27 research outputs found

    la DECLARATION DE PATRIMOINE COMME MESURE PREVENTIVE CONTRE LA CORRUPTION: « L’expérience ALgérienne »

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    LA DECLARATION DE PATRIMOINE COMME MESURE PREVENTIVE CONTRE LA CORRUPTION: « L’expérience ALgérienne

    Mechanical properties and bio-tribological performance of PVD (Ta/ZrN)n multilayer coatings on UHMWPE in bovine serum lubrication

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    This work investigated the tribological performance of (Ta/ZrN)n multilayer coatings against ultrahigh molecular weight polyethylene (UHMWPE) material. Three multilayer coatings with different designs were deposited on Ti-6Al-4 V substrate and subjected to wear testing under lubrication of diluted bovine calf serum. The results revealed an improvement in wear resistance of (Ta/ZrN)n multilayer coatings and low coefficient of friction under an applied load of 1 N. High hardness, excellent biotribological properties, and low residual stresses were obtained in the multilayer coating with the thinnest ZrN as the topmost layer of 100 nm. This work demonstrates that Ta/ZrN multilayers can be promising coatings for prosthesis applications

    Critical Role of Methylglyoxal and AGE in Mycobacteria-Induced Macrophage Apoptosis and Activation

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    Apoptosis and activation of macrophages play an important role in the host response to mycobacterial infection involving TNF-α as a critical autocrine mediator. The underlying mechanisms are still ill-defined. Here, we demonstrate elevated levels of methylglyoxal (MG), a small and reactive molecule that is usually a physiological product of various metabolic pathways, and advanced glycation end products (AGE) during mycobacterial infection of macrophages, leading to apoptosis and activation of macrophages. Moreover, we demonstrate abundant AGE in pulmonary lesions of tuberculosis (TB) patients. Global gene expression profiling of MG-treated macrophages revealed a diverse spectrum of functions induced by MG, including apoptosis and immune response. Our results not only provide first evidence for the involvement of MG and AGE in TB, but also form a basis for novel intervention strategies against infectious diseases in which MG and AGE play critical roles

    Art as an Investment

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    During the 1970s and 1980s, the art markets gave abnormal returns. Individuals started speculating on art prices, and institutional investors soon entered the scene. Economists then began evaluating this new alternative asset class. In this thesis, we review global art markets, analyze the methodologies employed for studying art as an investment, and seek answers to some fundamental questions. To build solid conclusions, we developed the largest up-to-date dataset of repeat sales of art objects. Our main additional contributions to the literature can be summarized as follows. First, we review and explain the growth in international art markets. Second, we show that it is unreasonable to make a comparison between the two main methodologies used for studying the investment perspective of art: the repeat-sales and hedonic regression frameworks. The returns estimated using the hedonic approach depend greatly on the specifications of the model. Thus, we find that of the two, the repeat-sales models are the most robust. Third, we study the returns on art after accounting for transaction costs. Importantly, we show that taking this fair view renders impractical the widely used art-investment measurement methodologies. Fourth, we revisit the “masterpiece effect”, and find strong evidence supporting its existence. Fifth, we investigate the potential of art investment. We find that the inclusion of art in an optimal portfolio depends significantly on the abnormal returns seen in the 1980s. Omitting these years leads to its exclusion. However, art may add a diversification benefit to an investment portfolio due to its low-to-negative correlation with other asset classes. Sixth, we analyze the optimal holding period of art and find that, in general, the returns increase with the length of the holding period. Nevertheless, we observe significant returns, accompanied with high levels of volatility, for trades made over very short time horizons. We notice that this “flipping” practice has been increasing in recent decades. Finally, we consider the effect some special cases have on art investment returns. We find that artworks that trade frequently tend not to outperform the market. Moreover, the nature of an artwork’s ownership history doesn’t alter returns. We also examine the returns on artworks selected by experts, and find that, surprisingly, they underperform

    A Multicistronic DNA Vaccine Induces Significant Protection against Tuberculosis in Mice and Offers Flexibility in the Expressed Antigen Repertoire▿

