Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis

Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms’ Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8–1.4 x 106). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1126-134 (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1950-958 epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients

Cancer data and Aboriginal disparities (CanDAD)-developing an Advanced Cancer Data System for Aboriginal people in South Australia: a mixed methods research protocol

Introduction: In Australia, Aboriginal and Torres Strait Islander People carry a greater burden of cancerrelated mortality than non-Aboriginal Australians. The Cancer Data and Aboriginal Disparities Project aims to develop and test an integrated, comprehensive cancer monitoring and surveillance system capable of incorporating epidemiological and narrative data to address disparities and advocate for clinical system change. Methods and analysis: The Advanced Cancer Data System will integrate routinely collected unit record data from the South Australian Population Cancer Registry and a range of other data sources for a retrospective cohort of indigenous people with cancers diagnosed from 1990 to 2010. A randomly drawn non- Aboriginal cohort will be matched by primary cancer site, sex, age and year at diagnosis. Cross-tabulations and regression analyses will examine the extent to which demographic attributes, cancer stage and survival vary between the cohorts. Narratives from Aboriginal people with cancer, their families, carers and service providers will be collected and analysed using patient pathway mapping and thematic analysis. Statements from the narratives will structure both a concept mapping process of rating, sorting and prioritising issues, focusing on issues of importance and feasibility, and the development of a real-time Aboriginal Cancer Measure of Experience for ongoing linkage with epidemiological data in the Advanced Cancer Data System. Aboriginal Community engagement underpins this Project. Ethics and dissemination: The research has been approved by relevant local and national ethics committees. Findings will be disseminated in local and international peer-reviewed journals and conference presentations. In addition, the research will provide data for knowledge translation activities across the partner organisations and feed directly into the Statewide Cancer Control Plan. It will provide a mechanism for monitoring and evaluating the implementation of the recommendations in these documents.Paul Henry Yerrell, David Roder, Margaret Cargo, Rachel Reilly, David Banham, Jasmine May Micklem, Kim Morey, Harold Bundamurra Stewart, Janet Stajic, Michael Norris, Alex Brown, On behalf of the CanDAD Aboriginal Community Reference Group and CanDAD Investigator

A Lacustrine Paleoenvironment Recorded at Vera RubinRidge, Gale Crater: Overview of the Sedimentology and Stratigraphy Observed by the Mars ScienceLaboratory Curiosity Rover

For ~500 Martian solar days (sols), the Mars Science Laboratory team explored Vera Rubin ridge (VRR), a topographic feature on the northwest slope of Aeolis Mons. Here we review the sedimentary facies and stratigraphy observed during sols 1,800–2,300, covering more than 100 m of stratigraphic thickness. Curiosity's traverse includes two transects across the ridge, which enables investigation of lateral variability over a distance of ~300 m. Three informally named stratigraphic members of the Murray formation are described: Blunts Point, Pettegrove Point, and Jura, with the latter two exposed on VRR. The Blunts Point member, exposed just below the ridge, is characterized by a recessive, fine‐grained facies that exhibits extensive planar lamination and is crosscut by abundant curvi‐planar veins. The Pettegrove Point member is more resistant, fine‐grained, thinly planar laminated, and contains a higher abundance of diagenetic concretions. Conformable above the Pettegrove Point member is the Jura member, which is also fine‐grained and parallel stratified, but is marked by a distinct step in topography, which coincides with localized meter‐scale inclined strata, a thinly and thickly laminated facies, and occasional crystal molds. All members record low‐energy lacustrine deposition, consistent with prior observations of the Murray formation. Uncommon outcrops of low‐angle stratification suggest possible subaqueous currents, and steeply inclined beds may be the result of slumping. Collectively, the rocks exposed at VRR provide additional evidence for a long‐lived lacustrine environment (in excess of 106 years via comparison to terrestrial records of sedimentation), which extends our understanding of the duration of habitable conditions in Gale crater

The Stratigraphy of Central and Western Butte and the Greenheugh Pediment Contact

The Greenheugh pediment at the base of Aeolis Mons (Mt. Sharp), which may truncate units in the Murray formation and is capped by a thin sandstone unit, appears to represent a major shift in climate history within Gale crater. The pediment appears to be an erosional remnant of potentially a much more extensive feature. Curiositys traverse through the southern extent of Glen Torridon (south of Vera Rubin ridge) has brought the rover in contact with several new stratigraphic units that lie beneath the pediment. These strata were visited at two outcrop-forming buttes (Central and Western butte- both remnants of the retreating pediment) south of an orbitally defined boundary marking the transition from the Fractured Clay-bearing Unit (fCU) and the fractured Intermediate Unit (fIU). Here we present preliminary interpretations of the stratigraphy within Central and Western buttes and propose the Western butte cap rocks do not match the pediment capping unit

Critical Dimensions in Architectural Photography: Contributions to Architectural Knowledge

