High-throughput identification of chemical inhibitors of E. coli Group 2 capsule biogenesis as anti-virulence agents.

Rising antibiotic resistance among Escherichia coli, the leading cause of urinary tract infections (UTIs), has placed a new focus on molecular pathogenesis studies, aiming to identify new therapeutic targets. Anti-virulence agents are attractive as chemotherapeutics to attenuate an organism during disease but not necessarily during benign commensalism, thus decreasing the stress on beneficial microbial communities and lessening the emergence of resistance. We and others have demonstrated that the K antigen capsule of E. coli is a preeminent virulence determinant during UTI and more invasive diseases. Components of assembly and export are highly conserved among the major K antigen capsular types associated with UTI-causing E. coli and are distinct from the capsule biogenesis machinery of many commensal E. coli, making these attractive therapeutic targets. We conducted a screen for anti-capsular small molecules and identified an agent designated "C7" that blocks the production of K1 and K5 capsules, unrelated polysaccharide types among the Group 2-3 capsules. Herein lies proof-of-concept that this screen may be implemented with larger chemical libraries to identify second-generation small-molecule inhibitors of capsule biogenesis. These inhibitors will lead to a better understanding of capsule biogenesis and may represent a new class of therapeutics.

Mesoscale fronts as foraging habitats: composite front mapping reveals oceanographic drivers of habitat use for a pelagic seabird

The oceanographic drivers of marine vertebrate habitat use are poorly understood yet fundamental to our knowledge of marine ecosystem functioning. Here, we use composite front mapping and high-resolution GPS tracking to determine the significance of mesoscale oceanographic fronts as physical drivers of foraging habitat selection in northern gannets Morus bassanus. We tracked 66 breeding gannets from a Celtic Sea colony over 2 years and used residence time to identify area-restricted search (ARS) behaviour. Composite front maps identified thermal and chlorophyll-a mesoscale fronts at two different temporal scales—(i) contemporaneous fronts and (ii) seasonally persistent frontal zones. Using generalized additive models (GAMs), with generalized estimating equations (GEE-GAMs) to account for serial autocorrelation in tracking data, we found that gannets do not adjust their behaviour in response to contemporaneous fronts. However, ARS was more likely to occur within spatially predictable, seasonally persistent frontal zones (GAMs). Our results provide proof of concept that composite front mapping is a useful tool for studying the influence of oceanographic features on animal movements. Moreover, we highlight that frontal persistence is a crucial element of the formation of pelagic foraging hotspots for mobile marine vertebrates.

Mapping cosmopolis: moral topographies of the medieval city

Cosmopolis is a concept that has a long history in many cultures around the globe. It is a mirroring of the 'social' and 'natural' worlds, such that in one is seen the order and the structures of the other -- a mutual 'mapping'. In this paper I examine how the presence of cosmopolis -- a Christianised cosmopolis of the European Middle Ages -- was made evident in the representation and formation of cities at that time. I reveal a dualism between the social and spatial ordering of both city and cosmos which defined and reinforced social and spatial boundaries in urban landscapes, evident for example in the 11th and 12th centuries. Recently, Toulmin (1992) has taken the idea of cosmopolis to argue that it has been a persistent presence in Western - Enlightenment science, philosophy, and religion -- a 'hidden agenda of modernity'. I contend that, as an idea, cosmopolis has a much earlier circulation in European thinking, not least in the Middle Ages. Locating cosmopolis in the medieval and the modern periods then begs a question of what is it that really makes the two distinct and separate? All too often human geographers have emphasised discontinuities between the 'medieval' and 'modern' age, locating the 'rise of modernity' some time in the Enlightenment period. However, what 'mapping' cosmopolis reveals are continuities, binding time and space together, which when looked at begin to help query the modernity concept itself.

Reducing the mapping between perception and action facilitates imitation

This study investigated two hypotheses regarding the mapping of perception to action during imitation. The first hypothesis predicted that as children’s cognitive capacities increase the tendency to map one goal and disregard others during imitation should decrease. This hypothesis was tested by comparing the performances of 168 4- to 7-year-olds in a gestural imitation task developed by Bekkering, Wohlschläger, and Gattis. The second hypothesis predicted that reducing the mapping between perception and action should reduce the demands on the cognitive resources of the child. This hypothesis was tested by creating a condition in which perception and action overlapped by sharing objects between experimenter and child. In three experimental conditions, an adult modelled four gestures, directed at either: 1) one of two sets of round stickers (proprietary objects); 2) the same location on the table, without any sticker (no objects); or 3) one set of round stickers, which were shared with the child (shared objects). The results confirmed both hypotheses. Four- and five-year-olds imitated less accurately when imitation involved mapping of both objects and movements (proprietary and shared objects) than when imitation involved mapping movements only (no objects). Seven-year-olds imitated accurately in all three conditions, demonstrating that increased cognitive capacity allowed them to map multiple goals from perception to action. Most importantly, reducing the mapping between perception and action in the shared objects condition facilitated imitation, specifically for the transitional group, 6-year-olds. We conclude that mapping between perception and action is not direct, but resembles mapping relations in analogical reasoning: cognitive processes mediate mapping from perception to action.

