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A major barrier to the impact of genomic diagnosis in patients with congenital malformations is the lack of understanding regarding how sequence variants contribute to disease pathogenesis and whether this information could be used to generate patient-specific therapies. Congenital diaphragmatic hernia (CDH) is among the most common and severe of all structural malformations; however, its underlying mechanisms are unclear. We identified loss-of-function sequence variants in the epigenomic regulator gene SIN3A in two patients with complex CDH. Tissue-specific deletion of Sin3a in mice resulted in defects in diaphragm development, lung hypoplasia, and pulmonary hypertension, the cardinal features of CDH and major causes of CDH-associated mortality. Loss of SIN3A in the lung mesenchyme resulted in reduced cellular differentiation, impaired cell proliferation, and increased DNA damage. Treatment of embryonic Sin3a mutant mice with anacardic acid, an inhibitor of histone acetyltransferase, reduced DNA damage, increased cell proliferation and differentiation, improved lung and pulmonary vascular development, and reduced pulmonary hypertension. These findings demonstrate that restoring the balance of histone acetylation can improve lung development in the Sin3a mouse model of CDH.

Abstract While Early Live Adversity (ELA) is a known risk factor for mental and physical diseases, the investigation into the mechanisms behind this connection is ongoing. In the present study, we investigated whether ELA blunts the relaxation response in healthy adults. Using a within-subjects design, we employed a paced breathing exercise (four seconds inhale, six seconds exhale) and a 360° nature video as relaxation interventions while measuring physiological relaxation using heart rate variability and subjective relaxation using the Relaxation State Questionnaire. A total of 103 participants (63.11% female; agemean = 22.73 ± 3.43 years) completed the Parental Bonding Instrument and the Childhood Trauma Questionnaire to assess ELA retrospectively. For subjective relaxation, a blunted relaxation reaction was associated with lower scores of paternal care and higher scores of paternal overprotection, physical abuse, physical neglect, and emotional abuse. For heart rate variability emotional abuse in interaction with nicotine consumption was related to a blunted relaxation response. This indicates that experiencing ELA negatively affects the relaxation capability in a healthy sample and emphasizes the importance of assessing relaxation at a physiological and subjective level.

The spatiotemporal distribution of aerosol particles in the atmosphere has a great impact on radiative transfer, clouds, and air quality. Modern remote sensing methods, as well as airborne in situ measurements by unpiloted aerial vehicles (UAV) or balloons, are suitable tools to improve our understanding of the role of aerosol particles in the atmosphere. To validate the measurement capabilities of three relatively new measurement systems and to bridge the gaps that are often encountered between remote sensing and in situ observation, as well as to investigate aerosol particles in and above the boundary layer, we conducted two measurement campaigns and collected a comprehensive dataset employing a scanning aerosol lidar, a balloon-borne radiosonde with the Compact Optical Backscatter Aerosol Detector (COBALD), an optical particle counter (OPC) on a UAV, and a comprehensive set of ground-based instruments. The extinction coefficients calculated from near-ground-level aerosol size distributions measured in situ are well correlated with those retrieved from lidar measurements, with a slope of 1.037 ± 0.015 and a Pearson correlation coefficient of 0.878, respectively. Vertical profiles measured by an OPC-N3 on a UAV show similar vertical particle distributions and boundary layer heights to lidar measurements. However, the sensor, OPC-N3, shows a larger variability in the aerosol backscatter coefficient measurements, with a Pearson correlation coefficient of only 0.241. In contrast, the COBALD data from a balloon flight are well correlated with lidar-derived backscatter data from the near-ground level up to the stratosphere, with a slope of 1.063 ± 0.016 and a Pearson correlation coefficient of 0.925, respectively. This consistency between lidar and COBALD data reflects the good data quality of both methods and proves that lidar can provide reliable and spatial distributions of aerosol particles with high spatial and temporal resolutions. This study shows that the scanning lidar has the capability to retrieve backscatter coefficients near the ground level (from 25 to 50 m above ground level) when it conducts horizontal measurement, which is not possible for vertically pointing lidar. These near-ground-level retrievals compare well with ground-level in situ measurements. In addition, in situ measurements on the balloon and UAV validated the scanning lidar retrievals within and above the boundary layer. The scanning aerosol lidar allows us to measure aerosol particle distributions and profiles from the ground level to the stratosphere with an accuracy equal to or better than in situ measurements and with a similar spatial resolution.

Abstract Hospital-acquired pneumonia (HAP) is associated with high mortality and costs, and frequently caused by multidrug-resistant (MDR) bacteria. Although prior antimicrobial therapy is a major risk factor for HAP, the underlying mechanism remains incompletely understood. Here, we demonstrate that antibiotic therapy in hospitalized patients is associated with decreased diversity of the gut microbiome and depletion of short-chain fatty acid (SCFA) producers. Infection experiments with mice transplanted with patient fecal material reveal that these antibiotic-induced microbiota perturbations impair pulmonary defense against MDR Klebsiella pneumoniae. This is dependent on inflammatory monocytes (IMs), whose fatty acid receptor (FFAR)2/3-controlled and phagolysosome-dependent antibacterial activity is compromized in mice transplanted with antibiotic-associated patient microbiota. Collectively, we characterize how clinically relevant antibiotics affect antimicrobial defense in the context of human microbiota, and reveal a critical impairment of IM´s antimicrobial activity. Our study provides additional arguments for the rational use of antibiotics and offers mechanistic insights for the development of novel prophylactic strategies to protect high-risk patients from HAP.

Abstract The variability and trend of ozone (O3) in the Upper troposphere and Lower Stratosphere (UTLS) over the Asian region needs to be accurately quantified. Ozone in the UTLS radiatively heats this region and cools the upper parts of the stratosphere. This results in an impact on relative humidity, static stability in the UTLS region and tropical tropopause temperature. A major challenge for understanding ozone chemistry in the UTLS is sparse observations and thus the representation of precursor gases in model emission inventories. Here, we evaluate ozonesonde measurements during August 2016 at Nainital, in the Himalayas, against ozone from multiple reanalyses and the ECHAM6-HAMMOZ model. We find that compared to measurements both reanalyses and ECHAM6-HAMMOZ control simulation overestimate ozone mixing ratios in the troposphere (20 ppb) and in the UTLS (55 ppb). We performed sensitivity simulations using the ECHAM6-HAMMOZ model for a 50% reduction in the emission of (1) NOx and (2) VOCs. The model simulations with NOX reduction agree better with the ozonesonde observations in the lower troposphere and in the UTLS. Thus, neither reanalyses nor ECHAM6-HAMMOZ results can reproduce observed O3 over the South Asian region. For a better representation of O3 in the ECHAM6-HAMMOZ model, NOX emission should be reduced by 50% in the emission inventory. A larger number of observations of ozone and precursor gases over the South Asian region would improve the assessment of ozone chemistry in models.

