HSPG Modification by the Secreted Enzyme Notum Shapes the Wingless Morphogen Gradient

AbstractThe secreted signaling protein Wingless acts as a morphogen to pattern the imaginal discs of Drosophila. Here we report identification of a secreted repressor of Wingless activity, which we call Notum. Loss of Notum function leads to increased Wingless activity by altering the shape of the Wingless protein gradient. When overexpressed, Notum blocks Wingless activity. Notum encodes a member of the α/β-hydrolase superfamily, with similarity to pectin acetylesterases. We present evidence that Notum influences Wingless protein distribution by modifying the heparan sulfate proteoglycans Dally-like and Dally. High levels of Wingless signaling induce Notum expression. Thus, Wingless contributes to shaping its own gradient by regulating expression of a protein that modifies its interaction with cell surface proteoglycans

The C-Band All-Sky Survey: Instrument design, status, and first-look data

The C-Band All-Sky Survey (C-BASS) aims to produce sensitive, all-sky maps of diffuse Galactic emission at 5 GHz in total intensity and linear polarization. These maps will be used (with other surveys) to separate the several astrophysical components contributing to microwave emission, and in particular will allow an accurate map of synchrotron emission to be produced for the subtraction of foregrounds from measurements of the polarized Cosmic Microwave Background. We describe the design of the analog instrument, the optics of our 6.1 m dish at the Owens Valley Radio Observatory, the status of observations, and first-look data.Comment: 10 pages, 11 figures, published in Proceedings of SPIE MIllimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy V (2010), Vol. 7741, 77411I-1 - 77411I-1

The necessity of historical inquiry in educational research: the case of Religious Education

publication-status: PublishedThis is an Author's Original Manuscript of an article whose final and definitive form, the Version of Record, has been published in the British Journal of Religious Education, July 2010. Available online at: http://www.tandfonline.com/ or DOI: 10.1080/01416200.2010.498612This article explores the mixed fortunes of historical inquiry as a method in educational studies and exposes evidence for the neglect of this method in religious education research in particular. It argues that historical inquiry, as a counterpart to other research methods, can add depth and range to our understanding of education, including religious education, and can illuminate important longer‐term, broader and philosophical issues. The article also argues that many historical voices have remained silent in the existing historiography of religious education because such historiography is too generalised and too biased towards the development of national policy and curriculum and pedagogical theory. To address this limitation in educational research, this article promotes rigorous historical studies that are more substantially grounded in the appropriate historiographical literature and utilise a wide range of original primary sources. Finally, the article explores a specific example of the way in which a historical approach may be fruitfully applied to a particular contemporary debate concerning the nature and purpose of religious education

Context, Complexity and Contestation: Birmingham's Agreed Syllabuses for Religious Education since the 1970s

publication-status: AcceptedThis is an Author's Original Manuscript of an article whose final and definitive form, the Version of Record, has been published in the Journal of Beliefs and Values, September 2011. Available online at: http://www.tandfonline.com/ or DOI: 10.1080/13617672.2011.600823The present article offers an historical perspective on the 1975, 1995 and 2007 Birmingham Agreed Syllabuses for Religious Education. It draws upon historical evidence uncovered as part of ‘The hidden history of curriculum change in religious education in English schools, 1969–1979’ project, and curriculum history theories, especially David Labaree’s observations about the distance between the ‘rhetorical’ and ‘received’ curricula. We argue that, contrary to the existing historiography, curriculum change in religious education (RE) has been evolutionary not revolutionary. Multiple reasons are posited to explain this, not least among which is the capacity and agency of teachers. Furthermore, we argue that ongoing debates about the nature and purpose of RE, as exemplified in the Birmingham context, reflect the multiple expectations that religious educators and other stakeholders had, and continue to have, of the curriculum subject. These debates contribute to the inertia evident in the implementation of RE curriculum reforms. A consciousness of the history of RE enables curriculum contestations to be contextualised and understood, and, thereby, provides important insights which can be applied to ongoing and future debates and developments

Celtic censure: representing Wales in eighteenth-century Germany

Drawing on Pierre Bourdieu's notion of regionalist discourse as the performative legitimation of specific frontiers, this article examines how the English traveller Samuel Jackson Pratt mediated a picture of the Welsh to late eighteenth-century readers in his Gleanings Through Wales, Holland and Westphalia (1795). This process of mediation was further complicated by the translation of this work into German as the Aehrenlese auf einer Reise durch Wallis, which appeared with the Leipzig publisher Lincke in 1798. While this work made an important contribution to German Celtophilia in the Romantic period, the German translator was careful to omit its more Sternean passages, in favour of factual narrative. Pratt's account of his travel through Wales, mediated in turn to a German audience through its Leipzig translator, therefore embodies several layers of cultural transfer that generate a complex and multifaceted image of Wales at the close of the eighteenth century