Identification of candidate small-molecule therapeutics to cancer by gene-signature perturbation in connectivity mapping.

Connectivity mapping is a recently developed technique for discovering the underlying connections between different biological states based on gene-expression similarities. The sscMap method has been shown to provide enhanced sensitivity in mapping meaningful connections leading to testable biological hypotheses and in identifying drug candidates with particular pharmacological and/or toxicological properties. Challenges remain, however, as to how to prioritise the large number of discovered connections in an unbiased manner such that the success rate of any following-up investigation can be maximised. We introduce a new concept, gene-signature perturbation, which aims to test whether an identified connection is stable enough against systematic minor changes (perturbation) to the gene-signature. We applied the perturbation method to three independent datasets obtained from the GEO database: acute myeloid leukemia (AML), cervical cancer, and breast cancer treated with letrozole. We demonstrate that the perturbation approach helps to identify meaningful biological connections which suggest the most relevant candidate drugs. In the case of AML, we found that the prevalent compounds were retinoic acids and PPAR activators. For cervical cancer, our results suggested that potential drugs are likely to involve the EGFR pathway; and with the breast cancer dataset, we identified candidates that are involved in prostaglandin inhibition. Thus the gene-signature perturbation approach added real values to the whole connectivity mapping process, allowing for increased specificity in the identification of possible therapeutic candidates.

Mapping public sector organizations:An agenda for future research

This article summarizes the key findings from the five mapping case studies presented in this special issue and relates them back to the conceptual, definitional, and theoretical issues presented in the opening article (MacCarthaigh & Roness, 2012). In so doing, the article considers the alternative ways in which organizational change can best be captured, mapped, and explained and the key issues to be considered when conducting such exercises. As well as identifying how the case studies have advanced the possibilities for mapping public sector organizational change over time in a cross-national context and the benefits this offers for other aspects of public administration research, the article identifies some impediments to future research and collaboration in the field and suggests ways to overcome them. © Taylor & Francis Group, LLC.

Mapping and understanding organizational change:Ireland 1922-2010

Capturing, mapping, and understanding organizational change within bureaucracies is inherently problematic, and the paucity of empirical research in this area reflects the traditional reluctance of scholars to pursue this endeavor. In this article, drawing on the Irish case of organizational change, potential avenues for overcoming such challenges are presented. Drawing on the resources of a time-series database that captures and codes the life cycle of all Irish public organizations since independence, the article explores the evolution of the Irish administrative system since the independence of the state in 1922. These findings provide some pointers toward overcoming the challenges associated with studying change in Whitehall-type bureaucracies. © Taylor & Francis Group, LLC.

Mapping worlds? Excavating cartographic encounters in Plantation Ireland through GIS

This paper uses the analytical potential of Geographical Information Systems (GIS) to explore processes of map production and circulation in early-seventeenth century Ireland. The paper focuses on a group of historic maps, attributed to Josias Bodley, which were commissioned in 1609 by the English Crown to assist in the Plantation of Ulster. Through GIS and digitizing map-features, and in particular by quantifying map-distortion, it is possible to examine how these maps were made, and by whom. Statistical analyses of spatial data derived from the GIS are shown to provide a methodological basis for ‘excavating’ historical geographies of Plantation map-making. These techniques, when combined with contemporary written sources, reveal further insight on the ‘cartographic encounters’ taking place between surveyors and map-makers working in Ireland in the early 1600s, opening up the ‘mapping worlds’ which linked Ireland and Britain through the networks and embodied practices of Bodley and his map-makers.

Introduction: Mapping Gwen John: Lives, Lines and Images

Nomadic Narratives, Visual Forces explores issues, questions, and problems emerging in the analysis of epistolary and visual narratives. This book focuses in particular on Gwen John's letters and paintings. It offers an innovative theoretical approach to narrative analysis by drawing on Foucault's theory of power, Deleuze and Guattari's analytics of desire, and Cavarero's concept of the narratable self. Furthermore, it examines the use of letters as documents of life in narrative research and highlights the dynamics of spatiality in the constitution of the female self in art. This study brings together theoretical insights that emerge from the analysis of life documents - some of them previously unpublished - combining innovative research with specific methodological suggestions on doing narrative analysis.

