1,177 research outputs found
Dengue virus downregulates TNFR1- and TLR3-stimulated NF-kB activation by targeting RIPK1
Dengue virus (DENV) infection is the most prevalent arthropod-borne virus disease and is endemic in more than 100 countries. Several DENV proteins have been shown to target crucial human host proteins to evade innate immune responses and establish a productive infection. Here we report that the DENV NS3 protein targets RIPK1 (Receptor Interacting Protein Kinase I), a central mediator of inflammation and cell death, and decreases intracellular RIPK1 levels during DENV infection. The interaction of NS3 with RIPK1 results in the inhibition of NF-κB activation in response to TNFR or TLR3 stimulation. Also, we observed that the effects of NS3 on RIPK1 were independent of NS3 protease activity. Our data demonstrate a novel mechanism by which DENV suppresses normal cellular functions to evade host innate immune response
A model for the creation of human-generated metadata within communities
This paper considers situations for which detailed metadata descriptions of learning resources are necessary, and focuses on human generation of such metadata. It describes a model which facilitates human production of good quality metadata by the development and use of structured vocabularies. Using examples, this model is applied to single and multiple communities of metadata creators. The approach for transferring vocabularies across communities is related to similar work on the use of ontologies to support the development of the semantic web. Notable conclusions from this work are the need to encourage collaboration between the metadata specialists, content authors and system designers, and the scope for using accurate and consistent metadata created for one context in another context by producing descriptions of the relationships between those contexts
Cardiac rupture after myocardial infarction treated with tissue plasminogen activator: Results fron TIMI-II
OA04-03. Characterization of cell-mediated immune responses generated by recombinant modified vaccinia Ankara (rMVA)-HIV-1 in a phase I vaccine trial
Topological Defects and Interactions in Nematic Emulsions
Inverse nematic emulsions in which surfactant-coated water droplets are
dispersed in a nematic host fluid have distinctive properties that set them
apart from dispersions of two isotropic fluids or of nematic droplets in an
isotropic fluid. We present a comprehensive theoretical study of the
distortions produced in the nematic host by the dispersed droplets and of
solvent mediated dipolar interactions between droplets that lead to their
experimentally observed chaining. A single droplet in a nematic host acts like
a macroscopic hedgehog defect. Global boundary conditions force the nucleation
of compensating topological defects in the nematic host. Using variational
techniques, we show that in the lowest energy configuration, a single water
droplet draws a single hedgehog out of the nematic host to form a tightly bound
dipole. Configurations in which the water droplet is encircled by a
disclination ring have higher energy. The droplet-dipole induces distortions in
the nematic host that lead to an effective dipole-dipole interaction between
droplets and hence to chaining.Comment: 17 double column pages prepared by RevTex, 15 eps figures included in
text, 2 gif figures for Fig. 1
Aerodynamics of Pitching Wings: Theory and Experiments
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140444/1/6.2014-2881.pd
P04-12. Characterization of leukopak PBMC phenotypes and biotypes for optimal performance in HIV-1 neutralization assays
Cell-Mediated Immunity Generated in Response to a Purified Inactivated Vaccine for Dengue Virus Type 1
Dengue is the most prevalent arboviral disease afflicting humans, and a vaccine appears to be the most rational means of control. Dengue vaccine development is in a critical phase, with the first vaccine licensed in some countries where dengue is endemic but demonstrating insufficient efficacy in immunologically naive populations. Since virus-neutralizing antibodies do not invariably correlate with vaccine efficacy, other markers that may predict protection, including cell-mediated immunity, are urgently needed. Previously, the Walter Reed Army Institute of Research developed a monovalent purified inactivated virus (PIV) vaccine candidate against dengue virus serotype 1 (DENV-1) adjuvanted with alum. The PIV vaccine was safe and immunogenic in a phase I dose escalation trial in healthy, flavivirus-naive adults in the United States. From that trial, peripheral blood mononuclear cells obtained at various time points pre- and postvaccination were used to measure DENV-1-specific T cell responses. After vaccination, a predominant CD4+ T cell-mediated response to peptide pools covering the DENV-1 structural proteins was observed. Over half (13/20) of the subjects produced interleukin-2 (IL-2) in response to DENV peptides, and the majority (17/20) demonstrated peptide-specific CD4+ T cell proliferation. In addition, analysis of postvaccination cell culture supernatants demonstrated an increased rate of production of cytokines, including gamma interferon (IFN-γ), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Overall, the vaccine was found to have elicited DENV-specific CD4+ T cell responses as measured by enzyme-linked immunosorbent spot (ELISpot), intracellular cytokine staining (ICS), lymphocyte proliferation, and cytokine production assays. Thus, together with antibody readouts, the use of a multifaceted measurement of cell-mediated immune responses after vaccination is a useful strategy for more comprehensively characterizing immunity generated by dengue vaccines
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