To address the issue of estimating soil moisture at a hyper-resolution scale, a methodology referred to as Precision Irrigation Soil Moisture Mapper (PrISMM), that includes three key components, is developed: high-resolution remotely sensed optical and thermal data, surface energy balance modeling, and site-specific soil analysis. An Unmanned Aerial Vehicle/System (UAV or UAS) collects high-resolution multispectral imagery in the Dallas–Fort Worth metropolitan study area. Orthomosaics are converted to thermal inertia estimates in a spatially distributed format using the remotely sensed data combined with a set of surface energy balance modeling equations. Using thermal and physical properties of soil gained from site-specific soil analysis, thermal inertia estimates were further converted from thermal inertia to daily volumetric soil water content (VSWC) with a horizonal resolution of 8.6 cm. A ground truthing dataset of measured VSWC values taken from a Time Domain Reflectometer was compared with model results, producing a reasonable correlation with an average coefficient of determination of (R2) = 0.79, an average root mean square error (RMSE) = 0.0408, and mean absolute error (MAE) = 0.0308. This study highlights a practical approach of estimating VSWC for irrigation purposes while providing superior spatio-temporal coverage over in situ methods. The authors envision that PrISMM can be implemented in water usage management by relating VSWC with weather forecasts and evapotranspiration rates to develop time-based spatially distributed irrigation management plans.

Satellite observations have revealed an enhanced aerosol layer near the tropopause over Asia during the summer monsoon, called the “Asian Tropopause Aerosol Layer” (ATAL). In this work, aerosol particles in the ATAL were collected with a balloon-borne impactor near the tropopause region over India, using extended-duration balloon flights, in summer 2017 and winter 2018. The chemical composition of these particles was further investigated by quantitative analysis using offline ion chromatography. Nitrate (NO3-) and nitrite (NO2-) were found to be the dominant ions in the collected aerosols with values ranging between 87 and 343 ng m−3 at STP (standard temperature and pressure) during the summer campaign. In contrast, sulfate (SO42-) levels were found to be above the detection limit (>10 ng m−3 at STP) only in winter. In addition, we determined the origin of the air masses sampled during the flights using the analysis of back trajectories as well as a convective proxy from cloud-top temperature fields derived from a geostationary satellite. The results obtained from this analysis were put into the context of large-scale transport and aerosol distribution using GEOS-Chem chemical transport model simulations. The first flight in summer 2017 which sampled an air mass within the Asian monsoon anticyclone (AMA), influenced by convection over Western China, was associated with particle size diameters from 0.05 to 0.15 µm. In contrast, the second flight sampled air masses at the edge of the AMA associated with a larger particle size radius (>2 µm) with a higher NO2- concentration. The sampled air masses in winter 2018 were likely affected by smoke from the Pacific Northwest fire event in Canada, which occurred 7 months before our campaign, associated with concentration enhancements of SO42- and Ca2+. Overall, our results suggest that nitrogen-containing particles represent a large fraction of cloud-free and in-cloud aerosols populating the ATAL, which is partially in agreement with the results from aircraft measurements during the StratoClim (Stratospheric and upper tropospheric processes for better climate predictions) campaign. The exact nature of those particles is still unknown, but their coincidences with subvisible cirrus clouds and their sizes suggest nitric acid trihydrate (NAT) as a possible candidate, as NAT has already been observed in the tropical upper troposphere and lower stratosphere in other studies. Furthermore, GEOS-Chem model simulations indicate that lightning NOx emissions could have significantly impacted the production of nitrate aerosols sampled during the summer of 2017.

A better understanding of aerosol–cloud interaction processes is important to quantify the role of clouds and aerosols on the climate system. There have been significant efforts to explain the ways aerosols modulate cloud properties. However, from the observational point of view, it is indeed challenging to observe and/or verify some of these processes because no single instrument or platform has been proven to be sufficient. Discrimination between aerosol and cloud is vital for the quantification of aerosol–cloud interaction. With this motivation, a set of observational field campaigns named balloon-borne aerosol–cloud interaction studies (BACIS) is proposed and conducted using balloon-borne in situ measurements in addition to the ground-based (lidar; mesosphere, stratosphere and troposphere (MST) radar; lower atmospheric wind profiler; microwave radiometer; ceilometer) and space-borne (CALIPSO) remote sensing instruments from Gadanki (13.45∘ N, 79.2∘ E), India. So far, 15 campaigns have been conducted as a part of BACIS campaigns from 2017 to 2020. This paper presents the concept of the observational approach, lists the major objectives of the campaigns, describes the instruments deployed, and discusses results from selected campaigns. Balloon-borne measurements of aerosol and cloud backscatter ratio and cloud particle count are qualitatively assessed using the range-corrected data from simultaneous observations of ground-based and space-borne lidars. Aerosol and cloud vertical profiles obtained in multi-instrumental observations are found to reasonably agree. Apart from this, balloon-borne profiling is found to provide information on clouds missed by ground-based and/or space-borne lidar. A combination of the Compact Optical Backscatter AerosoL Detector (COBALD) and Cloud Particle Sensor (CPS) sonde is employed for the first time in this study to discriminate cloud and aerosol in an in situ profile. A threshold value of the COBALD colour index (CI) for ice clouds is found to be between 18 and 20, and CI values for coarse-mode aerosol particles range between 11 and 15. Using the data from balloon measurements, the relationship between cloud and aerosol is quantified for the liquid clouds. A statistically significant slope (aerosol–cloud interaction index) of 0.77 found between aerosol backscatter and cloud particle count reveals the role of aerosol in the cloud activation process. In a nutshell, the results presented here demonstrate the observational approach to quantifying aerosol–cloud interactions.

The "Vision and Change" report called for the biology community to mobilize around teaching the core concepts of biology. This essay describes a collection of resources developed by several different groups that can be used to respond to the report's call to transform undergraduate education at both the individual course and departmental levels. First, we present two frameworks that help articulate the "Vision and Change" core concepts, the "BioCore Guide" and the Conceptual Elements (CE) Framework, which can be used in mapping the core concepts onto existing curricula and designing new curricula that teach the biology core concepts. Second, we describe how the "BioCore Guide" and the CE Framework can be used alongside the Partnership for Undergraduate Life Sciences Education curricular rubric as a way for departments to self-assess their teaching of the core concepts. Finally, we highlight three sets of instruments that can be used to directly assess student learning of the core concepts: the Biology Card Sorting Task, the Biology Core Concept Instruments, and the Biology-Measuring Achievement and Progression in Science instruments. Approaches to using these resources independently and synergistically are discussed.

