115 research outputs found

    A hybrid backtracking algorithm for automatic test data generation

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    Kao osnovno pitanje u ispitivanju softvera, automatsko generiranje podataka za ispitivanje je od najveće važnosti, što je u biti problem zadovoljavanja ograničenja, a rješava se algoritmima pretraživanja. U našem prethodnom istraživanju za rješenje ograničenja predložena je metoda grananja i ograničavanja, a elaborirane su unaprijedne metode. Zasnovan na intervalnom aritmetičkom i simboličkom izvršenju, ovaj je rad usredotočen na unatražnu metodu, a to je povezivanje unaprijednog provjeravanja i unatražnog ispitivanja usmjerenog konflikta, u cilju poboljšanja učinkovitosti unatražnog praćenja u postupku traženja. Zatvaranja varijabli se koriste kako bi se olakšalo lociranje nesuglasica koje dovode do neriješenih rezultata (dead ends). Empirijski eksperimenti dokazuju učinkovitost predložene hibridne unatražne metode i njenu primjenljivost u inženjerstvu.As a fundamental issue in software testing, automatic test data generation is of crucial importance, which is essentially a constraint satisfaction problem and solved by search algorithms. In our previous research, branch and bound was proposed as our constraint solver and the look-ahead methods were elaborated. Based on interval arithmetic and symbolic execution, this paper focuses on the look-back or backtracking method, which is the hybridization of forward checking and conflict-directed backjumping, with the aim of improving the efficiency of backtracking in the search procedure. The closures of variables are used to facilitate the localization of the conflicts which cause dead ends. Empirical experiments prove the effectiveness of the proposed hybrid backtracking method and its applicability in engineering

    Direct Conversion of Mouse Fibroblasts into Cholangiocyte Progenitor Cells

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    Disorders of the biliary epithelium, known as cholangiopathies, cause severe and irreversible liver diseases. The limited accessibility of bile duct precludes modeling of several cholangiocyte-mediated diseases. Therefore, novel approaches for obtaining functional cholangiocytes with high purity are needed. Previous work has shown that the combination of Hnf1β and Foxa3 could directly convert mouse fibroblasts into bipotential hepatic stem cell-like cells, termed iHepSCs. However, the efficiency of converting fibroblasts into iHepSCs is low, and these iHepSCs exhibit extremely low differentiation potential into cholangiocytes, thus hindering the translation of iHepSCs to the clinic. Here, we describe that the expression of Hnf1α and Foxa3 dramatically facilitates the robust generation of iHepSCs. Notably, prolonged in vitro culture of Hnf1α- and Foxa3-derived iHepSCs induces a Notch signaling-mediated secondary conversion into cholangiocyte progenitor-like cells that display dramatically enhanced differentiation capacity into mature cholangiocytes. Our study provides a robust two-step approach for obtaining cholangiocyte progenitor-like cells using defined factors

    Easy and green route towards nanostructured ZnO as active sensing material with unexpected H2S dosimeter-type behaviour

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    Nanostructured ZnO particles were prepared through a straightforward, quick and low\u2010temperature synthesis route involving coprecipitation of the metal precursor salts with oxalic acid, followed by hydrothermal treatment at 135 or 160 \ub0C. The synthesised nanostructured powders were thoroughly characterised by a wide array of analytical techniques from the morphological (Scanning Electron Microscopy \u2013SEM\u2010, Transmission Electron Microscopy \u2010TEM\u2010, Energy\u2010dispersive X\u2010ray Spectroscopy \u2010EDXS\u2010), structural (Powder X\u2010Ray Diffraction \u2010PXRD\u2010, Selected Area Electron Diffraction \u2010SAED\u2010), compositional (X\u2010ray Photoelectron Spectroscopy \u2010XPS\u2010) and physical (thermal stability) point of view. As far as functional applications are concerned, the powders were tested as gas sensor materials for H2S detection. Thereby these ZnO particles show unexpected gas dosimeter behaviour at 150 \ub0C. Based on these observations and on a comparison with literature a new model for the interaction of ZnO nanostructures with H2S is proposed

    Characterization of the metabolism of eupalinolide A and B by carboxylesterase and cytochrome P450 in human liver microsomes

