The Role of Peroxisome Proliferator-Activated Receptors in Pulmonary Vascular Disease

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily that regulate diverse physiological processes ranging from lipogenesis to inflammation. Recent evidence has established potential roles of PPARs in both systemic and pulmonary vascular disease and function. Existing treatment strategies for pulmonary hypertension, the most common manifestation of pulmonary vascular disease, are limited by an incomplete understanding of the underlying disease pathogenesis and lack of efficacy indicating an urgent need for new approaches to treat this disorder. Derangements in pulmonary endothelial-derived mediators and endothelial dysfunction have been shown to play a pivotal role in pulmonary hypertension pathogenesis. Therefore, the following review will focus on selected mediators implicated in pulmonary vascular dysfunction and evidence that PPARs, in particular PPARγ, participate in their regulation and may provide a potential novel therapeutic target for the treatment of pulmonary hypertension

Endogenous Quasicycles and Stochastic Coherence in a Closed Endemic Model

We study the role of demographic fluctuations in typical endemics as exemplified by the stochastic SIRS model. The birth-death master equation of the model is simulated using exact numerics and analysed within the linear noise approximation. The endemic fixed point is unstable to internal demographic noise, and leads to sustained oscillations. This is ensured when the eigenvalues ($\lambda$) of the linearised drift matrix are complex, which in turn, is possible only if detailed balance is violated. In the oscillatory state, the phases decorrelate asymptotically, distinguishing such oscillations from those produced by external periodic forcing. These so-called quasicycles are of sufficient strength to be detected reliably only when the ratio $|Im(\lambda)/Re(\lambda)|$ is of order unity. The coherence or regularity of these oscillations show a maximum as a function of population size, an effect known variously as stochastic coherence or coherence resonance. We find that stochastic coherence can be simply understood as resulting from a non-monotonic variation of $|Im(\lambda)/Re(\lambda)|$ with population size. Thus, within the linear noise approximation, stochastic coherence can be predicted from a purely deterministic analysis. The non-normality of the linearised drift matrix, associated with the violation of detailed balance, leads to enhanced fluctuations in the population amplitudes.Comment: 21 pages, 8 figure

Methane Mitigation:Methods to Reduce Emissions, on the Path to the Paris Agreement

The atmospheric methane burden is increasing rapidly, contrary to pathways compatible with the goals of the 2015 United Nations Framework Convention on Climate Change Paris Agreement. Urgent action is required to bring methane back to a pathway more in line with the Paris goals. Emission reduction from “tractable” (easier to mitigate) anthropogenic sources such as the fossil fuel industries and landfills is being much facilitated by technical advances in the past decade, which have radically improved our ability to locate, identify, quantify, and reduce emissions. Measures to reduce emissions from “intractable” (harder to mitigate) anthropogenic sources such as agriculture and biomass burning have received less attention and are also becoming more feasible, including removal from elevated-methane ambient air near to sources. The wider effort to use microbiological and dietary intervention to reduce emissions from cattle (and humans) is not addressed in detail in this essentially geophysical review. Though they cannot replace the need to reach “net-zero” emissions of CO2, significant reductions in the methane burden will ease the timescales needed to reach required CO2 reduction targets for any particular future temperature limit. There is no single magic bullet, but implementation of a wide array of mitigation and emission reduction strategies could substantially cut the global methane burden, at a cost that is relatively low compared to the parallel and necessary measures to reduce CO2, and thereby reduce the atmospheric methane burden back toward pathways consistent with the goals of the Paris Agreement

A genomic analysis and transcriptomic atlas of gene expression in Psoroptes ovis reveals feeding- and stage-specific patterns of allergen expression

Background: Psoroptic mange, caused by infestation with the ectoparasitic mite, Psoroptes ovis, is highly contagious, resulting in intense pruritus and represents a major welfare and economic concern for the livestock industry Worldwide. Control relies on injectable endectocides and organophosphate dips, but concerns over residues, environmental contamination, and the development of resistance threaten the sustainability of this approach, highlighting interest in alternative control methods. However, development of vaccines and identification of chemotherapeutic targets is hampered by the lack of P. ovis transcriptomic and genomic resources. Results: Building on the recent publication of the P. ovis draft genome, here we present a genomic analysis and transcriptomic atlas of gene expression in P. ovis revealing feeding- and stage-specific patterns of gene expression, including novel multigene families and allergens. Network-based clustering revealed 14 gene clusters demonstrating either single- or multi-stage specific gene expression patterns, with 3075 female-specific, 890 male-specific and 112, 217 and 526 transcripts showing larval, protonymph and tritonymph specific-expression, respectively. Detailed analysis of P. ovis allergens revealed stage-specific patterns of allergen gene expression, many of which were also enriched in "fed" mites and tritonymphs, highlighting an important feeding-related allergenicity in this developmental stage. Pair-wise analysis of differential expression between life-cycle stages identified patterns of sex-biased gene expression and also identified novel P. ovis multigene families including known allergens and novel genes with high levels of stage-specific expression. Conclusions: The genomic and transcriptomic atlas described here represents a unique resource for the acarid-research community, whilst the OrcAE platform makes this freely available, facilitating further community-led curation of the draft P. ovis genome

