72 research outputs found

    Analysis of IPTV Channels Watching Preferences in Bosnia and Herzegovina

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    IPTV service is a new service which is today offered from almost every Telecom operator. One of the advantages of IPTV service stemming from its architecture is certainly the fact that it is very easy to measure what TV channels are the ones mostly watched. This papers desribes this measurement and analysis results in one Telecom operator in Bosnia and Herzegovina. They describe what TV channels are mostly watched in different time periods. We developed a simple weighting algorithm to order the channels by watching rate. Based on it we are providing extensive tables. This paper forms an industrial contribution with results important for marketing but also is scientific contribution because it introduces one new method of scoring TV channels based on previous measurements in their audience. We also developed IPTV Statistics model and described results from this research for a new statistics model. This paper is the continuous of previously published contributions from this area

    ISO-1 Binding to the Tautomerase Active Site of MIF Inhibits Its Pro-inflammatory Activity and Increases Survival in Severe Sepsis

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    MIF is a proinflammatory cytokine that has been implicated in the pathogenesis of sepsis, arthritis, and other inflammatory diseases. Antibodies against MIF are effective in experimental models of inflammation, and there is interest in strategies to inhibit its deleterious cytokine activities. Here we identify a mechanism of inhibiting MIF pro-inflammatory activities by targeting MIF tautomerase activity. We designed small molecules to inhibit this tautomerase activity; a lead molecule, "ISO-1 ((S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester)," significantly inhibits the cytokine activity in vitro. Moreover, ISO-1 inhibits tumor necrosis factor release from macrophages isolated from LPStreated wild type mice but has no effect on cytokine release from MIFdeficient macrophages. The therapeutic importance of the MIF inhibition by ISO-1 is demonstrated by the significant protection from sepsis, induced by cecal ligation and puncture in a clinically relevant time frame. These results identify ISO-1 as the first small molecule inhibitor of MIF proinflammatory activities with therapeutic implications and indicate the potential of the MIF active site as a novel target for therapeutic interventions in human sepsis

    Технологическое управление наследованием эксплуатационных параметров качества деталей машин

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    To describe the technological inheritance of operational properties in the processes of the parts manufacturing, a graph reflecting the transfer coefficients and interaction of physical and mechanical and geometrical parameters is proposed. The methods of process control of the parts operational properties inheritance including: measurement of parameters, the most critical parts; identifying of mechanisms of technological inheritance based on the coefficients of transmission and interaction of the performance properties; analysis of technological barriers at the impact of intensive energy flows, development of measures for technological process control were also considered.Технологическое наследование эксплуатационных свойств в процессах изготовления деталей предложено описывать графом, отражающим коэффициенты передачи и взаимовлияния физико-механических и геометрических параметров. Рассмотрены методы технологического управления наследованием эксплуатационных параметров качества деталей, включающие измерения параметров наиболее ответственных деталей; определение механизмов технологического наследования на основе коэффициентов передачи и взаимовлияния эксплуатационных свойств; анализ технологических барьеров при интенсивных воздействиях потоками энергии, разработку мероприятий по управлению технологическими процессами

    Level of uncertainty about the affective nature of a pictorial stimulus influences anticipatory neural processes: An event-related potential (ERP) study

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    Uncertainty about the emotional impact of future events is a common part of everyday life. However, relatively little is known about whether the level of uncertainty about the affective nature of an upcoming visual image influences anticipatory neurocognitive processes. To investigate this, participants viewed a series of negative and neutral pictures, which were preceded by abstract anticipatory cues. Neural activity was measured using event-related potentials (ERPs). In the ‘uncertain’ cue condition, the cue could be followed by either a negative or a neutral picture with equal probability; in the ‘fairly uncertain’ condition the cue was followed by a negative picture on 70% of trials, and by a neutral picture on 30% of trials. In the ‘certain’ condition, the cue was always followed by a negative picture. For the P200 component, reflecting early stages of selective attention, there was no amplitude difference between cue conditions. At later stages of processing, the early posterior negativity (EPN) amplitude was enhanced for cues indicating a greater level of certainty, and the late positive potential (LPP) amplitude was greater for certain, compared to fairly uncertain and uncertain cues. The stimulus preceding negativity (SPN), an index of anticipatory processing, was more negative for certain cues compared to fairly uncertain and uncertain cues. For the SPN there was no difference between fairly uncertain and uncertain cues. These results provide evidence that the level of uncertainty regarding the affective nature of an upcoming picture influenced several stages of processing during the anticipation of the stimulus

    Use of limited proteolysis and mutagenesis to identify folding domains and sequence motifs critical for wax ester synthase/acyl coenzyme A:Diacylglycerol acyltransferase activity

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    Triacylglycerols and wax esters are synthesized as energy storage molecules by some proteobacteria and actinobacteria under stress. The enzyme responsible for neutral lipid accumulation is the bifunctional wax ester synthase/acyl-coenzyme A (CoA): diacylglycerol acyltransferase (WS/DGAT). Structural modeling of WS/DGAT suggests that it can adopt an acyl-CoA-dependent acyltransferase fold with the N-terminal and C-terminal domains connected by a helical linker, an architecture demonstrated experimentally by limited proteolysis. Moreover, we found that both domains form an active complex when coexpressed as independent polypeptides. The structural prediction and sequence alignment of different WS/DGAT proteins indicated catalytically important motifs in the enzyme. Their role was probed by measuring the activities of a series of alanine scanning mutants. Our study underscores the structural understanding of this protein family and paves the way for their modification to improve the production of neutral lipids

    The Mycobacterium Tuberculosis FAS-II Dehydratases and Methyltransferases Define the Specificity of the Mycolic Acid Elongation Complexes

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    BACKGROUND: The human pathogen Mycobacterium tuberculosis (Mtb) has the originality of possessing a multifunctional mega-enzyme FAS-I (Fatty Acid Synthase-I), together with a multi-protein FAS-II system, to carry out the biosynthesis of common and of specific long chain fatty acids: the mycolic acids (MA). MA are the main constituents of the external mycomembrane that represents a tight permeability barrier involved in the pathogenicity of Mtb. The MA biosynthesis pathway is essential and contains targets for efficient antibiotics. We have demonstrated previously that proteins of FAS-II interact specifically to form specialized and interconnected complexes. This finding suggested that the organization of FAS-II resemble to the architecture of multifunctional mega-enzyme like the mammalian mFAS-I, which is devoted to the fatty acid biosynthesis. PRINCIPAL FINDINGS: Based on conventional and reliable studies using yeast-two hybrid, yeast-three-hybrid and in vitro Co-immunoprecipitation, we completed here the analysis of the composition and architecture of the interactome between the known components of the Mtb FAS-II complexes. We showed that the recently identified dehydratases HadAB and HadBC are part of the FAS-II elongation complexes and may represent a specific link between the core of FAS-II and the condensing enzymes of the system. By testing four additional methyltransferases involved in the biosynthesis of mycolic acids, we demonstrated that they display specific interactions with each type of complexes suggesting their coordinated action during MA elongation. SIGNIFICANCE: These results provide a global update of the architecture and organization of a FAS-II system. The FAS-II system of Mtb is organized in specialized interconnected complexes and the specificity of each elongation complex is given by preferential interactions between condensing enzymes and dehydratase heterodimers. This study will probably allow defining essential and specific interactions that correspond to promising targets for Mtb FAS-II inhibitors

    Mu2e Technical Design Report

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    The Mu2e experiment at Fermilab will search for charged lepton flavor violation via the coherent conversion process mu- N --> e- N with a sensitivity approximately four orders of magnitude better than the current world's best limits for this process. The experiment's sensitivity offers discovery potential over a wide array of new physics models and probes mass scales well beyond the reach of the LHC. We describe herein the preliminary design of the proposed Mu2e experiment. This document was created in partial fulfillment of the requirements necessary to obtain DOE CD-2 approval.Comment: compressed file, 888 pages, 621 figures, 126 tables; full resolution available at http://mu2e.fnal.gov; corrected typo in background summary, Table 3.
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