Chemical modulation of airway epithelial permeability.

The mucosal surface of the conducting airways has specialized structures for respiratory defense. Glands secret mucus that may act as a barrier to particle penetration and participate in particle clearance. Intraepithelial irritant receptors aid in particle clearance through airway constriction and cough. The epithelium acts as a barrier to the penetration of inhaled material into the airway wall. Morphologic studies have identified the tight junctions adjoining respiratory epithelial cells as the principal barrier to passive solute translocation across the airway. New approaches have been used to study airway epithelial function. Use of excised canine trachea mounted in Ussing chambers has permitted quantitative estimates of probe molecule permeation, the correlation of permeability with bioelectric properties, and estimation of equivalent pore radii. Probe molecule diffusion across canine trachea [mean transmucosal electric potential difference (PD) = 33 mV, lumen negative] is directly related to conductance (2.9 mS/cm2) and is compatible with an equivalent pore radius of 7.5 nm. Direct measurement of tracheal PD in vivo (-29 mV) facilitates study of the genesis of the biopotential in intact animals. Measurement of the movement of HRP by radioimmunoassay has allowed correlation of the rate of probe flow across airway walls in vivo with ultrastructure. These approaches lend themselves to the study of pharmacologic and toxicologic effects on epithelial function. Antigen challenge, diethyl ether, and unfractionated cigarette smoke have been shown to increase epithelial permeability to HRP accompanied by ultrastructural evidence of tight junctional damage. Application of pharmacologic agents, e.g. amphotericin, ouabain, onto the respiratory epithelium induces similar changes in in vitro and in vivo PD. We conclude that techniques that have been used to measure permeability and transport in other epithelia may help elucidate modes of action of environmental agents on airways

Polarized distribution of HCO3- transport in human normal and cystic fibrosis nasal epithelia

The polarized distribution of HCO3− transport was investigated in human nasal epithelial cells from normal and cystic fibrosis (CF) tissues. To test for HCO3− transport via conductive versus electroneutral Cl−/HCO3− exchange (anion exchange, AE) pathways, nasal cells were loaded with the pH probe 2′,7′-bis(carboxyethyl)-5(6)-carboxyfluorescein and mounted in a bilateral perfusion chamber. In normal, but not CF, epithelia, replacing mucosal Cl− with gluconate caused intracellular pH (pHi) to increase, and the initial rates (ΔpH min−1) of this increase were modestly augmented (∼26 %) when normal cells were pretreated with forskolin (10 μm). Recovery from this alkaline shift was dependent on mucosal Cl−, was insensitive to the AE inhibitor 4,4′-diisothiocyanatodihydrostilbene-2,2′-disulfonic acid (H2DIDS; 1.5 mm), but was sensitive to the cystic fibrosis transmembrane conductance regulator (CFTR) channel inhibitor diphenylamine-2-carboxylate (DPC; 100 μm). In contrast, removal of serosal Cl− caused pHi to alkalinize in both normal and CF epithelia. Recovery from this alkaline challenge was dependent on serosal Cl− and blocked by H2DIDS. Additional studies showed that serosally applied Ba2+ (5.0 mm) in normal, but not CF, cells induced influx of HCO3− across the apical membrane that was reversibly blocked by mucosal DPC. In a final series of studies, normal and CF cells acutely alkaline loaded by replacing bilateral Krebs bicarbonate Ringer (KBR) with Hepes-buffered Ringer solution exhibited basolateral, but not apical, recovery from an alkaline challenge that was dependent on Cl−, independent of Na+ and blocked by H2DIDS. We conclude that: (1) normal, but not CF, nasal epithelia have a constitutively active DPC-sensitive HCO3− influx/efflux pathway across the apical membrane of cells, consistent with the movement of HCO3− via CFTR; and (2) both normal and CF nasal epithelia have Na+-independent, H2DIDS-sensitive AE at their basolateral domain

Flight demonstration of flight termination system and solid rocket motor ignition using semiconductor laser initiated ordnance

Solid State Laser Initiated Ordnance (LIO) offers new technology having potential for enhanced safety, reduced costs, and improved operational efficiency. Concerns over the absence of programmatic applications of the technology, which has prevented acceptance by flight programs, should be abated since LIO has now been operationally implemented by the Laser Initiated Ordnance Sounding Rocket Demonstration (LOSRD) Program. The first launch of solid state laser diode LIO at the NASA Wallops Flight Facility (WFF) occurred on March 15, 1995 with all mission objectives accomplished. This project, Phase 3 of a series of three NASA Headquarters LIO demonstration initiatives, accomplished its objective by the flight of a dedicated, all-LIO sounding rocket mission using a two-stage Nike-Orion launch vehicle. LIO flight hardware, made by The Ensign-Bickford Company under NASA's first Cooperative Agreement with Profit Making Organizations, safely initiated three demanding pyrotechnic sequence events, namely, solid rocket motor ignition from the ground and in flight, and flight termination, i.e., as a Flight Termination System (FTS). A flight LIO system was designed, built, tested, and flown to support the objectives of quickly and inexpensively putting LIO through ground and flight operational paces. The hardware was fully qualified for this mission, including component testing as well as a full-scale system test. The launch accomplished all mission objectives in less than 11 months from proposal receipt. This paper concentrates on accomplishments of the ordnance aspects of the program and on the program's implementation and results. While this program does not generically qualify LIO for all applications, it demonstrated the safety, technical, and operational feasibility of those two most demanding applications, using an all solid state safe and arm system in critical flight applications

