732 research outputs found

    Development of a gemcitabine-polymer conjugate with prolonged cytotoxicity against a pancreatic cancer cell line

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    Gemcitabine (GEM) is a nucleoside analogue of deoxycytidine with limited therapeutic efficacy due to enzymatic hydrolysis by cytidine deaminase (CDA) resulting in compromised half-life in the bloodstream and poor pharmacokinetics. To overcome these limitations, we have developed a methacrylate-based GEM-monomer conjugate, which was polymerized by reversible addition–fragmentation chain transfer (RAFT) polymerization with high monomer conversion (∌90%) and low dispersity (<1.4). The resulting GEM-polymer conjugates were found to form well-defined sub-90 nm nanoparticles (NPs) in aqueous suspension. Subsequently, the GEM release was studied at different pH (∌7 and ∌5) with and without the presence of an enzyme, Cathepsin B. The GEM release profiles followed a pseudo zero-order rate and the GEM-polymer conjugate NPs were prone to acidic and enzymatic degradation, following a two-step hydrolysis mechanism. Furthermore, the NPs exhibited significant cytotoxicity in vitro against a model pancreatic cell line. Although, the half-maximal inhibitory concentration (IC50) of the GEM-monomer and -polymer conjugate NPs was higher than free GEM, the conjugates showed superiorly prolonged activity compared to the parent drug

    Microwave-assisted methods for the synthesis of pentacyclo[5.4.0.02,6.03,10.05,9]undecylamines

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    Efficient methodologies for the preparation of pentacyclo[5..4.0.02,6.03,10.05,9]undecane (PCU) amine derivatives are described via microwave-assisted synthesis. The obtained results revealed that microwave-assisted synthetic procedures under controlled conditions (power, temperature and time) are very convenient, high yielding, efficient and low-cost methods for the preparation of PCU amine derivatives. The new methods show several advantages including operational simplicity, good performance, significant reduction in reaction time, less by-product formation and easier purification.Web of Scienc

    De novo assembled expressed gene catalog of a fast-growing Eucalyptus tree produced by Illumina mRNA-Seq

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    <p>Abstract</p> <p>Background</p> <p><it>De novo </it>assembly of transcript sequences produced by short-read DNA sequencing technologies offers a rapid approach to obtain expressed gene catalogs for non-model organisms. A draft genome sequence will be produced in 2010 for a <it>Eucalyptus </it>tree species (<it>E. grandis</it>) representing the most important hardwood fibre crop in the world. Genome annotation of this valuable woody plant and genetic dissection of its superior growth and productivity will be greatly facilitated by the availability of a comprehensive collection of expressed gene sequences from multiple tissues and organs.</p> <p>Results</p> <p>We present an extensive expressed gene catalog for a commercially grown <it>E. grandis </it>× <it>E. urophylla </it>hybrid clone constructed using only Illumina mRNA-Seq technology and <it>de novo </it>assembly. A total of 18,894 transcript-derived contigs, a large proportion of which represent full-length protein coding genes were assembled and annotated. Analysis of assembly quality, length and diversity show that this dataset represent the most comprehensive expressed gene catalog for any <it>Eucalyptus </it>tree. mRNA-Seq analysis furthermore allowed digital expression profiling of all of the assembled transcripts across diverse xylogenic and non-xylogenic tissues, which is invaluable for ascribing putative gene functions.</p> <p>Conclusions</p> <p><it>De novo </it>assembly of Illumina mRNA-Seq reads is an efficient approach for transcriptome sequencing and profiling in <it>Eucalyptus </it>and other non-model organisms. The transcriptome resource (Eucspresso, <url>http://eucspresso.bi.up.ac.za/</url>) generated by this study will be of value for genomic analysis of woody biomass production in <it>Eucalyptus </it>and for comparative genomic analysis of growth and development in woody and herbaceous plants.</p

    Comparative Analysis of Practice Research in Australia and the UK : The Shift to Practice-driven Research

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    Australia and the UK share many historic connections. These connections have influenced developments in welfare systems, and the bi-directional migration of social work practitioners between Australia and the UK has helped to support the sharing of knowledge in social work education, research and practice. However, developments in practice research in both countries has largely been influenced by local activity rather than cross-national collaboration, though there have been similar growth trajectories. This article uses a comparative case study methodology to analyse the development of practice research in Australia and the UK since the Salisbury Statement on social work practice research. Each case study explores and provides examples of the nature of the relationship between practitioners and academic researchers; how practice questions are generated; how methodologies are selected; how data are collected within social work practice and the impact of practice research on practice in both countries. The comparative analysis provides a unique insight into how local, and often small, projects provide a more significant narrative about the creation of knowledge in social work practice. These insights have the potential to inform and stimulate the development of practice research in other countries which are earlier in the journey towards practice-driven research

    Site Occupancy and Lattice Parameters in Sigma-Phase Co-Cr alloys

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    Neutron diffraction technique was used to study distribution of Co and Cr atoms over different lattice sites as well as lattice paramaters in sigma-phase Co100-xCrx compounds with x = 57.0, 62.7 and 65.8. From the diffractograms recorded in the temperature range of 4.2 - 300 K it was found that all five sites A, B, C, D and E are populated by both kinds of atoms. Sites A and D are predominantly occupied by Co atoms while sites B, C and E by Cr atoms. The unit cell parameters a and c, hence the unit cell volume, increase with x, the increase being characteristic of the lattice paramater and temperature. Both a and c show a non-linear increase with temperature.Comment: 5 figure

    Myths and lessons of liberal intervention: The British campaign for the abolition of the Atlantic slave trade to Brazil

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    This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2012 Martinus NijhoffThis article takes issue with recent references to the British nineteenth century campaign for the abolition of the trans-Atlantic slave trade to Brazil that serve to bolster interventionist or imperialist agendas. In particular, such accounts reproduce two and a half myths about the campaign: that it can serve as a model for the present age; that the success of the campaign can be explained through the actions of the intervening party alone (with a corresponding neglect of those of the ‘target’ state); and the half-myth that the campaign’s success was due to military action (at the expense of institutional (legal) and normative factors and the capacity of the target state). I argue instead that this case – and interventions more generally – would benefit from an analysis that considers the role of force in relation to a series of residual institutional and cultural constraints within the liberal state and to political conditions in the target state. In light of the complexities and contingencies that these factors present the underlying lesson is that military force should be used sparingly, if at all

    Essais d’infection et d’immunisation du Furet par le virus de CarrĂ© adaptĂ© au Lapin

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    Le virus de CarrĂ© adaptĂ© au lapin perd trĂšs rapidement son pouvoir pathogĂšne pour le furet. La perte de la virulence s’accompagne de la perte du pouvoir immunigĂšne
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