Blockade of PD-1/PD-L1 promotes adoptive T-Cell immunotherapy in a tolerogenic environment

Adoptive cellular immunotherapy using in vitro expanded CD8+ T cells shows promise for tumour immunotherapy but is limited by eventual loss of function of the transferred T cells through factors that likely include inactivation by tolerogenic dendritic cells (DC). The coinhibitory receptor programmed death-1 (PD-1), in addition to controlling T-cell responsiveness at effector sites in malignancies and chronic viral diseases is an important modulator of dendritic cell-induced tolerance in naive T cell populations. The most potent therapeutic capacity amongst CD8+ T cells appears to lie within Tcm or Tcm-like cells but memory T cells express elevated levels of PD-1. Based on established trafficking patterns for Tcm it is likely Tcm-like cells interact with lymphoid-tissue DC that present tumour-derived antigens and may be inherently tolerogenic to develop therapeutic effector function. As little is understood of the effect of PD-1/PD-L1 blockade on Tcm-like CD8+ T cells, particularly in relation to inactivation by DC, we explored the effects of PD-1/PD-L1 blockade in a mouse model where resting DC tolerise effector and memory CD8+ T cells. Blockade of PD-1/PDL1 promoted effector differentiation of adoptively-transferred Tcm-phenotype cells interacting with tolerising DC. In tumour-bearing mice with tolerising DC, effector activity was increased in both lymphoid tissues and the tumour-site and anti-tumour activity was promoted. Our findings suggest PD-1/PD-L1 blockade may be a useful adjunct for adoptive immunotherapy by promoting effector differentiation in the host of transferred Tcmlike cells. © 2015 Blake et al.

Design a simulated multimedia enriched immersive learning environment (SMILE) for nursing care of dementia patient

This thesis is to establish a framework to guide the development of a simulated, multimedia-enriched, immersive, learning environment (SMILE) framework. This framework models essential media components used to describe a scenario applied in healthcare (in a dementia context), demonstrates interactions between the components, and enables scalability of simulation implementation. The thesis outcomes also include a simulation system developed in accordance with the guidance framework and a preliminary evaluation through a user study involving ten nursing students and practicioners. The results show that the proposed framework is feasible and effective for designing a simulation system in dementia healthcare training.

Scalable fault tolerant agent grooming environment-SAGE

Multi-agent systems (MAS) advocate an agent-based approach to software engineering based on decomposing problems in terms of decentralized, autonomous agents that can engage in flexible, high-level interactions. This chapter introduces scalable fault tolerant agent grooming environment (SAGE), a second-generation Foundation for Intelligent Physical Agents (FIPA)-compliant multi-agent system developed at NIIT-Comtec, which provides an environment for creating distributed, intelligent, and autonomous entities that are encapsulated as agents. The chapter focuses on the highlight of SAGE, which is its decentralized fault-tolerant architecture that can be used to develop applications in a number of areas such as e-health, e-government, and e-science. In addition, SAGE architecture provides tools for runtime agent management, directory facilitation, monitoring, and editing messages exchange between agents. SAGE also provides a built-in mechanism to program agent behavior and their capabilities with the help of its autonomous agent architecture, which is the other major highlight of this chapter. The authors believe that the market for agent-based applications is growing rapidly, and SAGE can play a crucial role for future intelligent applications development. © 2007, IGI Global.

Modulating the preferred O-H center dot center dot center dot O hydrogen-bonding motif in a conformationally constrained environment through hydroxy-group derivatization

