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Howard Van Doren Shaw designed stately country houses in and around Chicago--from affluent Lake Forest, Illinois, and Lake Geneva, Wisconsin, to Iowa, Minnesota, Ohio, and Indiana--from 1894 to 1926, a period in American architecture that spanned the Gilded Age, the adoption of Beaux-Arts classicism as the ideal for civic architecture, the invention of the skyscraper, and the beginning of modernism.

T-cell based vaccines have been considered as attractive candidates for prevention of hepatitis C virus (HCV) infections. In this study we compared the magnitude and phenotypic characteristics of CD8+ T-cells induced by three commonly used viral vectors, Adenovirus-5 (Ad5), Vaccinia virus (VV) and Modified Vaccinia Ankara (MVA) expressing the HCV NS3/4A protein. C57/BL6 mice were primed with DNA expressing NS3/4A and boosted with each of the viral vectors in individual groups of mice. We then tracked the vaccine-induced CD8+ T-cell responses using pentamer binding and cytokine production analysis. Overall, our data indicate that the memory cells induced by Ad5 were inferior to those induced by VV or MVA. We found that Ad5 boosting resulted in rapid expansion and significantly higher frequencies of NS3-specific T-cells compared to VV and MVA boosting. However, the functional profiles, assessed through analysis of the memory cell marker CD127 and the anti-apoptotic molecule Bcl-2 in the blood, spleen, and liver; and measurements of interferon-gamma, tumor necrosis factor-alpha, and interleukin-2 production indicated significantly lower frequencies of long-lived memory T-cells following Ad5 boosting compared to VV and MVA. This same set of analyses suggested that the memory cells induced following boosting with MVA were superior to those induced by both Ad5 and VV. This superiority of the MVA-induced CD8+ T-cells was confirmed following surrogate challenge of mice with a recombinant mouse herpes virus expressing the HCV NS3 protein. Higher levels of NS3-specific CD8+ T-cells displaying the functional markers CD69, Ki67 and Granzyme B were found in the spleens of mice boosted with MVA compared to VV and Ad5, both alone and in combination. These data suggest that MVA may be a more successful viral vector for induction of effective CD8+ T-cell responses against hepatitis C virus.

► We have identified 3 new regions important for neutralization of hepatitis C virus. ► One of these regions is highly conserved (85–95%) amongst genotypes. ► Antibodies to this epitope can cross neutralize 1a, 1b and 2a HCVcc chimeras. ► This epitope provides an important target for prophylactic and therapeutic vaccines. One of the greatest challenges to HCV vaccine development is the induction of effective immune responses using recombinant proteins or vectors. In order to better understand which vaccine-induced antibodies contribute to neutralization of HCV the quality of polyclonal anti-E1E2 antibody responses in immunized mice and chimpanzees was assessed at the level of epitope recognition using peptide scanning and neutralization of chimeric 1a/2a, 1b/2a and 2a HCVcc after blocking or affinity elution of specific antibodies. Mice and chimpanzees were immunized with genotype 1a (H77) HCV gpE1E2; all samples contained cross-neutralizing antibody against HCVcc. By functionally dissecting the polyclonal immune responses we identified three new regions important for neutralization within E1 (aa264–318) and E2 (aa448–483 and aa496–515) of the HCV glycoproteins, the third of which (aa496–515) is highly conserved (85–95%) amongst genotypes. Antibodies to aa496–515 were isolated by affinity binding and elution from the serum of a vaccinated chimpanzee and found to specifically neutralize chimeric 1a/2a, 1b/2a and 2a HCVcc. IC50 titres (IgG ng/mL) for the aa496–515 eluate were calculated as 142.1, 239.37 and 487.62 against 1a/2a, 1b/2a and 2a HCVcc, respectively. Further analysis demonstrated that although antibody to this new, conserved neutralization epitope is efficiently induced with recombinant proteins in mice and chimpanzees; it is poorly induced during natural infection in patients and chimpanzees (7 out of 68 samples positive) suggesting the epitope is poorly presented to the immune system in the context of the viral particle. These findings have important implications for the development of HCV vaccines and strategies designed to protect against heterologous viruses. The data also suggest that recombinant or synthetic antigens may be more efficient at inducing neutralizing antibodies to certain epitopes and that screening virally infected patients may not be the best approach for finding new cross-reactive epitopes.

Developing Inquiry for Learning shows how university tutors can help students to improve their abilities to learn and to become professional inquirers. An increasing proportion of students entering higher education seem to assume that learning is a relatively passive process. This may be the largest single limitation on their achievement. University tutors need to be able to respond creatively to students' learning needs and difficulties. The modern teaching environment in higher education demands a sophisticated approach to teaching, learning and assessment i.e. the curriculum: its planning, its development and tutors' professional development. Tutors need fresh ideas about how to challenge students' spoon-fed approach, to enable them to become collaborative, yet independently motivated learners. In the innovative and practically proven approach developed by the authors of this book, students are guided to implement action research into their learning practices and reflections. Using a rolling programme of cyclical inquiries and whole group 'conferences' on improving learning, students write 'patches' on learning development which are then shared across the year group online. Each student's cumulative set of patches, together with their regular reflective writing, provide the basis for assembling a composite final assignment, a 'Patchwork Text', for assessment. This style of curriculum and assessment organisation encourages regular peer feedback and formative assessment, as part of the whole module process. This is a dynamic approach which builds personal confidence within students, both as learners and as professionals. Providing teaching materials and examples of students' responses, including the use of blogs, wikis and discussion boards, Developing Inquiry for Learning analyses and theorises on the deeper characteristics of the difficulties being addressed. With the provision of relevant frameworks of theory and values, readers are