Identification of GSK3186899/DDD853651 as a Preclinical Development Candidate for the Treatment of Visceral Leishmaniasis

The leishmaniases are diseases that affect millions of people across the world, in particular visceral leishmaniasis (VL) which is fatal unless treated. Current standard of care for VL suffers from multiple issues and there is a limited pipeline of new candidate drugs. As such, there is a clear unmet medical need to identify new treatments. This paper describes the optimization of a phenotypic hit against Leishmania donovani, the major causative organism of VL. The key challenges were to balance solubility and metabolic stability while maintaining potency. Herein, strategies to address these shortcomings and enhance efficacy are discussed, culminating in the discovery of preclinical development candidate GSK3186899/DDD853651 (<b>1</b>) for VL

Regions of High Out-Of-Hospital Cardiac Arrest Incidence and Low Bystander CPR Rates in Victoria, Australia

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a major public health issue and research has shown that large regional variation in outcomes exists. Of the interventions associated with survival, the provision of bystander CPR is one of the most important modifiable factors. The aim of this study is to identify census areas with high incidence of OHCA and low rates of bystander CPR in Victoria, Australia. METHODS: We conducted an observational study using prospectively collected population-based OHCA data from the state of Victoria in Australia. Using ArcGIS (ArcMap 10.0), we linked the location of the arrest using the dispatch coordinates (longitude and latitude) to Victorian Local Government Areas (LGAs). We used Bayesian hierarchical models with random effects on each LGA to provide shrunken estimates of the rates of bystander CPR and the incidence rates. RESULTS: Over the study period there were 31,019 adult OHCA attended, of which 21,436 (69.1%) cases were of presumed cardiac etiology. Significant variation in the incidence of OHCA among LGAs was observed. There was a 3 fold difference in the incidence rate between the lowest and highest LGAs, ranging from 38.5 to 115.1 cases per 100,000 person-years. The overall rate of bystander CPR for bystander witnessed OHCAs was 62.4%, with the rate increasing from 56.4% in 2008-2010 to 68.6% in 2010-2013. There was a 25.1% absolute difference in bystander CPR rates between the highest and lowest LGAs. CONCLUSION: Significant regional variation in OHCA incidence and bystander CPR rates exists throughout Victoria. Regions with high incidence and low bystander CPR participation can be identified and would make suitable targets for interventions to improve CPR participation rates

Roadmap on Li-ion battery manufacturing research

Growth in the Li-ion battery market continues to accelerate, driven primarily by the increasing need for economic energy storage for electric vehicles. Electrode manufacture by slurry casting is the first main step in cell production but much of the manufacturing optimisation is based on trial and error, know-how and individual expertise. Advancing manufacturing science that underpins Li-ion battery electrode production is critical to adding to the electrode manufacturing value chain. Overcoming the current barriers in electrode manufacturing requires advances in materials, manufacturing technology, in-line process metrology and data analytics, and can enable improvements in cell performance, quality, safety and process sustainability. In this roadmap we explore the research opportunities to improve each stage of the electrode manufacturing process, from materials synthesis through to electrode calendering. We highlight the role of new process technology, such as dry processing, and advanced electrode design supported through electrode level, physics-based modelling. Progress in data driven models of electrode manufacturing processes is also considered. We conclude there is a growing need for innovations in process metrology to aid fundamental understanding and to enable feedback control, an opportunity for electrode design to reduce trial and error, and an urgent imperative to improve the sustainability of manufacture

The Professionalisation of Non-Denominational Religious Education in England: politics, organisation and knowledge

ArticleIn response to contemporary concerns, and using neglected primary sources, this article explores the professionalisation of teachers of Religious Education (RI/RE) in non-denominational, state-maintained schools in England. It does so from the launch of Religion in Education (1934) and the Institute for Christian Education at Home and Abroad (1935) to the founding of the Religious Education Council of England and Wales (1973) and the British Journal of Religious Education (1978). Professionalisation is defined as a collective historical process in terms of three inter-related concepts: (1) professional self-organisation and professional politics, (2) professional knowledge, and (3) initial and continuing professional development. The article sketches the history of non-denominational religious education prior to the focus period, to contextualise the emergence of the professionalising processes under scrutiny. Professional self-organisation and professional politics are explored by reconstructing the origins and history of the Institute of Christian Education at Home and Abroad, which became the principal body offering professional development provision for RI/RE teachers for some fifty years. Professional knowledge is discussed in relation to the content of Religion in Education which was oriented around Christian Idealism and interdenominational networking. Changes in journal name in the 1960s and 1970s reflected uncertainties about the orientation of the subject and shifts in understanding over the nature and character of professional knowledge. The article also explores a particular case of resistance, in the late 1960s, to the prevailing consensus surrounding the nature and purpose of RI/RE, and the representativeness and authority of the pre-eminent professional body of the time. In conclusion, the article examines some implications which may be drawn from this history for the prospects and problems of the professionalisation of RE today