8,026 research outputs found
CCR2âşCD103âť intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells
The identification of intestinal macrophages (m phi s) and dendritic cells (DCs) is a matter of intense debate. Although CD103(+) mononuclear phagocytes (MPs) appear to be genuine DCs, the nature and origins of CD103(-) MPs remain controversial. We show here that intestinal CD103(-)CD11b(+) MPs can be separated clearly into DCs and m phi s based on phenotype, gene profile, and kinetics. CD64(-)CD103(-)CD11b(+) MPs are classical DCs, being derived from Flt3 ligand-dependent, DC-committed precursors, not Ly6C hi monocytes. Surprisingly, a significant proportion of these CD103(-)CD11b(+) DCs express CCR2 and there is a selective decrease in CD103(-)CD11b(+) DCs in mice lacking this chemokine receptor. CCR2(+)CD103(-) DCs are present in both the murine and human intestine, drive interleukin (IL)-17a production by Tcells in vitro, and show constitutive expression of IL-12/IL-23p40. These data highlight the heterogeneity of intestinal DCs and reveal a bona fide population of CCR2(+) DCs that is involved in priming mucosal T helper type 17 (Th17) responses
Moody's Correlated Binomial Default Distributions for Inhomogeneous Portfolios
This paper generalizes Moody's correlated binomial default distribution for
homogeneous (exchangeable) credit portfolio, which is introduced by Witt, to
the case of inhomogeneous portfolios. As inhomogeneous portfolios, we consider
two cases. In the first case, we treat a portfolio whose assets have uniform
default correlation and non-uniform default probabilities. We obtain the
default probability distribution and study the effect of the inhomogeneity on
it. The second case corresponds to a portfolio with inhomogeneous default
correlation. Assets are categorized in several different sectors and the
inter-sector and intra-sector correlations are not the same. We construct the
joint default probabilities and obtain the default probability distribution. We
show that as the number of assets in each sector decreases, inter-sector
correlation becomes more important than intra-sector correlation. We study the
maximum values of the inter-sector default correlation. Our generalization
method can be applied to any correlated binomial default distribution model
which has explicit relations to the conditional default probabilities or
conditional default correlations, e.g. Credit Risk, implied default
distributions. We also compare some popular CDO pricing models from the
viewpoint of the range of the implied tranche correlation.Comment: 29 pages, 17 figures and 1 tabl
Using Bars As Signposts of Galaxy Evolution at High and Low Redshifts
An analysis of the NICMOS Deep Field shows that there is no evidence of a
decline in the bar fraction beyond z~0.7, as previously claimed; both
bandshifting and spatial resolution must be taken into account when evaluating
the evolution of the bar fraction. Two main caveats of this study were a lack
of a proper comparison sample at low redshifts and a larger number of galaxies
at high redshifts. We address these caveats using two new studies. For a proper
local sample, we have analyzed 134 spirals in the near-infrared using 2MASS
(main results presented by Menendez-Delmestre in this volume) which serves as
an ideal anchor for the low-redshift Universe. In addition to measuring the
mean bar properties, we find that bar size is correlated with galaxy size and
brightness, but the bar ellipticity is not correlated with these galaxy
properties. The bar length is not correlated with the bar ellipticity. For
larger high redshift samples we analyze the bar fraction from the 2-square
degree COSMOS ACS survey. We find that the bar fraction at z~0.7 is ~50%,
consistent with our earlier finding of no decline in bar fraction at high
redshifts.Comment: In the proceedings of "Penetrating Bars through Masks of Cosmic Dust:
The Hubble Tuning Fork strikes a New Note
Sensing electric fields using single diamond spins
The ability to sensitively detect charges under ambient conditions would be a
fascinating new tool benefitting a wide range of researchers across
disciplines. However, most current techniques are limited to low-temperature
methods like single-electron transistors (SET), single-electron electrostatic
force microscopy and scanning tunnelling microscopy. Here we open up a new
quantum metrology technique demonstrating precision electric field measurement
using a single nitrogen-vacancy defect centre(NV) spin in diamond. An AC
electric field sensitivity reaching ~ 140V/cm/\surd Hz has been achieved. This
corresponds to the electric field produced by a single elementary charge
located at a distance of ~ 150 nm from our spin sensor with averaging for one
second. By careful analysis of the electronic structure of the defect centre,
we show how an applied magnetic field influences the electric field sensing
properties. By this we demonstrate that diamond defect centre spins can be
switched between electric and magnetic field sensing modes and identify
suitable parameter ranges for both detector schemes. By combining magnetic and
electric field sensitivity, nanoscale detection and ambient operation our study
opens up new frontiers in imaging and sensing applications ranging from
material science to bioimaging
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Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption.
