314 research outputs found
Near real-time estimation of water vapour in the troposphere using ground GNSS and the meteorological data
Diesel Exhaust Particle (DEP)-induced glucose intolerance is driven by an intestinal innate immune response and NLRP3 activation in mice
BACKGROUND
We previously found that air pollution particles reaching the gastrointestinal tract elicit gut inflammation as shown by up-regulated gene expression of pro-inflammatory cytokines and monocyte/macrophage markers. This inflammatory response was associated with beta-cell dysfunction and glucose intolerance. So far, it remains unclear whether gut inflammatory changes upon oral air pollution exposure are causally linked to the development of diabetes. Hence, our aim was to assess the role of immune cells in mediating glucose intolerance instigated by orally administered air pollutants.
METHODS
To assess immune-mediated mechanisms underlying air pollution-induced glucose intolerance, we administered diesel exhaust particles (DEP; NIST 1650b, 12 ”g five days/week) or phosphate-buffered saline (PBS) via gavage for up to 10 months to wild-type mice and mice with genetic or pharmacological depletion of innate or adaptive immune cells. We performed unbiased RNA-sequencing of intestinal macrophages to elucidate signaling pathways that could be pharmacologically targeted and applied an in vitro approach to confirm these pathways.
RESULTS
Oral exposure to air pollution particles induced an interferon and inflammatory signature in colon macrophages together with a decrease of CCR2 anti-inflammatory/resident macrophages. Depletion of macrophages, NLRP3 or IL-1ÎČ protected mice from air pollution-induced glucose intolerance. On the contrary, Rag2-/- mice lacking adaptive immune cells developed pronounced gut inflammation and glucose intolerance upon oral DEP exposure.
CONCLUSION
In mice, oral exposure to air pollution particles triggers an immune-mediated response in intestinal macrophages that contributes to the development of a diabetes-like phenotype. These findings point towards new pharmacologic targets in diabetes instigated by air pollution particles
Fivebranes and 4-manifolds
We describe rules for building 2d theories labeled by 4-manifolds. Using the
proposed dictionary between building blocks of 4-manifolds and 2d N=(0,2)
theories, we obtain a number of results, which include new 3d N=2 theories
T[M_3] associated with rational homology spheres and new results for
Vafa-Witten partition functions on 4-manifolds. In particular, we point out
that the gluing measure for the latter is precisely the superconformal index of
2d (0,2) vector multiplet and relate the basic building blocks with coset
branching functions. We also offer a new look at the fusion of defect lines /
walls, and a physical interpretation of the 4d and 3d Kirby calculus as
dualities of 2d N=(0,2) theories and 3d N=2 theories, respectivelyComment: 81 pages, 18 figures. v2: misprints corrected, clarifications and
references added. v3: additions and corrections about lens space theory,
4-manifold gluing, smooth structure
Gaugino Condensation in M-theory on S^1/Z_2
In the low energy limit of for M-theory on S^1/Z_2, we calculate the gaugino
condensate potential in four dimensions using the background solutions due to
Horava. We show that this potential is free of delta-function singularities and
has the same form as the potential in the weakly coupled heterotic string. A
general flux quantization rule for the three-form field of M-theory on S^1/Z_2
is given and checked in certain limiting cases. This rule is used to fix the
free parameter in the potential originating from a zero mode of the form field.
Finally, we calculate soft supersymmetry breaking terms. We find that
corrections to the Kahler potential and the gauge kinetic function, which can
be large in the strongly coupled region, contribute significantly to certain
soft terms. In particular, for supersymmetry breaking in the T-modulus
direction, the small values of gaugino masses and trilinear couplings that
occur in the weakly coupled, large radius regime are enhanced to order m_3/2 in
M-theory. The scalar soft masses remain small even, in the strong coupling
M-theory limit.Comment: 20 pages, LATE
Binary Cosmic Strings
The properties of cosmic strings have been investigated in detail for their
implications in early-universe cosmology. Although many variations of the basic
structure have been discovered, with implications for both the microscopic and
macroscopic properties of cosmic strings, the cylindrical symmetry of the
short-distance structure of the string is generally unaffected. In this paper
we describe some mechanisms leading to an asymmetric structure of the string
core, giving the defects a quasi-two-dimensional character. We also begin to
investigate the consequences of this internal structure for the microscopic and
macroscopic physics.Comment: 19 pages; uses harvmac (not included
Supersymmetric Electroweak Cosmic Strings
We study the connection between supersymmetry and a topological bound
in a two-Higgs-doublet system with an gauge group. We derive the Bogomol'nyi equations from
supersymmetry considerations showing that they hold provided certain conditions
on the coupling constants, which are a consequence of the huge symmetry of the
theory, are satisfied. Their solutions, which can be interpreted as electroweak
cosmic strings breaking one half of the supersymmetries of the theory, are
studied. Certain interesting limiting cases of our model which have recently
been considered in the literature are finally analyzed.Comment: 20 pages, RevTe
Lung versus gut exposure to air pollution particles differentially affect metabolic health in mice
BACKGROUND
Air pollution has emerged as an unexpected risk factor for diabetes. However, the mechanism behind remains ill-defined. So far, the lung has been considered as the main target organ of air pollution. In contrast, the gut has received little scientific attention. Since air pollution particles can reach the gut after mucociliary clearance from the lungs and through contaminated food, our aim was to assess whether exposure deposition of air pollution particles in the lung or the gut drive metabolic dysfunction in mice.
