The expression and prognostic significance of bcl-2-associated transcription factor 1 in rectal cancer following neoadjuvant therapy

Date of Acceptance: 12/07/2015 © 2015 John Wiley & Sons Ltd. Acknowledgements This study was supported by funding from the Encompass kick start and SMART:Scotland award schemes of Scottish Enterprise and Friends of Anchor. The Grampian Biorepository assisted with the immunohistochemical investigations.

The Hippo effector TAZ (WWTR1) transforms myoblasts and its abundance is associated with reduced survival in embryonal rhabdomyosarcoma

Acknowledgements This study was funded by Sarcoma UK, Friends of Anchor and the Medical Research Council grant number 99477 awarded to HW and PSZ. This work was also supported, in part, by NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and the Institute of Cancer Research, and the Chris Lucas Trust, UK. We also thank the CCLG Tissue Bank for access to samples, and contributing CCLG centres, including members of the ECMC paediatric network. The CCLG Tissue Bank is funded by Cancer Research UK and CCLG. In addition we would like to thank Prof KunLiang Guan and Prof Malcolm Logan for kindly providing constructs

The Hippo effector TAZ (WWTR1) transforms myoblasts and TAZ abundance is associated with reduced survival in embryonal rhabdomyosarcoma

Acknowledgements This study was funded by Sarcoma UK, Friends of Anchor and the Medical Research Council grant number 99477 awarded to HW and PSZ. This work was also supported, in part, by NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and the Institute of Cancer Research, and the Chris Lucas Trust, UK. We also thank the CCLG Tissue Bank for access to samples, and contributing CCLG centres, including members of the ECMC paediatric network. The CCLG Tissue Bank is funded by Cancer Research UK and CCLG. In addition we would like to thank Prof KunLiang Guan and Prof Malcolm Logan for kindly providing constructs

Opening Basement Membrane Gaps During C. elegans Uterine-Vulval Attachment

The basement membrane (BM) is a highly conserved form of extracellular matrix that underlies or surrounds and supports most animal tissues. BMs are crossed by cells during various remodeling events in development, immune surveillance, or during cancer metastasis. Because BMs are dense and not easily penetrable, most of these cells must open a gap in order to facilitate their migration. The mechanisms by which cells execute these changes are poorly understood. A developmental event that requires the opening of a BM gap is C. elegans uterine-vulval connection. The anchor cell (AC), a specialized uterine cell, creates a de novo BM gap. Subsequent widening of the BM gap involves the underlying vulval precursor cells (VPCs) and the π cells, uterine neighbors of the AC through non-proteolytic BM sliding. Using forward and reverse genetic screening, transcriptome profiling, and live-cell imaging, I investigated how the cells in these tissues accomplish BM gap formation. In Chapter 2, I identify two potentially novel regulators of BM breaching, isolated through a large-scale forward genetic screen and characterize the invasion defect in these mutants. In Chapter 3, I describe single-cell transcriptome sequencing of the invasive AC. In Chapter 4, I describe the role of the π cells in opening the nascent BM gap. A complete developmental pathway for this process has been elucidated: the AC induces the π fate through Notch signaling, after which the π cells upregulate the Sec14 family protein CTG-1, which in turn restricts the trafficking of DGN-1 (dystroglycan), a laminin receptor, allowing the BM to slide. Chapter 5 outlines the implications of these discoveries.

