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Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD.
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I-II/A-B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography-high resolution mass spectrometry metabolomics platform.Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10-7). Sex stratification indicated that the separation was driven by females (p=2.4×10-7) relative to males (p=4.0×10-4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10-3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung.These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin-lysoPA axis, are associated with disease mechanisms and/or prevalence
A Global Photometric Analysis of 2MASS Calibration Data
We present results from the application of a global photometric calibration
(GPC) procedure to calibration data from the first 2 years of The Two Micron
All Sky Survey (2MASS). The GPC algorithm uses photometry of both primary
standards and moderately bright `tracer' stars in 35 2MASS calibration fields.
During the first two years of the Survey, each standard was observed on
approximately 50 nights, with about 900 individual measurements. Based on the
photometry of primary standard stars and secondary tracer stars and under the
assumption that the nightly zeropoint drift is linear, GPC ties together all
calibration fields and all survey nights simultaneously, producing a globally
optimized solution. Calibration solutions for the Northern and Southern
hemisphere observatories are found separately, and are tested for global
consistency based on common fields near the celestial equator.
Several results from the GPC are presented, including establishing candidate
secondary standards, monitoring of near-infrared atmospheric extinction
coefficients, and verification of global validity of the standards. The
solution gives long-term averages of the atmospheric extinction coefficients,
A_J=0.096, A_H=0.026, A_{K_s}=0.066 (North) and A_J=0.092, A_H=0.031,
A_{K_s}=0.065 (South), with formal error of 0.001. The residuals show small
seasonal variations, most likely due to changing atmospheric content of water
vapor. Extension of the GPC to approximately 100 field stars in each of the 35
calibration fields yields a catalog of more than two thousand photometric
standards ranging from 10th to 14th magnitude, with photometry that is globally
consistent to .Comment: 19 pages, 10 figures; Submitted to AJ. The table of secondary
standards is available from ftp://nova.astro.umass.edu/pub/nikolaev/ or
ftp://anon-ftp.ipac.caltech.edu/pub/2mass/globalcal
miRNA-mRNA-protein dysregulated network in COPD in women
Rationale: Chronic obstructive pulmonary disease (COPD) is a complex disease caused by a multitude of underlying mechanisms, and molecular mechanistic modeling of COPD, especially at a multi-molecular level, is needed to facilitate the development of molecular diagnostic and prognostic tools and efficacious treatments.Objectives: To investigate the miRNA-mRNA-protein dysregulated network to facilitate prediction of biomarkers and disease subnetwork in COPD in women.Measurements and Results: Three omics data blocks (mRNA, miRNA, and protein) collected from BAL cells from female current-smoker COPD patients, smokers with normal lung function, and healthy never-smokers were integrated with miRNA-mRNA-protein regulatory networks to construct a COPD-specific dysregulated network. Furthermore, downstream network topology, literature annotation, and functional enrichment analysis identified both known and novel disease-related biomarkers and pathways. Both abnormal regulations in miRNA-induced mRNA transcription and protein translation repression play roles in COPD. Finally, the let-7-AIFM1-FKBP1A pathway is highlighted in COPD pathology.Conclusion: For the first time, a comprehensive miRNA-mRNA-protein dysregulated network of primary immune cells from the lung related to COPD in females was constructed to elucidate specific biomarkers and disease pathways. The multi-omics network provides a new molecular insight from a multi-molecular aspect and highlights dysregulated interactions. The highlighted let-7-AIFM1-FKBP1A pathway also indicates new hypotheses of COPD pathology.Peer reviewe
Studies of uncontrolled air traffic patterns, phase 1
The general aviation air traffic flow patterns at uncontrolled airports are investigated and analyzed and traffic pattern concepts are developed to minimize the midair collision hazard in uncontrolled airspace. An analytical approach to evaluate midair collision hazard probability as a function of traffic densities is established which is basically independent of path structure. Two methods of generating space-time interrelationships between terminal area aircraft are presented; one is a deterministic model to generate pseudorandom aircraft tracks, the other is a statistical model in preliminary form. Some hazard measures are presented for selected traffic densities. It is concluded that the probability of encountering a hazard should be minimized independently of any other considerations and that the number of encounters involving visible-avoidable aircraft should be maximized at the expense of encounters in other categories
Millimeter observations and modeling of the AB Aurigae system
(Abriged) We present the results of millimeter observations and a suitable
chemical and radiative transfer model of the AB Aur (HD 31293) circumstellar
disk and surrounding envelope. The integral molecular content of this system is
studied by observing CO, CO, CS, HCO, DCO, HCO, HCN, HNC,
and SiO rotational lines with the IRAM 30-m antenna, while the disk is mapped
in the HCO(1-0) transition with the Plateau de Bure interferometer. Using a
flared disk model with a vertical temperature gradient and an isothermal
spherical envelope model with a shadowed midplane and two unshielded cones
together with a gas-grain chemical network, time-dependent abundances of
observationally important molecules are calculated. Then a 2D non-LTE line
radiative transfer code is applied to compute excitation temperatures of
several rotational transitions of HCO, CO, CO, and CS molecules. We
synthesize the HCO(1-0) interferometric map along with single-dish CO(2-1),
CO(2-1), HCO(1-0), HCO(3-2), CS(2-1), and CS(5-4) spectra and
compared them with the observations. Our disk model successfully reproduces
observed interferometric HCO(1-0) data, thereby constraining the following
disk properties: (1) the inclination angle \iota=17^{+6}_{-3}\degr, (2) the
position angle \phi=80\pm30\degr, (3) the size AU,
(4) the mass M_\mathrm{disk}=1.3\cdot10^{-2} M_{\sun} (with a factor of
uncertainty), and (5) that the disk is in Keplerian rotation.
Furthermore, indirect evidence for a local inhomogeneity of the envelope at
\ga600 AU is found...Comment: 62 pages, 13 figures, 7 tables, accepted for publication in Ap
Important steps towards a big change for lung health: a joint approach by the European Respiratory Society, the European Society of Radiology and their partners to facilitate implementation of the European Union's new recommendations on lung cancer screening.
Enormous progress has been made on the epic journey towards implementation of lung cancer screening in Europe. A breakthrough for lung health has been achieved with the EU proposal for a Council recommendation on cancer screening. https://bit.ly/3J4O0Jb
Initial Performance of the NEOWISE Reactivation Mission
NASA's Wide-field Infrared Survey Explorer (WISE) spacecraft has been brought out of hibernation and has resumed surveying the sky at 3.4 and 4.6 μm. The scientific objectives of the NEOWISE reactivation mission are to detect, track, and characterize near-Earth asteroids and comets. The search for minor planets resumed on 2013 December 23, and the first new near-Earth object (NEO) was discovered 6 days later. As an infrared survey, NEOWISE detects asteroids based on their thermal emission and is equally sensitive to high and low albedo objects; consequently, NEOWISE-discovered NEOs tend to be large and dark. Over the course of its three-year mission, NEOWISE will determine radiometrically derived diameters and albedos for ~2000 NEOs and tens of thousands of Main Belt asteroids. The 32 months of hibernation have had no significant effect on the mission's performance. Image quality, sensitivity, photometric and astrometric accuracy, completeness, and the rate of minor planet detections are all essentially unchanged from the prime mission's post-cryogenic phase
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