420 research outputs found
The Transcription Factor T-bet Regulates Mucosal T Cell Activation in Experimental Colitis and Crohn's Disease
The balance between pro and antiinflammatory cytokines secreted by T cells regulates both the initiation and perpetuation of inflammatory bowel diseases (IBD). In particular, the balance between interferon (IFN)-γ/interleukin (IL)-4 and transforming growth factor (TGF)-β activity controls chronic intestinal inflammation. However, the molecular pathways that evoke these responses are not well understood. Here, we describe a critical role for the transcription factor T-bet in controlling the mucosal cytokine balance and clinical disease. We studied the expression and function of T-bet in patients with IBD and in mucosal T cells in various T helper (Th)1- and Th2-mediated animal models of chronic intestinal inflammation by taking advantage of mice that lack T-bet and retroviral transduction techniques, respectively. Whereas retroviral transduction of T-bet in CD62L+ CD4+ T cells exacerbated colitis in reconstituted SCID mice, T-bet–deficient T cells failed to induce colitis in adoptive transfer experiments suggesting that overexpression of T-bet is essential and sufficient to promote Th1-mediated colitis in vivo. Furthermore, T-bet–deficient CD62L− CD4+ T cells showed enhanced protective functions in Th1-mediated colitis and exhibited increased TGF-β signaling suggesting that a T-bet driven pathway of T cell activation controls the intestinal balance between IFN-γ/IL-4 and TGF-β responses and the development of chronic intestinal inflammation in T cell–mediated colitis. Furthermore, TGF-β was found to suppress T-bet expression suggesting a reciprocal relationship between TGF-β and T-bet in mucosal T cells. In summary, our data suggest a key regulatory role of T-bet in the pathogenesis of T cell–mediated colitis. Specific targeting of this pathway may be a promising novel approach for the treatment of patients with Crohn's disease and other autoimmune diseases mediated by Th1 T lymphocytes
LD Hub:a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis
Motivation: LD score regression is a reliable and efficient method of using genome-wide association study (GWAS) summary-level results data to estimate the SNP heritability of complex traits and diseases, partition this heritability into functional categories, and estimate the genetic correlation between different phenotypes. Because the method relies on summary level results data, LD score regression is computationally tractable even for very large sample sizes. However, publicly available GWAS summary-level data are typically stored in different databases and have different formats, making it difficult to apply LD score regression to estimate genetic correlations across many different traits simultaneously. Results: In this manuscript, we describe LD Hub - a centralized database of summary-level GWAS results for 173 diseases/traits from different publicly available resources/consortia and a web interface that automates the LD score regression analysis pipeline. To demonstrate functionality and validate our software, we replicated previously reported LD score regression analyses of 49 traits/diseases using LD Hub; and estimated SNP heritability and the genetic correlation across the different phenotypes. We also present new results obtained by uploading a recent atopic dermatitis GWAS meta-analysis to examine the genetic correlation between the condition and other potentially related traits. In response to the growing availability of publicly accessible GWAS summary-level results data, our database and the accompanying web interface will ensure maximal uptake of the LD score regression methodology, provide a useful database for the public dissemination of GWAS results, and provide a method for easily screening hundreds of traits for overlapping genetic aetiologies
Monte Carlo Methods for Estimating Interfacial Free Energies and Line Tensions
Excess contributions to the free energy due to interfaces occur for many
problems encountered in the statistical physics of condensed matter when
coexistence between different phases is possible (e.g. wetting phenomena,
nucleation, crystal growth, etc.). This article reviews two methods to estimate
both interfacial free energies and line tensions by Monte Carlo simulations of
simple models, (e.g. the Ising model, a symmetrical binary Lennard-Jones fluid
exhibiting a miscibility gap, and a simple Lennard-Jones fluid). One method is
based on thermodynamic integration. This method is useful to study flat and
inclined interfaces for Ising lattices, allowing also the estimation of line
tensions of three-phase contact lines, when the interfaces meet walls (where
"surface fields" may act). A generalization to off-lattice systems is described
as well.
