2,176 research outputs found

    Tourism discourse: Languages and banal globalization

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    Topical Calcineurin Inhibitors and Lymphoma Risk: Evidence Update with Implications for Daily Practice

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    Topical calcineurin inhibitors (TCIs), commercially available since 2000–2001, are the first and only topical medications approved for chronic treatment of atopic dermatitis (AD) in pediatric patients and remain a welcomed alternative to topical corticosteroids. In January 2006, the US Food and Drug Administration (FDA) issued a boxed warning requirement based on a theoretical risk of malignancy (including lymphoma) with TCI use. However, in the years since, analyses of epidemiologic and clinical data have failed to demonstrate a causal relationship between TCI use and malignancy or lymphoma risk, especially for pimecrolimus cream. In fact, the observed number of malignancies and lymphomas observed both in post-marketing surveillance and reported to the FDA using its adverse events reporting system is much lower among TCI-exposed patients than the expected number for the general population. Furthermore, among children enrolled in post-marketing pediatric registry studies for both tacrolimus and pimecrolimus followed for up to 5.5 years [10,724 patient-years (PY)] or 6.5 years (16,219 PY), respectively, the observed number of malignancies and lymphomas is very low and similar to the number expected for a sample of similar size in the general population. In addition to reporting these comparative malignancy and lymphoma data, this article provides a historical overview of the boxed warning requirement and critically evaluates the preclinical, clinical, and epidemiological evidence that has thus far failed to substantiate a relationship between TCI use and malignancy. The authors also provide practical clinical advice for optimizing AD management and patient care in the context of the boxed warning

    Time as an operator/observable in nonrelativistic quantum mechanics

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    The nonrelativistic Schroedinger equation for motion of a structureless particle in four-dimensional space-time entails a well-known expression for the conserved four-vector field of local probability density and current that are associated with a quantum state solution to the equation. Under the physical assumption that each spatial, as well as the temporal, component of this current is observable, the position in time becomes an operator and an observable in that the weighted average value of the time of the particle's crossing of a complete hyperplane can be simply defined: ... When the space-time coordinates are (t,x,y,z), the paper analyzes in detail the case that the hyperplane is of the type z=constant. Particles can cross such a hyperplane in either direction, so it proves convenient to introduce an indefinite metric, and correspondingly a sesquilinear inner product with non-Hilbert space structure, for the space of quantum states on such a surface. >... A detailed formalism for computing average crossing times on a z=constant hyperplane, and average dwell times and delay times for a zone of interaction between a pair of z=constant hyperplanes, is presented.Comment: 31 pages, no figures. Differs from published version by minor corrections and additions, and two citation

    A geometric interpretation of the spectral parameter for surfaces of constant mean curvature

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    Considering the kinematics of the moving frame associated with a constant mean curvature surface immersed in S^3 we derive a linear problem with the spectral parameter corresponding to elliptic sinh-Gordon equation. The spectral parameter is related to the radius R of the sphere S^3. The application of the Sym formula to this linear problem yields constant mean curvature surfaces in E^3. Independently, we show that the Sym formula itself can be derived by an appropriate limiting process R -> infinity.Comment: 12 page

    Vaccination with an Attenuated Mutant of Ehrlichia chaffeensis Induces Pathogen-Specific CD4(+) T Cell Immunity and Protection from Tick-Transmitted Wild-Type Challenge in the Canine Host

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    Citation: McGill, J. L., Nair, A. D. S., Cheng, C. M., Rusk, R. A., Jaworski, D. C., & Ganta, R. R. (2016). Vaccination with an Attenuated Mutant of Ehrlichia chaffeensis Induces Pathogen-Specific CD4(+) T Cell Immunity and Protection from Tick-Transmitted Wild-Type Challenge in the Canine Host. Plos One, 11(2), 15. doi:10.1371/journal.pone.0148229Ehrlichia chaffeensis is a tick-borne rickettsial pathogen and the causative agent of human monocytic ehrlichiosis. Transmitted by the Amblyomma americanum tick, E. chaffeensis also causes disease in several other vertebrate species including white-tailed deer and dogs. We have recently described the generation of an attenuated mutant strain of E. chaffeensis, with a mutation in the Ech_0660 gene, which is able to confer protection from secondary, intravenous-administered, wild-type E. chaffeensis infection in dogs. Here, we extend our previous results, demonstrating that vaccination with the Ech_0660 mutant protects dogs from physiologic, tick-transmitted, secondary challenge with wild-type E. chaffeensis; and describing, for the first time, the cellular and humoral immune responses induced by Ech_0660 mutant vaccination and wild-type E. chaffeensis infection in the canine host. Both vaccination and infection induced a rise in E. chaffeensis-specific antibody titers and a significant Th1 response in peripheral blood as measured by E. chaffeensis antigen-dependent CD4(+) T cell proliferation and IFN. production. Further, we describe for the first time significant IL-17 production by peripheral blood leukocytes from both Ech_0660 mutant vaccinated animals and control animals infected with wild-type E. chaffeensis, suggesting a previously unrecognized role for IL-17 and Th17 cells in the immune response to rickettsial pathogens. Our results are a critical first step towards defining the role of the immune system in vaccine-induced protection from E. chaffeensis infection in an incidental host; and confirm the potential of the attenuated mutant clone, Ech_0660, to be used as a vaccine candidate for protection against tick-transmitted E. chaffeensis infection

    Unique and Universal Features of Epsilonproteobacterial Origins of Chromosome Replication and DnaA-DnaA Box Interactions