A critical event in the adaptation to extrauterine life is relaxation of the pulmonary vasculature at birth, allowing for a rapid increase in pulmonary blood flow that is essential for efficient gas exchange. Failure of this transition leads to pulmonary hypertension (PH), a major cause of newborn mortality associated with preterm birth, infection, hypoxia, and malformations including congenital diaphragmatic hernia (CDH). While individual vasoconstrictor and dilator genes have been identified, the coordination of their expression is not well understood. Here, we found that lung mesenchyme-specific deletion of CDH-implicated genes encoding pre-B cell leukemia transcription factors (Pbx) led to lethal PH in mice shortly after birth. Loss of Pbx genes resulted in the misexpression of both vasoconstrictors and vasodilators in multiple pathways that converge to increase phosphorylation of myosin in vascular smooth muscle (VSM) cells, causing persistent constriction. While targeting endothelin and angiotensin, which are upstream regulators that promote VSM contraction, was not effective, treatment with the Rho-kinase inhibitor Y-27632 reduced vessel constriction and PH in Pbx-mutant mice. These results demonstrate a lung-intrinsic, herniation-independent cause of PH in CDH. More broadly, our findings indicate that neonatal PH can result from perturbation of multiple pathways and suggest that targeting the downstream common effectors may be a more effective treatment for neonatal PH.

The identification of flood hazards during emerging public safety crises such as hurricanes or flash floods is an invaluable tool for first responders and managers yet remains out of reach in any comprehensive sense when using traditional remote-sensing methods, due to cloud cover and other data-sourcing restrictions. While many remote-sensing techniques exist for floodwater identification and extraction, few studies demonstrate an up-to-day understanding with better techniques in isolating the spectral properties of floodwaters from collected data, which vary for each event. This study introduces a novel method for delineating near-real-time inundation flood extent and depth mapping for storm events, using an inexpensive unmanned aerial vehicle (UAV)-based multispectral remote-sensing platform, which was designed to be applicable for urban environments, under a wide range of atmospheric conditions. The methodology is demonstrated using an actual flooding-event—Hurricane Zeta during the 2020 Atlantic hurricane season. Referred to as the UAV and Floodwater Inundation and Depth Mapper (FIDM), the methodology consists of three major components, including aerial data collection, processing, and flood inundation (water surface extent) and depth mapping. The model results for inundation and depth were compared to a validation dataset and ground-truthing data, respectively. The results suggest that UAV-FIDM is able to predict inundation with a total error (sum of omission and commission errors) of 15.8% and produce flooding depth estimates that are accurate enough to be actionable to determine road closures for a real event.

Measurements of the spectrum of the atmospheric emission in the far-infrared (FIR) range, between 100 and 667 cm−1 (100–15 µm) are scarce because of the detection complexity and of the strong absorption of air at ground level preventing the sounding of the FIR from low altitude. Consequently, FIR measurements need to be made from high-altitude sites or on board airborne platforms or satellites. This paper describes the dataset of FIR spectral radiances of the atmosphere and snow surface emission measured in the 100–1000 cm−1 range by the Far-Infrared Radiation Mobile Observation System (FIRMOS) instrument during a 2-month campaign carried out from the ground at about 3000 m of altitude on the top of Mt. Zugspitze in the German Alps in 2018–2019. This campaign is part of the preparatory activity of a new space FIR mission, named Far-infrared Outgoing Radiation Understanding and Monitoring (FORUM), which is under development by the European Space Agency (ESA). The dataset acquired during the campaign also includes all the additional measurements needed to provide a full characterisation of the observed atmospheric state and the local atmospheric and surface conditions. It includes co-located spectral measurements in the infrared range from 400 to 1800 cm−1; lidar backscatter profiles; radio soundings of temperature, humidity and aerosol backscatter profiles; local weather parameters; and snow/ice microphysical properties. These measurements provide a unique dataset that can be used to perform radiative closure experiments to improve modelling parameters in the FIR that are not well-characterised, such as water vapour spectroscopy, scattering properties of cirrus clouds, and the FIR emissivity of the surface covered by snow. The consolidated dataset is freely available via the ESA campaign dataset website at https://doi.org/10.5270/ESA-38034ee (Palchetti et al., 2020a).

The immune response is key in determining disease severity of COVID19. Here Nouailles et al., apply bulk proteomics and scRNA-Seq of lung and blood samples of SARS-CoV-2 infected Syrian hamsters and provide a temporal atlas of the systemic and pulmonary cellular responses.

Constant exposure of the airways to inhaled pathogens requires efficient early immune responses protecting against infections. How bacteria on the epithelial surface are detected and first-line protective mechanisms are initiated are not well understood. We have recently shown that tracheal brush cells (BCs) express functional taste receptors. Here we report that bitter taste signaling in murine BCs induces neurogenic inflammation. We demonstrate that BC signaling stimulates adjacent sensory nerve endings in the trachea to release the neuropeptides CGRP and substance P that mediate plasma extravasation, neutrophil recruitment, and diapedesis. Moreover, we show that bitter tasting quorum-sensing molecules from Pseudomonas aeruginosa activate tracheal BCs. BC signaling depends on the key taste transduction gene Trpm5, triggers secretion of immune mediators, among them the most abundant member of the complement system, and is needed to combat P. aeruginosa infections. Our data provide functional insight into first-line defense mechanisms against bacterial infections of the lung.

The exploration of aerosol retrieval synergies from diverse combinations of ground-based passive Sun-photometric measurements with collocated active lidar ground-based and radiosonde observations using versatile Generalized Retrieval of Atmosphere and Surface Properties (GRASP) algorithm is presented. Several potentially fruitful aspects of observation synergy were considered. First, a set of passive and active ground-based observations collected during both day- and nighttime was inverted simultaneously under the assumption of temporal continuity of aerosol properties. Such an approach explores the complementarity of the information in different observations and results in a robust and consistent processing of all observations. For example, the interpretation of the nighttime active observations usually suffers from the lack of information about aerosol particles sizes, shapes and complex refractive index. In the realized synergy retrievals, the information propagating from the nearby Sun-photometric observations provides sufficient constraints for reliable interpretation of both day- and nighttime lidar observations. Second, the synergetic processing of such complementary observations with enhanced information content allows for optimizing the aerosol model used in the retrieval. Specifically, the external mixture of several aerosol components with predetermined sizes, shapes and composition has been identified as an efficient approach for achieving reliable retrieval of aerosol properties in several situations. This approach allows for achieving consistent and accurate aerosol retrievals from processing stand-alone advanced lidar observations with reduced information content about aerosol columnar properties. Third, the potential of synergy processing of the ground-based Sun-photometric and lidar observations, with the in situ backscatter sonde measurements was explored using the data from KAUST.15 and KAUST.16 field campaigns held at King Abdullah University of Science and Technology (KAUST) in the August of 2015 and 2016. The inclusion of radiosonde data has been demonstrated to provide significant additional constraints to validate and improve the accuracy and scope of aerosol profiling. The results of all retrieval setups used for processing both synergy and stand-alone observation data sets are discussed and intercompared.

