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Background The immune mechanisms associated with infection-induced disease exacerbations in asthma and COPD are not fully understood. Toll-like receptor (TLR) 3 has an important role in recognition of double-stranded viral RNA, which leads to the production of various inflammatory mediators. Thus, an understanding of TLR3 activation should provide insight into the mechanisms underlying virus-induced exacerbations of pulmonary diseases. Methods TLR3 knock-out (KO) mice and C57B6 (WT) mice were intranasally administered repeated doses of the synthetic double stranded RNA analog poly(I:C). Results There was a significant increase in total cells, especially neutrophils, in BALF samples from poly(I:C)-treated mice. In addition, IL-6, CXCL10, JE, KC, mGCSF, CCL3, CCL5, and TNFα were up regulated. Histological analyses of the lungs revealed a cellular infiltrate in the interstitium and epithelial cell hypertrophy in small bronchioles. Associated with the pro-inflammatory effects of poly(I:C), the mice exhibited significant impairment of lung function both at baseline and in response to methacholine challenge as measured by whole body plethysmography and an invasive measure of airway resistance. Importantly, TLR3 KO mice were protected from poly(I:C)-induced changes in lung function at baseline, which correlated with milder inflammation in the lung, and significantly reduced epithelial cell hypertrophy. Conclusion These findings demonstrate that TLR3 activation by poly(I:C) modulates the local inflammatory response in the lung and suggest a critical role of TLR3 activation in driving lung function impairment. Thus, TLR3 activation may be one mechanism through which viral infections contribute toward exacerbation of respiratory disease.

It is dusk in the desert — that bewitching hour when the intensity of today's unrelenting heat suddenly lifts with the hint of a breeze and a promise of darkness. Worn and weary with dust trailing my every movement, I am inexorably drawn forward by the distant sounds of drums and community. I am curious to see what lies ahead, but for one brief minute I look back from where I have come. A single window penetrates the gloom. It opens on a small room, cluttered with mementos celebrating a long history of great artistry. I feel the weight of this history, even at this distance; but what captures my attention is the music making in the only uncluttered corner of the room where four musicians are poring over a recently discovered score of a late Beethoven string quartet. While the music making appears to be motivated and bound by the score, it is as if the musicians are searching for something that lies beyond the score. At times, the searching seems to question the shape or presence of a particular note or melodic motive; other times, it appears to be a quest for “the work,” the string quartet written by Beethoven. As I continue to eavesdrop, I am struck by the way in which the searching in both instances ultimately seems to evolve into a question of ensemble. It is as if the musicians are not only trying to discover the music implied by the score notations, but also trying to find themselves, trying to get a sense of who they are in relationship to this music. It is a phenomenon that I have encountered frequently in my travels, and I wonder, as the sounds in the distance reenter my consciousness, why of all possibilities the window of my mind opened on this particular room.1

[...]she refocused her career outside of music education, partly because she realized she had much to say, do, and create within a limited lifespan and partly because music education did not have room for such brilliance and creativity. [...]music education gave Eleanor a not so gentle shove. Because she maintained such high standards for herself, she maintained them for others: [...]writing this In Memoriam challenged me to respect that privacy while sharing something of the person I knew. Because her death affected me so deeply emotionally, because I doubted my ability to write about her appropriately, because she meant a great deal to many people, I sought contributions in general from colleagues and students.

A concept of the user is fundamental to much of the research and practice of information systems design, development, and evaluation. Usercentered information studies have relied on individualistic cognitive models to carefully examine the criteria that influence the selection of information and communication technologies (ICTs) that people make. In many ways, these studies have improved our understanding of how a good information resource fits the people who use it. However, research approaches based on an individualistic user concept are limited. In this paper, we examine the theoretical constructs that shape this user concept and contrast these with alternative views that help to reconceptualize the user as a social actor. Despite pervasive ICT use, social actors are not primarily users of ICTs. Most people who use ICT applications utilize multiple applications, in various roles, and as part of their efforts to produce goods and services while interacting with a variety of other people, and often in multiple social contexts. Moreover, the socially thin user construct limits our understanding of information selection, manipulation, communication, and exchange within complex social contexts. Using analyses from a recent study of online information service use, we develop an institutionalist concept of a social actor whose everyday interactions are infused with ICT use. We then encourage a shift from the user concept to a concept of the social actor in IS research. We suggest that such a shift will sharpen perceptions of how organizational contexts shape ICT-related practices, and at the same time will help researchers more accurately portray the complex and multiple roles that people fulfill while adopting, adapting, and using information systems.

A number of unassigned viruses in the family Paramyxoviridae need to be classified either as a new genus or placed into one of the seven genera currently recognized in this family. Furthermore, numerous new paramyxoviruses continue to be discovered. However, attempts at classification have highlighted the difficulties that arise by applying historic criteria or criteria based on sequence alone to the classification of the viruses in this family. While the recent taxonomic change that elevated the previous subfamily Pneumovirinae into a separate family Pneumoviridae is readily justified on the basis of RNA dependent -RNA polymerase (RdRp or L protein) sequence motifs, using RdRp sequence comparisons for assignment to lower level taxa raises problems that would require an overhaul of the current criteria for assignment into genera in the family Paramyxoviridae . Arbitrary cut off points to delineate genera and species would have to be set if classification was based on the amino acid sequence of the RdRp alone or on pairwise analysis of sequence complementarity (PASC) of all open reading frames (ORFs). While these cut-offs cannot be made consistent with the current classification in this family, resorting to genus-level demarcation criteria with additional input from the biological context may afford a way forward. Such criteria would reflect the increasingly dynamic nature of virus taxonomy even if it would require a complete revision of the current classification.

In academia, a Festschrift [1] is a publication honoring a respected academic. It contains original contributions from former PhD students and close colleagues which advance the scholarship or science of a specific discipline. Typically published on the academic's birthday or on some notable anniversary, it is a \"celebration publication\".

Purpose - To extend the work of Rob Kling, whose research interests, and advocacy were at the center of a movement in analytical inquiry and empirical research now known as \"social informatics\".Design methodology approach - Reviews the work of those who engage in social informatics research to strengthen and further the conceptual perspective, analytical approaches, and intellectual contributions of social informatics.Findings - The vibrant and growing international community of active social informatics scholars has assembled a social informatics resource kit that includes: perspective lenses through which research data can be viewed critically; techniques for building theory and developing models from socially rich empirical data; and a common body of knowledge regarding the uses and effects of ICTs.Originality value - The paper identifies opportunities to engage new scholars in social informatics discussions, and suggests new venues for promoting and extending the work of scholars already enrolled in the social informatics movement.

Systems integration (SI) has been examined from two main vantage points. External B2B SI focuses on transactional interactions between customers and suppliers in the value chain. Internal intraorganizational SI focuses on structural interactions between functional units of the firm. Both approaches present problems for intranet integrations that serve communities of practice and formal project teams that cross organizational boundaries. This paper examines a few nontransactional intranet integrations, using a model of social actor interactions, affiliations, environments, and identities, to characterize integration types. The analysis identifies an alternative, project-based integration approach that may be more appropriate for intranets shared by interorganizational teams and communities. The model-driven evaluation also demonstrates how practitioners can use pre-integration intranet boundaries as guidelines for selectively implementing transactional, structural, and project-based integration approaches.

A music educator discusses her observations of music classrooms from elementary schools to universities, noting both the progress made in gender equity and the lingering discrimination and stereotypes that remain.