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    In bacteria, chromosome replication is initiated by the interaction of the initiator protein DnaA with a defined region of a chromosome at which DNA replication starts (oriC). While DnaA proteins share significant homology regardless of phylogeny, oriC regions exhibit more variable structures. The general architecture of oriCs is universal, i.e., they are composed of a cluster of DnaA binding sites, a DNA-unwinding element, and sequences that bind regulatory proteins. However, detailed structures of oriCs are shared by related species while being significantly different in unrelated bacteria. In this work, we characterized Epsilonproteobacterial oriC regions. Helicobacter pylori was the only species of the class for which oriC was characterized. A few unique features were found such as bipartite oriC structure, not encountered in any other Gram-negative species, and topology-sensitive DnaA-DNA interactions, which have not been found in any other bacterium. These unusual H. pylori oriC features raised questions of whether oriC structure and DnaA-DNA interactions are unique to this bacterium or whether they are common to related species. By in silico and in vitro analyses we identified putative oriCs in three Epsilonproteobacterial species: pathogenic Arcobacter butzleri, symbiotic Wolinella succinogenes, and free-living Sulfurimonas denitrificans. We propose that oriCs typically co-localize with ruvC-dnaA-dnaN in Epsilonproteobacteria, with the exception of Helicobacteriaceae species. The clusters of DnaA boxes localize upstream (oriC1) and downstream (oriC2) of dnaA, and they likely constitute bipartite origins. In all cases, DNA unwinding was shown to occur in oriC2. Unlike the DnaA box pattern, which is not conserved in Epsilonproteobacterial oriCs, the consensus DnaA box sequences and the mode of DnaA-DnaA box interactions are common to the class. We propose that the typical Epsilonproteobacterial DnaA box consists of the core nucleotide sequence 5'-TTCAC-3' (4-8 nt), which, together with the significant changes in the DNA-binding motif of corresponding DnaAs, determines the unique molecular mechanism of DnaA-DNA interaction. Our results will facilitate identification of oriCs and subsequent identification of factors which regulate chromosome replication in other Epsilonproteobacteria. Since replication is controlled at the initiation step, it will help to better characterize life cycles of these species, many of which are considered as emerging pathogens

    ICME international survey on teachers working and learning through collaboration

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    This article presents preliminary results from a survey commissioned for ICME 13 (2016) focusing on "Teachers Working and Learning Through Collaboration". It takes as a starting point a previous survey, commissioned for ICME 10 in 2004 that focused on Mathematics Teacher Education. The current survey focuses centrally on teachers involved in collaborations, sometimes in formal settings of professional development, but also in a more diverse range of collaborative settings including research initiatives. The roles of teachers involved in the collaboration, survey methods, decisions and limitations are described. While some of the findings to date resonate with those of the earlier survey, other findings highlight characteristics and issues relating to the differing ways in which teachers collaborate, either with other teachers or the various 'others', most notably mathematics teacher educator researchers. The roles and relationships that contribute to learning in such collaborations, as well as theories and methodologies found in survey sources, are a focus of the findings presented here. Studies rarely theorised collaboration, and few of those that did so reported explicitly on how their theoretical frame shaped the design of research methodologies/approaches guiding activities with teachers. One significant outcome has been the difficulty of relating teachers' learning to collaboration within a project, although many initiatives report developments in teaching, teacher learning and students' learning

    Putative Cooperative ATP-DnaA Binding to Double-Stranded DnaA Box and Single-Stranded DnaA-Trio Motif upon Helicobacter pylori Replication Initiation Complex Assembly

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    oriC is a region of the bacterial chromosome at which the initiator protein DnaA interacts with specific sequences, leading to DNA unwinding and the initiation of chromosome replication. The general architecture of oriCs is universal; however, the structure of oriC and the mode of orisome assembly differ in distantly related bacteria. In this work, we characterized oriC of Helicobacter pylori, which consists of two DnaA box clusters and a DNA unwinding element (DUE); the latter can be subdivided into a GC-rich region, a DnaA-trio and an AT-rich region. We show that the DnaA-trio submodule is crucial for DNA unwinding, possibly because it enables proper DnaA oligomerization on ssDNA. However, we also observed the reverse effect: DNA unwinding, enabling subsequent DnaA–ssDNA oligomer formation—stabilized DnaA binding to box ts1. This suggests the interplay between DnaA binding to ssDNA and dsDNA upon DNA unwinding. Further investigation of the ts1 DnaA box revealed that this box, together with the newly identified c-ATP DnaA box in oriC1, constitute a new class of ATP–DnaA boxes. Indeed, in vitro ATP–DnaA unwinds H. pylori oriC more efficiently than ADP–DnaA. Our results expand the understanding of H. pylori orisome formation, indicating another regulatory pathway of H. pylori orisome assembly

    Chern - Simons Gauge Field Theory of Two - Dimensional Ferromagnets

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    A Chern-Simons gauged Nonlinear Schr\"odinger Equation is derived from the continuous Heisenberg model in 2+1 dimensions. The corresponding planar magnets can be analyzed whithin the anyon theory. Thus, we show that static magnetic vortices correspond to the self-dual Chern - Simons solitons and are described by the Liouville equation. The related magnetic topological charge is associated with the electric charge of anyons. Furthermore, vortex - antivortex configurations are described by the sinh-Gordon equation and its conformally invariant extension. Physical consequences of these results are discussed.Comment: 15 pages, Plain TeX, Lecce, June 199
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