Home: the foundations of belonging

To be at home means to be embedded in a dense pattern of relationships to people and place which gives rise to an inherently meaningful experience of the world. This order is neither abstract nor imposed from without, but crystallises from the shared experience of people inhabiting a concrete location. Home involves the localisation of meaning in a concrete setting and in the activities of everyday life, and this embodies an ongoing process of ‘cosmicisation’ which is vital for both social life and individual well-being. Home is not a fixed structure, static and frozen, which shuts out the external world; it is a dynamic centre which draws in experience and gives it meaning. It is a constellation of significance rather than a singular and unitary essence. It is produced by localising processes, which work to concentrate and stabilise value around a secure centre. The elaboration of seven interlinked localising processes forms the core of the thesis: The cultivation of place The accumulation of collective memory The crystallisation of life-ways and their evolution into tradition The generation of mutuality of being through sharing in fundamental biological processes which generate and preserve life Social circles of gift exchange and recognition which reinforce this mutuality of being The elaboration of symbolic boundaries The counterparts of localising processes are globalising ones. These involve the dismantling of the taken-for-granted relationships of everyday life and their reconstitution within spatially extended networks, governed by rationalised institutions, within separate spheres of economic production, commercial transactions, political administration and cultural exchange. The global market, the public arena, technological development and the bureaucratic state are all solvents of localised associations, which result in the dissipation and relativisation of value. However globalising processes never entirely displace localising ones. Even today, localising processes shape those areas of our lives which anchor our identities and provide a sense of meaning: the everyday interactions of home, family, community and intimate circles of friendship.

Middle Eocene Fe and Ca counts, Ca/Fe ratios, revised splices and astronomical age models form different Sites of IODP Exp342

Accurate age models are a tool of utmost important in paleoclimatology. Constraining the rate and pace of past climate change are at the core of paleoclimate research, as such knowledge is crucial to our understanding of the climate system. Indeed, it allows for the disentanglement of the various drivers of climate change. The scarcity of highly resolved sedimentary records from the middle Eocene (Bartonian - Lutetian Stages; 47.8 - 37.8 Ma) has led to the existence of the "Eocene astronomical time scale gap" and hindered the establishment of a comprehensive astronomical time scale (ATS) for the entire Cenozoic. Sediments from the Newfoundland Ridge drilled during Integrated Ocean Drilling Program (IODP) Expedition 342 span the Eocene gap at an unprecedented stratigraphic resolution with carbonate bearing sediments. Moreover, these sediments exhibit cyclic lithological changes that allow for an astronomical calibration of geologic time. In this study, we use the dominant obliquity imprint in XRF-derived calcium-iron ratio series (Ca/Fe) from three sites drilled during IODP Expedition 342 (U1408, U1409, U1410) to construct a floating astrochronology. We then anchor this chronology to numerical geological time by tuning 173-kyr cycles in the amplitude modulation pattern of obliquity to an astronomical solution. This study is one of the first to use the 173-kyr obliquity amplitude cycle for astrochronologic purposes, as previous studies primarily use the 405-kyr long eccentricity cycle as a tuning target to calibrate the Paleogene geologic time scale. We demonstrate that the 173-kyr cycles in obliquity's amplitude are stable between 40 and 50 Ma, which means that one can use the 173-kyr cycle for astrochronologic calibration in the Eocene. Our tuning provides new age estimates for magnetochron reversals C18n.1n - C21r and a stratigraphic framework for key sites from Expedition 342 for the Eocene. Some disagreements emerge when we compare our tuning for the interval between C19r and C20r with previous tuning attempts from the South Atlantic. We therefore present a revision of the original astronomical interpretations for the latter records, so that the various astrochronologic age models for the middle Eocene in the North- and South-Atlantic are consistent.

(Table 1) Clay and non-clay mineral composition of dirty ice samples from across the Arctic

Extensive dirty ice patches with up to 7 kg/m**2 sediment concentrations in layers of up to 10 cm thickness were encountered in 2005 and 2007 in numerous areas across the central Arctic. The Fe grain fingerprint determination of sources for these sampled dirty ice floes indicated both Russian and Canadian sources, with the latter dominating. The presence of benthic shells and sea weeds along with thick layers (2-10 cm) of sediment covering 5-10 m2 indicates an anchor ice entrainment origin as opposed to suspension freezing for some of these floes. The anchor ice origin might explain the dominance of Canadian sources where only narrow flaw leads occur that would not favor suspension freezing as an entrainment process. Expandable clays, commonly used as an indicator of a Kara Sea origin for dirty sea ice, are present in moderately high percentages (>20%) in many circum-Arctic source areas, including the Arctic coasts of North America. Some differences between the Russian and the North American coastal areas are found in clay mineral abundance, primarily the much higher abundance of chlorite in North America and the northern Barents Sea as opposed to the rest of the Russian Arctic. However, sea ice clay mineralogy matched many source areas, making it difficult to use as a provenance tool by itself. The bulk mineralogy (clay and non-clay) does not match specific sources possibly due to reworking of the sediment in dirty floes through summer melting or the failure to characterize all possible source areas.