This paper illustrates and explores three critical dimensions of photography in architecture, each of which informs the production of images, texts, and other artifacts which establish what might be called a building’s media footprint. The paper’s broad goal is to question the extent to which these critical dimensions are relevant to architectural decision-making processes. Acknowledging that such dimensions as the ones examined here rarely predict an architect’s specific design decisions in a transparent manner, the paper discusses not only the decisions made by architects during the process of designing buildings, but the decisions made by critics, visitors, and members of the general public as they engage in activities such as visiting buildings, writing about them and, particularly, photographing them. First, the text discusses the potential of buildings to operate as mechanisms for producing images, in the sense originated by Beatriz Colomina. The question is developed through the analysis of the space of photography – mapping of points of view, directions of view, and fields of view of defined photographic collections. Secondly, it considers photography’s complicity in the canonization of buildings, and specifically, the extent to which photography is responsible for distinguishing between major and minor architectural works. Finally, the essay examines the erosion over time of photography’s historical power to frame when confronted with contemporary technologies of virtual reality and photo realistically rendered digital models. Each of these critical dimensions, or concepts, develops a specific aspect of how photographic information about buildings is organized, structured, and disseminated, and is thus only part of the larger project of architectural epistemology, which inquires into this wider field. This will be done through an examination of the Mies van der Rohe-designed Commons Building at ITT in Chicago and the evolution of its relationship with architectural photography and photographic representation – both on its own terms and through the prism of the Rem Koolhaas-designed McCormick Tribune Student Center, which adds to and incorporates the Commons Building. Until the end of the twentieth century, the Commons Building on the campus of the Illinois Institute of Technology was generally considered one of Mies van der Rohe’s lesser works. Reportedly neglected by its own architect during the design process, and frequently marginalized in academic discussions of the campus, when mentioned at all the building was often cited as an unrefined prototype of Crown Hall. This discourse took a new direction when in 1998, Rem Koolhaas/OMA won a design competition for a student center on the IIT campus: uniquely among the competition entries, Koolhaas’s design incorporated the Commons Building within a new context – what ultimately became the McCormick Tribune Campus Center (MTCC). When critics concluded that the incorporation of the Commons Building into the larger whole could compromise its integrity as an exemplar of Mies’s work, the building became the object of renewed interest and controversy. The two projects considered here show a clear evolution in architecture’s relationship with the photographic image. Specifically, the history of the Commons Building can be traced through photographs: during and shortly following its construction, the building was photographed as part of Mies’s own attention to publicity; it was documented as part of historical analyses; and over time it was visited and photographed by casual and amateur photographers. Following the competition results, photographs of the Commons Building were strategically deployed by both proponents and critics of Koolhaas’s design. Contemporary photographs of the building appear in architectural and campus guidebooks and on websites such as Flickr.com. Examining the ways in which photographs of the Commons Building appear in these various contexts allows discussion of the critical dimensions identified above and permits us to trace the evolution of the mutually reinforcing relationship between architecture and photography

Extraformational sediment recycling on Mars

Extraformational sediment recycling (old sedimentary rock to new sedimentary rock) is a fundamental aspect of Earth's geological record; tectonism exposes sedimentary rock, whereupon it is weathered and eroded to form new sediment that later becomes lithified. On Mars, tectonism has been minor, but two decades of orbiter instrument-based studies show that some sedimentary rocks previously buried to depths of kilometers have been exposed, by erosion, at the surface. Four locations in Gale crater, explored using the National Aeronautics and Space Administration's Curiosity rover, exhibit sedimentary lithoclasts in sedimentary rock: At Marias Pass, they are mudstone fragments in sandstone derived from strata below an erosional unconformity; at Bimbe, they are pebble-sized sandstone and, possibly, laminated, intraclast-bearing, chemical (calcium sulfate) sediment fragments in conglomerates; at Cooperstown, they are pebble-sized fragments of sandstone within coarse sandstone; at Dingo Gap, they are cobble-sized, stratified sandstone fragments in conglomerate derived from an immediately underlying sandstone. Mars orbiter images show lithified sediment fans at the termini of canyons that incise sedimentary rock in Gale crater; these, too, consist of recycled, extraformational sediment. The recycled sediments in Gale crater are compositionally immature, indicating the dominance of physical weathering processes during the second known cycle. The observations at Marias Pass indicate that sediment eroded and removed from craters such as Gale crater during the Martian Hesperian Period could have been recycled to form new rock elsewhere. Our results permit prediction that lithified deltaic sediments at the Perseverance (landing in 2021) and Rosalind Franklin (landing in 2023) rover field sites could contain extraformational recycled sediment.With funding from the Spanish government through the "María de Maeztu Unit of Excellence" accreditation (MDM-2017-0737

Revealing Repton: bringing landscape to life at Sheringham Park

The year 2012 marked 200 years since Humphry Repton (1752–1818) produced his design for Sheringham Park in north Norfolk, bound as one of his Red Books. On paper, Repton is England’s best-known and most influential landscape gardener. On the ground, his work is much harder to identify, focused as it was on light touches that equated more to landscape makeover than the landscape making of his predecessor Lancelot “Capability” Brown. This paper documents and evaluates a project that celebrated this bicentenary through a temporary exhibition within the visitor centre of Sheringham Park, whilst also making reference to the commemoration of his work in other places and on paper. In attempting to reveal Repton at Sheringham, we explore the context of the 1812 commission and the longer landscape history of the site, as well as the different methods of representing Repton on site that are open to site owners and managers

Swimming against the tide: A case study of an integrated social studies department

A recent trend in developed countries’ school curricula has been the transition from disciplinary to generic forms of knowledge, resulting in an emphasis on interdisciplinary organisation and more active forms of learning. Subject specialists are increasingly expected to demonstrate how their subject interconnects and equips pupils with key life skills. Such a change requires a major cultural shift and has been controversial, particularly in Scotland where Curriculum for Excellence, the latest curriculum reform, has seen this debate re-emerge. A detailed empirical case study of one secondary school Social Studies department that has already negotiated these shifts is presented. The case study provides insights into how school and department structures and cultures conducive to a more integrated approach have been developed. Leadership, increased opportunities for teachers to exercise greater autonomy in their work, sources of impetus and support for innovation, and the co-construction of meaning through dialogue are important themes in this process. This case study connects with current policy and provides an insight into strategies that other schools might employ when seeking to embed integrative practices. The department is identified as a significant locus for innovation and one which appears to challenge the norm