Instruments for teaching and assessing student understanding of the five core concepts in biology from "Vision and Change" are needed. We developed four Biology Core Concept Instruments (BCCIs) that teach and assess students' ability to describe a concept in their own words, identify concepts represented in biological phenomena, and make connections between concepts. The BCCI includes a narrative, followed by a series of 10 true-false/identify (TF/I) and three open-ended questions. The TF/I questions are aligned with Cary and Branchaw's Conceptual Elements Framework and were iteratively developed with feedback from biology experts and student performance and feedback obtained during think-aloud interviews. A component scoring system was developed to discriminate between a student's ability to apply and identify each core concept from his or her ability to make connections between concepts. We field-tested the BCCIs (n = 152-191) with students in a first-year course focused on learning the five core concepts in biology and collected evidence of interrater reliability (a = 0.70) and item validity. With component scoring, we identified examples in which students were able to identify concepts singularly, but not make connections between concepts, or were better able to apply concepts to one biological phenomenon than another. Identifying these nuanced differences in learning can guide instruction to improve students' conceptual understanding.

Remote-sensing measurements by light detection and ranging (lidar) instruments are fundamental for the monitoring of altitude-resolved aerosol optical properties. Here we validate vertical profiles of aerosol backscatter coefficient (βaer) measured by two independent lidar systems using co-located balloon-borne measurements performed by Compact Optical Backscatter Aerosol Detector (COBALD) sondes. COBALD provides high-precision in situ measurements of βaer at two wavelengths (455 and 940 nm). The two analyzed lidar systems are the research Raman Lidar for Meteorological Observations (RALMO) and the commercial CHM15K ceilometer (Lufft, Germany). We consider in total 17 RALMO and 31 CHM15K profiles, co-located with simultaneous COBALD soundings performed throughout the years 2014–2019 at the MeteoSwiss observatory of Payerne (Switzerland). The RALMO (355 nm) and CHM15K (1064 nm) measurements are converted to 455 and 940 nm, respectively, using the Ångström exponent profiles retrieved from COBALD data. To account for the different receiver field-of-view (FOV) angles between the two lidars (0.01–0.02∘) and COBALD (6∘), we derive a custom-made correction using Mie-theory scattering simulations. Our analysis shows that both lidar instruments achieve on average a good agreement with COBALD measurements in the boundary layer and free troposphere, up to 6 km altitude. For medium-high-aerosol-content measurements at altitudes below 3 km, the mean ± standard deviation difference in βaer calculated from all considered soundings is −2 % ± 37 % (−0.018 ± 0.237 Mm−1 sr−1 at 455 nm) for RALMO−COBALD and +5 % ± 43 % (+0.009 ± 0.185 Mm−1 sr−1 at 940 mm) for CHM15K−COBALD. Above 3 km altitude, absolute deviations generally decrease, while relative deviations increase due to the prevalence of air masses with low aerosol content. Uncertainties related to the FOV correction and spatial- and temporal-variability effects (associated with the balloon's drift with altitude and different integration times) contribute to the large standard deviations observed at low altitudes. The lack of information on the aerosol size distribution and the high atmospheric variability prevent an accurate quantification of these effects. Nevertheless, the excellent agreement observed in individual profiles, including fine and complex structures in the βaer vertical distribution, shows that under optimal conditions, the discrepancies with the in situ measurements are typically comparable to the estimated statistical uncertainties in the remote-sensing measurements. Therefore, we conclude that βaer profiles measured by the RALMO and CHM15K lidar systems are in good agreement with in situ measurements by COBALD sondes up to 6 km altitude.

Balloon-borne water vapour measurements in the upper troposphere and lower stratosphere (UTLS) by means of frost point hygrometers provide important information on air chemistry and climate. However, the risk of contamination from sublimating hydrometeors collected by the intake tube may render these measurements unusable, particularly after crossing low clouds containing supercooled droplets. A large set of (sub)tropical measurements during the 2016–2017 StratoClim balloon campaigns at the southern slopes of the Himalayas allows us to perform an in-depth analysis of this type of contamination. We investigate the efficiency of wall contact and freezing of supercooled droplets in the intake tube and the subsequent sublimation in the UTLS using computational fluid dynamics (CFD). We find that the airflow can enter the intake tube with impact angles up to 60∘, owing to the pendulum motion of the payload. Supercooled droplets with radii > 70 µm, as they frequently occur in mid-tropospheric clouds, typically undergo contact freezing when entering the intake tube, whereas only about 50 % of droplets with 10 µm radius freeze, and droplets < 5 µm radius mostly avoid contact. According to CFD, sublimation of water from an icy intake can account for the occasionally observed unrealistically high water vapour mixing ratios (χH2O > 100 ppmv) in the stratosphere. Furthermore, we use CFD to differentiate between stratospheric water vapour contamination by an icy intake tube and contamination caused by outgassing from the balloon and payload, revealing that the latter starts playing a role only during ascent at high altitudes (p < 20 hPa).

The South Asian summer monsoon is associated with a large-scale anticyclonic circulation in the upper troposphere and lower stratosphere (UTLS), which confines the air mass inside. During boreal summer, the confinement of this air mass leads to an accumulation of aerosol between about 13 and 18 km (360 and 440 K potential temperature); this accumulation of aerosol constitutes the Asian Tropopause Aerosol Layer (ATAL). We present balloon-borne aerosol backscatter measurements of the ATAL performed by the Compact Optical Backscatter Aerosol Detector (COBALD) instrument in Nainital in northern India in August 2016, and compare these with COBALD measurements in the post-monsoon time in November 2016. The measurements demonstrate a strong variability of the ATAL's altitude, vertical extent, aerosol backscatter intensity and cirrus cloud occurrence frequency. Such a variability cannot be deduced from climatological means of the ATAL as they are derived from satellite measurements. To explain this observed variability we performed a Lagrangian back-trajectory analysis using the Chemical Lagrangian Model of the Stratosphere (CLaMS). We identify the transport pathways as well as the source regions of air parcels contributing to the ATAL over Nainital in August 2016. Our analysis reveals a variety of factors contributing to the observed day-to-day variability of the ATAL: continental convection, tropical cyclones (maritime convection), dynamics of the anticyclone and stratospheric intrusions. Thus, the air in the ATAL is a mixture of air masses coming from different atmospheric altitude layers. In addition, contributions from the model boundary layer originate in different geographic source regions. The location of the strongest updraft along the backward trajectories reveals a cluster of strong upward transport at the southern edge of the Himalayan foothills. From the top of the convective outflow level (about 13 km; 360 K) the air parcels ascend slowly to ATAL altitudes within a large-scale upward spiral driven by the diabatic heating in the anticyclonic flow of the South Asian summer monsoon at UTLS altitudes. Cases with a strong ATAL typically show boundary layer contributions from the Tibetan Plateau, the foothills of the Himalayas and other continental regions below the Asian monsoon. Weaker ATAL cases show higher contributions from the maritime boundary layer, often related to tropical cyclones, indicating a mixing of clean maritime and polluted continental air. On the one hand increasing anthropogenic emissions in the future are expected due to the strong growth of Asian economies; on the other hand the implementation of new emission control measures (in particular in China) has reduced the anthropogenic emissions of some pollutants contributing to the ATAL substantially. It needs to be monitored in the future whether the thickness and intensity of the ATAL will further increase, which will likely impact the surface climate.

