Human papillomavirus oncoproteins induce a reorganization of epithelial-associated γδ T cells promoting tumor formation.

It has been shown that γδ T cells protect against the formation of squamous cell carcinoma (SCC) in several models. However, the role of γδ T cells in human papillomavirus (HPV)-associated uterine cervical SCC, the third-leading cause of death by cancer in women, is unknown. Here, we investigated the impact of γδ T cells in a transgenic mouse model of carcinogenesis induced by HPV16 oncoproteins. Surprisingly, γδ T cells promoted the development of HPV16 oncoprotein-induced lesions. HPV16 oncoproteins induced a decrease in epidermal Skint1 expression and the associated antitumor Vγ5 <sup>+</sup> γδ T cells, which were replaced by γδ T-cell subsets (mainly Vγ6 <sup>+</sup> γδ <sup>low</sup> CCR2 <sup>+</sup> CCR6 <sup>-</sup> ) actively producing IL-17A. Consistent with a proangiogenic role, γδ T cells promoted the formation of blood vessels in the dermis underlying the HPV-induced lesions. In human cervical biopsies, IL-17A <sup>+</sup> γδ T cells could only be observed at the cancer stage (SCC), where HPV oncoproteins are highly expressed, supporting the clinical relevance of our observations in mice. Overall, our results suggest that HPV16 oncoproteins induce a reorganization of the local epithelial-associated γδ T-cell subpopulations, thereby promoting angiogenesis and cancer development

A Theory of Explicit Substitutions with Safe and Full Composition

Many different systems with explicit substitutions have been proposed to implement a large class of higher-order languages. Motivations and challenges that guided the development of such calculi in functional frameworks are surveyed in the first part of this paper. Then, very simple technology in named variable-style notation is used to establish a theory of explicit substitutions for the lambda-calculus which enjoys a whole set of useful properties such as full composition, simulation of one-step beta-reduction, preservation of beta-strong normalisation, strong normalisation of typed terms and confluence on metaterms. Normalisation of related calculi is also discussed.Comment: 29 pages Special Issue: Selected Papers of the Conference "International Colloquium on Automata, Languages and Programming 2008" edited by Giuseppe Castagna and Igor Walukiewic

Social work discourses and the social work interview

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.It will be argued that, in order to understand particular exchanges between social workers and clients, it is essential to go beyond the view that sees them simply in terms of interaction between unique persons, and locate them within the wider discursive settings within which they occur. Most of the talk which takes place in these interviews concerns problematic issues within family life, particularly in terms of the relationships between parents and children. Behind these apparently mundane conversations lie agendas of social work issues which have been constructed historically with the rise of the caring professions. The early part of the thesis is concerned with uncovering the historically constructed norms of acceptable motherhood which underpin social work strategies with families and which help set the agendas of interviews. Then the analysis focuses on how general norms and objectives are translated into operational, professional techniques. This theme is carried forward through a focus on the social settings in which interviews take place, the building up of subject positions within interviews, for social worker and client, and the implications of translating from a predominantly oral to a literate based, professional mode of discourse. Finally, the analysis is concerned with the tentative attempts, marked by ambiguity and resistance, to go beyond the mere monitoring of the life of the client, and draw her/him into a form of discourse which is openly committed to social work aims, where the client seems to want to present his or her life problems in terms which are intelligible to, and manageable within, the strategies open to the social worker

The Language of Paul Muldoon

This book interprets the multifarious writing of the Irish-American word wizard, Paul Muldoon, who has been described by The Times Literary Supplement as ‘the most significant English-language poet born since the second World War’. Readership: All interested in poetry and writing from Ireland and the English-speaking world, and in the enigma of language

Conjunctive Types and SKInT

International audienc