261 research outputs found
ON T CELL FATE DECISIONS: RETINOL, METABOLISM AND ITREG DIFFERENTIATION
The mammalian immune system is equipped to both eliminate pathogenic microorganisms and tumors, while remaining in homeostasis with commensal species at mucosal surfaces and tolerant towards self. Suppressor regulatory T cells (Tregs) are a major sentinel of this immunological tolerance. Induced Tregs (iTregs) arise in the periphery following the integration of cues from the metabolites, cytokines, etc. which make up its milieu. Dysregulation of iTreg development, function or homing underlies the etiology of many autoimmune diseases and immunopathologies. The amelioration or prevention of multiple murine disease models by boosting Treg cell numbers foreshadows clinical efficacy of iTreg therapy, but an incomplete understanding of Treg development has thus far prevented successful translation. Therefore, we considered the basic biology of T cell fate decision making from two unique, but integrated angles. First, we show that the stimulation of PPARγ in human T cells upregulates RDH10, a molecule which catalyzes the rate limiting step in the oxidation of retinol to transcriptionally active all-trans retinoic acid (ATRA), a positive regulator of iTreg development. This functionally intact pathway endows T cells the ability to autonomously sense and respond to retinoid signals present during Treg development and at tissue sites. Next, we asked questions about how T cells sense nutrient and oxygen availability as they differentiate. Tregs lacking the serine/threonine kinase PINK1 have limited activation-induced phosphorylation of Akt and oxidative phosphorylation rates, and reduced suppressor function. Notably, the uncoupling of iTreg function from normal FoxP3 expression reinforces the recent hypothesis that the PI3K/Akt/mTORC1 axis and metabolic checkpoints are decisive players in the acquisition of suppressor activity. Ultimately, the studies described herein converge on Akt and metabolism, and contribute to our understanding of how T cells integrate diverse signals present during fate determinism, provoking future Treg based therapeutics
Possible Evidence of Disoriented Chiral Condensates from the Anomaly in Omega and AntiOmega Abundances at the SPS
No conventional picture of nucleus-nucleus collisions has yet been able to
explain the abundance of Omega and AntiOmega in central collisions between Pb
nuclei at 158 A GeV at the CERN SPS. We argue that such a deviation from
predictions of statistical thermal models and numerical simulations is evidence
that they are produced as topological defects in the form of skyrmions arising
from the formation of disoriented chiral condensates. The estimated domain size
falls in the right range to be consistent with the so far non-observation of
DCC from the distribution of neutral pions.Comment: paper presented at the ICPAQGP-2001, Jaipur, Indi
Is Anomalous Production of Omega and anti-Omega Evidence for Disoriented Chiral Condensates?
No conventional picture of nucleus-nucleus collisions has yet been able to
explain the abundance of Omega and anti-Omega hyperons in central collisions
between Pb nuclei at 158 A GeV at the CERN SPS. We argue that this is evidence
that they are produced as topological defects arising from the formation of
disoriented chiral condensates (DCC) with an average domain size of about 2 fm.Comment: version 2 containing formulas, accepted by PR
Diffuse Traumatic Brain Injury Induces Prolonged Immune Sysregulation and Potentiates Hyperalgesia Following a Peripheral Immune Challenge
Background: Nociceptive and neuropathic pain occurs as part of the disease process after traumatic brain injury (TBI) in humans. Central and peripheral inflammation, a major secondary injury process initiated by the traumatic brain injury event, has been implicated in the potentiation of peripheral nociceptive pain. We hypothesized that the inflammatory response to diffuse traumatic brain injury potentiates persistent pain through prolonged immune dysregulation.
Results: To test this, adult, male C57BL/6 mice were subjected to midline fluid percussion brain injury or to sham procedure. One cohort of mice was analyzed for inflammation-related cytokine levels in cortical biopsies and serum along an acute time course. In a second cohort, peripheral inflammation was induced seven days after surgery/injury with an intraplantar injection of carrageenan. This was followed by measurement of mechanical hyperalgesia, glial fibrillary acidic protein and Iba1 immunohistochemical analysis of neuroinflammation in the brain, and flow cytometric analysis of T-cell differentiation in mucosal lymph. Traumatic brain injury increased interleukin-6 and chemokine ligand 1 levels in the cortex and serum that peaked within 1–9 h and then resolved. Intraplantar carrageenan produced mechanical hyperalgesia that was potentiated by traumatic brain injury. Further, mucosal T cells from brain-injured mice showed a distinct deficiency in the ability to differentiate into inflammation-suppressing regulatory T cells (Tregs).
