Electron density extrapolation above F2 peak by the linear Vary-Chap model supporting new Global Navigation Satellite Systems-LEO occultation missions

The new radio-occultation (RO) instrument on board the future EUMETSAT Polar System-Second Generation (EPS-SG) satellites, flying at a height of 820 km, is primarily focusing on neutral atmospheric profiling. It will also provide an opportunity for RO ionospheric sounding, but only below impact heights of 500 km, in order to guarantee a full data gathering of the neutral part. This will leave a gap of 320 km, which impedes the application of the direct inversion techniques to retrieve the electron density profile. To overcome this challenge, we have looked for new ways (accurate and simple) of extrapolating the electron density (also applicable to other low-Earth orbiting, LEO, missions like CHAMP): a new Vary-Chap Extrapolation Technique (VCET). VCET is based on the scale height behavior, linearly dependent on the altitude above hmF2. This allows extrapolating the electron density profile for impact heights above its peak height (this is the case for EPS-SG), up to the satellite orbital height. VCET has been assessed with more than 3700 complete electron density profiles obtained in four representative scenarios of the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) in the United States and the Formosa Satellite Mission 3 (FORMOSAT-3) in Taiwan, in solar maximum and minimum conditions, and geomagnetically disturbed conditions, by applying an updated Improved Abel Transform Inversion technique to dual-frequency GPS measurements. It is shown that VCET performs much better than other classical Chapman models, with 60% of occultations showing relative extrapolation errors below 20%, in contrast with conventional Chapman model extrapolation approaches with 10% or less of the profiles with relative error below 20%.Peer ReviewedPostprint (published version

Extensive Genomic Variation within Clonal Complexes of Neisseria meningitidis

Meningococcal disease is a widely distributed complex disease affecting all age categories. It can cause severe meningitis and septicemia, especially in unvaccinated infants and young children. The causative agent, Neisseria meningitidis (Nm), can be phenotypically and genetically differentiated into serogroups and sequence types (STs) and has a highly dynamic population structure. To obtain a deeper understanding of the epidemiology of Nm, we sequenced seven Nm genomes. Large-scale genomic analysis was conducted with these 7 Nm genomes, 27 additional Nm genomes from GenBank, and 4 other Neisseria genomes. We observed extensive homologous recombination in all gene functional categories among different Nm genomes. Homologous recombination is so frequent that it has resulted in numerous chimeric open reading frames, including genes in the capsule biosynthesis cluster and loci targeted by commercial vaccines. Our results reveal that, despite widespread use, evolutionary relationships inferred from the standard seven-gene multilocus sequence typing (MLST) method could not predict virulence gene content or strain phenotype. In fact, up to 28% of the virulence-associated genes could differ between strains of identical STs. Consistent with previous studies, we found that allelic recombination is also associated with alterations in antibiotic susceptibility. Overall, these findings emphasize the extensive genomic plasticity of Nm and the limitations of standard molecular methods to quantify this genotypic and phenotypic diversity

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Fast ionospheric correction using Galileo Az coefficients and the NTCM model

Europe’s Global Navigation Satellite System (GNSS) Galileo broadcasts three parameters for ionospheric correction as part of satellite navigation messages. They are called effective ionization coefficients and are used to drive the NeQuickG model in single frequency Galileo operations. The NeQuickG is a three-dimensional electron density model based on several Epstein layers whose anchor points, such as ionospheric peak densities and heights, are derived using the spatial and temporal interpolation of numerous global maps. This makes the NeQuickG computationally more expensive when compared with the GPS equivalent, the Klobuchar model. We propose here an alternative ionospheric correction approach for single frequency Galileo users. In the proposed approach, the broadcast coefficients are used to drive another ionospheric model called the Neustrelitz Total Electron Content Model (NTCM) instead of the NeQuickG. The proposed NTCM is driven by Galileo broadcast parameters and the investigation shows that it performs better than the NeQuickG when compared with the reference Vertical Total Electron Content (VTEC) data. It is found that the Root Mean Squares (RMS) and Standard Deviations (STD) of residuals are approx. 1.6 and 1.2 TECU (1 TECU = 1016 electrons/m2) less for the NTCM than the NeQuickG. A comparison with the slant TEC reference data shows that the STD, mean and RMS residuals are approx. 9.5, 0.6, 10.0 TECU for the NeQuickG whereas for the NTCM, they are 9.3, 2.5, 10.1 TECU respectively. A comparison with Jason-2 altimeter datasets reveals that the NTCM performs better than the NeQuickG with RMS/STD deviations of approx. 7.5/7.4 and 8.2/7.9 TECU respectively. The investigation shows that the Galileo broadcast messages can be effectively used for driving the NTCM

MONITOR Ionospheric Network: two case studies on scintillation and electron content variability