METHODS
To study the effects of gut versus lung exposure, we exposed mice on standard diet to diesel exhaust particles (DEP; NIST 1650b), particulate matter (PM; NIST 1649b) or phosphate-buffered saline by either intratracheal instillation (30 ”g 2 days/week) or gavage (12 ”g 5 days/week) over at least 3 months (total dose of 60 ”g/week for both administration routes, equivalent to a daily inhalation exposure in humans of 160 ”g/m PM) and monitored metabolic parameters and tissue changes. Additionally, we tested the impact of the exposure route in a "prestressed" condition (high-fat diet (HFD) and streptozotocin (STZ)).
RESULTS
Mice on standard diet exposed to particulate air pollutants by intratracheal instillation developed lung inflammation. While both lung and gut exposure resulted in increased liver lipids, glucose intolerance and impaired insulin secretion was only observed in mice exposed to particles by gavage. Gavage with DEP created an inflammatory milieu in the gut as shown by up-regulated gene expression of pro-inflammatory cytokines and monocyte/macrophage markers. In contrast, liver and adipose inflammation markers were not increased. Beta-cell secretory capacity was impaired on a functional level, most likely induced by the inflammatory milieu in the gut, and not due to beta-cell loss. The differential metabolic effects of lung and gut exposures were confirmed in a "prestressed" HFD/STZ model.
CONCLUSIONS
We conclude that separate lung and gut exposures to air pollution particles lead to distinct metabolic outcomes in mice. Both exposure routes elevate liver lipids, while gut exposure to particulate air pollutants specifically impairs beta-cell secretory capacity, potentially instigated by an inflammatory milieu in the gut
Closed String Tachyons and Semi-Classical Instabilities
We conjecture that the end point of bulk closed string tachyon decay at any
non-zero coupling, is the annihilation of space time by Witten's bubble of
nothing, resulting in a topological phase of the theory. In support of this we
present a variety of situations in which there is a correspondence between the
existence of perturbative tachyons in one regime and the semi-classical
annihilation of space-time. Our discussion will include many recently
investigated scenarios in string theory including Scherk-Schwarz
compactifications, Melvin magnetic backgrounds, and noncompact orbifolds. We
use this conjecture to investigate a possible web of dualities relating the
eleven-dimensional Fabinger-Horava background with nonsupersymmetric string
theories. Along the way we point out where our conjecture resolves some of the
puzzles associated with bulk closed string tachyon condensation.Comment: 31 pages, 5 figures 3 figures added, typos corrected and references
added. Discussion of Type 0/Heterotic s-duality extended and some other
points clarified Revision of discussion on Fabinger-Horava string
descendents, section on Scherk-Schwarz compactification of Horava-Witten
removed, some references adde
Black Holes and Five-brane Thermodynamics
The phase diagram for Dp-branes in M-theory compactified on , ,
, and is constructed. As for the lower-dimensional tori considered
in our previous work (hep-th/9810224), the black brane phase at high entropy
connects onto matrix theory at low entropy; we thus recover all known instances
of matrix theory as consequences of the Maldacena conjecture. The difficulties
that arise for are reviewed. We also analyze the D1-D5 system on ;
we exhibit its relation to matrix models of M5-branes, and use spectral flow as
a tool to investigate the dependence of the phase structure on angular
momentum.Comment: 57 pages, 6 eps figures, latex. v2: DLCQ limit of 5-brane corrected;
typos corrected, references added. v3: reference added, typos corrected v4:
comments on DLCQ limit of 5-brane corrected one last time. Final version, to
appear in Phys. Rev.
String Universality
If there is a single underlying "theory of everything" which in some limits
of its "moduli space" reduces to the five weakly coupled string theories in
10D, and 11D SUGRA, then it is possible that all six of them have some common
domain of validity and that they are in the same universality class, in the
sense that the 4D low energy physics of the different theories is the same. We
call this notion String Universality. This suggests that the true vacuum of
string theory is in a region of moduli space equally far (in some sense) from
all perturbative theories, most likely around the self-dual point with respect
to duality symmetries connecting them. We estimate stringy non-perturbative
effects from wrapped brane instantons in each perturbative theory, show how
they are related by dualities, and argue that they are likely to lead to moduli
stabilization only around the self-dual point. We argue that moduli
stabilization should occur near the string scale, and SUSY breaking should
occur at a much lower intermediate scale, and that it originates from different
sources. We discuss the problems of moduli stabilization and SUSY breaking in
currently popular scenarios, explain why these problems are generic, and
discuss how our scenario can evade them. We show that String Universality is
not inconsistent with phenomenology but that it is in conflict with some
popular versions of brane world scenarios.Comment: 48 pages, 1 figure; one reference adde
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