From "Spaces of Fear" to "Fearscapes": Mapping for Reframing Theories About the Spatialization of Fear in Urban Space

The article engages with theory about the processes of spatialization of fear in contemporary Western urban space (fortification, privatization, exclusion/seclusion, fragmentation, polarization) and their relation to fear of crime and violence. A threefold taxonomy is outlined (Enclosure, Post-Public Space, Barrier), and “spaces of fear” in the city of Palermo are mapped with the aim of exploring the cumulative large-scale effects of the spatialization of fear on a concrete urban territory. Building on empirical evidence, the author suggests that mainstream theories be reframed as part of a less hegemonic and more discursive approach and that theories mainly based on the analyses of global cities be deprovincialized. The author argues for the deconstruction of the concept of “spaces of fear” in favor of the more discursive concept of “fearscapes” to describe the growing landscapes of fear in contemporary Western cities.

Popular music exhibitions in Portugal: practices of representation from 2007 to 2013

This thesis focuses on the representation of Popular Music in museums by mapping, analyzing, and characterizing its practices in Portugal at the beginning of the 21st century. Now that museums' ability to shape public discourse is acknowledged, the examination of popular music's discourses in museums is of the utmost importance for Ethnomusicology and Popular Music Studies as well as for Museum Studies. The concept of 'heritage' is at the heart of this processes. The study was designed with the aim of moving the exhibiting of popular music in museums forward through a qualitative inquiry of case studies. Data collection involved surveying pop-rock music exhibitions as a qualitative sampling of popular music exhibitions in Portugal from 2007 to 2013. Two of these exhibitions were selected as case studies: No Tempo do Gira-Discos: Um Percurso pela Produção Fonográfica Portuguesa at the Museu da Música in Lisbon in 2007 (also Faculdade de Letras, 2009), and A Magia do Vinil, a Música que Mudou a Sociedade at the Oficina da Cultura in Almada in 2008 (and several other venues, from 2009 to 2013). Two specific domains were observed: popular music exhibitions as instances of museum practice and museum professionals. The first domain encompasses analyzing the types of objects selected for exhibition; the interactive museum practices fostered by the exhibitions; the concepts and narratives used to address popular music discursively, as well as the interpretative practices they allow. The second domain, focuses museum professionals and curators of popular music exhibitions as members of a group, namely their goals, motivations and perspectives. The theoretical frameworks adopted were drawn from the fields of ethnomusicology, popular music studies, and museum studies. The written materials of the exhibitions were subjected of methods of discourse analysis methods. Semi-structured interviews with curators and museum professional were also conducted and analysed. From the museum studies perspective, the study research suggests that the practice adopted by popular music museums largely matches that of conventional museums. From the ethnomusicological and popular music studies stand point, the two case studies reveal two distinct conceptual worlds: the first exhibition, curated by an academic and an independent researcher, points to a mental configuration where popular music is explained through a framework of genres supported by different musical practices. Moreover, it is industry actors such as decision makers and gatekeepers that govern popular music, which implies that the visitors' romantic conception of the musician is to some extent dismantled; the second exhibition, curated by a record collector and specialist, is based on a more conventional process of the everyday historical speech that encodes a mismatch between “good” and “bad music”. Data generated by a survey shows that only one curator, in fact that of my first case study, has an academic background. The backgrounds of all the others are in some way similar to the curator of the second case study. Therefore, I conclude that the second case study best conveys the current practice of exhibiting Popular Music in Portugal.

Adolescent females' self-concept and physical education : a Q-sort analysis /

This research illuminates the relationship between female adolescents' self-concept and their experience of physical education. This was accomplished through three stages of interviews and a Qsort. The topics through which the research was categorized included peer support, teachers as significant others, meaningful connections to the body, and curriculum content. During stage one female physical education specialists, curriculum coordinators, and adolescents were interviewed to develop Q-items for the Q-sort. The second stage Involved two groups of females between the ages of 12 and 14 years who participated in the Q-sort. The final stage involved an insight group that consisted of four Q-sort participants who interpreted the highest ranking Q-items. Critical to this research was giving these adolescents the opportunity to voice what was important to them. The results of the research included descriptions of the elements in physical education that were deemed most important by female adolescent students. The topics of "peer support" and "meaningful connections to the body" were ranked the highest. By interpreting the rich insights of the discussion group, it was found that peers were most influential to these young girls. Perceiving and bestowing respect were imperative in this stage of their lives.