Community-acquired pneumonia remains a major contributor to global communicable disease-mediated mortality. Neutrophils play a leading role in trying to contain bacterial lung infection, but they also drive detrimental pulmonary inflammation, when dysregulated. Here we aimed at understanding the role of microRNA-223 in orchestrating pulmonary inflammation during pneumococcal pneumonia. Serum microRNA-223 was measured in patients with pneumococcal pneumonia and in healthy subjects. Pulmonary inflammation in wild-type and microRNA-223-knockout mice was assessed in terms of disease course, histopathology, cellular recruitment and evaluation of inflammatory protein and gene signatures following pneumococcal infection. Low levels of serum microRNA-223 correlated with increased disease severity in pneumococcal pneumonia patients. Prolonged neutrophilic influx into the lungs and alveolar spaces was detected in pneumococci-infected microRNA-223-knockout mice, possibly accounting for aggravated histopathology and acute lung injury. Expression of microRNA-223 in wild-type mice was induced by pneumococcal infection in a time-dependent manner in whole lungs and lung neutrophils. Single-cell transcriptome analyses of murine lungs revealed a unique profile of antimicrobial and cellular maturation genes that are dysregulated in neutrophils lacking microRNA-223. Taken together, low levels of microRNA-223 in human pneumonia patient serum were associated with increased disease severity, whilst its absence provoked dysregulation of the neutrophil transcriptome in murine pneumococcal pneumonia.

Phage therapy of ventilator-associated pneumonia (VAP) is of great interest due to the rising incidence of multidrug-resistant bacterial pathogens. However, natural or therapy-induced immunity against therapeutic phages remains a potential concern. In this study, we investigated the innate and adaptive immune responses to two different phage cocktails targeting either Pseudomonas aeruginosa or Escherichia coli—two VAP-associated pathogens—in naïve mice without the confounding effects of a bacterial infection. Active or UV-inactivated phage cocktails or buffers were injected intraperitoneally daily for 7 days in C57BL/6J wild-type mice. Blood cell analysis, flow cytometry analysis, assessment of phage distribution and histopathological analysis of spleens were performed at 6 h, 10 days and 21 days after treatment start. Phages reached the lungs and although the phage cocktails were slightly immunogenic, phage injections were well tolerated without obvious adverse effects. No signs of activation of innate or adaptive immune cells were observed; however, both active phage cocktails elicited a minimal humoral response with secretion of phage-specific antibodies. Our findings show that even repetitive injections lead only to a minimal innate and adaptive immune response in naïve mice and suggest that systemic phage treatment is thus potentially suitable for treating bacterial lung infections.

Technologies enabling on-site environmental detection or medical diagnostics in resource-limited settings have a strong disruptive potential compared to current analytical approaches that require trained personnel in laboratories with immobile, resource intensive instrumentation. Handheld devices, such as smartphones, are now routinely produced with CPUs, RAM, wireless data transfer capabilities, and high-resolution complementary metal oxide semiconductor (CMOS) cameras capable of supporting the capture and processing of bioluminescent signals. In theory, combining the capabilities of these devices with continuously bioluminescent human cell-based bioreporters would allow them to replicate the functionality of more expensive, more complex, and less flexible platforms while supporting human-relevant conclusions. In this work, we compare the performance of smartphone (CMOS) and night vision (image intensifier) devices with in vivo (CCD camera), and in vitro (photomultiplier tube) laboratory instrumentation for monitoring signal dynamics from continuously bioluminescent human cellular models under toxic, stable, and induced expression scenarios. All systems detected bioluminescence from cells at common plating densities. While the in vivo and in vitro systems were more sensitive and detected signal dynamics representing cellular health changes earlier, the night vision and smartphone systems also detected these changes with relatively similar coefficients of variation and linear detection capabilities. The smartphone system did not detect transcriptional induction. The night vision system did detect transcriptional activation, but was less sensitive than the in vivo or in vitro systems and required a stronger induction before the change could be resolved.

The transition to college is challenging for most students, especially those who aspire to major in the science, technology, engineering, or mathematics disciplines, in which introductory courses can be large and instruction less than optimal. This paper describes a novel, disciplinary first-year seminar (FYS) course, Exploring Biology, designed to address many of the challenges facing aspiring biology students beginning their academic careers at a large public research university. The course addresses typical FYS goals, such as community building, introduction to resources, and academic skill development, and introduces students to the core concepts of biology defined in the 2011 "Vision and Change" report. Relative to a matched comparison group of students, Exploring Biology alumni were retained at higher rates and had higher levels of academic performance in a subsequent introductory biology course, suggesting Exploring Biology has a positive impact on future academic performance in the discipline. Results from course evaluations and an alumni survey show that, overall, students valued both the FYS components and biology components of the course. These results provide evidence that the Exploring Biology disciplinary FYS model is an intervention that may increase academic success and retention in biology.

We measured the vertical profiles of backscatter ratio (BSR) using the balloon-borne, lightweight Compact Optical Backscatter AerosoL Detector (COBALD) instruments above Linzhi, located in the southeastern Tibetan Plateau, in the summer of 2014. An enhanced aerosol layer in the upper troposphere–lower stratosphere (UTLS), with BSR (455 nm) > 1.1 and BSR (940 nm) > 1.4, was observed. The color index (CI) of the enhanced aerosol layer, defined as the ratio of aerosol backscatter ratios (ABSRs) at wavelengths of 940 and 455 nm, varied from 4 to 8, indicating the prevalence of fine particles with a mode radius of less than 0.1 µm. We find that unlike the very small particles (mode radius smaller than 0.04 µm) at low relative humidity (RHi < 40 %), the relatively large particles in the aerosol layer were generally very hydrophilic as their size increased dramatically with relative humidity. This result indicates that water vapor can play a very important role in increasing the size of fine particles in the UTLS over the Tibetan Plateau. Our observations provide observation-based evidence supporting the idea that aerosol particle hygroscopic growth is an important factor influencing the radiative properties of the Asian Tropopause Aerosol Layer (ATAL) during the Asian summer monsoon.

