A visionary report on the revitalization of the liberal arts tradition in the electronically inflected, design-driven, multimedia language of the twenty-first century.
Digital_Humanities is a ...compact, game-changing report on the state of contemporary knowledge production. Answering the question “What is digital humanities?,” it provides an in-depth examination of an emerging field. This collaboratively authored and visually compelling volume explores methodologies and techniques unfamiliar to traditional modes of humanistic inquiry—including geospatial analysis, data mining, corpus linguistics, visualization, and simulation—to show their relevance for contemporary culture. Written by five leading practitioner-theorists whose varied backgrounds embody the intellectual and creative diversity of the field, Digital_Humanities is a vision statement for the future, an invitation to engage, and a critical tool for understanding the shape of new scholarship.
Telemedicine programs provide specialty health services to remote populations using telecommunications technology. This innovative approach to medical care delivery has been expanding for several ...years and currently covers various specialty areas such as cardiology, dermatology, and pediatrics. Economic evaluations of telemedicine, however, remain rare, and few of those conducted have accounted for the wide range of economic costs and benefits. Rigorous benefit-cost analyses of telemedicine programs could provide credible and comparative evidence of their economic viability and thus lead to the adoption and/or expansion of the most successful programs. To facilitate more advanced economic evaluations, this article presents research guidelines for conducting benefit-cost analyses of telemedicine programs, emphasizing opportunity cost estimation, commonly used program outcomes, and monetary conversion factors to translate outcomes to dollar values. The article concludes with specific recommendations for future research.
Effective innate immunity against many microbial pathogens requires macrophage programs that upregulate phagocytosis and direct antimicrobial pathways, two functions generally assumed to be ...coordinately regulated. We investigated the regulation of these key functions in human blood-derived macrophages. Interleukin-10 (IL-10) induced the phagocytic pathway, including the C-type lectin CD209 and scavenger receptors, resulting in phagocytosis of mycobacteria and oxidized low-density lipoprotein. IL-15 induced the vitamin D-dependent antimicrobial pathway and CD209, yet the cells were less phagocytic. The differential regulation of macrophage functional programs was confirmed by analysis of leprosy lesions: the macrophage phagocytosis pathway was prominent in the clinically progressive, multibacillary form of the disease, whereas the vitamin D-dependent antimicrobial pathway predominated in the self-limited form and in patients undergoing reversal reactions from the multibacillary to the self-limited form. These data indicate that macrophage programs for phagocytosis and antimicrobial responses are distinct and differentially regulated in innate immunity to bacterial infections.
Neutrophil recruitment is pivotal to the host defense against microbial infection, but it also contributes to the immunopathology of disease.We investigated the mechanism of neutrophil recruitment in ...human infectious disease by means of bioinformatic pathways analysis of the gene expression profiles in the skin lesions of leprosy. In erythema nodosum leprosum (ENL), which occurs in patients with lepromatous leprosy and is characterized by neutrophil infiltration in lesions, the most overrepresented biological functional group was cell movement, including E-selectin, which was coordinately regulated with interleukin 1β (IL-1β). In vitro activation of Toll-like receptor 2 (TLR2), up-regulated in ENL lesions, triggered induction of IL-1β, which together with interferon γ induced E-selectin expression on and neutrophil adhesion to endothelial cells. Thalidomide, an effective treatment for ENL, inhibited this neutrophil recruitment pathway. The gene expression profile of ENL lesions comprised an integrated pathway of TLR2 and Fc receptor activation, neutrophil migration, and inflammation, providing insight into mechanisms of neutrophil recruitment in human infectious disease.
Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately ...classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.
This paper identifies opportunities for design thinking to be integrated into digital learning and digital scholarship initiatives. The paper traces how the rise of digital culture has led to the ...reconsideration of models for learning and the call for new modes of knowledge production, spearheaded by an array of fields from writing programs to computer science. Drawing upon case studies from new media education and the digital humanities, the paper argues that design thinking that is situated, interpretive, and user-oriented is well suited to these initiatives. The paper concludes with a call for design thinking research to engage with emerging models for learning and knowledge production, work whose effects could be felt at an epistemic level for generations.
