PULMONARY ARTERY REMODELING IN SEVERE EQUINE ASTHMA

Recurrent episodes of airway obstruction, hypoxemia and pulmonary hypertension (PH) are present during exacerbations of severe equine asthma (SEA). Pulmonary hypoxic vasoconstriction is known to contribute to the development of PH, which may lead to cor pulmonale. However, as PH is only partially reversible by oxygen administration, other etiological factors are likely to be involved. In human chronic obstructive pulmonary disease, pulmonary artery (PA) remodeling contributes to the development of PH. Furthermore, allergic airway inflammation results in remodeling of pulmonary vasculature in mouse models, suggesting that similar findings may be present in asthma. We therefore postulated that PA remodeling is present in SEA and contributes to PH. The project aimed to investigate 1) the presence of PA remodeling in severe equine asthma and its distribution throughout the lungs, 2) the involvement of vascular smooth muscle (VSM) alterations, and 3) their reversibility following long-term antigen avoidance strategies or inhaled corticosteroids administration. Using histomorphometry and tissue bank (ERTB) lung samples, the PA wall was measured on sections stained with hematoxylin-eosin saffron, collected post-mortem from different lung regions of 12 asthmatic horses and 6 age-matched controls. Pulmonary vascular smooth muscle (VSM) mass was also measured on sections stained for \u3b1-smooth muscle actin collected with in vivo thoracoscopy or post-mortem peripheral lung biopsy from 5 controls, 6 asthmatic horses in remission, and 11 asthmatic horses while exacerbation and after 1 year of antigen avoidance alone (5 horses) or treatments with fluticasone (6 horses). Data were compared using one tailed unpaired t tests with Welch correction or paired t tests (p<0.05). Increased PA wall surface was detected in apical (p=0.002) and caudodorsal (p=0.03) lung regions of asthmatic horses in both exacerbation and remission, when compared to controls. The VSM mass was similarly increased (p=0.03) when compared to controls. A tendency for a normalization of the VSM mass was observed after treatment with antigen avoidance (p=0.05), but not with fluticasone (p=0.27). Remodeling of the PA develops in SEA and is associated with an increase in VSM. The resulting narrowing of the lumen of the PA could enhance hypoxic vasoconstriction, contributing to PH during exacerbation of SEA. VSM mass normalization is better achieved by antigen avoidance than by corticosteroids

Accelerating the convergence of path integral dynamics with a generalized Langevin equation

The quantum nature of nuclei plays an important role in the accurate modelling of light atoms such as hydrogen, but it is often neglected in simulations due to the high computational overhead involved. It has recently been shown that zero-point energy effects can be included comparatively cheaply in simulations of harmonic and quasi-harmonic systems by augmenting classical molecular dynamics with a generalized Langevin equation (GLE). Here we describe how a similar approach can be used to accelerate the convergence of path integral (PI) molecular dynamics to the exact quantum mechanical result in more strongly anharmonic systems exhibiting both zero point energy and tunnelling effects. The resulting PI-GLE method is illustrated with applications to a double-well tunnelling problem and to liquid water

Diffusion and desorption of SiH3 on hydrogenated H:Si(100)-(2x1) from first principles

We have studied diffusion pathways of a silyl radical adsorbed on the hydrogenated Si (100)-(2x1) surface by density-functional theory. The process is of interest for the growth of crystalline silicon by plasma-enhanced chemical vapor deposition. Preliminary searches for migration mechanisms have been performed using metadynamics simulations. Local minima and transition states have been further refined by using the nudged-elastic-band method. Barriers for diffusion from plausible adsorption sites as low as 0.2 eV have been found, but trap states have also been spotted, leading to a more stable configuration, with escape barriers of 0.7 eV. Diffusion among weakly bound physisorbed states is also possible with very low activation barriers (<50 meV). However, desorption mechanisms (either as SiH3 or as SiH4) from physisorbed or more strongly bound adsorption configurations turn out to have activation energies similar to diffusion barriers. Kinetic Monte Carlo simulations based on ab initio activation energies show that the silyl radical diffuses at most by a few lattice spacing before desorbing at temperatures in the range 300-1000 K

Natural and sail-displaced doubly-symmetric Lagrange point orbits for polar coverage

This paper proposes the use of doubly-symmetric, eight-shaped orbits in the circular restricted three-body problem for continuous coverage of the high-latitude regions of the Earth. These orbits, for a range of amplitudes, spend a large fraction of their period above either pole of the Earth. It is shown that they complement Sun-synchronous polar and highly eccentric Molniya orbits, and present a possible alternative to low thrust pole-sitter orbits. Both natural and solar-sail displaced orbits are considered. Continuation methods are described and used to generate families of these orbits. Starting from ballistic orbits, other families are created either by increasing the sail lightness number, varying the period or changing the sail attitude. Some representative orbits are then chosen to demonstrate the visibility of high-latitude regions throughout the year. A stability analysis is also performed, revealing that the orbits are unstable: it is found that for particular orbits, a solar sail can reduce their instability. A preliminary design of a linear quadratic regulator is presented as a solution to stabilize the system by using the solar sail only. Finally, invariant manifolds are exploited to identify orbits that present the opportunity of a ballistic transfer directly from low Earth orbit

