The radio counter-jet of the QSO 3C~48

We present multi--frequency radio observational results of the quasar 3C~48. The observations were carried out with the Very Large Array (VLA) at five frequencies of 0.33, 1.5, 4.8, 8.4, and 22.5 GHz, and with the Multi--Element Radio Linked Interferometer Network (MERLIN) at the two frequencies of 1.6 and 5 GHz. The source shows a one--sided jet to the north within 1\arcsec, which then extends to the northeast and becomes diffuse. Two bright components (N2 and N3), containing most of the flux density are present in the northern jet. The spectral index of the two components is $\alpha_{N2}\sim-0.99\pm0.12$ and $\alpha_{N3}\sim-0.84\pm0.23$ ($S\propto\nu^{\alpha}$). Our images show the presence of an extended structure surrounding component N2, suggestive of strong interaction between the jet and the interstellar medium (ISM) of the host galaxy. A steep--spectrum component, labelled as S, located 0.25 ardsec southwest to the flat--spectrum component which could be the core of 3C 48, is detected at a significance of $>15\sigma$. Both the location and the steepness of the spectrum of component S suggest the presence of a counter--jet in 3C 48.Comment: 7 pages, 6 figures, accepted by A&

In vitro characterization and in vivo comparison of the pulmonary outcomes of Poractant alfa and Calsurf in ventilated preterm rabbits

Poractant alfa and Calsurf are two natural surfactants widely used in China for the treatment of neonatal respiratory distress syndrome, which are extracted from porcine and calf lungs, respectively. The purpose of this experimental study was to compare their in vitro characteristics and in vivo effects in the improvement of pulmonary function and protection of lung injury. The biophysical properties, ultrastructure, and lipid composition of both surfactant preparations were respectively analysed in vitro by means of Langmuir-Blodgett trough (LBT), atomic force microscopy (AFM), and liquid-chromatography mass-spectrometry (LC-MS). Then, as core pharmacological activity, both head-to-head (100 and 200 mg/kg for both surfactants) and licensed dose comparisons (70 mg/kg Calsurf vs. 200 mg/kg Poractant alfa) between the two surfactants were conducted as prophylaxis in preterm rabbits with primary surfactant deficiency, assessing survival time and rate and dynamic compliance of the respiratory system (Cdyn). Intrapulmonary surfactant pools, morphometric volume density as alveolar expansion (Vv), and lung injury scores were determined post mortem. AFM and LC-MS analysis revealed qualitative differences in the ultrastructure as well as in the lipid composition of both preparations. Calsurf showed a longer plateau region of the LBT isotherm and lower film compressibility. In vivo, both surfactant preparations improved Cdyn at any dose, although maximum benefits in terms of Vv and intrapulmonary surfactant pools were seen with the 200 mg/kg dose in both surfactants. The group of animals treated with 200 mg/kg of Poractant alfa showed a prolonged survival time and rate compared to untreated but ventilated controls, and significantly ameliorated lung injury compared to Calsurf at any dose, including 200 mg/kg. The overall outcomes suggest the pulmonary effects to be dose dependent for both preparations. The group of animals treated with 200 mg/kg of Poractant alfa showed a significant reduction of mortality. Compared to Calsurf, Poractant alfa exerted better effects if licensed doses were compared, which requires further investigation

The follow-up EVN observations of twelve GPS radio sources at 5 GHz

We defined a sub-sample of twelve GPS sources which have not been observed with the VLBI before, from the Parkes half-Jansky sample, and carried out VLBI observations at 1.6 GHz and 5 GHz with the European VLBI Network (EVN) in 2006 and 2008, respectively, to classify the source structure and to find compact symmetric objects (CSOs). Additionally, we carried out the 4.85 GHz flux density observations for these sources with the Urumqi 25-m telescope between the years 2007 and 2009 to study whether there is any variability in the total flux density of the GPS sources. The results of the 5 GHz VLBI observations and total flux densities of these sources are presented in this paper. From the VLBI morphologies, the spectral indices of components and the total flux variability of the twelve targets, we firmly classify three sources J0210+0419, J1135$-$0021, and J2058+0540 as CSOs, and classify J1057+0012, J1203+0414, and J1600$-$0037 as core-jet sources. The others J0323+0534, J0433$-$0229, J0913+1454, J1109+1043, and J1352+0232 are labelled CSO candidates, and J1352+1107 is a complex feature. Apart from core-jet sources, the total flux densities of the CSOs and candidates are quite stable at 5 GHz both during a long-term of $\sim$20 years relative to the PKS90 data and in a period between 2007 and 2009. The total flux densities are resolved-out by more than 20\% in the 5 GHz VLBI images for 6 sources, probably because of diffuse emission. In addition, we estimated the jet viewing angles $\Theta$ for the confirmed CSOs by using the double-lobe flux ratio of the sources, the result being indicative of relatively large $\Theta$ for the CSOs.Comment: 9 pages, 12 figures, accepted for publication in A&A

