significant changes of important environmental variables and water quality after the shift from surface to groundwater supply

    The EFSUMB Guidelines and Recommendations for the Clinical Practice of Elastography in Non-Hepatic Applications : Update 2018

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    Funding Information: Odd Helge Gilja: Advisory Board/Consultant fee from: AbbVie, Bracco, GE Healthcare, Samsung, and Takeda Paul S. Sidhu: Speaker honoraria, Bracco, Siemens, Samsung, Hiatchi, GE and Philips Christoph F. Dietrich: Speaker honoraria, Bracco, Hitachi, GE, Mindray, Supersonic, Pentax, Olympus, Fuji, Boston Scientific, AbbVie, Falk Foundation, Novartis, Roche; Advisory, Board Member, Hitachi, Mindray, Siemens; Research grant, GE, Mindray, SuperSonic Vito Cantisani: Speaker honoraria, Canon/Toshiba, Bracco, Samsung Dominique Amy: Speaker honoraria, Hitachi, Supersonic, EpiSonica Marco Brock: Speaker honoraria, Hitachi Fabrizio Calliada: Speaker honoraria, Bracco, Hitachi, Shenshen Mindray Dirk Andre Clevert: Speaker honoraria, Siemens, Samsung, GE, Bracco, Philips; Advisory Board, Siemens, Samsung, Bracco, Philips Jean-Michel Correas: Speaker honoraria, Hitachi-Aloka, Canon/Toshiba, Philips, Supersonic, Bracco, Guerbet; Research collaboration, Bracco Sonocap, Guerbet NsSafe and Secure protocols Mirko D’Onofrio: Speaker honoraria, Siemens, Bracco, Hitachi; Advisory Board Siemens, Bracco Andre Farrokh: Speaker honoraria, Hitachi Pietro Fusaroli: Speaker honoraria, Olympus Roald Flesland Havre: Speaker honoraria, GE Healthcare, Conference participation support from Pharmacosmos, Ultrasound equipment from Samsung Medison André Ignee: Speaker honoraria: Siemens, Canon/Toshiba, Hitachi, Boston Scientific, Bracco, Supersonic, Abbvie Christian Jenssen: Speaker honoraria, Bracco, Hitachi, Canon/Toshiba, Falk Foundation, Covidien; Research grant, Novartis Maija Radzina: Speaker honoraria, Bracco, Canon/Toshiba Luca Sconfienza: Travel grants from Bracco Imaging Italia Srl, Esaote SPA, Abiogen SPA, Fidia Middle East. Speaker honoraria from Fidia Middle East Ioan Sporea: Speaker honoraria, Philips, GE, Canon/Toshiba; Advisory Board Member, Siemens; Congress participation support, Siemens Mickael Tanter: Speaker honoraria, Supersonic; Co Founder and shareholder, Supersonic; Research collaboration, Supersonic Peter Vilmann: Speaker honoraria, Pentax, Norgine; Advisory Board, Boston Scientific; Consultancy MediGlobe The following members declared no conflicts of interest: Adrian Săftoiu, Michael Bachmann Nielsen, Flaviu Bob, Jörg Bojunga, Caroline Ewertsen, Michael Hocke, Andrea Klauser, Christian Kollmann, Kumar V Ramnarine, Carolina Solomon, Daniela Fodor, Horia Ștefănescu Publisher Copyright: © 2019 Georg Thieme Verlag KG Stuttgart New York.This manuscript describes the use of ultrasound elastography, with the exception of liver applications, and represents an update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography.Peer reviewe

    Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

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    INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

    Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

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    A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

    Experimental progress in positronium laser physics

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    Search for single production of vector-like quarks decaying into Wb in pp collisions at s=8\sqrt{s} = 8 TeV with the ATLAS detector

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    Measurements of top-quark pair differential cross-sections in the eμe\mu channel in pppp collisions at s=13\sqrt{s} = 13 TeV using the ATLAS detector

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