► Digital technology has had an impact on learning models and scholarly production. ► Digital learning initiatives value abilities claimed by design thinking. ► The design of platforms and interfaces for scholarship has epistemic impact. ► This calls for design thinking defined by interpretive, situated ways of knowing. ► Digital educators and design thinkers can create new modes of learning and research.
A novel mechanism by which T cells contribute to host defense against microbial pathogens is release of the antimicrobial protein granulysin. We investigated the role of granulysin in human ...infectious disease using leprosy as a model. Granulysin-expressing T cells were detected in cutaneous leprosy lesions at a six-fold greater frequency in patients with the localized tuberculoid as compared with the disseminated lepromatous form of the disease. In contrast, perforin, a cytolytic molecule that colocalizes with granulysin in cytotoxic granules, was expressed at similar levels across the spectrum of disease. Within leprosy lesions, granulysin colocalized in CD4+ T cells and was expressed in CD4+ T-cell lines derived from skin lesions. These CD4+ T-cell lines lysed targets by the granule exocytosis pathway and reduced the viability of mycobacteria in infected targets. Given the broad antimicrobial spectrum of granulysin, these data provide evidence that T-cell release of granulysin contributes to host defense in human infectious disease.
Lepromatous leprosy is a model of immune evasion wherein pathogen-specific IL-10-secreting T cells and concomitant failure of Th-1 immunity permit uncontrolled proliferation of the intracellular ...pathogen, Mycobacterium leprae (M. leprae). The mechanism of this immune escape is unknown. Here, the authors report that phenolic glycolipid-1 (PGL-1), a major and distinguishing feature of the M. leprae cell wall, is expressed in the cell membrane of M. leprae-infected human dendritic cells, where it can activate complement in human serum. The authors demonstrate that PGL-1 and the C3 component of complement colocalize in lipid rafts in the dendritic cell membrane, and enter the immune synapse upon co-culture of M. leprae-infected DCs and T cells. Hence, activated C3 is strategically located to costimulate naïve T cells via the complement regulatory protein, CD46, a process known to stimulate the differentiation of IL-10-secreting regulatory T cells. These observations suggest a potential novel mechanism of immune evasion, wherein M. leprae may subvert host natural immunity to provoke an adaptive response that favors bacillary survival.
Axillary polymastia Burdick, Anne E.; Thomas, Kavita A.; Welsh, Esperanza ...
Journal of the American Academy of Dermatology,
12/2003, Letnik:
49, Številka:
6
Journal Article
Recenzirano
“Polymastia” is a term used to describe the presence of more than 2 breasts in human beings. It is synonymous with supernumerary or accessory breast tissue. Accessory breast tissue has the potential ...to undergo the same benign and malignant changes as normal pectoral breast tissue.
Both the CD4-CD8- (double negative) and CD4-CD8+ T cell lineages have been shown to contain T cells which recognize microbial lipid and glycolipid Ags in the context of human CD1 molecules. To ...determine whether T cells expressing the CD4 coreceptor could recognize Ag in the context of CD1, we derived CD4+ T cell lines from the lesions of leprosy patients. We identified three CD4+ Mycobacterium leprae-reactive, CD1-restricted T cell lines: two CD1b restricted and one CD1c restricted. These T cell lines recognize mycobacterial Ags, one of which has not been previously described for CD1-restricted T cells. The response of CD4+ CD1-restricted T cells, unlike MHC class II-restricted T cells, was not inhibited by anti-CD4 mAb, suggesting that the CD4 coreceptor does not impact positive or negative selection of CD1-restricted T cells. The CD4+ CD1-restricted T cell lines produced IFN-gamma and GM-CSF, the Th1 pattern of cytokines required for cell-mediated immunity against intracellular pathogens, but no detectable IL-4. The existence of CD4+ CD1-restricted T cells that produce a Th1 cytokine pattern suggests a contributory role in immunity to mycobacterial infection.
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