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    Concerns about the safety and efficacy of Mycobacterium bovis bacillus Calmette-Guérin (BCG) emphasize the need for alternative tuberculosis (TB) vaccines. DNA vaccines are interesting candidates but are limited by the restricted antigen repertoire that they express. Traditional polycistronic vectors are large and have imbalanced expression. Recent advances in molecular genetics and cellular immunology have paved the way toward the rational design of an efficacious vaccine. We exploited self-cleaving peptide 2A from the foot-and-mouth disease virus, because of its small size and high cleavage activity, to generate an efficient TB DNA vaccine (V-2A). V-2A expresses three mycobacterial antigens, Rv3407, Ag85A, and HspX, in a single open reading frame joined by the 2A sequences, which lead to the segmentation of the long translated polypeptide into individual proteins by posttranslational modification. Our in vitro measurements revealed no differences at the transcriptional or translational level between V-2A and the monocistronic expression of the individual antigens. Mice vaccinated with V-2A developed antigen-specific cellular and humoral responses against all three antigens, imparting protection against Mycobacterium tuberculosis aerosol challenge equivalent to that imparted by BCG. These results have important implications for the rational design and development of efficacious recombinant subunit vaccines

    Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of Rv2827c from Mycobacterium tuberculosis

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    M. tuberculosis hypothetical protein Rv2827c was cloned, expressed, purified and crystallized. Preliminary X-ray diffraction data were collected to a resolution of 1.93 Å

    Multi-organ damage induced by anabolic steroid supplements: a case report and literature review

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    Abstract Introduction The use of anabolic supplements and other related drugs for body building and to enhance athletic performance is nowadays widespread and acutely pervasive all around the world. This alarming increase in the use of anabolic and amino acid supplements has been linked to a diverse array of pathologies. As previously reported, the abuse of androgenic steroids is not without severe physiological, psychiatric and physical costs. The case we report here describes multi-organ damage resulting from the abuse and uncontrolled use of anabolic steroid supplements, mainly testosterone. Case presentation A 24-year-old white man presented with abdominal pain concomitant with nausea and vomiting. Laboratory analysis revealed hypercalcemia, elevated liver enzymes and high levels of amylase, lipase and creatine protein kinase. Conclusion Amino acid as well as anabolic supplements may lead to abnormal functioning of many organs, which could be fatal in some instances. This mandates worldwide and concerted efforts to educate the public, especially the youth, about the dangers of these increasingly abused drugs.</p

    X-ray Structure of 4,4′-Dihydroxybenzophenone Mimicking Sterol Substrate in the Active Site of Sterol 14α-Demethylase (CYP51)

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    A universal step in the biosynthesis of membrane sterols and steroid hormones is the oxidative removal of the 14α-methyl group from sterol precursors by sterol 14α-demethylase (CYP51). This enzyme is a primary target in treatment of fungal infections in organisms ranging from humans to plants, and development of more potent and selective CYP51 inhibitors is an important biological objective. Our continuing interest in structural aspects of substrate and inhibitor recognition in CYP51 led us to determine (to a resolution of 1.95Å) the structure of CYP51 from Mycobacterium tuberculosis (CYP51Mt) co-crystallized with 4,4′-dihydroxybenzophenone (DHBP), a small organic molecule previously identified among top type I binding hits in a library screened against CYP51Mt. The newly determined CYP51Mt-DHBP structure is the most complete to date and is an improved template for three-dimensional modeling of CYP51 enzymes from fungal and prokaryotic pathogens. The structure demonstrates the induction of conformational fit of the flexible protein regions and the interactions of conserved Phe-89 essential for both fungal drug resistance and catalytic function, which were obscure in the previously characterized CYP51Mt-estriol complex. DHBP represents a benzophenone scaffold binding in the CYP51 active site via a type I mechanism, suggesting (i) a possible new class of CYP51 inhibitors targeting flexible regions, (ii) an alternative catalytic function for bacterial CYP51 enzymes, and (iii) a potential for hydroxybenzophenones, widely distributed in the environment, to interfere with sterol biosynthesis. Finally, we show the inhibition of M. tuberculosis growth by DHBP in a mouse macrophage model
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