The ESA MONITOR network is composed of high-frequency-sampling global navigation satellite systems (GNSS) receivers deployed mainly at low and high latitudes to study ionosphere variability and jointly with global GNSS data and ionospheric processing software in support of the GNSS and its satellite-based augmentation systems (SBAS) like the European EGNOS. In a recent phase of the project, the network was merged with the CNES/ASECNA network and new receivers were added to complement the latter in the western African sector. This paper summarizes MONITOR, presenting two case studies on scintillations (using almost 2 years of data measurements). The first case occurred during the major St. Patrick's Day geomagnetic storm in 2015. The second case study was performed in the last phase of the project, which was supported by ESA EGNOS Project Office, when we paid special attention to extreme events that might degrade the system performance of the European EGNOS

New 3-[4-(aryl)piperazin-1-yl]-1(benzo[b]thiophen-3-yl) propane derivatives with dual action at 5-HT1A serotonin receptors and serotonin transporter as a new class of antidepressants

A series of new 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propane derivatives were synthesized in an attempt to find a new class of antidepressant drugs with dual activity at 5-HT1A serotonin receptors and serotonin transporter. Title compounds were evaluated for in vitro activity on 5-HT1A receptor and 5-HT transporter. They show high nanomolar affinity for both activities, and in particular, compounds 1-(5-chlorobenzo[b]thiophen-3-yl)-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-ol (7) and 1-(5-fluorobenzo[b]thiophen-3-yl)-3-[4-(2-methoxyphenyl) piperain-1-yl]propan-1-ol (8) show values (nM) of K-i = 30 and 2.3 for 5-HT1A receptors and K-i = 30 and 12 for serotonin transporters, respectively. In GTP gammaS binding assays, compound 8 revealed antagonist properties to 5-HT1A receptors. Such a pharmacological profile could lead to potent antidepressant agents with new dual mechanism of action. (C) 2001 Editions scientifiques et medicales Elsevier SAS

New 1-aryl-3-(4-arylpiperazin-1-yl)propane derivatives, with dual action at 5-HT1A serotonin receptors and serotonin transporter, as a new class of antidepressant

In a search toward new and efficient antidepressants, 1-aryl-3-(4-arylpiperazin-1-yl)propane derivatives were designed, synthesized, and evaluated for 5-HT reuptake inhibition and 5-HT1A receptor antagonism. This dual pharmacological profile should lead, in principle, to a rapid and pronounced enhancement in serotoninergic neurotransmission and consequently to a more efficacious treatment of depression. The design was based on coupling structural moieties related to inhibition of serotonin reuptake, such as gamma -phenoxypropylamines, to arylpiperazines, typical 5-HT1A ligands. In binding studies, several compounds showed affinity at the 5-HT transporter and 5-HT1A receptors. Antidepressant-like activity was initially assayed in the forced swimming test with those compounds with K-i ( 200 nM in both binding studies. Functional characterization was performed by measuring the intrinsic effect on rectal temperature in mice and also the antagonism to 8-OH-DPAT-induced hypothermia. The most efficacious compounds (12f, 23gE, 28a, and 28b) were further explored for their ability to antagonize 8-OH-DPAT-induced inhibition of forskolin-stimulated cAMP formation in a cell line expressing the 5-HT1A receptor. Furthermore, the antidepressant-like properties of 12f, 28a, and 28b, which exhibited 5-HT1A receptor antagonistic property in the latter study, were also evaluated in the learned helplessness test in rats. Among these three compounds, 28b (1-benzo[b]thiophene-3-yl)-3-[4-(2-methoxyphenyl)-1-ylpropan-1-ol) showed the higher affinity at both the 5-HT transporter and 5-HT1A receptors (K-i = 20 nM in both cases) and was also active in the other pharmacological tests. Such a pharmacological profile could lead to a new class of antidepressants with a dual mechanism of action and a faster onset of action

Atmospheric signal propagation

GNSS satellites emit signals which propagate as electromagnetic waves through space to the receivers which are located on or near the Earth’s surface or on other satellites. Thereby, electromagnetic waves travel through the ionosphere and the neutral atmosphere (troposphere) which causes signals to be delayed, damped and refracted as the refractivity index of the propagation media is not equal to one. In this chapter, the nature and effects of GNSS signal propagation in both the troposphere and the ionosphere, is examined. After a brief review of the fundamentals of electromagnetic waves their propagation in refractive media, the effects of the neutral atmosphere are discussed. In addition empirical correction models as well as state-of- the-art atmosphere delay estimation approaches are presented. Effects related to signal propagtion through the ionosphere are dealt in a dedicated section by describing the error contribution of first up to third order terms in the refractive index and ray path bending. After discussing diffraction and scattering phenomena due to ionospheric irregularities, mitigation techniques for different types of applications are presented