Conclusions: We conclude that traumatic brain injury increased the inflammatory pain associated with cutaneous inflammation by contributing to systemic immune dysregulation. Regulatory T cells are immune suppressors and failure of T cells to differentiate into regulatory T cells leads to unregulated cytokine production which may contribute to the potentiation of peripheral pain through the excitation of peripheral sensory neurons. In addition, regulatory T cells are identified as a potential target for therapeutic rebalancing of peripheral immune homeostasis to improve functional outcome and decrease the incidence of peripheral inflammatory pain following traumatic brain injury
Giant QCD K-factors beyond NLO
Hadronic observables in Z+jet events can be subject to large NLO corrections
at TeV scales, with K-factors that even reach values of order 50 in some cases.
We develop a method, LoopSim, by which approximate NNLO predictions can be
obtained for such observables, supplementing NLO Z+jet and NLO Z+2-jet results
with a unitarity-based approximation for missing higher loop terms. We first
test the method against known NNLO results for Drell-Yan lepton pt spectra. We
then show our approximate NNLO results for the Z+jet observables. Finally we
examine whether the LoopSim method can provide useful information even in cases
without giant K-factors, with results for observables in dijet events that can
be compared to early LHC data.Comment: 38 pages, 13 figures; v2 includes additional reference
Dynamical Evolution of the Scalar Condensate in Heavy Ion Collisions
We derive the effective coarse-grained field equation for the scalar
condensate of the linear sigma model in a simple and straightforward manner
using linear response theory. The dissipative coefficient is calculated at tree
level on the basis of the physical processes of sigma-meson decay and of
thermal sigma-mesons and pions knocking sigma-mesons out of the condensate. The
field equation is solved for hot matter undergoing either one or three
dimensional expansion and cooling in the aftermath of a high energy nuclear
collision. The results show that the time constant for returning the scalar
condensate to thermal equilibrium is of order 2 fm/c.Comment: 19 pages, 3 figures are embedded at the end. The effect of the time
dependence of the condensate v is included in this revised version. Numerical
work is redone accordingl
Dynamical Color Correlations in a Quark Exchange Model of Nuclear Matter
The quark exchange model is a simple realization of an adiabatic
approximation to the strong-coupling limit of Quantum Chromodynamics (QCD): the
quarks always coalesce into the lowest energy set of flux tubes. Nuclear matter
is thus modeled in terms of its quarks. We wish to study the correlations
imposed by total wavefunction antisymmetry when color degrees of freedom are
included. To begin with, we have considered one-dimensional matter with a
color internal degree of freedom only. We proceed by constructing a
totally antisymmetric, color singlet {\it Ansatz} characterized by a
variational parameter (which describes the length scale over which
two quarks in the system are clustered into hadrons) and by performing a
variational Monte Carlo calculation of the energy to optimize for a
fixed density. We calculate the correlation function as well, and discuss
the qualitative differences between the system at low and high density.Comment: 32 pages in REVTeX, IU/NTC 93-28, FSU-SCRI-93-161. The postscript
file, including 12 figures, is available via anonymous ftp from
ftp.scri.fsu.edu in /pub/jorgep/magic.p
How To Find Charm in Nuclear Collisions at RHIC and LHC
Measurements of dilepton production from charm decay and Drell-Yan processes
respectively probe the gluon and sea quark distributions in hadronic
collisions. In nucleus-nucleus collisions, these hard scattering processes
constitute a `background' to thermal contributions from the hot matter produced
by the collision. To determine the magnitude and behavior of this background,
we calculate the hard scattering contribution to dilepton production in nuclear
collisions at RHIC and LHC at next to leading order in perturbative QCD.
Invariant mass, rapidity and transverse momentum distributions are presented.
We compare these results to optimistic hydrodynamic estimates of the thermal
dilepton production. We find that charm production from hard scattering is by
far the dominant contribution. Experiments therefore can measure the gluon
distribution in the nuclear target and projectile and, consequently, can
provide new information on gluon shadowing. We then illustrate how experimental
cuts on the rapidity gap between the leptons can aid in reducing the charm
background, thereby enhancing thermal information.Comment: 32 pages, latex, 19 figure
Antiproton Production in 11.5 A GeV/c Au+Pb Nucleus-Nucleus Collisions
We present the first results from the E864 collaboration on the production of
antiprotons in 10% central 11.5 A GeV/c Au+Pb nucleus collisions at the
Brookhaven AGS. We report invariant multiplicities for antiproton production in
the kinematic region 1.4<y<2.2 and 50<p_T<300 MeV/c, and compare our data with
a first collision scaling model and previously published results from the E878
collaboration. The differences between the E864 and E878 antiproton
measurements and the implications for antihyperon production are discussed.Comment: 4 pages, 4 figures; accepted for publication in Physical Review
Letter
Event shapes in e+e- annihilation and deep inelastic scattering
This article reviews the status of event-shape studies in e+e- annihilation
and DIS. It includes discussions of perturbative calculations, of various
approaches to modelling hadronisation and of comparisons to data.Comment: Invited topical review for J.Phys.G; 40 pages; revised version
corrects some nomenclatur
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