Abstract Background Electronic patient portals are increasingly being implemented, also in (haemato) oncology. However, portal usage is low and depends on user and provider engagement. We explored wishes, expectations and thoughts of patients with a haematologic malignancy and their physicians with regard to the electronic patient portal. Methods Based on insights from literature and a focus group discussion we built a 44-item questionnaire. This questionnaire was spread amongst patients with a haematologic malignancy at the outpatient clinic that was not yet exposed to patient portal facilities. Haematologists completed a questionnaire based on literature. Results Patients were interested in many different types of access to information and portal functionalities. However, their opinions varied about the provision of access to the portal to other people, the role of the physician, possibilities for communication via the portal and timing of access. The physicians acknowledged the relevance of the electronic patient portal, but had some worries about the patients’ autonomous information handling, organizational and technical issues. Patients frequently expressed to be open about the potential of the patient portal to orchestrate their care. Nevertheless, most physicians appreciated their supporting role towards the patient. Conclusions Patients and physicians appreciated the electronic patient portal. Both groups need to be involved in further portal development to improve engagement by meeting patients’ wishes, taking into account organizational and professional issues and managing expectations for both parties. To fit various patient profiles, portal design should be flexible and individualized. Further research should focus on the perceived added value and the impact on patient related outcome measures of portals.

Selectively methylated analogues of naturally occurring 2-heptyl-4(1H)-quinolones, which are alkaloids common within the Rutaceae family and moreover are associated with quorum sensing and virulence of the human pathogen Pseudomonas aeruginosa, have been prepared. While the synthesis by direct methylation was successful for 3-unsubstituted 2-heptyl-4(1H)-quinolones, methylated derivatives of the Pseudomonas quinolone signal (PQS) were synthesized from 3-iodinated quinolones by methylation and iodine–metal exchange/oxidation. The two N- and O-methylated derivatives of the PQS showed strong quorum sensing activity comparable to that of PQS itself. Staphylococcus aureus, another pathogenic bacterium often co-occurring with P. aeruginosa especially in the lung of cystic fibrosis patients, was inhibited in planktonic growth and cellular respiration by the 4-O-methylated derivatives of HQNO and HHQ, respectively.

Abstract The Soil Management Assessment Framework (SMAF) is a quantitative soil quality (SQ) evaluation tool that is widely applied to assess soil response to specific agricultural management practices over time. Considering the reported SQ benefits of agroforestry (AF) systems and the potential usefulness of SMAF, the objective of this study was to evaluate the effects of tree species (pecan [Carya illinoinensis (Wangenh.) K. Koch] and northern red oak [Quercus rubra L.]), soil fertility source (poultry litter [PL] and inorganic N fertilizer [control]), and soil depth (0–15 and 15–30 cm) on SMAF‐derived SQ indices after 17 yr of management at an AF site in northwest Arkansas. Averaged across soil depth, soil organic C scores under red oak with PL application had a lower score (0.48) than red oak fertilized with inorganic N (0.60) and pecan receiving long‐term PL applications (0.60), which did not differ from pecan with inorganic N fertilizer application (0.51). Averaged across soil depth, the soil quality index (SQI) for pecan receiving PL applications was 1.1 times greater than that under red oak receiving PL and soils under pecan receiving inorganic N fertilizer. Soil quality assessments use in AF are novel, as SMAF has not been used to identify soil health in these systems, although specific tree crop codes need to be developed in SMAF. Results of this study demonstrate that soils planted under various tree species respond dissimilarly to fertilizer sources and that management may improve overall SQ.

Rare isotope tracer injection represents an established way for following particle transport in fusion research, but a tracer experiment is only as good as the tracer can be followed and separated from the common isotope. Physical models for transport analysis such as ERO2.0 require accurate total amounts of deposition with high spatial resolution. This work describes an extended high throughput NRA post analysis approach together with the surface analysis results of 2 technically rough graphite-tiles of 150x150 mm2 surface area exposed to D and He plasmas in EAST.The applied 1.43 MeV deuteron beam NRA offers percent range accuracy for layer thicknesses ranging from few 10 nm to 20 µm. Optimisation of the beam line and beam optics enables operation with ≤20 nA without reaching critical radiation levels, resulting in a measurement time of 5–10 s per spot. This enabled acquiring in total 3070 NRA points on the central 46 × 46 mm2 cut-outs of each sample and an adjacent part of equal size within 12 h of analysis time.The layers contained 50–60% D, ~2% 12C, and ~3% O. The central 20 mm radius around the injection hole contains 98% of the total 13C deposition. NRA finds up to 5.8 ± 0.9 × 1022 13C/m2 close to the hole with an e-folding fall-off length of about 3–10 mm in every radial direction. In the D discharge 24 ± 2% and 16 ± 2% in He of the injected 13C are found on the tiles with triangle shaped deposition profiles following ExB. The comparison to colour fringe analysis and SIMS reveals the particular strength of D-NRA regarding roughness, thick layers, and the separation of 12C and 13C deposits, but in compatible regions all methods agree. Compared to these, the NRA yields additional information indicating depositing species and physical processes.

Abstract Understanding the impacts of long‐term fertilizer management and rotation diversity on soil C and N is needed under a changing climate. The objective of this study was to evaluate the effects of N fertilizer level and crop rotation diversity on soil organic carbon (SOC) and soil N stocks from a 34‐yr study located in eastern Nebraska. Seven crop rotations (three continuous cropping systems; two 2‐yr crop rotations; and two 4‐yr crop rotations) and three N levels were compared. Soil samples were taken to a depth of 150 cm. Differences in SOC stocks were largely confined to the 0‐ to 7.5‐cm depth, with greater SOC (P = .0002) in rotations than continuous cropping systems and greater SOC (P = .0004) in 4‐yr vs. 2‐yr rotations. Total soil N was greater with increased crop rotation diversity for the 0‐ to 30‐cm soil profile. Greater SOC levels occurred with N fertilization for the 0‐ to 7.5‐cm depth. At the 0‐ to 150‐cm soil depth, SOC stocks were similar between N levels and greater for the 4‐yr vs. 2‐yr crop rotations (P = .0492). Trends in total N stocks were similar to those of SOC stocks. Overall, crop rotation had a larger effect on SOC and N stocks than N fertilizer.