Effects of deposition dynamics on epitaxial growth

The dynamic effects, such as the steering and the screening effects during deposition, on an epitaxial growth (Cu/Cu(001)), is studied by kinetic Monte Carlo simulation that incorporates molecular dynamic simulation to rigorously take the interaction of the deposited atom with the substrate atoms into account. We find three characteristic features of the surface morphology developed by grazing angle deposition: (1) enhanced surface roughness, (2) asymmetric mound, and (3) asymmetric slopes of mound sides. Regarding their dependence on both deposition angle and substrate temperature, a reasonable agreement of the simulated results with the previous experimental ones is found. The characteristic growth features by grazing angle deposition are mainly caused by the inhomogeneous deposition flux due to the steering and screening effects, where the steering effects play the major role rather than the screening effects. Newly observed in the present simulation is that the side of mound in each direction is composed of various facets instead of all being in one selected mound angle even if the slope selection is attained, and that the slope selection does not necessarily mean the facet selection.Comment: 9 pages, 10 figure

Efficient stochastic thermostatting of path integral molecular dynamics

The path integral molecular dynamics (PIMD) method provides a convenient way to compute the quantum mechanical structural and thermodynamic properties of condensed phase systems at the expense of introducing an additional set of high-frequency normal modes on top of the physical vibrations of the system. Efficiently sampling such a wide range of frequencies provides a considerable thermostatting challenge. Here we introduce a simple stochastic path integral Langevin equation (PILE) thermostat which exploits an analytic knowledge of the free path integral normal mode frequencies. We also apply a recently-developed colored-noise thermostat based on a generalized Langevin equation (GLE), which automatically achieves a similar, frequency-optimized sampling. The sampling efficiencies of these thermostats are compared with that of the more conventional Nos\'e-Hoover chain (NHC) thermostat for a number of physically relevant properties of the liquid water and hydrogen-in-palladium systems. In nearly every case, the new PILE thermostat is found to perform just as well as the NHC thermostat while allowing for a computationally more efficient implementation. The GLE thermostat also proves to be very robust delivering a near-optimum sampling efficiency in all of the cases considered. We suspect that these simple stochastic thermostats will therefore find useful application in many future PIMD simulations.Comment: Accepted for publication on JC

Analysis of 22 mutations within milk protein genes in Italian Friesian cattle

The bovine milk protein caseins, αS1-CN, β-CN, αS2-CN, and κ-CN are codified by four well characterized genes, named CSN1S1, CSN2, CSN1S2, and CSN3 respectively and clustered in a region of 250-kb of chromosome 6. A recent revision of milk protein nomenclature considering only protein polymorphisms indicates 8 αS1-CN, 4 αS2-CN, 12 β-CN, and 11 κ-CN variants within the genus Bos. Other mutations were found in the non-coding regions of the cluster, such as the promoter regions or the 3'UTR. Many of these polymorphisms, together with others in various genes, such as the one coding for β-lactoglobulin (LGB), show important associations with different milk quality traits. Analyzing all these polymorphisms could help clarify the role of both the casein haplotype and the other polymorphisms in milk composition and cheese-making properties, and could explain which polymorphisms are really or mostly involved. The mPCR-LDR-UA approach recently developed to test simultaneously 22 SNPs in DNA regions responsible for milk protein expression was used to type 250 Italian Friesian cattle. In perfect agreement with literature, the most frequent alleles were CSN1S1*B, CSN2*A2, CSN3*A, variant 2 of CSN1S1 promoter, and variant A of Bov-A2 element. A quite balanced frequency was observed for the LGB*A and LGB*B. No CSN2*C, CSN3*C, and CSN3*H alleles were found. The CSN1S1*C, CSN2*A3, CSN2*I alleles were detected only at the heterozygous condition and at a frequency lower than 2%. The method allowed also finding some unusual intragenic haplotype, such as the Bov-A2 element-CSN3 haplotypes A-B and B-E. As to LGB one of the four SNPs tested was always homozygous for the same mutation, as already noticed. This finding confirms that this synonymous SNP is probably a sequencing mistake or a rare mutation not decisive for the LGB typing in the Italian Friesian. Reducing cost and time for typing simultaneously many SNPs, the method will be applied to a greater number of individuals and to other breeds, aiming to find out a number of animals for each haplotype sufficient for accurate statistical analysis to give a better understanding of the significance of milk protein polymorphism