Control of pathogenic effector T-cell activities in situ by PD-L1 expression on respiratory inflammatory dendritic cells during respiratory syncytial virus infection

Respiratory syncytial virus (RSV) infection is a leading cause of severe lower respiratory tract illness in young infants, the elderly and immunocompromised individuals. We demonstrate here that the co-inhibitory molecule programmed cell death 1 (PD-1) is selectively upregulated on T cells within the respiratory tract during both murine and human RSV infection. Importantly, the interaction of PD-1 with its ligand PD-L1 is vital to restrict the pro-inflammatory activities of lung effector T cells in situ, thereby inhibiting the development of excessive pulmonary inflammation and injury during RSV infection. We further identify that PD-L1 expression on lung inflammatory dendritic cells is critical to suppress inflammatory T-cell activities, and an interferon-STAT1-IRF1 axis is responsible for increased PD-L1 expression on lung inflammatory dendritic cells. Our findings suggest a potentially critical role of PD-L1 and PD-1 interactions in the lung for controlling host inflammatory responses and disease progression in clinical RSV infection

Identification of culturable vaginal Lactobacillus species among reproductive age women in Mysore, India

A healthy vaginal environment is predominated by certain Lactobacillus species, which lead to the prevention of infections of the reproductive tract. This study examined the characteristics of cultivable Lactobacillus species in both healthy women and women with bacterial vaginosis (BV). Between November 2011 and September 2013, 139 women attending a women\u27s clinic in Mysore, India, were evaluated for BV in a cross-sectional study. BV was diagnosed using Amsel\u27s criteria: homogeneous vaginal discharge, vaginal pH \u3e4.5, production of amines, and presence of “clue” cells. Those with three or more of the characteristics were considered to have BV. Vaginal swabs were then cultured in Rogosa agar and de Man-Rogosa-Sharpe broth. Gram-positive lactobacilli generating 600–800 bp amplicons by16 sRNA were further characterized by sequencing. Cultivable vaginal samples were obtained from 132 women (94.9 %). According to the Amsel criteria, 83 women (62.1 %) were healthy, and 49 (37.1 %) had BV. Eleven different Lactobacillus species were isolated from 47 women. The common lactobacilli species found in this sample included L. crispatus (39.6 %), L. gasseri (45.8 %), and L. jensenii (14.6 %). Lactobacilli were isolated from 39 healthy women and eight with BV. L. gasseri was cultured from 18.8 % of healthy women and 6.1 % with BV. The presence of L. reuteri was significantly associated with normal vaginal microbiota (P-value = 0.026). These results further our understanding of vaginal lactobacilli colonization and richness in this particular population. Our findings showed that lactobacilli species present in the vaginas of healthy women in India do not differ from those reported from other countries

Peripheral Nα\alpha Scattering: A Tool For Identifying The Two Pion Exchange Component Of The NN Potential

We study elastic N$\alpha$ scattering and produce a quantitative correlation between the range of the effective potential and the energy of the system. This allows the identification of the waves and energies for which the scattering may be said to be peripheral. We then show that the corresponding phase shifts are sensitive to the tail of the NN potential, which is due to the exchange of two pions. However, the present uncertainties in the experimental phase shifts prevent the use of N$\alpha$ scattering to discriminate the existing models for the NN interaction.Comment: 19 pages, 6 PostScript figures, RevTeX, to be appear in Phys. Rev.

Modeling magnetospheric fields in the Jupiter system

The various processes which generate magnetic fields within the Jupiter system are exemplary for a large class of similar processes occurring at other planets in the solar system, but also around extrasolar planets. Jupiter's large internal dynamo magnetic field generates a gigantic magnetosphere, which is strongly rotational driven and possesses large plasma sources located deeply within the magnetosphere. The combination of the latter two effects is the primary reason for Jupiter's main auroral ovals. Jupiter's moon Ganymede is the only known moon with an intrinsic dynamo magnetic field, which generates a mini-magnetosphere located within Jupiter's larger magnetosphere including two auroral ovals. Ganymede's magnetosphere is qualitatively different compared to the one from Jupiter. It possesses no bow shock but develops Alfv\'en wings similar to most of the extrasolar planets which orbit their host stars within 0.1 AU. New numerical models of Jupiter's and Ganymede's magnetospheres presented here provide quantitative insight into the processes that maintain these magnetospheres. Jupiter's magnetospheric field is approximately time-periodic at the locations of Jupiter's moons and induces secondary magnetic fields in electrically conductive layers such as subsurface oceans. In the case of Ganymede, these secondary magnetic fields influence the oscillation of the location of its auroral ovals. Based on dedicated Hubble Space Telescope observations, an analysis of the amplitudes of the auroral oscillations provides evidence that Ganymede harbors a subsurface ocean. Callisto in contrast does not possess a mini-magnetosphere, but still shows a perturbed magnetic field environment. Callisto's ionosphere and atmospheric UV emission is different compared to the other Galilean satellites as it is primarily been generated by solar photons compared to magnetospheric electrons.Comment: Chapter for Book: Planetary Magnetis