Abstract The Soil Management Assessment Framework (SMAF) may provide insight into how conservation practices affect soil quality (SQ) regionally. Therefore, we aimed to quantify SQ in a long‐term (15‐yr) crop rotation and bio‐covers experiment under no‐tillage using SMAF. Main effects were cropping rotations of soybean [Glycine max (L.) Merr.], corn (Zea mays L.), and cotton (Gossypium hirsutum L.). Split‐block bio‐cover treatments consisted of winter wheat (Triticum aestivum L.), Austrian winter pea (Pisum sativum L. sativum var. arvense), hairy vetch (Vicia villosa Roth), poultry litter, and fallow (control). Seven SQ indicators—soil pH, total organic carbon (TOC), bulk density (BD), soil extractable P and K, electrical conductivity (EC), and sodium adsorption ration (SAR)—were scored using SMAF algorithms, and investigated individually and as an overall soil quality index (SQI). Simple linear regressions were performed between SQI and crop yields. Differences (p

Pneumonia is one of the leading causes of death worldwide. The course of the disease is often highly dynamic with unforeseen critical deterioration within hours in a relevant proportion of patients. Besides antibiotic treatment, novel adjunctive therapies are under development. Their additive value needs to be explored in preclinical and clinical studies and corresponding therapy schedules require optimization prior to introduction into clinical practice. Biomathematical modeling of the underlying disease and therapy processes might be a useful aid to support these processes. We here propose a biomathematical model of murine immune response during infection with Streptococcus pneumoniae aiming at predicting the outcome of different treatment schedules. The model consists of a number of non-linear ordinary differential equations describing the dynamics and interactions of the pulmonal pneumococcal population and relevant cells of the innate immune response, namely alveolar- and inflammatory macrophages and neutrophils. The cytokines IL-6 and IL-10 and the chemokines CCL2, CXCL1 and CXCL5 are considered as major mediators of the immune response. We also model the invasion of peripheral blood monocytes, their differentiation into macrophages and bacterial penetration through the epithelial barrier causing blood stream infections. We impose therapy effects on this system by modelling antibiotic therapy and treatment with the novel C5a-inactivator NOX-D19. All equations are derived by translating known biological mechanisms into equations and assuming appropriate response kinetics. Unknown model parameters were determined by fitting the predictions of the model to time series data derived from mice experiments with close-meshed time series of state parameters. Parameter fittings resulted in a good agreement of model and data for the experimental scenarios. The model can be used to predict the performance of alternative schedules of combined antibiotic and NOX-D19 treatment. We conclude that we established a comprehensive biomathematical model of pneumococcal lung infection, immune response and barrier function in mice allowing simulations of new treatment schedules. We aim to validate the model on the basis of further experimental data. We also plan the inclusion of further novel therapy principles and the translation of the model to the human situation in the near future.

This paper quantifies the tropical stratospheric aerosol content as impacted by volcanic events over the 2013–2019 period. We use global model simulations by the Whole Atmosphere Community Climate Model (WACCM) which is part of the Community Earth System Model version 1.0 (CESM1). WACCM is associated with the Community Aerosol and Radiation Model for Atmospheres (CARMA) sectional aerosol microphysics model which includes full sulphur chemical and microphysical cycles with no a priori assumption on particle size. Five main volcanic events (Kelud, Calbuco, Ambae, Raikoke and Ulawun) have been reported and are shown to have significantly influenced the stratospheric aerosol layer in the tropics, either through direct injection in this region or through transport from extra-tropical latitudes. Space-borne data as well as ground-based lidar and balloon-borne in situ observations are used to evaluate the model calculations in terms of aerosol content, vertical distribution, optical and microphysical properties, transport and residence time of the various volcanic plumes. Overall, zonal mean model results reproduce the occurrence and vertical extents of the plumes derived from satellite observations but shows some discrepancies for absolute values of extinction and of stratospheric aerosol optical depth (SAOD). Features of meridional transport of the plumes emitted from extra-tropical latitudes are captured by the model but simulated absolute values of SAOD differ from 6 to 200% among the various eruptions. Simulations tend to agree well with observed in situ vertical profiles for the Kelud and Calbuco plumes but this is likely to depend on the period for which comparison is done. Some explanations for the model–measurement discrepancies are discussed such as the inaccurate knowledge of the injection parameters and the presence of ash not accounted in the simulations.

ABSTRACT: Before decommissioning of the TEXTOR tokamak in 2013, the machine was conditioned with a comprehensive migration experiment where MoF6 and 15N2 were injected on the very last operation day. Thereafter, all plasma-facing components (PFCs) were available for extensive studies of both local and global migration of impurities – Mo, W, Inconel alloy constituents, 15 N, F – and fuel retention studies. Measurements were performed on 140 limiter tiles out of 864 throughout the whole machine to map global transport. One fifth of the introduced molybdenum could be found. Wherever possible, the findings are compared to results obtained previously in other machines. This review incorporates both published and unpublished results from this TEXTOR study and combines findings with analytical methods as well as modelling results from two codes, ERO and ASCOT. The main findings are: • Both local and global molybdenum transport can be explained by toroidal plasma flow and E⇀×B⇀ drift. The suggested transport scheme for molybdenum holds also for other analysed species, namely tungsten from previous experiments and medium-Z metals (Cr-Cu) introduced on various occasions. • Analytical interpretation of several deposition profile features is possible with basic geometrical and plasma physics considerations. These are deposition profiles on the collector probe, the lower part of the inner bumper limiter, the poloidal cross-section of the inner bumper limiter, and the poloidal limiter. • Any deposition pattern found in this TEXTOR study, including fuel retention, has neither poloidal nor toroidal symmetry, which is often assumed when determining deposition profiles on global scale. • Fuel retention is highly inhomogeneous due to local variation of plasma parameters – by auxiliary heating systems and impurity injection – and PFC temperature. • Local modelling with ERO yields good qualitative agreement but too high local deposition efficiency. • Global modelling with ASCOT shows that the radial electric field and source form have a high impact on global deposition patterns, while toroidal flow has little influence. Some of the experimental findings could be reproduced. Still, qualitative differences between simulated and experimental global deposition patterns remain.The review closes with lessons learnt during this extensive TEXTOR study which might be helpful for future scientific exploitation of other tokamaks to be decommissioned. Keywords: Global migration, Tokamak, high-Z material, Molybdenum, Modelling, ASCOT, ERO, Fuel retention, Deposition

Abstract Background Community-acquired pneumonia (CAP) remains a major cause of death worldwide. Mechanisms underlying the detrimental outcome despite adequate antibiotic therapy and comorbidity management are still not fully understood. Methods To model timely versus delayed antibiotic therapy in patients, mice with pneumococcal pneumonia received ampicillin twice a day starting early (24 h) or late (48 h) after infection. Clinical readouts and local and systemic inflammatory mediators after early and late antibiotic intervention were examined. Results Early antibiotic intervention rescued mice, limited clinical symptoms and restored fitness, whereas delayed therapy resulted in high mortality rates. Recruitment of innate immune cells remained unaffected by antibiotic therapy. However, both early and late antibiotic intervention dampened local levels of inflammatory mediators in the alveolar spaces. Early treatment protected from barrier breakdown, and reduced levels of vascular endothelial growth factor (VEGF) and perivascular and alveolar edema formation. In contrast, at 48 h post infection, increased pulmonary leakage was apparent and not reversed by late antibiotic treatment. Concurrently, levels of VEGF remained high and no beneficial effect on edema formation was evident despite therapy. Moreover, early but not late treatment protected mice from a vast systemic inflammatory response. Conclusions Our data show that only early antibiotic therapy, administered prior to breakdown of the alveolar–capillary barrier and systemic inflammation, led to restored fitness and rescued mice from fatal streptococcal pneumonia. The findings highlight the importance of identifying CAP patients prior to lung barrier failure and systemic inflammation and of handling CAP as a medical emergency.

