206 research outputs found
CD4+ CD25+ Regulatory T Cells Control T Helper Cell Type 1 Responses to Foreign Antigens Induced by Mature Dendritic Cells In Vivo
Recent evidence suggests that in addition to their well known stimulatory properties, dendritic cells (DCs) may play a major role in peripheral tolerance. It is still unclear whether a distinct subtype or activation status of DC exists that promotes the differentiation of suppressor rather than effector T cells from naive precursors. In this work, we tested whether the naturally occurring CD4+ CD25+ regulatory T cells (Treg) may control immune responses induced by DCs in vivo. We characterized the immune response induced by adoptive transfer of antigen-pulsed mature DCs into mice depleted or not of CD25+ cells. We found that the development of major histocompatibility complex class I and II–restricted interferon γ–producing cells was consistently enhanced in the absence of Treg. By contrast, T helper cell (Th)2 priming was down-regulated in the same conditions. This regulation was independent of interleukin 10 production by DCs. Of note, splenic DCs incubated in vitro with Toll-like receptor ligands (lipopolysaccharide or CpG) activated immune responses that remained sensitive to Treg function. Our data further show that mature DCs induced higher cytotoxic activity in CD25-depleted recipients as compared with untreated hosts. We conclude that Treg naturally exert a negative feedback mechanism on Th1-type responses induced by mature DCs in vivo
A Modular Regularized Variational Multiscale Proper Orthogonal Decomposition for Incompressible Flows
In this paper, we propose, analyze and test a post-processing implementation
of a projection-based variational multiscale (VMS) method with proper
orthogonal decomposition (POD) for the incompressible Navier-Stokes equations.
The projection-based VMS stabilization is added as a separate post-processing
step to the standard POD approximation, and since the stabilization step is
completely decoupled, the method can easily be incorporated into existing
codes, and stabilization parameters can be tuned independent from the time
evolution step. We present a theoretical analysis of the method, and give
results for several numerical tests on benchmark problems which both illustrate
the theory and show the proposed method's effectiveness
A perspective on using experiment and theory to identify design principles in dye-sensitized solar cells
Dye-sensitized solar cells (DSCs) have been the subject of wide-ranging studies for many
years because of their potential for large-scale manufacturing using roll-to-roll processing
allied to their use of earth abundant raw materials. Two main challenges exist for DSC
devices to achieve this goal; uplifting device efficiency from the 12 to 14% currently
achieved for laboratory-scale ‘hero’ cells and replacement of the widely-used liquid
electrolytes which can limit device lifetimes. To increase device efficiency requires optimized
dye injection and regeneration, most likely from multiple dyes while replacement
of liquid electrolytes requires solid charge transporters (most likely hole transport materials
– HTMs). While theoretical and experimental work have both been widely applied to
different aspects of DSC research, these approaches are most effective when working in
tandem. In this context, this perspective paper considers the key parameters which
influence electron transfer processes in DSC devices using one or more dye molecules
and how modelling and experimental approaches can work together to optimize electron
injection and dye regeneration.
This paper provides a perspective that theory and experiment are best used in tandem to study
DSC device
Leukocyte-Released Mediators in Response to Both Bacterial and Fungal Infections Trigger IFN Pathways, Independent of IL-1 and TNF-alpha, in Endothelial Cells
In sepsis, dysregulated immune responses to infections cause damage to the host. Previous studies have attempted to capture pathogen-induced leukocyte responses. However, the impact of mediators released after pathogen-leukocyte interaction on endothelial cells, and how endothelial cell responses vary depending on the pathogen-type is lacking. Here, we comprehensively characterized the transcriptomic responses of human leukocytes and endothelial cells to Gram negative-bacteria, Gram positive-bacteria, and fungi. We showed that whole pathogen lysates induced strong activation of leukocytes but not endothelial cells. Interestingly, the common response of leukocytes to various pathogens converges on endothelial activation. By exposing endothelial cells to leukocyte-released mediators, we observed a strong activation of endothelial cells at both transcription and protein levels. By adding IL-1RA and TNF-α antibody in leukocyte-released mediators before exposing to endothelial cells, we identified specific roles for IL-1 and TNF-α in driving the most, but not all, endothelial activation. We also showed for the first time, activation of interferon response by endothelial cells in response to leukocyte-released mediators, independently from IL-1 and TNF-α pathways. Our study therefore, not only provides pathogen-dependent transcriptional changes in leukocytes and endothelial cells during infections, but also reveals a role for IFN, together with IL1 and TNFα signaling, in mediating leukocyte-endothelial interaction in infections
Precise measurement of the W-boson mass with the CDF II detector
We have measured the W-boson mass MW using data corresponding to 2.2/fb of
integrated luminosity collected in proton-antiproton collisions at 1.96 TeV
with the CDF II detector at the Fermilab Tevatron collider. Samples consisting
of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement
MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most
precise measurement of the W-boson mass to date and significantly exceeds the
precision of all previous measurements combined
STAT5 Is an Ambivalent Regulator of Neutrophil Homeostasis
BACKGROUND: Although STAT5 promotes survival of hematopoietic progenitors, STAT5-/- mice develop mild neutrophilia. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that in STAT5-/- mice, liver endothelial cells (LECs) autonomously secrete high amounts of G-CSF, allowing myeloid progenitors to overcompensate for their intrinsic survival defect. However, when injected with pro-inflammatory cytokines, mutant mice cannot further increase neutrophil production, display a severe deficiency in peripheral neutrophil survival, and are therefore unable to maintain neutrophil homeostasis. In wild-type mice, inflammatory stimulation induces rapid STAT5 degradation in LECs, G-CSF production by LECs and other cell types, and then sustained mobilization and expansion of long-lived neutrophils. CONCLUSION: We conclude that STAT5 is an ambivalent factor. In cells of the granulocytic lineage, it exerts an antiapoptotic function that is required for maintenance of neutrophil homeostasis, especially during the inflammatory response. In LECs, STAT5 negatively regulates granulopoiesis by directly or indirectly repressing G-CSF expression. Removal of this STAT5-imposed brake contributes to induction of emergency granulopoiesis.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe
Measurement of the tau lepton lifetime
The mean lifetime of the tau lepton is measured in a sample of 25700 tau pairs collected in 1992 with the ALEPH detector at LEP. A new analysis of the 1-1 topology events is introduced. In this analysis, the dependence of the impact parameter sum distribution on the daughter track momenta is taken into account, yielding improved precision compared to other impact parameter sum methods. Three other analyses of the one- and three-prong tau decays are updated with increased statistics. The measured lifetime is 293.5+/-3.1+/-1.7 fs. Including previous (1989-1991) ALEPH measurements, the combined tau lifetime is 293.7+/-2.7+/-1.6 fs
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