Pathway to the Square Kilometre Array - The German White Paper -

The Square Kilometre Array (SKA) is the most ambitious radio telescope ever planned. With a collecting area of about a square kilometre, the SKA will be far superior in sensitivity and observing speed to all current radio facilities. The scientific capability promised by the SKA and its technological challenges provide an ideal base for interdisciplinary research, technology transfer, and collaboration between universities, research centres and industry. The SKA in the radio regime and the European Extreme Large Telescope (E-ELT) in the optical band are on the roadmap of the European Strategy Forum for Research Infrastructures (ESFRI) and have been recognised as the essential facilities for European research in astronomy. This "White Paper" outlines the German science and R&D interests in the SKA project and will provide the basis for future funding applications to secure German involvement in the Square Kilometre Array.Comment: Editors: H. R. Kl\"ockner, M. Kramer, H. Falcke, D.J. Schwarz, A. Eckart, G. Kauffmann, A. Zensus; 150 pages (low resolution- and colour-scale images), published in July 2012, language English (including a foreword and an executive summary in German), the original file is available via the MPIfR homepag

Indirect calibration between clinical observers - application to the New York Heart Association functional classification system

<p>Abstract</p> <p>Background</p> <p>Previous studies showed an inter-observer agreement for the NYHA classification of approximately 55%. The aim of this study was to calibrate the New York Heart Association (NYHA) classification system between observers, increasing its reliability.</p> <p>Results</p> <p>Among 1136 community-dwellers in Porto, Portugal, aged ≥ 45 years, 265 reporting breathlessness answered a 4-item questionnaire to characterize symptom severity. The questionnaire was administered by 7 physicians who also classified the subject's functional capacity according to NYHA. Each subject was assessed by one physician. We calibrated NYHA classifications by the concurrent method, using 1-parameter logistic graded response model. Discrepancies between observers were assessed by differences in ability thresholds between NYHA classes I-II and II-III. The ability estimated by the model was used to predict the NYHA classification for each observer.</p> <p>Estimates of the first and second thresholds for each observer ranged from -1.92 to 0.46 and from 1.42 to 2.30, respectively. The agreement between estimated ability and the observers' NYHA classification was 88% (kappa = 0.61).</p> <p>Conclusions</p> <p>The study objectively indicates the main reason why several studies have reported low inter-observer is the existence of discrepant thresholds between observers in the definition of NYHA classes. The concurrent method can be used to minimize the reliability problem of NYHA classification.</p

Statistical Study of the Energetic Proton Environment at Titan’s Orbit From the Cassini Spacecraft

A statistical study of the energetic proton environment at Titan’s orbit as captured by the MIMI/LEMMS and MIMI/CHEMS instruments is performed. The data analyzed cover all the dedicated flybys of Titan by Cassini as well as the orbit crossings that happen far from the moon. The energetic environment is found to be highly variable on timescales comparable to that of the duration of a flyby. Analysis of H+ ion fluxes reveals a weak asymmetry in Saturn local time with the highest fluxes occurring in the premidnight sector of the magnetosphere. A correlation between the energetic ion fluxes and the location of Cassini in the magnetosphere with respect to the center of the current sheet can be observed. Finally, an empirical model of proton spectra for energies above 20 keV is derived based on fits to Kappa distribution functions. This model can be used to better understand the interaction of Titan with the magnetosphere and the energy deposition by energetic particles below the main ionospheric peak.Key PointsEnergetic particle environment at Titan’s orbit is highly variableIon data present SLT asymmetry with higher fluxes in the premidnight sectorDerivation of empirical model of ion spectra based on Kappa distribution function is presentedPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145346/1/jgra54321_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145346/2/jgra54321.pd

Callisto's Atmosphere and Its Space Environment: Prospects for the Particle Environment Package on Board JUICE

The JUpiter ICy moons Explorer (JUICE) of the European Space Agency will investigate Jupiter and its icy moons Europa, Ganymede, and Callisto, with the aim to better understand the origin and evolution of our Solar System and the emergence of habitable worlds around gas giants. The Particle Environment Package (PEP) on board JUICE is designed to measure neutrals and ions and electrons at thermal, suprathermal, and radiation belt energies (eV to MeV). In the vicinity of Callisto, PEP will characterize the plasma environment, the outer parts of Callisto's atmosphere and ionosphere and their interaction with Jupiter's dynamic magnetosphere. Roughly 20 Callisto flybys with closest approaches between 200 and 5,000 km altitude are planned over the course of the JUICE mission. In this article, we review the state of the art regarding Callisto's ambient environment and magnetospheric interaction with recent modeling efforts for Callisto's atmosphere and ionosphere. Based on this review, we identify science opportunities for the PEP observations to optimize scientific insight gained from the foreseen JUICE flybys. These considerations will inform both science operation planning of PEP and JUICE and they will guide future model development for Callisto's atmosphere, ionosphere, and their interaction with the plasma environment

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis

Abstract (provisional) Background Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. Methods This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. Discussion This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Trial registration: Current Controlled Trials ISRCTN7651747

Cusp observation at Saturn's high-latitude magnetosphere by the Cassini spacecraft

We report on the first analysis of magnetospheric cusp observations at Saturn by multiple in situ instruments onboard the Cassini spacecraft. Using this we infer the process of reconnection was occurring at Saturn's magnetopause. This agrees with remote observations that showed the associated auroral signatures of reconnection. Cassini crossed the northern cusp around noon local time along a poleward trajectory. The spacecraft observed ion energy-latitude dispersions—a characteristic signature of the terrestrial cusp. This ion dispersion is “stepped,” which shows that the reconnection is pulsed. The ion energy-pitch angle dispersions suggest that the field-aligned distance from the cusp to the reconnection site varies between ∼27 and 51 RS. An intensification of lower frequencies of the Saturn kilometric radiation emissions suggests the prior arrival of a solar wind shock front, compressing the magnetosphere and providing more favorable conditions for magnetopause reconnection