Clinical biological and genetic heterogeneity of the inborn errors of pulmonary surfactant metabolism

Pulmonary surfactant is a multimolecular complex located at the air-water interface within the alveolus to which a range of physical (surface-active properties) and immune functions has been assigned. This complex consists of a surface-active lipid layer (consisting mainly of phospholipids), and of an aqueous subphase. From discrete surfactant sub-fractions one can isolate strongly hydrophobic surf acta nt proteins B (SP-B) and C (SP-C) as well as collectins SP-A and SP-D, which were shown to have specific structural, metabolic, or immune properties. Inborn or acquired abnormalities of the surfactant, qualitative or quantitative in nature, account for a number of human diseases. Beside hyaline membrane disease of the preterm neonate, a cluster of hereditary or acquired lung diseases has been characterized by periodic acid-Schiff-positive material filling the alveoli. From this heterogeneous nosologic group, at least two discrete entities presently emerge. The first is the SP-B deficiency, in which an essentially proteinaceous material is stored within the alveoli, and which represents an autosomal recessive Mendelian entity linked to the SFTPB gene (MIM 1786640). The disease usually generally entails neonatal respiratory distress with rapid fatal outcome, although partial or transient deficiencies have also been observed. The second is alveolar proteinosis, characterized by the storage of a mixed protein and lipid material, which constitutes a relatively heterogeneous clinical and biological syndrome, especially with regard to age at onset (from the neonate through to adulthood) as well as the severity of associated signs. Murine models, with a targeted mutation of the gene encoding granulocyte macrophage colony-stimulating factor (GM-CSF) (Csfgm) or the beta subunit of its receptor (II3rb1) support the hypothesis of an abnormality of surfactant turnover in which the alveolar macrophage is a key player. Apart from SP-B deficiency, in which a near-consensus diagnostic chart can be designed, the ascertainment of other abnormalities of surfactant metabolism is not straightforward. The disentanglement of this disease cluster is however essential to propose specific therapeutic procedures: repeated broncho-alveolar ravages, GM-CSF replacement, bone marrow grafting or lung transplantation

Extreme Emission Line Galaxies in CANDELS: Broad-Band Selected, Star-Bursting Dwarf Galaxies at Z greater than 1

We identify an abundant population of extreme emission line galaxies (EELGs) at redshift z approx. 1.7 in the Cosmic Assembly Near-IR Deep Extragalactic Legacy Survey (CANDELS) imaging from Hubble Space Telescope/Wide Field Camera 3 (HST/WFC3). 69 EELG candidates are selected by the large contribution of exceptionally bright emission lines to their near-infrared broad-band magnitudes. Supported by spectroscopic confirmation of strong [OIII] emission lines . with rest-frame equivalent widths approx. 1000A in the four candidates that have HST/WFC3 grism observations, we conclude that these objects are galaxies with approx.10(exp 8) Solar Mass in stellar mass, undergoing an enormous starburst phase with M*/M* of only approx. 15 Myr. These bursts may cause outflows that are strong enough to produce cored dark matter profiles in low-mass galaxies. The individual star formation rates and the co-moving number density (3.7x10(exp -4) Mpc(sup -3) can produce in approx.4 Gyr much of the stellar mass density that is presently contained in 10(exp 8) - 10(exp 9) Solar Mass dwarf galaxies. Therefore, our observations provide a strong indication that many or even most of the stars in present-day dwarf galaxies formed in strong, short-lived bursts, mostly at z > 1

Perceived academic performance as an indicator of risk of attempted suicide in young adolescents

This study investigated perceived academic performance and self-reported suicidal behavior in adolescents (n=2,596), mean age 13 years, from 27 South Australian high schools. Groups perceiving their academic performance as failing, below average, average and above average were significantly different on measures of self-esteem, locus of control, depressive symptoms, suicidal thoughts, plans, threats, deliberate self-injury, and suicide attempts. Multivariate logistic regression analyses revealed that failing academic performance (compared to above average) is associated with a fivefold increased likelihood of a suicide attempt, controlling for self-esteem, locus of control and depressive symptoms. Teachers should note that a student presenting with low selfesteem, depressed mood and perceptions of failure may be at increased risk for suicidal thoughts and behaviors, and need referral for clinical assessment

Characterisation of the muon beams for the Muon Ionisation Cooling Experiment

A novel single-particle technique to measure emittance has been developed and used to characterise seventeen different muon beams for the Muon Ionisation Cooling Experiment (MICE). The muon beams, whose mean momenta vary from 171 to 281 MeV/c, have emittances of approximately 1.2–2.3 π mm-rad horizontally and 0.6–1.0 π mm-rad vertically, a horizontal dispersion of 90–190 mm and momentum spreads of about 25 MeV/c. There is reasonable agreement between the measured parameters of the beams and the results of simulations. The beams are found to meet the requirements of MICE

Multiplicity distribution and spectra of negatively charged hadrons in Au+Au collisions at sqrt(s_nn) = 130 GeV

The minimum bias multiplicity distribution and the transverse momentum and pseudorapidity distributions for central collisions have been measured for negative hadrons (h-) in Au+Au interactions at sqrt(s_nn) = 130 GeV. The multiplicity density at midrapidity for the 5% most central interactions is dNh-/deta|_{eta = 0} = 280 +- 1(stat)+- 20(syst), an increase per participant of 38% relative to ppbar collisions at the same energy. The mean transverse momentum is 0.508 +- 0.012 GeV/c and is larger than in central Pb+Pb collisions at lower energies. The scaling of the h- yield per participant is a strong function of pt. The pseudorapidity distribution is almost constant within |eta|<1.Comment: 6 pages, 3 figure