(Table 1) Age markers and errors for the last 1215 ka in IODP Exp302

Despite its importance in the global climate system, age-calibrated marine geologic records reflecting the evolution of glacial cycles through the Pleistocene are largely absent from the central Arctic Ocean. This is especially true for sediments older than 200 ka. Three sites cored during the Integrated Ocean Drilling Program's Expedition 302, the Arctic Coring Expedition (ACEX), provide a 27 m continuous sedimentary section from the Lomonosov Ridge in the central Arctic Ocean. Two key biostratigraphic datums and constraints from the magnetic inclination data are used to anchor the chronology of these sediments back to the base of the Cobb Mountain subchron (1215 ka). Beyond 1215 ka, two best fitting geomagnetic models are used to investigate the nature of cyclostratigraphic change. Within this chronology we show that bulk and mineral magnetic properties of the sediments vary on predicted Milankovitch frequencies. These cyclic variations record ''glacial'' and ''interglacial'' modes of sediment deposition on the Lomonosov Ridge as evident in studies of ice-rafted debris and stable isotopic and faunal assemblages for the last two glacial cycles and were used to tune the age model. Potential errors, which largely arise from uncertainties in the nature of downhole paleomagnetic variability, and the choice of a tuning target are handled by defining an error envelope that is based on the best fitting cyclostratigraphic and geomagnetic solutions.

The Olivia Framework:Concepts for Use in Finely-Grained, Integrated Social Policy Analysis (Working Paper 45)

The Olivia framework is a set of concepts and measures that, when mature, will allow users to describe, in a consistent and integrated manner, everything about individuals and institutions that is of potential interest to social policy. The present paper summarizes the current stage of development in achieving this highly ambitious goal. The current version of the framework supports analysis of social trends and policy responses from many perspectives: • The point-in-time, resource-flow perspectives that underlie most traditional, economics-based policy analysis. • Life-course perspectives, including both transitions/trajectories analysis and asset-based analysis. • Spatial perspectives that anchor people in space and history and that provide a link to macro-analysis. • The perspective of the purposes/goals of individuals and institutions, including the objectives of different types of government programming. The concepts of the framework, which are all potentially measurable, provide a language that can support integrated analysis in all these areas at a much finer level of description than is customary. It provides a language that is especially well suited for analysis of the incremental policy changes that are typical of a mature welfare state. It supports both qualitative and quantitative analysis, enabling some integration between the two. It supports citizen-centric as well as a government-centric view of social policy. In its current version, the concepts are most highly developed as they related to social policies as they related to labour markets, equality and social integration, care-giving, immigration, income security, sustainability, and social and economic well-being more generally. However the paper points to likely extensions in the areas of health, justice and safety.

What is this thing called Historical Archaeology?

Historical archaeology, in its narrow temporal sense -as an archaeology of the emergence and subsequent evolution of the Modern world- is steadily taking pace in Spanish academia. This paper aims at provoking a more robust debate through understanding how Spanish historical archaeology is placed in the international scene and some of its more relevant particularities. In so doing, the paper also stresses the strong links that have united historical and prehistorical archaeology since its inception, both in relation to the ontological, epistemological and methodological definition of the first as to the influence of socio-political issues in the latter. Such reflection is partly a situated reflection from prehistory as one of the paper’s authors has been a prehistorian for most of her professional life.

