Mapping Henry: Dendrochronological Analysis of a Sixteenth-Century Panel Painting Based Upon Synchrotron-Sourced X-ray Fluorescence Mapping

The study of materials that comprise artworks significantly contributes to understanding of age and provenance. While dendrochronology is a particularly valuable and well-established technique for panel paintings comprising oak timber, conventional practices of resurfacing end-grains to reveal tree rings is becoming less acceptable because it removes material, modifying the painting. Recently, application of non-destructive X-ray fluorescence (XRF) spectroscopy to a portrait of Henry VIII held by the Art Gallery of New South Wales (AGNSW), Sydney, Australia revealed tree-ring boundaries in the resulting high-resolution elastic scatter XRF map. In this study, we examine the dendrochronological potential of that mapping with the aim of contributing to resolving the relationship of the AGNSW portrait to similar paintings elsewhere. Examination of the timber revealed affinities with Quercus petraea (Matt.). We measured tree-ring widths along multiple paths in the XRF scatter map and crossdated the resulting 81-year XRF ring-width (XRF portrait ) series against master chronologies of English, western European, and Baltic origin. Rather than an arbitrarily defined threshold, we used a Bonferroni correction to determine a minimum significance level for crossdating. While the XRF portrait series did not crossdate with the continental European chronologies, we identified a single significant (α = 3.4 × 10−6) dating position with the English chronology (1400–1480 CE). Cross-matching with site-level chronologies revealed a cluster of high t-values in central-southern England. The earliest date of felling precedes the documented date of completion for the AGNSW and two similar Tudor portraits of Henry VIII held by the National Portrait Gallery (NPG), London and one at the Society of Antiquaries, London. While the apparent British provenance of timber used in the AGNSW portrait contrasts to Baltic origin of timbers used for the two NPG portraits and the majority of English panel paintings, it is consistent with the provenance of the timber used for the Society of Antiquaries portrait

Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects

The anti-tumour effects of thalidomide have been associated with its anti-angiogenic properties. Second generation thalidomide analogues are distinct compounds with enhanced therapeutic potential. Although these compounds are beginning to enter trials for the treatment of cancer there is very little information regarding the anti-angiogenic activity of these clinically relevant compounds. Furthermore, it is not known how the various immunomodulatory activities of these compounds relate to anti-angiogenic activity. In this study we assessed the anti-angiogenic activity of compounds from both IMiD™ and SelCID™ classes of analogues using a novel in vitro multicellular human assay system and the established rat aorta assay. Our results show that both the IMiDs and SelCIDs tested are significantly more potent than thalidomide. The anti-angiogenic potency of the analogues was not related to inhibition of endothelial cell proliferation, nor their TNF-α/PDE type 4 inhibitory properties. However, anti-migratory effects in vitro and inhibition of tumour growth in vivo was observed with the analogue IMiD-1 (clinically known as REVIMID™). Our results show that anti-angiogenic activity spans both currently defined classes of thalidomide analogue and is not related to their previously described immunomodulatory properties. Identification of the differential effects of these compounds will enable targeting of such compounds into the appropriate clinical setting

Analysis of the UK Government's 2011 tourism policy

This review considers the UK Government's 2011 tourism policy document. The policy was produced during a period of public sector restructuring in the UK and also during the global economic crisis, which began in 2008. The policy sets out a number of reforms to the governance of tourism at the national and local levels, which aim to increase the level of private sector involvement in leading and developing the tourism sector and to reduce the sector's dependence on public funding. During a period of economic slowdown in the UK, the tourism industry can make a significant contribution to growth, but it is not yet clear whether these proposed reforms will support or impede the future development of the tourism industry in the UK

Production studies, transformations in children’s television and the global turn

Moving away from the dominant discourse of US experience, this article looks at how the production of local content for children remains a central issue in many parts of the world, in spite of the growth of transnational media and the apparent abundance of content for children worldwide. Drawing on a pre-summit workshop on Children’s Content at the Core of Public Service Media, held at the 2014 World Summit on Media for Children, it considers the lack of academic perspectives on production, before exploring with workshop participants the regulatory and funding frameworks for quality children’s content, and the conditions for their successful implementation. There is a continuing problem about producing sustainable children’s content, and western models are not always the most appropriate at providing solutions, which need to be nuanced and tailored to different national, regional and local contexts

Drivers of success in implementing sustainable tourism policies in urban areas

The existing literature in the field of sustainable tourism highlights a number of barriers that impede the implementation of policies in this area. Yet, not many studies have so far considered the factors that would contribute to putting this concept into practice, and few address the case of urban areas. The concept of sustainability has only received limited attention in urban tourism research, even though large cities are recognised as one of the most important tourist destinations that attract vast numbers of visitors. Adopting a case study approach, this paper discusses a number of drivers of success identified by policy-makers in London to contribute to the implementation of sustainable tourisms policies at the local level, and briefly looks at the relationship between these drivers and the constraints perceived by the respondents to hinder the implementation of such policies in practice. These findings may help policy-makers in other large cities to successfully develop and implement policies towards sustainable development of tourism in their area

Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers

We assessed the safety, tolerability and efficacy of the immunomodulatory drug, CC-5013 (REVIMID(TM)), in the treatment of patients with metastatic malignant melanoma and other advanced cancers. A total of 20 heavily pretreated patients received a dose-escalating regimen of oral CC-5013. Maximal tolerated dose, toxicity and clinical responses were evaluated and analysis of peripheral T-cell surface markers and serum for cytokines and proangiogenic factors were performed. CC-5013 was well tolerated. In all, 87% of adverse effects were classified as grade 1 or grade 2 according to Common Toxicity Criteria and there were no serious adverse events attributable to CC-5013 treatment. Six patients failed to complete the study, three because of disease progression, two withdrew consent and one was entered inappropriately and withdrawn from the study. The remaining 14 patients completed treatment without dose reduction, with one patient achieving partial remission. Evidence of T-cell activation was indicated by significantly increased serum levels of sIL-2 receptor, granulocyte- macrophage colony-stimulating factor, interleukin-12 (IL-12), tumour necrosis factor-alpha and IL-8 in nine patients from whom serum was available. However, levels of proangiogenic factors vascular endothelial growth factor and basic foetal growth factor were not consistently affected, This study demonstrates the safety, tolerability and suggests the clinical activity of CC-5013 in the treatment of refractory malignant melanoma. Furthermore, this is the first report demonstrating T-cell stimulatory activity of this class of compound in patients with advanced cancer

PG545, a dual heparanase and angiogenesis inhibitor, induces potent anti-tumour and anti-metastatic efficacy in preclinical models

BACKGROUND: PG545 is a heparan sulfate (HS) mimetic that inhibits tumour angiogenesis by sequestering angiogenic growth factors in the extracellular matrix (ECM), thus limiting subsequent binding to receptors. Importantly, PG545 also inhibits heparanase, the only endoglycosidase which cleaves HS chains in the ECM. The aim of the study was to assess PG545 in various solid tumour and metastasis models

Py-GC/MS applied to the analysis of synthetic organic pigments: characterization and identification in paint samples

A collection of 76 synthetic organic pigments was analysed using pyrolysis–gas chromatography/mass spectrometry (Py-GC/MS). The purpose of this work was to expand the knowledge on synthetic pigments and to assess characteristic pyrolysis products that could help in the identification of these pigments in paint samples. We analysed several classes of synthetic pigments not previously reported as being analysed by this technique: some metal complexes, β-naphthol pigment lakes, BONA pigment lakes, disazopyrazolone, triarylcarbonium, dioxazine, anthraquinone, indanthrone, isoindoline and thioindigo classes. We also report for the first time the Py-GC/MS analysis of a number of naphthol AS, benzimidazolone, phthalocyanine and perylene pigments and other miscellaneous pigments including pigments with unpublished chemical structure. We successfully used the Py-GC/MS technique for the analysis of paints by artists Clyfford Still and Jackson Pollock to identify the synthetic organic pigments and the binding media

The CUGBP2 Splicing Factor Regulates an Ensemble of Branchpoints from Perimeter Binding Sites with Implications for Autoregulation

Alternative pre-mRNA splicing adjusts the transcriptional output of the genome by generating related mRNAs from a single primary transcript, thereby expanding protein diversity. A fundamental unanswered question is how splicing factors achieve specificity in the selection of target substrates despite the recognition of information-poor sequence motifs. The CUGBP2 splicing regulator plays a key role in the brain region-specific silencing of the NI exon of the NMDA R1 receptor. However, the sequence motifs utilized by this factor for specific target exon selection and its role in splicing silencing are not understood. Here, we use chemical modification footprinting to map the contact sites of CUGBP2 to GU-rich motifs closely positioned at the boundaries of the branch sites of the NI exon, and we demonstrate a mechanistic role for this specific arrangement of motifs for the regulation of branchpoint formation. General support for a branch site-perimeter–binding model is indicated by the identification of a group of novel target exons with a similar configuration of motifs that are silenced by CUGBP2. These results reveal an autoregulatory role for CUGBP2 as indicated by its direct interaction with functionally significant RNA motifs surrounding the branch sites upstream of exon 6 of the CUGBP2 transcript itself. The perimeter-binding model explains how CUGBP2 can effectively embrace the branch site region to achieve the specificity needed for the selection of exon targets and the fine-tuning of alternative splicing patterns