MICE: The muon ionization cooling experiment. Step I: First measurement of emittance with particle physics detectors

Copyright @ 2011 APSThe Muon Ionization Cooling Experiment (MICE) is a strategic R&D project intended to demonstrate the only practical solution to providing high brilliance beams necessary for a neutrino factory or muon collider. MICE is under development at the Rutherford Appleton Laboratory (RAL) in the United Kingdom. It comprises a dedicated beamline to generate a range of input muon emittances and momenta, with time-of-flight and Cherenkov detectors to ensure a pure muon beam. The emittance of the incoming beam will be measured in the upstream magnetic spectrometer with a scintillating fiber tracker. A cooling cell will then follow, alternating energy loss in Liquid Hydrogen (LH2) absorbers to RF cavity acceleration. A second spectrometer, identical to the first, and a second muon identification system will measure the outgoing emittance. In the 2010 run at RAL the muon beamline and most detectors were fully commissioned and a first measurement of the emittance of the muon beam with particle physics (time-of-flight) detectors was performed. The analysis of these data was recently completed and is discussed in this paper. Future steps for MICE, where beam emittance and emittance reduction (cooling) are to be measured with greater accuracy, are also presented.This work was supported by NSF grant PHY-0842798

Performance of wide-area power system stabilizers during major system upsets: investigation and proposal of solutions

© 2021 Springer Nature Switzerland AG. This is a post-peer-review, pre-copyedit version of Benasla, M., Denaï, M., Liang, J. et al. Performance of wide-area power system stabilizers during major system upsets: investigation and proposal of solutions. Electr Eng (2021). The final authenticated version is available online https://doi.org/10.1007/s00202-020-01168-3Wide-area damping controllers (WADCs) are effective means of improving the damping of inter-area oscillations and thereby ensuring a secure operation of modern highly stressed interconnected power systems; however, their implementation costs are high. Therefore, the controller must be well configured and designed to ensure its cost-effectiveness. Several techniques have been proposed in the literature to design effective controllers and good results have been achieved. However, some important practical aspects that could potentially impact the performance of the designed controller have not been addressed or studied in sufficient detail in these previous works. One such aspect is assessing the performance of the designed controllers under major system upsets resulting in large deviations in the frequency and fluctuations in the power. These may lead to controller saturation which could negatively impact its damping performance or even cause instability. In this paper, the impact of such large upsets is investigated on several test systems via extensive small- and large-signal analyses and it is shown that, during severe transients, controller saturation may occur and persist over a long period of time, posing a potential threat to the power system stability. This paper presents a very effective solution to alleviate this problem and help design more robust WADCs. The simulation results show that the proposed solution works well and leads to improved power system stabilisers performance during transient upsets.Peer reviewedFinal Accepted Versio

The Role of Alveolar Epithelial Cells in Initiating and Shaping Pulmonary Immune Responses: Communication between Innate and Adaptive Immune Systems

Macrophages and dendritic cells have been recognized as key players in the defense against mycobacterial infection. However, more recently, other cells in the lungs such as alveolar epithelial cells (AEC) have been found to play important roles in the defense and pathogenesis of infection. In the present study we first compared AEC with pulmonary macrophages (PuM) isolated from mice in their ability to internalize and control Bacillus Calmette-Guérin (BCG) growth and their capacity as APCs. AEC were able to internalize and control bacterial growth as well as present antigen to primed T cells. Secondly, we compared both cell types in their capacity to secrete cytokines and chemokines upon stimulation with various molecules including mycobacterial products. Activated PuM and AEC displayed different patterns of secretion. Finally, we analyzed the profile of response of AEC to diverse stimuli. AEC responded to both microbial and internal stimuli exemplified by TLR ligands and IFNs, respectively. The response included synthesis by AEC of several factors, known to have various effects in other cells. Interestingly, TNF could stimulate the production of CCL2/MCP-1. Since MCP-1 plays a role in the recruitment of monocytes and macrophages to sites of infection and macrophages are the main producers of TNF, we speculate that both cell types can stimulate each other. Also, another cell-cell interaction was suggested when IFNs (produced mainly by lymphocytes) were able to induce expression of chemokines (IP-10 and RANTES) by AEC involved in the recruitment of circulating lymphocytes to areas of injury, inflammation, or viral infection. In the current paper we confirm previous data on the capacity of AEC regarding internalization of mycobacteria and their role as APC, and extend the knowledge of AEC as a multifunctional cell type by assessing the secretion of a broad array of factors in response to several different types of stimuli

Demonstration of cooling by the Muon Ionization Cooling Experiment

The use of accelerated beams of electrons, protons or ions has furthered the development of nearly every scientific discipline. However, high-energy muon beams of equivalent quality have not yet been delivered. Muon beams can be created through the decay of pions produced by the interaction of a proton beam with a target. Such ‘tertiary’ beams have much lower brightness than those created by accelerating electrons, protons or ions. High-brightness muon beams comparable to those produced by state-of-the-art electron, proton and ion accelerators could facilitate the study of lepton–antilepton collisions at extremely high energies and provide well characterized neutrino beams1,2,3,4,5,6. Such muon beams could be realized using ionization cooling, which has been proposed to increase muon-beam brightness7,8. Here we report the realization of ionization cooling, which was confirmed by the observation of an increased number of low-amplitude muons after passage of the muon beam through an absorber, as well as an increase in the corresponding phase-space density. The simulated performance of the ionization cooling system is consistent with the measured data, validating designs of the ionization cooling channel in which the cooling process is repeated to produce a substantial cooling effect9,10,11. The results presented here are an important step towards achieving the muon-beam quality required to search for phenomena at energy scales beyond the reach of the Large Hadron Collider at a facility of equivalent or reduced footprint6