Desde una arqueología inclusiva, por un pasado mejor. Un ensayo epistemológico y axiológico

En este trabajo se reflexiona sobre la necesidad de un marco epistemológico inclusivo que aborde la multivocalidad de los procesos históricos objeto de estudio y permita crear relatos históricos más plurales y representativos. Pero el relato sobre el pasado será mejor si, además de ser inclusivo a nivel epistemológico, también contribuye de alguna manera a mejorar la sociedad actual. Por ello se reclama una arqueología que incluya una preocupación axiológica y busque posibles ámbitos de aplicación para los resultados de sus investigaciones. Ejemplificamos esta reivindicación con un caso de estudio sobre cerámica, que subraya que los objetos cotidianos fueron y son utilizados en las estrategias de construcción social de la desigualdad. En este contexto se reclama la toma de consciencia de esta práctica en la actualidad y la renuncia a determinados recursos discursivos. Por ejemplo, se propone retomar el concepto inclusivo, este vez para oponerlo a la significación social del adjetivo exclusivo. Aunque todas estas reflexiones derivan de casos de estudio de arqueología histórica, pueden ser útiles a la arqueología en general, sin sesgo cronológico alguno.

Tifones y gigantes en el mundo macedonio: el rey como símbolo del orden cósmico

Este artículo analiza la existencia de un posible ritual en la antigua Macedonia que fuese similar al Akîtu babilonio. Pensamos que la victoria de Zeus sobre sus enemigos en la gigantomaquia y tifonomaquia fue celebrada por los reyes macedonios para fortalecer su posición en el poder. Aunque no hay evidencias directas de ello, tenemos una serie de diferentes fuentes en las cuales los macedonios están relacionados directa o indirectamente con Tifón y los gigantes. Además, la estratégica importancia del monte Olimpo para los macedonios nos hace pensar que la victoria de Zeus sobre las fuerzas del mal fue conmemorada de alguna forma por ellos.

Item and task difficulty in a B2 reading examination: perceptions of test-takers and CEFR alignment experts compared with psychometric measurements

The article presents a study of a CEFR B2-level reading subtest that is part of the Slovenian national secondary school leaving examination in English as a foreign language, and compares the test-taker actual performance (objective difficulty) with the test-taker and expert perceptions of item difficulty (subjective difficulty). The study also analyses the test-takers’ comments on item difficulty obtained from a while-reading questionnaire. The results are discussed in the framework of the existing research in the fields of (the assessment of) reading comprehension, and are addressed with regard to their implications for item-writing, FL teaching and curriculum development.

CoO nanoparticles embedded in three-dimensional nitrogen/sulfur co-doped carbon nanofiber networks as a bifunctional catalyst for oxygen reduction/evolution reactions

High-performance and low-cost bifunctional electrocatalysts play crucial roles in oxygen reduction and evolution reactions. Herein, a novel three-dimensional (3D) bifunctional electrocatalyst was prepared by embedding CoO nanoparticles into nitrogen and sulfur co-doped carbon nanofiber networks (denoted as CoO@N/S-CNF) through a facile approach. The carbon nanofiber networks were derived from a nanostructured biological material which provided abundant functional groups to nucleate and anchor nanoparticles while retaining its interconnected 3D porous structure. The composite possesses a high specific surface area and graphitization degree, which favors both mass transport and charge transfer for electrochemical reaction. The CoO@N/S-CNF not only exhibits highly efficient catalytic activity towards oxygen reduction reaction (ORR) in alkaline media with an onset potential of about 0.84 V, but also shows better stability and stronger resistance to methanol than Pt/C. Furthermore, it only needs an overpotential of 1.55 V to achieve a current density of 10 mA cm^-2, suggesting that it is an efficient electrocatalyst for oxygen evolution reaction (OER). The ΔE value (oxygen electrode activity parameter) of CoO@N/S-CNF is calculated to be 0.828 V, which demonstrates that the composite could be a promising bifunctional electrocatalyst for both ORR and OER.

The International

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