This chapter is an exploration of some aspects of student responses to the Inquiry Into Learning 1 module that have been examined in depth as part of my contribution to the teaching team's action research. Our module development has been through weekly team meetings to which tutors brought issues arising from their observations of their seminar sessions. Often our meetings had a primary school staffroom feeling to me, in that discussion was focused on students' contributions and our personal responses. It might begin with comments like 'I was amazed by ...' or 'What can I do to help move this student's issue forward?' or 'I can't believe it - they've said ... what could I try next?'. This mutual, collegial support was crucial since we were opening ourselves up to shared observations of the student experience, listening to their views and problems. We were often faced with the very unexpected. We had to hear their authentic student voice in order to support them to be reflective and assess themselves; opening up this dialogue provided great insights and great challenges. This chapter explores how we responded as part of our ongoing research into strategies that might support students in developing growing intrapersonal awareness of their learning. It begins by focusing on students' interpersonal and intrapersonal kinds of reflective activity and the use of the Intervision method. Through examples of students' mutual support in learning how to learn, attention is given to learning-oriented goals rather than performance-oriented goals, and how students decide whether to attribute a difficulty they experience in a task to either the hard effort needed to complete it or to their own limited ability as a learner. The chapter concludes with ways in which the person-centred principles which underpin our relationships with students apply to spoken as well as written contexts for reflective learning.

Developing Inquiry for Learning shows how university tutors can help students to improve their abilities to learn and to become professional inquirers. An increasing proportion of students entering higher education seem to assume that learning is a relatively passive process. This may be the largest single limitation on their achievement. University tutors need to be able to respond creatively to students' learning needs and difficulties. The modern teaching environment in higher education demands a sophisticated approach to teaching, learning and assessment i.e. the curriculum: its planning, its development and tutors' professional development. Tutors need fresh ideas about how to challenge students' spoon-fed approach, to enable them to become collaborative, yet independently motivated learners. In the innovative and practically proven approach developed by the authors of this book, students are guided to implement action research into their learning practices and reflections. Using a rolling programme of cyclical inquiries and whole group 'conferences' on improving learning, students write 'patches' on learning development which are then shared across the year group online. Each student's cumulative set of patches, together with their regular reflective writing, provide the basis for assembling a composite final assignment, a 'Patchwork Text', for assessment. This style of curriculum and assessment organisation encourages regular peer feedback and formative assessment, as part of the whole module process. This is a dynamic approach which builds personal confidence within students, both as learners and as professionals. Providing teaching materials and examples of students' responses, including the use of blogs, wikis and discussion boards, Developing Inquiry for Learning analyses and theorises on the deeper characteristics of the difficulties being addressed. With the provision of relevant frameworks of theory and values, readers are amply equipped to adopt, adapt and experiment within their own developments of teaching and curricula. Tutors, particularly programme leaders, and those who are responsible for the quality of student learning across programmes, are challenged in various ways to re-evaluate current provision and are helped to improve it in ways which can be matched to local situations and priorities. Peter Ovens was Principal Lecturer in Professional and Curriculum Development at Nottingham Trent University and is now a Senior Research Fellow at the University of Cumbria. Frances Wells is a Principal Lecturer in Education at Nottingham Trent University Pat Wallis is a Senior lecturer in Professional Studies at Nottingham Trent University. Cyndy Hawkins is a Senior Lecturer in the School of Education at Nottingham Trent University

The RNA genome of the hepatitis delta virus (HDV) appears to be made up of two parts: a small domain with a high degree of sequence conservation and structural features likely to promote replication; plus a second, larger domain that is less conserved and encodes the delta antigen. This report focuses on one of the several sets of data that have led to the proposal of this model: the existence of a novel structural element in HDV genomic RNA. This structural element lies within the highly conserved domain of HDV RNA and may be related to the local tertiary structure previously mapped to the central conserved region of the plant viroid genome. Both elements occur in regions with no apparent coding capacity and are distinctively responsive to ultraviolet (UV) light. Transcripts containing partial and full-length genomic sequences of HDV readily undergo a UV-induced crosslinking reaction, which establishes a covalent bond between two noncontiguous segments. By locking two segments of the overall structure into place, this crosslink has permitted the unbranched, rodlike model of HDV RNA to be examined and confirmed in the portion of the RNA analyzed. The clustering of the novel tertiary structure and the recently discovered self-cleavage sites into a highly conserved, but apparently noncoding, portion of the genome defines a viroid-like domain in HDV RNA and raises questions about the possible events leading up to the association of free-living RNAs with messenger RNAs and other RNA molecules.

This chapter is about the design of the IIL curriculum and its distinctive assessment. Some fundamental thinking about what a curriculum is and what the design process can be like opens the chapter. Next, aspects of the story of how the Patchwork Texts approach was developed, to explain and justify its special characteristics, is given. Finally, advice about how to adapt any module and the PT approach to work in a complementary manner is offered. This work has been made possible by the extensive and inspirational contributions to curriculum development by John Elliott and the magnificent leadership of the Patchwork Texts Project by Richard Winter.

This chapter is about a particular vision for learning to learn in higher education which stimulated the educational explorations, professional developments and curriculum achievements presented in this book. A good place to start is the university classroom.