Exact steady-state velocity of ratchets driven by random sequential adsorption

We solve the problem of discrete translocation of a polymer through a pore, driven by the irreversible, random sequential adsorption of particles on one side of the pore. Although the kinetics of the wall motion and the deposition are coupled, we find the exact steady-state distribution for the gap between the wall and the nearest deposited particle. This result enables us to construct the mean translocation velocity demonstrating that translocation is faster when the adsorbing particles are smaller. Monte-Carlo simulations also show that smaller particles gives less dispersion in the ratcheted motion. We also define and compare the relative efficiencies of ratcheting by deposition of particles with different sizes and we describe an associated "zone-refinement" process.Comment: 11 pages, 4 figures New asymptotic result for low chaperone density added. Exact translocation velocity is proportional to (chaperone density)^(1/3

Stable Isotropic Cosmological Singularities in Quadratic Gravity

We show that, in quadratic lagrangian theories of gravity, isotropic cosmological singularities are stable to the presence of small scalar, vector and tensor inhomogeneities. Unlike in general relativity, a particular exact isotropic solution is shown to be the stable attractor on approach to the initial cosmological singularity. This solution is also known to act as an attractor in Bianchi universes of types I, II and IX, and the results of this paper reinforce the hypothesis that small inhomogeneous and anisotropic perturbations of this attractor form part of the general cosmological solution to the field equations of quadratic gravity. Implications for the existence of a 'gravitational entropy' are also discussed.Comment: 18 pages, no figure

RLZAP: Relative Lempel-Ziv with Adaptive Pointers

Relative Lempel-Ziv (RLZ) is a popular algorithm for compressing databases of genomes from individuals of the same species when fast random access is desired. With Kuruppu et al.'s (SPIRE 2010) original implementation, a reference genome is selected and then the other genomes are greedily parsed into phrases exactly matching substrings of the reference. Deorowicz and Grabowski (Bioinformatics, 2011) pointed out that letting each phrase end with a mismatch character usually gives better compression because many of the differences between individuals' genomes are single-nucleotide substitutions. Ferrada et al. (SPIRE 2014) then pointed out that also using relative pointers and run-length compressing them usually gives even better compression. In this paper we generalize Ferrada et al.'s idea to handle well also short insertions, deletions and multi-character substitutions. We show experimentally that our generalization achieves better compression than Ferrada et al.'s implementation with comparable random-access times

On the Asymptotic Stability of De-Sitter Spacetime: a non-linear perturbative approach

We derive evolution and constraint equations for second order perturbations of flat dust homogeneous and isotropic solutions to the Einstein field equations using all scalar, vector and tensor perturbation modes. We show that the perturbations decay asymptotically in time and that the solutions converge to the De-Sitter solution. By induction, this result is valid for perturbations of arbitrary order. This is in agreement with the cosmic no-hair conjecture of Gibbons and Hawking.Comment: 11 pages, 2 figure

On the Decoherence of Primordial Fluctuations During Inflation

We study the process whereby quantum cosmological perturbations become classical within inflationary cosmology. By setting up a master-equation formulation we show how quantum coherence for super-Hubble modes can be destroyed by their coupling to the environment provided by sub-Hubble modes. We identify what features the sub-Hubble environment must have in order to decohere the longer wavelengths, and identify how the onset of decoherence (and how long it takes) depends on the properties of the sub-Hubble physics which forms the environment. Our results show that the decoherence process is largely insensitive to the details of the coupling between the sub- and super-Hubble scales. They also show how locality implies, quite generally, that the decohered density matrix at late times is diagonal in the field representation (as is implicitly assumed by extant calculations of inflationary density perturbations). Our calculations also imply that decoherence can arise even for couplings which are as weak as gravitational in strength.Comment: 31 pages, 1 figur

From Skew-Cyclic Codes to Asymmetric Quantum Codes

We introduce an additive but not $\mathbb{F}_4$-linear map $S$ from $\mathbb{F}_4^{n}$ to $\mathbb{F}_4^{2n}$ and exhibit some of its interesting structural properties. If $C$ is a linear $[n,k,d]_4$-code, then $S(C)$ is an additive $(2n,2^{2k},2d)_4$-code. If $C$ is an additive cyclic code then $S(C)$ is an additive quasi-cyclic code of index $2$. Moreover, if $C$ is a module $\theta$-cyclic code, a recently introduced type of code which will be explained below, then $S(C)$ is equivalent to an additive cyclic code if $n$ is odd and to an additive quasi-cyclic code of index $2$ if $n$ is even. Given any $(n,M,d)_4$-code $C$, the code $S(C)$ is self-orthogonal under the trace Hermitian inner product. Since the mapping $S$ preserves nestedness, it can be used as a tool in constructing additive asymmetric quantum codes.Comment: 16 pages, 3 tables, submitted to Advances in Mathematics of Communication