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    Eupalinolide A (EA; Z-configuration) and eupalinolide B (EB; E-configuration) are bioactive cis-trans isomers isolated from Eupatorii Lindleyani Herba that exert anti-inflammatory and antitumor effects. Although one pharmacokinetic study found that the metabolic parameters of the isomers were different in rats, metabolic processes relevant to EA and EB remain largely unknown. Our preliminary findings revealed that EA and EB are rapidly hydrolyzed by carboxylesterase. Here, we investigated the metabolic stability and enzyme kinetics of carboxylesterase-mediated hydrolysis and cytochrome P450 (CYP)-mediated oxidation of EA and EB in human liver microsomes (HLMs). We also explored differences in the hydrolytic stability of EA and EB in human liver microsomes and rat liver microsomes (RLMs). Moreover, cytochrome P450 reaction phenotyping of the isomers was performed via in silico methods (i.e., using a quantitative structure-activity relationship model and molecular docking) and confirmed using human recombinant enzymes. The total normalized rate approach was considered to assess the relative contributions of five major cytochrome P450s to EA and EB metabolism. We found that EA and EB were eliminated rapidly, mainly by carboxylesterase-mediated hydrolysis, as compared with cytochrome P450-mediated oxidation. An inter-species difference was observed as well, with faster rates of EA and EB hydrolysis in rat liver microsomes. Furthermore, our findings confirmed EA and EB were metabolized by multiple cytochrome P450s, among which CYP3A4 played a particularly important role

    Kv7.4 Channel Contribute to Projection-Specific Auto-Inhibition of Dopamine Neurons in the Ventral Tegmental Area

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    Dopaminergic neurons in the ventral tegmental area (VTA) encode behavioral patterns important in reward and drug addiction as well as in emotional disorders. These functions of dopamine neurons are directly related to the release of dopamine in the targeted regions of the brain which are, thus, controlled by the excitability of dopamine neurons. One mechanism for modulation of dopamine neuronal excitability is mediated by the auto dopamine type 2 (D2) receptors, through activation of a Kir3/GIRK K+ channel which inhibits the firing of dopamine neurons. In this study, we provide evidence that Kv7.4, in addition to Kir3.2 channels, contributes to dopamine (DA)-mediated auto-inhibition of DA activity projecting to NAc and to basolateral amygdale (BLA). Furthermore, we demonstrate that D2 receptors enhance Kv7.4 currents through Gi/o protein and redox-dependent cellular pathway. Finally, we show this D2 mediated auto-inhibition is blunted in a social defeat mice model of depression, a phenomenon that may contribute to the altered excitability of VTA DA neurons in depressed animals. These results provide a new perspective for understanding the molecular mechanism of the excitability of VTA DA neurons and for potential new strategies against mental disorders involving altered excitability of DA neurons, such as major depression and drug addictions

    Improved electrocatalytic stability in ethanol oxidation by microwave-assisted selective deposition of SnO2 and Pt onto carbon

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    Pt/SnO2/C nanostructures with SnO2/Pt molar ratios ranging from 2.5 to 0.6 were synthesized by simple and fast microwave-assisted routes. The materials are composed of 3-5 nm SnO2 and Pt nanoparticles dispersed on the carbon support, with the morphology of the coating depending on the SnO2/Pt ratio: a homogenous layer of nanoparticles coating the carbon surface is obtained for SnO2/Pt of 2.5, whereas small Pt-SnO2 clusters are formed for lower ratios. The electrocatalytic activity of the composites on the ethanol oxidation reaction (EOR) was studied by cyclic voltammetry and chronoamperometry. All the binary catalysts exhibited lower onset potentials for the EOR and slower decay of the current density with time than a commercial Pt/C catalyst. However, improved peak current densities were only observed for the composites with ratios 1.6, 1.0 and 0.6, indicating that the formation of metal and metal oxide nanoparticles clusters is favorable for the EOR. This morphology facilitates the hydroxyl groups transfer from the metal oxide to the platinum at low potentials and also the electron transfer between carbon and platinum. The best overall performance was found for the catalyst with SnO2/Pt = 1, on which the number of three-phase boundaries is maximized. Moreover, the catalyst with SnO2/Pt = 1 continued to exhibit significantly better catalytic performance on the EOR than the commercial catalyst after potential cycling

    The Murchison Widefield Array: The Square Kilometre Array Precursor at Low Radio Frequencies

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    The Murchison Widefield Array (MWA) is one of three Square Kilometre Array Precursor telescopes and is located at the Murchison Radio-astronomy Observatory in the Murchison Shire of the mid-west of Western Australia, a location chosen for its extremely low levels of radio frequency interference. The MWA operates at low radio frequencies, 80–300 MHz, with a processed bandwidth of 30.72 MHz for both linear polarisations, and consists of 128 aperture arrays (known as tiles) distributed over a ~3-km diameter area. Novel hybrid hardware/software correlation and a real-time imaging and calibration systems comprise the MWA signal processing backend. In this paper, the as-built MWA is described both at a system and sub-system level, the expected performance of the array is presented, and the science goals of the instrument are summarised

    Etude de fiabilité des modules d'électronique de puissance à base de composant SiC pour applications hautes températures

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    The environments tend to be more severe (hotter and sometimes colder). As such, the high temperature power electronics is a major challenge for the future. Concerning the technologies for high temperature assembly, high temperature brazing alloy as 88Au / 12Ge, 97Au / 3Si and 5Sn / 95Pb could support these levels of thermal stresses, which are being developed to answer these requirements. We performed the electric, mechanical and thermomechanical characterizations for the materials of assembly. A thermal study was realized by experimental methods and numerical simulations, the numerical study is carried out in ANSYS in order to estimate the influences of the various parameters on the thermal performance of the assembly. In addition, the passive thermal cycles of large amplitude are conducted to analyze the reliability of the power modules in these conditions.Les environnements ont tendance à être plus sévères (plus chauds et quelquefois plus froids). À ce titre, l'électronique de puissance haute température est un enjeu majeur pour le futur. Concernant les technologies d'assemblage à haute température, les brasures haute température comme l'alliage 88Au/12Ge, 97Au/3Si et 5Sn/95Pb pourraient supporter ces niveaux de contraintes thermiques, qui sont actuellement développées pour répondre à ces exigences. Nous avons effectué les caractérisations électriques, mécaniques et thermomécaniques des matériaux d'assemblage. Une étude thermique a réalisée par des méthodes expérimentales et des simulations numériques, l'étude numérique est réalisée sous ANSYS dans le but d'estimer les influences des différents paramètres sur la performance thermique de l'assemblage. En plus, les cyclages thermiques passif de grande amplitude sont effectués pour analyser la fiabilité des modules de puissance dans ces conditions d'utilisation

    Etude de fiabilité des modules d'électronique de puissance à base de composant SiC pour applications hautes températures

    No full text
    Les environnements ont tendance à être plus sévères (plus chauds et quelquefois plus froids). À ce titre, l’électronique de puissance haute température est un enjeu majeur pour le futur. Concernant les technologies d’assemblage à haute température, les brasures haute température comme l'alliage 88Au/12Ge, 97Au/3Si et 5Sn/95Pb pourraient supporter ces niveaux de contraintes thermiques, qui sont actuellement développées pour répondre à ces exigences. Nous avons effectué les caractérisations électriques, mécaniques et thermomécaniques des matériaux d’assemblage. Une étude thermique a réalisée par des méthodes expérimentales et des simulations numériques, l’étude numérique est réalisée sous ANSYS dans le but d’estimer les influences des différents paramètres sur la performance thermique de l’assemblage. En plus, les cyclages thermiques passif de grande amplitude sont effectués pour analyser la fiabilité des modules de puissance dans ces conditions d’utilisation.The environments tend to be more severe (hotter and sometimes colder). As such, the high temperature power electronics is a major challenge for the future. Concerning the technologies for high temperature assembly, high temperature brazing alloy as 88Au / 12Ge, 97Au / 3Si and 5Sn / 95Pb could support these levels of thermal stresses, which are being developed to answer these requirements. We performed the electric, mechanical and thermomechanical characterizations for the materials of assembly. A thermal study was realized by experimental methods and numerical simulations, the numerical study is carried out in ANSYS in order to estimate the influences of the various parameters on the thermal performance of the assembly. In addition, the passive thermal cycles of large amplitude are conducted to analyze the reliability of the power modules in these conditions
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