Marginal/minority popular music : the concept of the "third space" and the case for "hybridities" of cultures/identities /

The topic of this thesis is marginaVminority popular music and the question of identity; the term "marginaVminority" specifically refers to members of racial and cultural minorities who are socially and politically marginalized. The thesis argument is that popular music produced by members of cultural and racial minorities establishes cultural identity and resists racist discourse. Three marginaVminority popular music artists and their songs have been chosen for analysis in support of the argument: Gil Scott-Heron's "Gun," Tracy Chapman's "Fast Car" and Robbie Robertson's "Sacrifice." The thesis will draw from two fields of study; popular music and postcolonialism. Within the area of popular music, Theodor Adorno's "Standardization" theory is the focus. Within the area of postcolonialism, this thesis concentrates on two specific topics; 1) Stuart Hall's and Homi Bhabha's overlapping perspectives that identity is a process of cultural signification, and 2) Homi Bhabha's concept of the "Third Space." For Bhabha (1995a), the Third Space defines cultures in the moment of their use, at the moment of their exchange. The idea of identities arising out of cultural struggle suggests that identity is a process as opposed to a fixed center, an enclosed totality. Cultures arise from historical memory and memory has no center. Historical memory is de-centered and thus cultures are also de-centered, they are not enclosed totalities. This is what Bhabha means by "hybridity" of culture - that cultures are not unitary totalities, they are ways of knowing and speaking about a reality that is in constant flux. In this regard, the language of "Otherness" depends on suppressing or marginalizing the productive capacity of culture in the act of enunciation. The Third Space represents a strategy of enunciation that disrupts, interrupts and dislocates the dominant discursive construction of US and THEM, (a construction explained by Hall's concept of binary oppositions, detailed in Chapter 2). Bhabha uses the term "enunciation" as a linguistic metaphor for how cultural differences are articulated through discourse and thus how differences are discursively produced. Like Hall, Bhabha views culture as a process of understanding and of signification because Bhabha sees traditional cultures' struggle against colonizing cultures as transforming them. Adorno's theory of Standardization will be understood as a theoretical position of Western authority. The thesis will argue that Adorno's theory rests on the assumption that there is an "essence" to music, an essence that Adorno rationalizes as structure/form. The thesis will demonstrate that constructing music as possessing an essence is connected to ideology and power and in this regard, Adorno's Standardization theory is a discourse of White Western power. It will be argued that "essentialism" is at the root of Western "rationalization" of music, and that the definition of what constitutes music is an extension of Western racist "discourses" of the Other. The methodological framework of the thesis entails a) applying semiotics to each of the three songs examined and b) also applying Bhabha's model of the Third Space to each of the songs. In this thesis, semiotics specifically refers to Stuart Hall's retheorized semiotics, which recognizes the dual function of semiotics in the analysis of marginal racial/cultural identities, i.e., simultaneously represent embedded racial/cultural stereotypes, and the marginal raciaVcultural first person voice that disavows and thus reinscribes stereotyped identities. (Here, and throughout this thesis, "first person voice" is used not to denote the voice of the songwriter, but rather the collective voice of a marginal racial/cultural group). This dual function fits with Hall's and Bhabha's idea that cultural identity emerges out of cultural antagonism, cultural struggle. Bhabha's Third Space is also applied to each of the songs to show that cultural "struggle" between colonizers and colonized produces cultural hybridities, musically expressed as fusions of styles/sounds. The purpose of combining semiotics and postcolonialism in the three songs to be analyzed is to show that marginal popular music, produced by members of cultural and racial minorities, establishes cultural identity and resists racist discourse by overwriting identities of racial/cultural stereotypes with identities shaped by the first person voice enunciated in the Third Space, to produce identities of cultural hybridities. Semiotic codes of embedded "Black" and "Indian" stereotypes in each song's musical and lyrical text will be read and shown to be overwritten by the semiotic codes of the first person voice, which are decoded with the aid of postcolonial concepts such as "ambivalence," "hybridity" and "enunciation."

The effect of literacy training on the self-concept of moderately mentally handicapped adults

In this single group, pretest/posttest design study the literacy level and self-concept of nine moderately mentally handicapped adults was assessed. The participants in the study were involved in reading lessons using the Ball-Stick-Bird reading system, a brainbased program. No significant differences were found in either literacy level or reading level after intervention. However, there were changes in reading behaviour. These changes occurred in the subskills ofdirectionality, letter-sound correspondence, wordreading, and use of reading materials.