Transcriptional response of human mast cells stimulated via the FcεRI and identification of mast cells as a source of IL-11

BACKGROUND: In asthma and other allergic disorders, the activation of mast cells by IgE and antigen induces the cells to release histamine and other mediators of inflammation, as well as to produce certain cytokines and chemokines. To search for new mast cell products, we used complementary DNA microarrays to analyze gene expression in human umbilical cord blood-derived mast cells stimulated via the high-affinity IgE receptor (FcεRI). RESULTS: One to two hours after FcεRI-dependent stimulation, more than 2,400 genes (about half of which are of unknown function) exhibited 2–200 fold changes in expression. The transcriptional program included changes in the expression of IL-11 and at least 30 other cytokines and chemokines. Human mast cells secreted 130–529 pg of IL-11/10(6) cells by 6 h after stimulation with anti-IgE. CONCLUSION: Our initial analysis of the transcriptional program induced in in vitro-derived human mast cells stimulated via the FcεRI has identified many products that heretofore have not been associated with this cell type, but which may significantly influence mast cell function in IgE-associated host responses. We also have demonstrated that mast cells stimulated via the FcεRI can secrete IL-11. Based on the previously reported biological effects of IL-11, our results suggest that production of IL-11 may represent one link between IgE-dependent mast cell activation in subjects with allergic asthma and the development of a spectrum of structural changes in the airways of these individuals; such changes, collectively termed "airway remodeling," can constitute an important long term consequence of asthma

Anomalous critical fields in quantum critical superconductors.

Fluctuations around an antiferromagnetic quantum critical point (QCP) are believed to lead to unconventional superconductivity and in some cases to high-temperature superconductivity. However, the exact mechanism by which this occurs remains poorly understood. The iron-pnictide superconductor BaFe2(As(1-x)P(x))2 is perhaps the clearest example to date of a high-temperature quantum critical superconductor, and so it is a particularly suitable system to study how the quantum critical fluctuations affect the superconducting state. Here we show that the proximity of the QCP yields unexpected anomalies in the superconducting critical fields. We find that both the lower and upper critical fields do not follow the behaviour, predicted by conventional theory, resulting from the observed mass enhancement near the QCP. Our results imply that the energy of superconducting vortices is enhanced, possibly due to a microscopic mixing of antiferromagnetism and superconductivity, suggesting that a highly unusual vortex state is realized in quantum critical superconductors.We thank Igor Mazin and Georg Knebel for useful discussions, and A. M. Adamska for experimental help. This work was supported by the Engineering and Physical Sciences Research Council (Grant No. EP/H025855/1), EuroMagNET II under the EU Contract No. 228043, National Physical Laboratory Strategic Research Programme, and KAKENHI from JSPS.This is the final published version. It first appeared at http://www.nature.com/ncomms/2014/141205/ncomms6679/full/ncomms6679.html

Casimir Energies for 6D Supergravities Compactified on T_2/Z_N with Wilson Lines

We compute (as functions of the shape and Wilson-line moduli) the one-loop Casimir energy induced by higher-dimensional supergravities compactified from 6D to 4D on 2-tori, and on some of their Z_N orbifolds. Detailed calculations are given for a 6D scalar field having an arbitrary 6D mass m, and we show how to extend these results to higher-spin fields for supersymmetric 6D theories. Particular attention is paid to regularization issues and to the identification of the divergences of the potential, as well as the dependence of the result on m, including limits for which m^2 A> 1 where A is the volume of the internal 2 dimensions. Our calculation extends those in the literature to very general boundary conditions for fields about the various cycles of these geometries. The results have potential applications towards Supersymmetric Large Extra Dimensions (SLED) as a theory of the Dark Energy. First, they provide an explicit calculation within which to follow the dependence of the result on the mass of the bulk states which travel within the loop, and for heavy masses these results bear out the more general analysis of the UV-sensitivity obtained using heat-kernel methods. Second, because the potentials we find describe the dynamics of the classical flat directions of these compactifications, within SLED they would describe the present-day dynamics of the Dark Energy.Comment: 40 pages, 7 figure

Critical Behavior of the Supersolid transition in Bose-Hubbard Models

We study the phase transitions of interacting bosons at zero temperature between superfluid (SF) and supersolid (SS) states. The latter are characterized by simultaneous off-diagonal long-range order and broken translational symmetry. The critical phenomena is described by a long-wavelength effective action, derived on symmetry grounds and verified by explicit calculation. We consider two types of supersolid ordering: checkerboard (X) and collinear (C), which are the simplest cases arising in two dimensions on a square lattice. We find that the SF--CSS transition is in the three-dimensional XY universality class. The SF--XSS transition exhibits non-trivial new critical behavior, and appears, within a $d=3-\epsilon$ expansion to be driven generically first order by fluctuations. However, within a one--loop calculation directly in $d=2$ a strong coupling fixed point with striking ``non-Bose liquid'' behavior is found. At special isolated multi-critical points of particle-hole symmetry, the system falls into the 3d Ising universality class.Comment: RevTeX, 24 pages, 16 figures. Also available at http://www.cip.physik.tu-muenchen.de/tumphy/d/T34/Mitarbeiter/frey.htm

Interacting Electrons on a Fluctuating String

We consider the problem of interacting electrons constrained to move on a fluctuating one-dimensional string. An effective low-energy theory for the electrons is derived by integrating out the string degrees of freedom to lowest order in the inverse of the string tension and mass density, which are assumed to be large. We obtain expressions for the tunneling density of states, the spectral function and the optical conductivity of the system. Possible connections with the phenomenology of the cuprate high temperature superconductors are discussed.Comment: 14 pages, 1 figur

Effective Field Theories and Inflation

We investigate the possible influence of very-high-energy physics on inflationary predictions focussing on whether effective field theories can allow effects which are parametrically larger than order H^2/M^2, where M is the scale of heavy physics and H is the Hubble scale at horizon exit. By investigating supersymmetric hybrid inflation models, we show that decoupling does not preclude heavy-physics having effects for the CMB with observable size even if H^2/M^2 << O(1%), although their presence can only be inferred from observations given some a priori assumptions about the inflationary mechanism. Our analysis differs from the results of hep-th/0210233, in which other kinds of heavy-physics effects were found which could alter inflationary predictions for CMB fluctuations, inasmuch as the heavy-physics can be integrated out here to produce an effective field theory description of low-energy physics. We argue, as in hep-th/0210233, that the potential presence of heavy-physics effects in the CMB does not alter the predictions of inflation for generic models, but does make the search for deviations from standard predictions worthwhile.Comment: 19 pages, LaTeX, no figures, uses JHEP

Towards Customary Legal Empowerment

Rule of Law and Development: Formation, Implementation and Improvement of Law and Governance in Developing Countrie

Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome