499 research outputs found
Weyl group multiple Dirichlet series constructed from quadratic characters
We construct multiple Dirichlet series in several complex variables whose
coefficients involve quadratic residue symbols. The series are shown to have an
analytic continuation and satisfy a certain group of functional equations.
These are the first examples of an infinite collection of unstable Weyl group
multiple Dirichlet series in greater than two variables.Comment: incorporated referee's comment
A Role for IFITM Proteins in Restriction of Mycobacterium tuberculosis Infection
SummaryThe interferon (IFN)-induced transmembrane (IFITM) proteins are critical mediators of the host antiviral response. Here, we expand the role of IFITM proteins to host defense against intracellular bacterial infection by demonstrating that they restrict Mycobacterium tuberculosis (MTb) intracellular growth. Simultaneous knockdown of IFITM1, IFITM2, and IFITM3 by RNAi significantly enhances MTb growth in human monocytic and alveolar/epithelial cells, whereas individual overexpression of each IFITM impairs MTb growth in these cell types. Furthermore, MTb infection, Toll-like receptor 2 and 4 ligands, and several proinflammatory cytokines induce IFITM1ā3 gene expression in human myeloid cells. We find that IFITM3 co-localizes with early and, in particular, late MTb phagosomes, and overexpression of IFITM3 enhances endosomal acidification in MTb-infected monocytic cells. TheseĀ findings provide evidence that the antiviral IFITMs participate in the restriction of mycobacterial growth, and they implicate IFITM-mediated endosomal maturation in its antimycobacterial activity
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Involvement of Bruton's tyrosine kinase in FcepsilonRI-dependent mast cell degranulation and cytokine production.
We investigated the role of Bruton's tyrosine kinase (Btk) in FcepsilonRI-dependent activation of mouse mast cells, using xid and btk null mutant mice. Unlike B cell development, mast cell development is apparently normal in these btk mutant mice. However, mast cells derived from these mice exhibited significant abnormalities in FcepsilonRI-dependent function. xid mice primed with anti-dinitrophenyl monoclonal IgE antibody exhibited mildly diminished early-phase and severely blunted late-phase anaphylactic reactions in response to antigen challenge in vivo. Consistent with this finding, cultured mast cells derived from the bone marrow cells of xid or btk null mice exhibited mild impairments in degranulation, and more profound defects in the production of several cytokines, upon FcepsilonRI cross-linking. Moreover, the transcriptional activities of these cytokine genes were severely reduced in FcepsilonRI-stimulated btk mutant mast cells. The specificity of these effects of btk mutations was confirmed by the improvement in the ability of btk mutant mast cells to degranulate and to secrete cytokines after the retroviral transfer of wild-type btk cDNA, but not of vector or kinase-dead btk cDNA. Retroviral transfer of Emt (= Itk/Tsk), Btk's closest relative, also partially improved the ability of btk mutant mast cells to secrete mediators. Taken together, these results demonstrate an important role for Btk in the full expression of FcepsilonRI signal transduction in mast cells
Preferred reporting items for studies mapping onto preference-based outcome measures: The MAPS statement
'Mapping' onto generic preference-based outcome measures is increasingly being used as a means of generating health utilities for use within health economic evaluations. Despite publication of technical guides for the conduct of mapping research, guidance for the reporting of mapping studies is currently lacking. The MAPS (MApping onto Preference-based measures reporting Standards) statement is a new checklist, which aims to promote complete and transparent reporting of mapping studies. The primary audiences for the MAPS statement are researchers reporting mapping studies, the funders of the research, and peer reviewers and editors involved in assessing mapping studies for publication. A de novo list of 29 candidate reporting items and accompanying explanations was created by a working group comprised of six health economists and one Delphi methodologist. Following a two-round, modified Delphi survey with representatives from academia, consultancy, health technology assessment agencies and the biomedical journal editorial community, a final set of 23 items deemed essential for transparent reporting, and accompanying explanations, was developed. The items are contained in a user friendly 23 item checklist. They are presented numerically and categorised within six sections, namely: (i) title and abstract; (ii) introduction; (iii) methods; (iv) results; (v) discussion; and (vi) other. The MAPS statement is best applied in conjunction with the accompanying MAPS explanation and elaboration document. It is anticipated that the MAPS statement will improve the clarity, transparency and completeness of reporting of mapping studies. To facilitate dissemination and uptake, the MAPS statement is being co-published by eight health economics and quality of life journals, and broader endorsement is encouraged. The MAPS working group plans to assess the need for an update of the reporting checklist in five years' time. This statement was published jointly in Applied Health Economics and Health Policy, Health and Quality of Life Outcomes, International Journal of Technology Assessment in Health Care, Journal of Medical Economics, Medical Decision Making, PharmacoEconomics, and Quality of Life Research
Elliptic curves of large rank and small conductor
For r=6,7,...,11 we find an elliptic curve E/Q of rank at least r and the
smallest conductor known, improving on the previous records by factors ranging
from 1.0136 (for r=6) to over 100 (for r=10 and r=11). We describe our search
methods, and tabulate, for each r=5,6,...,11, the five curves of lowest
conductor, and (except for r=11) also the five of lowest absolute discriminant,
that we found.Comment: 16 pages, including tables and one .eps figure; to appear in the
Proceedings of ANTS-6 (June 2004, Burlington, VT). Revised somewhat after
comments by J.Silverman on the previous draft, and again to get the correct
page break
Classroom promotion of oral language : Outcomes from a randomized controlled trial of a whole-of-classroom intervention to improve childrenās reading achievement
Children need rich language learning experiences in school to build language and reading skills. Research suggests that various effective ways to support teacher provision of these experiences. The Classroom Promotion of Oral Language cluster randomized controlled trial (n = 1,360 students; 687 intervention, 673 control) examined whether a teacher professional learning intervention targeting oral language in the first years of school led to improved student outcomes compared to usual teaching practices. The intervention comprised face-to-face professional learning and ongoing support. The primary outcome was student reading ability at Grade 3; secondary outcomes included oral language, reading, and mental health at Grades 1 and 3. No differences were detected between the intervention and control arms. Implications of results and future directions are explored
Driving precision policy responses to child health and developmental inequities
The
growing evidence base on the extent of and opportunities to reduce inequities
in childrenās health and development still lacks the specificity to inform
clear policy decisions. A new phase of research is needed that builds on
contemporary directions in precision medicine to develop precision policy
making; with the aim to redress child inequities. This would include
identifying effective interventions and their ideal time point(s), duration,
and intensity to maximise impact. Drawing on existing data sources and
innovations in epidemiology and biostatistics would be key. The economic and
social gains that could be achieved from reducing child inequities are immense.
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