Single spin asymmetries in DIS

We consider possible mechanisms for single spin asymmetries in inclusive Deep Inelastic Scattering (DIS) processes with unpolarized leptons and transversely polarized nucleons. Tests for the effects of non-zero \bfk_\perp, for the properties of spin dependent quark fragmentations and for quark helicity conservation are suggested.Comment: 5 pages, LaTeX, no figures. Revised version, to be published in Phys. Rev. D. Some equations and statements added to clarify text and notation

Modelling the bronchial barrier in pulmonary drug delivery: A human bronchial epithelial cell line supplemented with human tracheal mucus.

The airway epithelium together with the mucus layer coating it forms a protective system that efficiently filters and removes potentially harmful particles contained in inhaled air. The same mechanism, however, serves to entrap particulate drug carriers, precluding their interaction with their target. The mucus barrier is often neglected in in vitro testing setups employed for the assessment of pulmonary drug delivery strategies. Therefore, our aim was to more accurately model the bronchial barrier, by developing an in vitro system comprising a tight epithelial cell layer which may be optionally supplemented with a layer of human tracheal mucus. To form the epithelium in vitro, we used the cystic fibrosis cell line CFBE41o-, which can be grown as monolayers on Transwell® supports, expressing tight junctions as well as relevant transport proteins. In contrast to the cell line Calu-3, however, CFBE41o- does not produce mucus. Therefore, native human mucus, obtained from tracheal tubes of patients undergoing elective surgery, was used as a supplement. The compatibility of CFBE41o- cells with the human mucus was addressed with the MTT assay, and confirmed by fluorescein diacetate/propidium iodide live/dead staining. Moreover, the CFBE41o- cells retained their epithelial barrier properties after being supplemented with mucus, as evidenced by the high trans-epithelial electrical resistance values (∼1000Ωcm(2)) together with a continued low level of paracellular transport of sodium fluorescein. Fluorescently-labeled chitosan-coated PLGA nanoparticles (NP, ∼168nm) were used as a model drug delivery system to evaluate the suitability of this in vitro model for studying mucus permeation and cell uptake. Comparing CFBE41o- cell monolayers with and without mucus, resp., showed that the NP uptake was dramatically reduced in the presence of mucus. This model may therefore be used as a tool to study potential mucus interactions of aerosolized drugs, and more specifically NP-based drug delivery systems designed to exert their effect in the bronchial region

Phenomenology of single spin asymmetries in p(transv. polarized)-p -> pion + X

A phenomenological description of single transverse spin effects in hadron-hadron inclusive processes is proposed, assuming a generalized factorization scheme and pQCD hard interactions. The transverse momentum, k_T, of the quarks inside the hadrons and of the hadrons relatively to the fragmenting quark, is taken into account in distribution and fragmentation functions, and leads to possible non zero single spin asymmetries. The role of k_T and spin dependent quark fragmentations -- the so-called Collins effect -- is investigated in details in p(transv. polarized)-p -> pion + X processes: it is shown how the experimental data could be described, obtaining an explicit expression for the spin asymmetry of a polarized fragmenting quark, on which some comments are made. Predictions for other processes, possible further applications and experimental tests are discussed.Comment: 20+1 pages, LaTeX, 6 eps figures, uses epsfig.sty. Version v2: Some sentences rephrased and comments added throughout the paper; one reference added; no changes in results and figures. Final version to be published in Phys. Rev.

Surfactant lung delivery with LISA and InSurE in adult rabbits with respiratory distress