The second method is based on the sampling of the order parameter
distribution of the system throughout the two-phase coexistence region of the
model. Both the interface free energies of flat interfaces and of (spherical or
cylindrical) droplets (or bubbles) can be estimated, including also systems
with walls, where sphere-cap shaped wall-attached droplets occur. The
curvature-dependence of the interfacial free energy is discussed, and estimates
for the line tensions are compared to results from the thermodynamic
integration method. Basic limitations of all these methods are critically
discussed, and an outlook on other approaches is given
Proximity effect at superconducting Sn-Bi2Se3 interface
We have investigated the conductance spectra of Sn-Bi2Se3 interface junctions
down to 250 mK and in different magnetic fields. A number of conductance
anomalies were observed below the superconducting transition temperature of Sn,
including a small gap different from that of Sn, and a zero-bias conductance
peak growing up at lower temperatures. We discussed the possible origins of the
smaller gap and the zero-bias conductance peak. These phenomena support that a
proximity-effect-induced chiral superconducting phase is formed at the
interface between the superconducting Sn and the strong spin-orbit coupling
material Bi2Se3.Comment: 7 pages, 8 figure
Heavy Quarks and Heavy Quarkonia as Tests of Thermalization
We present here a brief summary of new results on heavy quarks and heavy
quarkonia from the PHENIX experiment as presented at the "Quark Gluon Plasma
Thermalization" Workshop in Vienna, Austria in August 2005, directly following
the International Quark Matter Conference in Hungary.Comment: 8 pages, 5 figures, Quark Gluon Plasma Thermalization Workshop
(Vienna August 2005) Proceeding
Centrality Dependence of the High p_T Charged Hadron Suppression in Au+Au collisions at sqrt(s_NN) = 130 GeV
PHENIX has measured the centrality dependence of charged hadron p_T spectra
from central Au+Au collisions at sqrt(s_NN)=130 GeV. The truncated mean p_T
decreases with centrality for p_T > 2 GeV/c, indicating an apparent reduction
of the contribution from hard scattering to high p_T hadron production. For
central collisions the yield at high p_T is shown to be suppressed compared to
binary nucleon-nucleon collision scaling of p+p data. This suppression is
monotonically increasing with centrality, but most of the change occurs below
30% centrality, i.e. for collisions with less than about 140 participating
nucleons. The observed p_T and centrality dependence is consistent with the
particle production predicted by models including hard scattering and
subsequent energy loss of the scattered partons in the dense matter created in
the collisions.Comment: 7 pages text, LaTeX, 6 figures, 2 tables, 307 authors, resubmitted to
Phys. Lett. B. Revised to address referee concerns. Plain text data tables
for the points plotted in figures for this and previous PHENIX publications
are publicly available at
http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm
Accounting for International War: The State of the Discipline
In studies of war it is important to observe that the processes leading to so frequent an event as conflict are not necessarily those that lead to so infrequent an event as war. Also, many models fail to recognize that a phenomenon irregularly distributed in time and space, such as war, cannot be explained on the basis of relatively invariant phenomena. Much research on periodicity in the occurrence of war has yielded little result, suggesting that the direction should now be to focus on such variables as diffusion and contagion. Structural variables, such as bipolarity, show contradictory results with some clear inter-century differences. Bipolarity, some results suggest, might have different effects on different social entities. A considerable number of studies analysing dyadic variables show a clear connection between equal capabilities among contending nations and escalation of conflict into war. Finally, research into national attributes often points to strength and geographical location as important variables. In general, the article concludes, there is room for modest optimism, as research into the question of war is no longer moving in non-cumulative circles. Systematic research is producing results and there is even a discernible tendency of convergence, in spite of a great diversity in theoretical orientations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69148/2/10.1177_002234338101800101.pd
Single Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s) = 200 GeV
The invariant differential cross section for inclusive electron production in
p+p collisions at sqrt(s) = 200 GeV has been measured by the PHENIX experiment
at the Relativistic Heavy Ion Collider over the transverse momentum range $0.4
<= p_T <= 5.0 GeV/c at midrapidity (eta <= 0.35). The contribution to the
inclusive electron spectrum from semileptonic decays of hadrons carrying heavy
flavor, i.e. charm quarks or, at high p_T, bottom quarks, is determined via
three independent methods. The resulting electron spectrum from heavy flavor
decays is compared to recent leading and next-to-leading order perturbative QCD
calculations. The total cross section of charm quark-antiquark pair production
is determined as sigma_(c c^bar) = 0.92 +/- 0.15 (stat.) +- 0.54 (sys.) mb.Comment: 329 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett.
Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
Nuclear Modification of Electron Spectra and Implications for Heavy Quark Energy Loss in Au+Au Collisions at sqrt(s_NN)=200 GeV
The PHENIX experiment has measured mid-rapidity transverse momentum spectra
(0.4 < p_T < 5.0 GeV/c) of electrons as a function of centrality in Au+Au
collisions at sqrt(s_NN)=200 GeV. Contributions from photon conversions and
from light hadron decays, mainly Dalitz decays of pi^0 and eta mesons, were
removed. The resulting non-photonic electron spectra are primarily due to the
semi-leptonic decays of hadrons carrying heavy quarks. Nuclear modification
factors were determined by comparison to non-photonic electrons in p+p
collisions. A significant suppression of electrons at high p_T is observed in
central Au+Au collisions, indicating substantial energy loss of heavy quarks.Comment: 330 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett.
Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
System Size and Energy Dependence of Jet-Induced Hadron Pair Correlation Shapes in Cu+Cu and Au+Au Collisions at sqrt(s_NN) = 200 and 62.4 GeV
We present azimuthal angle correlations of intermediate transverse momentum
(1-4 GeV/c) hadrons from {dijets} in Cu+Cu and Au+Au collisions at sqrt(s_NN) =
62.4 and 200 GeV. The away-side dijet induced azimuthal correlation is
broadened, non-Gaussian, and peaked away from \Delta\phi=\pi in central and
semi-central collisions in all the systems. The broadening and peak location
are found to depend upon the number of participants in the collision, but not
on the collision energy or beam nuclei. These results are consistent with sound
or shock wave models, but pose challenges to Cherenkov gluon radiation models.Comment: 464 authors from 60 institutions, 6 pages, 3 figures, 2 tables.
Submitted to Physical Review Letters. Plain text data tables for the points
plotted in figures for this and previous PHENIX publications are (or will be)
publicly available at http://www.phenix.bnl.gov/papers.htm
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