The crystal structures of three conformationally locked esters, namely the centrosymmetric tetrabenzoate of all-axial per-hydronaphthalene- 2,3,4a, 6,7,8a-hexaol, viz. trans-4a, 8a-dihydroxyperhydronaphthalene-2,3,6,7-tetrayl tetrabenzoate, C38H34O10, and the diacetate and dibenzoate of all-axial perhydronaphthalene-2,3,4a, 8a-tetraol, viz. (2R*,3R*,4aS*,8aS*)-4a, 8a-dihydroxyperhydronaphthalene-2,3-diyl diacetate, C-14-H22O6, and (2R*, 3R*, 4aS*, 8aS*)-4a, 8a-dihydroxyperhydronaphthalene- 2,3-diyl dibenzoate, C24H26O6, have been analyzed in order to examine the preference of their supramolecular assemblies towards competing inter-and intramolecular O-H center dot center dot center dot O hydrogen bonds. It was anticipated that the supramolecular assembly of the esters under study would adopt two principal hydrogen-bonding modes, namely one that employs intermolecular O-H center dot center dot center dot O hydrogen bonds (mode 1) and another that sacrifices those for intramolecular O-H center dot center dot center dot O hydrogen bonds and settles for a crystal packing dictated by weak intermolecular interactions alone (mode 2). Thus, while the molecular assembly of the two crystalline diacyl derivatives conformed to a combination of hydrogen-bonding modes 1 and 2, the crystal packing in the tetrabenzoate preferred to follow mode 2 exclusively.

Hot corrosion of γ-Y2Si2O7 in strongly basic Na2CO3 molten salt environment

γ-Y2Si2O7 is a promising candidate both for high temperature structural applications and as thermal barrier coatings due to its unique combination of properties, such as high melting point, good machinability, high thermal stability, low linear thermal expansion coefficient (3.9 × 10-6 K-1, 25-1400 °C) and low thermal conductivity (<3 W/m K above 300 °C). In this work, the hot corrosion behavior of γ-Y2Si2O7 in strongly basic Na2CO3 molten salt at 850-1000 °C for 20 h in flowing air was investigated. In the employed conditions, multi-layer corrosion scales with total thickness less than 90 μm were formed. At 850-900 °C, the outmost layer of the scale was composed of the reprecipitation of Y2O3, the bottom of a Si-rich Na2O·xSiO2 (x > 3.65) melt layer, and the middle of a NaYSiO4 layer. At 1000 °C, the corrosion products turned out to be a mixture of NaY9Si6O26 and Si-rich Na2O·xSiO2 (x > 3.65). In all cases, a thin layer of protective SiO2 formed under the Na2O·xSiO2 melt and protected the bulk material from further corrosion.

Modeling transport through an environment crowded by a mixture of obstacles of different shapes and sizes

Many biological environments are crowded by macromolecules, organelles and cells which can impede the transport of other cells and molecules. Previous studies have sought to describe these effects using either random walk models or fractional order diffusion equations. Here we examine the transport of both a single agent and a population of agents through an environment containing obstacles of varying size and shape, whose relative densities are drawn from a specified distribution. Our simulation results for a single agent indicate that smaller obstacles are more effective at retarding transport than larger obstacles; these findings are consistent with our simulations of the collective motion of populations of agents. In an attempt to explore whether these kinds of stochastic random walk simulations can be described using a fractional order diffusion equation framework, we calibrate the solution of such a differential equation to our averaged agent density information. Our approach suggests that these kinds of commonly used differential equation models ought to be used with care since we are unable to match the solution of a fractional order diffusion equation to our data in a consistent fashion over a finite time period.

Corporate America And The New Luminous Environment: Kelly’s work with Johnson, Mies, and Noyes

[book] The potential of electric light as a new building “material” was recognized in the 1920s and became a useful design tool by the mid-century. Skillful lighting allowed for theatricality, narrative, and a new emphasis on structure and space. The Structure of Light tells the story of the career of Richard Kelly, the field’s most influential figure. Six historians, architects, and practitioners explore Kelly’s unparalleled influence on modern architecture and his lighting designs for some of the 20th century’s most iconic buildings: Philip Johnson’s Glass House; Louis Kahn’s Kimbell Art Museum; Eero Saarinen’s GM Technical Center; and Mies van der Rohe’s Seagram Building, among many others. This beautifully illustrated history demonstrates the range of applications, building types, and artistic solutions he employed to achieve a “nocturnal modernity” that would render buildings evocatively different at night. The survival of Kelly’s rich correspondence and extensive diaries allows an in-depth look at the triumphs and uncertainties of a young profession in the making. The first book to focus on the contributions of a master in the field of architectural lighting, this fascinating volume celebrates the practice’s significance in modern design.

