Synergistic airway gland mucus secretion in response to vasoactive intestinal peptide and carbachol is lost in cystic fibrosis

Cystic fibrosis (CF) is caused by dysfunction of the CF transmembrane conductance regulator (CFTR), an anion channel whose dysfunction leads to chronic bacterial and fungal airway infections via a pathophysiological cascade that is incompletely understood. Airway glands, which produce most airway mucus, do so in response to both acetylcholine (ACh) and vasoactive intestinal peptide (VIP). CF glands fail to secrete mucus in response to VIP, but do so in response to ACh. Because vagal cholinergic pathways still elicit strong gland mucus secretion in CF subjects, it is unclear whether VIP-stimulated, CFTR-dependent gland secretion participates in innate defense. It was recently hypothesized that airway intrinsic neurons, which express abundant VIP and ACh, are normally active and stimulate low-level gland mucus secretion that is a component of innate mucosal defenses. Here we show that low levels of VIP and ACh produced significant mucus secretion in human glands via strong synergistic interactions; synergy was lost in glands of CF patients. VIP/ACh synergy also existed in pig glands, where it was CFTR dependent, mediated by both Cl– and HCO3–, and clotrimazole sensitive. Loss of “housekeeping” gland mucus secretion in CF, in combination with demonstrated defects in surface epithelia, may play a role in the vulnerability of CF airways to bacterial infections

ALICE: Physics Performance Report

ALICE is a general-purpose heavy-ion experiment designed to study the physics of strongly interacting matter and the quark-gluon plasma in nucleus-nucleus collisions at the LHC. It currently involves more than 900 physicists and senior engineers, from both the nuclear and high-energy physics sectors, from over 90 institutions in about 30 countries. The ALICE detector is designed to cope with the highest particle multiplicities above those anticipated for Pb-Pb collisions (dN ch/dy up to 8000) and it will be operational at the start-up of the LHC. In addition to heavy systems, the ALICE Collaboration will study collisions of lower-mass ions, which are a means of varying the energy density, and protons (both pp and pA), which primarily provide reference data for the nucleus-nucleus collisions. In addition, the pp data will allow for a number of genuine pp physics studies. The detailed design of the different detector systems has been laid down in a number of Technical Design Reports issued between mid-1998 and the end of 2004. The experiment is currently under construction and will be ready for data taking with both proton and heavy-ion beams at the start-up of the LHC. Since the comprehensive information on detector and physics performance was last published in the ALICE Technical Proposal in 1996, the detector, as well as simulation, reconstruction and analysis software have undergone significant development. The Physics Performance Report (PPR) provides an updated and comprehensive summary of the performance of the various ALICE subsystems, including updates to the Technical Design Reports, as appropriate. The PPR is divided into two volumes. Volume I, published in 2004 (CERN/LHCC 2003-049, ALICE Collaboration 2004 J. Phys. G: Nucl. Part. Phys. 30 1517-1763), contains in four chapters a short theoretical overview and an extensive reference list concerning the physics topics of interest to ALICE, the experimental conditions at the LHC, a short summary and update of the subsystem designs, and a description of the offline framework and Monte Carlo event generators. The present volume, Volume II, contains the majority of the information relevant to the physics performance in proton-proton, proton-nucleus, and nucleus-nucleus collisions. Following an introductory overview, Chapter 5 describes the combined detector performance and the event reconstruction procedures, based on detailed simulations of the individual subsystems. Chapter 6 describes the analysis and physics reach for a representative sample of physics observables, from global event characteristics to hard processes

ALICE: Physics performance report, volume I

Cortese P, Dellacasa G, Ramello L, et al. ALICE: Physics performance report, volume I. Journal of Physics G: Nuclear and Particle Physics. 2004;30(11):1517-1763.ALICE is a general-purpose heavy-ion experiment designed to study the physics of strongly interacting matter and the quark-gluon plasma in nucleus-nucleus collisions at the LHC. It currently includes more than 900 physicists and senior engineers, from both nuclear and high-energy physics, from about 80 institutions in 28 countries. The experiment was approved in February 1997. The detailed design of the different detector systems has been laid down in a number of Technical Design Reports issued between mid-1998 and the end of 2001 and construction has started for most detectors. Since the last comprehensive information on detector and physics performance was published in the ALICE Technical Proposal in 1996, the detector as well as simulation, reconstruction and analysis software have undergone significant development. The Physics Performance Report (PPR) will give an updated and comprehensive summary of the current status and performance of the various ALICE subsystems, including updates to the Technical Design Reports, where appropriate, as well as a description of systems which have not been published in a Technical Design Report. The PPR will be published in two volumes. The current Volume I contains: 1. a short theoretical overview and an extensive reference list concerning the physics topics of interest to ALICE, 2. relevant experimental conditions at the LHC, 3. a short summary and update of the subsystem designs, and 4. a description of the offline framework and Monte Carlo generators. Volume II, which will be published separately, will contain detailed simulations of combined detector performance, event reconstruction, and analysis of a representative sample of relevant physics observables from global event characteristics to hard processes. (Some figures in this article are in colour only in the electronic version.