High transonic speed transport aircraft study

An initial design study of high-transonic-speed transport aircraft has been completed. Five different design concepts were developed. These included fixed swept wing, variable-sweep wing, delta wing, double-fuselage yawed-wing, and single-fuselage yawed-wing aircraft. The boomless supersonic design objectives of range=5560 Km (3000 nmi), payload-18 143 kg (40 000lb), Mach=1.2, and FAR Part 36 aircraft noise levels were achieved by the single-fuselage yawed-wing configuration with a gross weight of 211 828 Kg (467 000 lb). A noise level of 15 EPNdB below FAR Part 36 requirements was obtained with a gross weight increase to 226 796 Kg (500 000 lb). Although wing aeroelastic divergence was a primary design consideration for the yawed-wing concepts, the graphite-epoxy wings of this study were designed by critical gust and maneuver loads rather than by divergence requirements. The transonic nacelle drag is shown to be very sensitive to the nacelle installation. A six-degree-of-freedom dynamic stability analysis indicated that the control coordination and stability augmentation system would require more development than for a symmetrical airplane but is entirely feasible. A three-phase development plan is recommended to establish the full potential of the yawed-wing concept

Diurnal, seasonal, and annual trends in atmospheric CO₂ at southwest London during 2000-2012:Wind sector analysis and comparison with Mace Head, Ireland

In-situ measurements of atmospheric CO have been made at Royal Holloway University of London (RHUL) in Egham (EGH), Surrey, UK from 2000 to 2012. The data were linked to the global scale using NOAA-calibrated gases. Measured CO varies on time scales that range from minutes to inter-annual and annual cycles. Seasonality and pollution episodes occur each year. Diurnal cycles vary with daylight and temperature, which influence the biological cycle of CO and the degree of vertical mixing. Anthropogenic emissions of CO dominate the variability during weekdays when transport cycles are greater than at weekends. Seasonal cycles are driven by temporal variations in biological activity and changes in combustion emissions. Maximum mole fractions (μmol/mol) (henceforth referred to by parts per million, ppm) occur in winter, with minima in late summer. The smallest seasonal amplitude observed, peak to trough, was 17.0ppm CO in 2003, whereas the largest amplitude observed was 27.1ppm CO in 2008.Meteorology can strongly modify the CO mole fractions at different time scales. Analysis of eight 45° wind sectors shows that the highest CO mole fractions were recorded from the E and SE sectors. Lowest mole fractions were observed for air masses from the S and SW. Back-trajectory and meteorological analyses of the data confirm that the dominant sources of CO are anthropogenic emissions from London and SE England. The largest annual rate of increase in the annual average of CO, 3.26ppmyr (

Genotypic and phenotypic characterization of enteric bacteria in an integrated population of swine and humans

In two longitudinal studies, we examined the transmission dynamics of antimicrobial resistance (AMR) in an integrated, semi-closed population of humans and swine

Hertz potentials approach to the dynamical Casimir effect in cylindrical cavities of arbitrary section

We study the creation of photons in resonant cylindrical cavities with time dependent length. The physical degrees of freedom of the electromagnetic field are described using Hertz potentials. We describe the general formalism for cavities with arbitrary section. Then we compute explicitly the number of TE and TM motion-induced photons for cylindrical cavities with rectangular and circular sections. We also discuss the creation of TEM photons in non-simply connected cylindrical cavities.Comment: 13 pages, 3 figures, revtex

Isolation of Salmonella spp. and bacteriophage active against Salmonella spp. from commercial swine

Bacteriophage are viruses that prey on bacteria and may be a potential strategy to reduce foodborne pathogemc bactena in the gastromtestlnal tract of food animals Phages are fairly common in the gastrointestinal microbial ecosystem of mammals, but the incidence is unknown. If phage are to be an intervention strategy, we must understand their role in the microbial ecology of the gut. From a regulatory perspective, knowing incidence of phage is crucial. Therefore the current study was designed to determine the incidence of phage active against Salmonella spp in the feces of commercial finishing swine in the United States. Fecal samples (n=60) were collected from each of six commercial swine finishing operations. Samples were collected from 10 randomly selected pens throughout each operation. Total number of fecal samples collected in this study was n=360 Salmonella spp were found in 66% of the fecal samples Salmonella spp. were isolated from only 2 farms and the serotypes represented were Schwarzengrund, Anatum, Ohio and Heidelberg Bacteriophages were isolated from fecal sample through 2 parallel methods, 1) initlal enrichment in Salmonella Typhimunum, or 2) initial ennchment in E. colt B (a strain very sensitive to phages), followed by direct spot-testing against Salmonella Typhimurium Bacteriophages active against Salmonella Typhimunum were isolated from 1.1% 4/360) of the individual fecal samples when initially enriched in Salmonella Typhimurium, but E coli S-killing phages were 1solated from 43.8% (158/360) of the fecal samples but only 2 of these Isolates were capable of k1ll1ng Salmonella Typhimunum. Our results mdicate that bactenophage capable of killing Salmonella Typh1murium are fairly w1despread across commercial swine production facilities but may be present at relatively low populat1ons These results md1cate that phage (predator) populations may vary along w1th Salmonella (prey) populations and that phage could potentially be used as a food safety pathogen reduction strategy