Clinical teaching: Maintaining an educational role for doctors in the new health care environment

Context and objectives: Good clinical teaching is central to medical education but there is concern about maintaining this in contemporary, pressured health care environments. This paper aims to demonstrate that good clinical practice is at the heart of good clinical teaching. Methods: Seven roles are used as a framework for analysing good clinical teaching. The roles are medical expert, communicator, collaborator, manager, advocate, scholar and professional. Results: The analysis of clinical teaching and clinical practice demonstrates that they are closely linked. As experts, clinical teachers are involved in research, information retrieval and sharing of knowledge or teaching. Good communication with trainees, patients and colleagues defines teaching excellence. Clinicians can 'teach' collaboration by acting as role models and by encouraging learners to understand the responsibilities of other health professionals. As managers, clinicians can apply their skills to the effective management of learning resources. Similarly skills as advocates at the individual, community and population level can be passed on in educational encounters. The clinicians' responsibilities as scholars are most readily applied to teaching activities. Clinicians have clear roles in taking scholarly approaches to their practice and demonstrating them to others. Conclusion: Good clinical teaching is concerned with providing role models for good practice, making good practice visible and explaining it to trainees. This is the very basis of clinicians as professionals, the seventh role, and should be the foundation for the further development of clinicians as excellent clinical teachers.

Problem-based learning in an e-learning environment: A case study at Griffith University School of Medicine

Increasing numbers of medical schools in Australia and overseas have moved away from didactic teaching methodologies and embraced problem-based learning (PBL) to improve clinical reasoning skills and communication skills as well as to encourage self-directed lifelong learning. In January 2005, the first cohort of students entered the new MBBS program at the Griffith University School of Medicine, Gold Coast, to embark upon an exciting, fully integrated curriculum using PBL, combining electronic delivery, communication and evaluation systems incorporating cognitive principles that underpin the PBL process. This chapter examines the educational philosophies and design of the e-learning environment underpinning the processes developed to deliver, monitor and evaluate the curriculum. Key initiatives taken to promote student engagement and innovative and distinctive approaches to student learning at Griffith promoted within the conceptual model for the curriculum are (a) Student engagement, (b) Pastoral care, (c) Staff engagement, (d) Monitoring and (e) Curriculum/Program Review. © 2007 Springer-Verlag Berlin Heidelberg.

Learning experiences in a giant interactive environment: Insights from The Cube

In November 2012, Queensland University of Technology in Australia launched a giant interactive learning environment known as The Cube. This article reports a phenomenographic investigation into visitors’ different experiences of learning in The Cube. At present very little is known about people’s learning experience in spaces featuring large interactive screens. We observed many visitors to The Cube and interviewed 26 people. Our analysis identified critical variation across the visitors’ experience of learning in The Cube. The findings are discussed as the learning strategy (in terms of Absorption, Exploration, Isolation and Collaboration); and the content learned (in terms of Technology, Skills and Topics). Other findings presented here are dimensions of the learning strategy and the content learned, with differing perspectives on each dimension. These outcomes provide early insights into the potential of giant interactive environments to enhance learning approaches and guide the design of innovative learning spaces in higher education.

Diverse bodies-space politics: Towards a critique of social (in)justice of built environment

Writing has long played an important role in the progression of architecture and the built environment. Histories of architecture are written, manifestoes that form the basis for a designer’s work are written and most importantly, the built environment advances itself through the act of critical writing. Not unlike the visual arts, literature and poetry, the tradition of written criticism has been crucial to the progression of architecture and its allied professions (Franz 2003). This article contributes to architecture and the built environment through the act of a written essay that critiques the problem of bodily diversity to architecture. In particular, the article explores the implications of body-space politics and abstracted body thinking on diverse bodies and their spatial justice. Using Soja’s Spatial Justice theory (2008), we seek to point out the underlying conceptions and power differentials assigned to different bodies spatially and how this leads to spatial injustices and contested spaces. The article also critically analyses the historical emergence of ‘the standardised body’ in architecture and its application in design theory and practice , and looks at how bodies often found on the outside of architecture highlight how such thinking creates in justices. Different theories are drawn on to help point to how design through the use of the upright, forward facing, male bod willingly and unwillingly denies access to resources and spatialities of everyday life. We also suggest ways to re-conceptualise the body in design practice and teaching.