344 research outputs found

    William Blake and the visionary poetry of the law.

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    PhDThis dissertation examines the meaning of law in Blake's work. I argue that Blake's poetry intersects with contemporaneous challenges to the traditional model of the ancient constitution, a debate which I present as a conflict between custom and code. Blake's support for the French Revolution's overthrow of the customary systems of the ancien regime is countered by his nervousness about the rights-based discourse advanced by leading radical intellectuals such as Thomas Paine, a belief that the new systems which they proposed merely re-stated those which they sought to replace within an even narrower compass. Law is also a contested ground within radical political discourse of this period; although the dominant proposals advocated the enshrinement of fundamental rights and the codification of law, there was also a tendency towards a more enthusiastic radicalism These millenarian groups, emerging from antinomian heresy, rejected the notion of life being framed within a set of moral laws. I argue that Blake cannot easily be placed in either group; his work exhibits a fidelity to the redemptive potential of law, coupled with a real concern that to define freedoms in legal terms serves to limit rather than to liberate. Blake's work thus engages with a problem of the period: how to understand the new discourses of law. The customary account of the ancient English conunon law is predicated on the idea that it is codified, yet not written down; secular, though grounded in divine principle. These ambivalences are exploited by Blake in his poetic exploration of the law in the 1790s. In his nineteenth-century epics, Blake finds increasing help in dissenting religion's reconstruction of a radicalized Jesus. Through this radical prophetic voice, Blake is able to construct a redemptive legality founded on a deinstitutio-nalized Christianity, a constitutionalism that is also recovered from the conventional customary account

    The global food chain

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    Jonathon Porritt is Founder Director of Forum for the Future www.forumforthefuture.org.uk; Chairman of the UK Sustainable Development Commission www.sd-commission.org.uk; and author of Capitalism as if the World Matters (Earthscan, 2007)

    Senescence-associated DNA methylation is stochastically acquired in subpopulations of mesenchymal stem cells

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    Replicative senescence has a major impact on function and integrity of cell preparations. This process is reflected by continuous DNA methylation (DNAm) changes at specific CpG dinucleotides in the course of in vitro culture, and such modifications can be used to estimate the state of cellular senescence for quality control of cell preparations. Still, it is unclear how senescence-associated DNAm changes are regulated and whether they occur simultaneously across a cell population. In this study, we analyzed global DNAm profiles of human mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs) to demonstrate that senescence-associated DNAm changes are overall similar in these different cell types. Subsequently, an Epigenetic-Senescence-Signature, based on six CpGs, was either analyzed by pyrosequencing or by bar-coded bisulfite amplicon sequencing. There was a good correlation between predicted and real passage numbers in bulk populations of MSCs (R2  = 0.67) and HUVECs (R2  = 0.97). However, when we analyzed the Epigenetic-Senescence-Signature in subclones of MSCs, the predictions revealed high variation and they were not related to the adipogenic or osteogenic differentiation potential of the subclones. Notably, in clonally derived subpopulations, the DNAm levels of neighboring CpGs differed extensively, indicating that these genomic regions are not synchronously modified during senescence. Taken together, senescence-associated DNAm changes occur in a highly reproducible manner, but they are not synchronously co-regulated. They rather appear to be acquired stochastically-potentially evoked by other epigenetic modifications

    A conceptual review of interprofessional expertise in child safeguarding

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    It is increasingly accepted that practitioners across a range of professional fields must work together in order to promote children's welfare and protect them from harm. However, it has also become apparent that interprofessional working is a challenging area of practice that cannot simply be prescribed through protocols and procedures, nor acquired as a set of technical competences. This article develops the concept of interprofessional expertise in order to explain how practitioners become more proficient at working with others to manage complex child welfare issues. Key principles are outlined with reference to relevant theoretical frameworks, including models of skill acquisition. The article concludes by discussing some potential implications for future research and contemporary developments in child safeguarding practice