The role of lymphoid tissue as a potential source of HIV-1 rebound following interruption of antiretroviral therapy (ART) is uncertain. To address this issue, we compared the latent viruses obtained from CD4+ T cells in peripheral blood and lymph nodes to viruses emerging during treatment interruption. Latent viruses were characterized by sequencing near-full-length (NFL) proviral DNA and env from viral outgrowth assays (VOAs). Five HIV-1-infected individuals on ART were studied, four of whom participated in a clinical trial of a TLR9 agonist that included an analytical treatment interruption. We found that 98% of intact or replication-competent clonal sequences overlapped between blood and lymph node. In contrast, there was no overlap between 205 latent reservoir and 125 rebound sequences in the four individuals who underwent treatment interruption. However, rebound viruses could be accounted for by recombination. The data suggest that CD4+ T cells carrying latent viruses circulate between blood and lymphoid tissues in individuals on ART and support the idea that recombination may play a role in the emergence of rebound viremia.IMPORTANCE HIV-1 persists as a latent infection in CD4+ T cells that can be found in lymphoid tissues in infected individuals during ART. However, the importance of this tissue reservoir and its contribution to viral rebound upon ART interruption are not clear. In this study, we sought to compare latent HIV-1 from blood and lymph node CD4+ T cells from five HIV-1-infected individuals. Further, we analyzed the contribution of lymph node viruses to viral rebound. We observed that the frequencies of intact proviruses were the same in blood and lymph node. Moreover, expanded clones of T cells bearing identical proviruses were found in blood and lymph node. These latent reservoir sequences did not appear to be the direct origin of rebound virus. Instead, latent proviruses were found to contribute to the rebound compartment by recombination
Drawing Trees with Perfect Angular Resolution and Polynomial Area
We study methods for drawing trees with perfect angular resolution, i.e.,
with angles at each node v equal to 2{\pi}/d(v). We show:
1. Any unordered tree has a crossing-free straight-line drawing with perfect
angular resolution and polynomial area.
2. There are ordered trees that require exponential area for any
crossing-free straight-line drawing having perfect angular resolution.
3. Any ordered tree has a crossing-free Lombardi-style drawing (where each
edge is represented by a circular arc) with perfect angular resolution and
polynomial area. Thus, our results explore what is achievable with
straight-line drawings and what more is achievable with Lombardi-style
drawings, with respect to drawings of trees with perfect angular resolution.Comment: 30 pages, 17 figure
Dose-response assessment of tariquidar for inhibition of P-glycoprotein at the human blood-brain barrier using (R)-[11C]verapamil PET
Maximizing the impact of malaria funding through allocative efficiency: using the right interventions in the right locations.
BACKGROUND: The high burden of malaria and limited funding means there is a necessity to maximize the allocative efficiency of malaria control programmes. Quantitative tools are urgently needed to guide budget allocation decisions. METHODS: A geospatial epidemic model was coupled with costing data and an optimization algorithm to estimate the optimal allocation of budgeted and projected funds across all malaria intervention approaches. Interventions included long-lasting insecticide-treated nets (LLINs), indoor residual spraying (IRS), intermittent presumptive treatment during pregnancy (IPTp), seasonal mass chemoprevention in children (SMC), larval source management (LSM), mass drug administration (MDA), and behavioural change communication (BCC). The model was applied to six geopolitical regions of Nigeria in isolation and also the nation as a whole to minimize incidence and malaria-attributable mortality. RESULTS: Allocative efficiency gains could avert approximately 84,000 deaths or 15.7 million cases of malaria in Nigeria over 5Â years. With an additional US$300 million available, approximately 134,000 deaths or 37.3 million cases of malaria could be prevented over 5Â years. Priority funding should go to LLINs, IPTp and BCC programmes, and SMC should be expanded in seasonal areas. To minimize mortality, treatment expansion is critical and prioritized over some LLIN funding, while to minimize incidence, LLIN funding remained a priority. For areas with lower rainfall, LSM is prioritized over IRS but MDA is not recommended unless all other programmes are established. CONCLUSIONS: Substantial reductions in malaria morbidity and mortality can be made by optimal targeting of investments to the right malaria interventions in the right areas
Performance of the 2007 WHO Algorithm to diagnose Smear-negative Pulmonary Tuberculosis in a HIV prevalent setting
The 2007 WHO algorithm for diagnosis of smear-negative pulmonary tuberculosis (PTB) including Mycobacterium tuberculosis (MTB) culture was evaluated in a HIV prevalent area of Kenya
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