Background: In preterm infants, InSurE (Intubation\u2013Surfactant\u2013Extubation) and LISA (less invasive surfactant administration) techniques allow for exogenous surfactant administration while reducing lung injury associated with mechanical ventilation. We compared the acute pulmonary response and lung deposition of surfactant by LISA and InSurE in surfactant-depleted adult rabbits. Methods: Twenty-six spontaneously breathing surfactant-depleted adult rabbits (6\u20137 weeks old) with moderate RDS and managed with nasal continuous positive airway pressure were randomized to 3 groups: (1) 200 mg/kg of surfactant by InSurE; (2) 200 mg/kg of surfactant by LISA; (3) no surfactant treatment (Control). Gas exchange and lung mechanics were monitored for 180 min. After that, surfactant lung deposition and distribution were evaluated monitoring disaturated-phosphatidylcholine (DSPC) and surfactant protein C (SP-C), respectively. Results: No signs of recovery were found in the untreated animals. After InSurE, oxygenation improved more rapidly compared to LISA. However, at 180\u2019 LISA and InSurE showed comparable outcomes in terms of gas exchange, ventilation parameters, and lung mechanics. Neither DSPC in the alveolar pool nor SP-C signal distributions in a frontal lung section were significantly different between InSurE and LISA groups. Conclusions: In an acute setting, LISA demonstrated efficacy and surfactant lung delivery similar to that of InSurE in surfactant-depleted adult rabbits. Impact: Although LISA technique is gaining popularity, there are still several questions to address. This is the first study comparing LISA and InSurE in terms of gas exchange, ventilation parameters, and lung mechanics as well as surfactant deposition and distribution.In our animal study, three hours post-treatment, LISA method seems to be as effective as InSurE and showed similar surfactant lung delivery.Our findings provide some clarifications on a fair comparison between LISA and InSurE techniques, particularly in terms of surfactant delivery. They should reassure some of the concerns raised by the clinical community on LISA adoption in neonatal units

Surfactant lung delivery with LISA and InSurE in adult rabbits with respiratory distress

Background In preterm infants, InSurE (Intubation–Surfactant–Extubation) and LISA (less invasive surfactant administration) techniques allow for exogenous surfactant administration while reducing lung injury associated with mechanical ventilation. We compared the acute pulmonary response and lung deposition of surfactant by LISA and InSurE in surfactant-depleted adult rabbits. Methods Twenty-six spontaneously breathing surfactant-depleted adult rabbits (6–7 weeks old) with moderate RDS and managed with nasal continuous positive airway pressure were randomized to 3 groups: (1) 200 mg/kg of surfactant by InSurE; (2) 200 mg/kg of surfactant by LISA; (3) no surfactant treatment (Control). Gas exchange and lung mechanics were monitored for 180 min. After that, surfactant lung deposition and distribution were evaluated monitoring disaturated-phosphatidylcholine (DSPC) and surfactant protein C (SP-C), respectively. Results No signs of recovery were found in the untreated animals. After InSurE, oxygenation improved more rapidly compared to LISA. However, at 180’ LISA and InSurE showed comparable outcomes in terms of gas exchange, ventilation parameters, and lung mechanics. Neither DSPC in the alveolar pool nor SP-C signal distributions in a frontal lung section were significantly different between InSurE and LISA groups. Conclusions In an acute setting, LISA demonstrated efficacy and surfactant lung delivery similar to that of InSurE in surfactant-depleted adult rabbits. Impact Although LISA technique is gaining popularity, there are still several questions to address. This is the first study comparing LISA and InSurE in terms of gas exchange, ventilation parameters, and lung mechanics as well as surfactant deposition and distribution. In our animal study, three hours post-treatment, LISA method seems to be as effective as InSurE and showed similar surfactant lung delivery. Our findings provide some clarifications on a fair comparison between LISA and InSurE techniques, particularly in terms of surfactant delivery. They should reassure some of the concerns raised by the clinical community on LISA adoption in neonatal units

Squalenyl Hydrogen Sulfate Nanoparticles for Simultaneous Delivery of Tobramycin and an Alkylquinolone Quorum Sensing Inhibitor Enable the Eradication of P. aeruginosa Biofilm Infections

Elimination of pulmonary Pseudomonas aeruginosa (PA) infections is challenging to accomplish with antibiotic therapies, mainly due to resistance mechanisms. Quorum sensing inhibitors (QSIs) interfering with biofilm formation can thus complement antibiotics. For simultaneous and improved delivery of both active agents to the infection sites, self-assembling nanoparticles of a newly synthesized squalenyl hydrogen sulfate (SqNPs) were prepared. These nanocarriers allowed for remarkably high loading capacities of hydrophilic antibiotic tobramycin (Tob) and a novel lipophilic QSI at 30 % and circa 10 %, respectively. The drug-loaded SqNPs showed improved biofilm penetration and enhanced efficacy in relevant biological barriers (mucin/human tracheal mucus, biofilm), leading to complete eradication of PA biofilms at circa 16-fold lower Tob concentration than Tob alone. This study offers a viable therapy optimization and invigorates the research and development of QSIs for clinical use

Schmallenberg virus pathogenesis, tropism and interaction with the innate immune system of the host

Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV