111,842 research outputs found

    Stereoselective synthesis of 3,4-diaryl-beta-lactams

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    Novel 3,4-diaryl beta-lactams were prepared with high stereoselectivity in an efficient manner by a palladium- catalyzed [2+2] carbonylative cycloaddition of benzyl halides with heteroarylidene amines. The type of alkyl group linked to the nitrogen atom influences the reaction’s stereoselectivity. Moreover, using chiral imines, separable diastereomeric mixtures of chiral 3,4-diaryl-beta-lactams were isolated with good yields and high trans diastereoselections

    Development and validation of a new storage procedure to extend the in-use stability of azacitidine in pharmaceutical formulations

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    Stability studies performed by the pharmaceutical industry are principally designed to fulfill licensing requirements. Thus, post-dilution or post-reconstitution stability data are frequently limited to 24 h only for bacteriological reasons, regardless of the true physicochemical stability which could, in many cases, be longer. In practice, the pharmacy-based centralized preparation may require preparation in advance for administration, for example, on weekends, holidays, or in general when pharmacies may be closed. We report an innovative strategy for storing resuspended solutions of azacitidine, a well-known chemotherapic agent, for which the manufacturer lists maximum stability of 22 h. By placing the syringe with the azacitidine reconstituted suspension between two refrigerant gel packs and storing it at 4 °C, we found that the concentration of azacitidine remained above 98% of the initial concentration for 48 h, and no change in color nor the physicochemical properties of the suspension were observed throughout the study period. The physicochemical and microbiological properties were evaluated by HPLC–UV and UHPLC-HRMS analysis, FTIR spectroscopy, pH determination, visual and subvisual examination, and sterility assay. The HPLC-UV method used for evaluating the chemical stability of azacitidine was validated according to ICH. Precise control of storage temperature was obtained by a digital data logger. Our study indicates that by changing the storage procedure of azacitidine reconstituted suspension, the usage window of the drug can be significantly extended to a time frame that better copes with its use in the clinical environment

    Human mesenchymal stem cell combined with a new strontium-enriched bioactive glass: An ex-vivo model for Bone Regeneration

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    A 3D cellular model that mimics the potential clinical application of a biomaterial is here applied for the first time to a bioactive glass, in order to assess its biological potential. A recently developed bioactive glass (BGMS10), whose composition contained strontium and magnesium, was produced in the form of granules and fully investigated in terms of biocompatibility in vitro. Apart from standard biological characterization (Simulated Body Fluid (SBF) testing and biocompatibility as per ISO10993), human bone marrow mesenchymal stromal/stem cells (BM-MSCs) were used to investigate the performance of the bioactive glass granules in an innovative 3D cellular model. The results showed that BGMS10 supported human BM-MSCs adhesion, colonization, and bone differentiation. Thus, bioactive glass granules seem to drive osteogenic differentiation and thus look particularly promising for orthopedic applications, bone tissue engineering and regenerative medicine

    author-bios-SRD-19-0063.R1 – Supplemental material for The Network Structure of Police Misconduct

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    Supplemental material, author-bios-SRD-19-0063.R1 for The Network Structure of Police Misconduct by George Wood, Daria Roithmayr and Andrew V. Papachristos in Socius</p

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    [Dilatation of benign colo-colonic and colo-rectal anastomotic stenosis with radiology-guided balloon catheter].

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    Eleven patients with benign postoperative colonic strictures were treated with balloon dilatation November, 1990, through November, 1995. The anastomosis was sigmoidrectal in 7 patients and colocolic in 4 patients. All patients were submitted to contrast enema and colonscopy to assess the site, shape, grade and length of the stenosis. Biopsy was performed in 7 patients whose strictures had developed 2 months or more postoperatively. The dilatation was performed with 20-mm balloon catheters in the strictures developed 30 days postoperatively, to avoid any complications, and with 30-mm balloon catheters in the other cases. Balloon dilatation was performed under fluoroscopic guidance, with no-drug treatment. The procedure was well tolerated by all patients. One or two dilatation sessions were performed in ten and one patients, respectively. No complications were observed. The results were satisfactory in all cases, with symptom resolution. Follow-up included clinical, endoscopic and radiologic assessment. At follow-up, the technical result was good in all patients and the symptoms were completely relieved. In our experience, radiologically-guided balloon catheter dilatation proved to be an easy, safe and effective tool to treat benign postoperative colonic strictures

    Decellularized Thymus for In Vitro Culture of Functional Adult Thymic Epithelial Cells

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    Thymic epithelial cells (TEC) are a critical component of the three-dimensional (3D) thymic stromal network mediating T-cell development and self-tolerance. Models supporting the culture of functionally competent adult TEC in vitro are currently lacking, hampering thymus engineering strategies and a deeper understanding of the development of a competent immune system. Therefore, we aimed to establish a 3D model based on decellularized thymus for ex vivo culture of functional TEC. A perfusion bioreactor-based protocol for decellularization of murine thymus was developed. Efficient DNA removal was verified by histology and PicoGreen assay. The main components of the thymus native extracellular matrix were preserved, as shown by immunofluorescence for collagen IV, laminin and fibronectin. The decellularized tissue was mechanically disrupted, lyophilized and cross-linked to produce 3D porous scaffolds (thymus scaffold, TS). Microstructure was characterized via scanning electron microscopy. TS supported adult TEC culture in vitro, with preserved TEC phenotype at 2 weeks (immunofluorescence staining, mostly K14+). Fetal TEC cultured with T cell precursors in TS supported thymocyte differentiation in vitro. TS were then seeded with TEC isolated from adult mice and grafted under the kidney capsule of athymic nude mice. Host derived CD4+/CD8+ double positive thymocytes were detected in the graft, and host-derived CD4+ or CD8+ T cells were found in lymph nodes after 7 weeks, demonstrating graft-derived thymopoiesis in vivo. We have developed a 3D model that supports culture and functionality of adult TEC, paving the way to a better understanding of TEC/thymocytes cross-talk and to unprecedented approaches for the treatment of thymic-related pathologies

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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