    Allylic C—H activation to access anti-1,3-amino alcohol motifs

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    1,3-Amino alcohols are common motifs in a variety of biologically active molecules including antivirals, antibiotics, antifungals, and various alkaloids. Due to their prevalence and utility as synthetic intermediates, a variety of methods have been developed to access these motifs in a diastereoselective fashion, which are outlined in detail herein. This thesis documents a novel approach to access anti-1,3-amino alcohols through an intramolecular palladium (II)/sulfoxide-oxazoline catalyzed C—H functionalization between a terminal olefin and an N-tosyl carbamate, generating anti-1,3-oxazinanones. These motifs can be further elaborated upon, making this method ideal for the late stage diversification of complex molecules and pharmaceuticals. This new method can be carried out in the presence of reactive functionality that is not well tolerated by existing methods.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2020-05-01The student, Jonathon Young, accepted the attached license on 2018-04-25 at 09:29.The student, Jonathon Young, submitted this Thesis for approval on 2018-04-25 at 09:40.This Thesis was approved for publication on 2018-04-25 at 14:08.DSpace SAF Submission Ingestion Package generated from Vireo submission #12470 on 2018-08-31 at 17:30:26Made available in DSpace on 2018-09-04T20:47:30Z (GMT). No. of bitstreams: 2 YOUNG-THESIS-2018.pdf: 17381393 bytes, checksum: e7e97dc99ab1ce290a64d3a5a9836002 (MD5) LICENSE.txt: 4211 bytes, checksum: 6e0b64d3ab5cba30177cd6924932d927 (MD5) Previous issue date: 2018-04-25Embargo set by: Seth Robbins for item 107460 Lift date: 2020-09-04T20:47:38Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 107460 Lift date: 2020-09-04T20:50:11Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemLimited Restriction Lifted for Item 107460 on 2020-09-05T09:15:26Z

    Blake

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    Data and script for Van Berkel et al: Can starlings use a reliable cue of future food deprivation to adaptively modify foraging and fat reserves?

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    Supporting materials for: Can starlings use a reliable cue of future food deprivation to adaptively modify foraging and fat reserves? Menno van Berkela, Melissa Batesona, Daniel Nettlea and Jonathon Dunna* aCentre for Behaviour and Evolution & Institute of Neuroscience, Newcastle University, Newcastle, UK *Author for correspondence (email: [email protected]; telephone: (+44)7730015855; postal address: Institute of Neuroscience, Henry Wellcome Building, The Medical School, Framlington Place, Newcastle University, Newcastle upon Tyne, UK, NE2 4HH). R script and 3 .csv files.</p

    Identification of MiR-21-5p as a functional regulator of mesothelin expression using microRNA capture affinity coupled with next generation sequencing

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    MicroRNAs (miRNAs) are small non-coding RNAs that regulate mRNA expression mainly by silencing target transcripts via binding to miRNA recognition elements (MREs) in the 3′untranslated region (3′UTR). The identification of bona fide targets is challenging for researchers working on the functional aspect of miRNAs. Recently, we developed a method (miR-CATCH) based on biotinylated DNA antisense oligonucleotides that capture the mRNA of interest and facilitates the characterisation of miRNAs::mRNA interactions in a physiological cellular context. Here, the miR-CATCH technique was applied to the mesothelin (MSLN) gene and coupled with next generation sequencing (NGS), to identify miRNAs that regulate MSLN mRNA and that may be responsible for its increased protein levels found in malignant pleural mesothelioma (MPM). Biotinylated MSLN oligos were employed to isolate miRNA::MSLN mRNA complexes from a normal cell line (Met-5A) which expresses low levels of MSLN. MiRNAs targeting the MSLN mRNA were identified by NGS and miR-21-5p and miR-100-5p were selected for further validation analyses. MiR-21-5p was shown to be able to modulate MSLN expression in miRNA mimic experiments in a panel of malignant and non-malignant cell lines. Further miRNA inhibitor experiments and luciferase assays in Mero-14 cells validated miR-21-5p as a true regulator of MSLN. Moreover, in vitro experiments showed that treatment with miR-21-5p mimic reduced proliferation of MPM cell lines. Altogether, this work shows that the miR-CATCH technique, coupled with NGS and in vitro validation, represents a reliable method to identify native miRNA::mRNA interactions. MiR-21-5p is suggested as novel regulator of MSLN with a possible functional role in cellular growth
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