The Asian summer monsoon anticyclone (ASMA) is a major meteorological system of the upper troposphere–lower stratosphere (UTLS) during boreal summer. It is known to contain enhanced tropospheric trace gases and aerosols, due to rapid lifting from the boundary layer by deep convection and subsequent horizontal confinement. Given its dynamical structure, the ASMA represents an efficient pathway for the transport of pollutants to the global stratosphere. A detailed understanding of the thermal structure and processes in the ASMA requires accurate in situ measurements. Within the StratoClim project we performed state-of-the-art balloon-borne measurements of temperature, water vapor, ozone and aerosol backscatter from two stations on the southern slopes of the Himalayas. In total, 63 balloon soundings were conducted during two extensive monsoon-season campaigns, in August 2016 in Nainital, India (29.4° N, 79.5° E), and in July–August 2017 in Dhulikhel, Nepal (27.6° N, 85.5° E); one shorter post-monsoon campaign was also carried out in November 2016 in Nainital. These measurements provide unprecedented insights into the UTLS thermal structure, the vertical distributions of water vapor, ozone and aerosols, cirrus cloud properties and interannual variability in the ASMA. Here we provide an overview of all of the data collected during the three campaign periods, with focus on the UTLS region and the monsoon season. We analyze the vertical structure of the ASMA in terms of significant levels and layers, identified from the temperature and potential temperature lapse rates and Lagrangian backward trajectories, which provides a framework for relating the measurements to local thermodynamic properties and the large-scale anticyclonic flow. Both the monsoon-season campaigns show evidence of deep convection and confinement extending up to 1.5–2 km above the cold-point tropopause (CPT), yielding a body of air with high water vapor and low ozone which is prone to being lifted further and mixed into the free stratosphere. Enhanced aerosol backscatter also reveals the signature of the Asian tropopause aerosol layer (ATAL) over the same region of altitudes. The Dhulikhel 2017 campaign was characterized by a 5 K colder CPT on average than in Nainital 2016 and a local water vapor maximum in the confined lower stratosphere, about 1 km above the CPT. Data assessment and modeling studies are currently ongoing with the aim of fully exploring this dataset and its implications with respect to stratospheric moistening via the ASMA system and related processes.

Abstract Background Antibiotic exposure alters the microbiota, which can impact the inflammatory immune responses. Critically ill patients frequently receive antibiotic treatment and are often subjected to mechanical ventilation, which may induce local and systemic inflammatory responses and development of ventilator-induced lung injury (VILI). The aim of this study was to investigate whether disruption of the microbiota by antibiotic therapy prior to mechanical ventilation affects pulmonary inflammatory responses and thereby the development of VILI. Methods Mice underwent 6–8 weeks of enteral antibiotic combination treatment until absence of cultivable bacteria in fecal samples was confirmed. Control mice were housed equally throughout this period. VILI was induced 3 days after completing the antibiotic treatment protocol, by high tidal volume (HTV) ventilation (34 ml/kg; positive end-expiratory pressure = 2 cmH2O) for 4 h. Differences in lung function, oxygenation index, pulmonary vascular leakage, macroscopic assessment of lung injury, and leukocyte and lymphocyte differentiation were assessed. Control groups of mice ventilated with low tidal volume and non-ventilated mice were analyzed accordingly. Results Antibiotic-induced microbiota depletion prior to HTV ventilation led to aggravation of VILI, as shown by increased pulmonary permeability, increased oxygenation index, decreased pulmonary compliance, enhanced macroscopic lung injury, and increased cytokine/chemokine levels in lung homogenates. Conclusions Depletion of the microbiota by broad-spectrum antibiotics prior to HTV ventilation renders mice more susceptible to developing VILI, which could be clinically relevant for critically ill patients frequently receiving broad-spectrum antibiotics.

Respiratory infections caused by multidrug-resistant Acinetobacter baumannii are difficult to treat and associated with high mortality among critically ill hospitalized patients. Bacteriophages (phages) eliminate pathogens with high host specificity and efficacy. However, the lack of appropriate preclinical experimental models hampers the progress of clinical development of phages as therapeutic agents. Therefore, we tested the efficacy of a purified lytic phage, vB_AbaM_Acibel004, against multidrug-resistant A. baumannii clinical isolate RUH 2037 infection in immunocompetent mice and a human lung tissue model. Sham- and A. baumannii-infected mice received a single-dose of phage or buffer via intratracheal aerosolization. Group-specific differences in bacterial burden, immune and clinical responses were compared. Phage-treated mice not only recovered faster from infection-associated hypothermia but also had lower pulmonary bacterial burden, lower lung permeability, and cytokine release. Histopathological examination revealed less inflammation with unaffected inflammatory cellular recruitment. No phage-specific adverse events were noted. Additionally, the bactericidal effect of the purified phage on A. baumannii was confirmed after single-dose treatment in an ex vivo human lung infection model. Taken together, our data suggest that the investigated phage has significant potential to treat multidrug-resistant A. baumannii infections and further support the development of appropriate methods for preclinical evaluation of antibacterial efficacy of phages.

Tracer injection experiments in TEXTOR with MoF6 and WF6 lead to local deposition of about 6% for Mo and about 1% for W relative to the injected amount of Mo and W atoms. Modelling of these experiments has been done with ERO applying updated data for physical sputtering. The dissociation of the injected molecules has been treated in a simplified manner due to the lack of dissociation rate coefficients. However, with this it was possible to reproduce the observed radial penetration of Mo and W atoms into the plasma. The modelled local deposition efficiencies are about 50% for Mo and 60% for W assuming typical plasma parameters for the experimental conditions used. To reproduce the measured deposition efficiencies an enhancement factor for the erosion of deposited Mo and W has to be assumed (∼10 for Mo and ∼25 for W). Due to the rather low electron temperature Te of these plasma conditions (Te∼15eV at the location of injection), Mo and W are mostly sputtered by impurities whereas sputtering due to deuterium is negligible. A parameter study applying larger electron temperature leads to increased sputtering and thus to reduced local deposition efficiencies of about 30% for Mo and 5% for W. Though, even under these conditions enhanced erosion, albeit with reduced enhancement factors, is needed in the modelling to obtain the small measured deposition efficiencies. keywords: Erosion & Deposition, Sputtering, Impurity transport, TEXTOR, PACS: 52.40.Hf, 52.77.Dq, 52.65.Pp

MoF6 injection from a localised source into plasma edge in the TEXTOR tokamak was the last experiment before the final shut-down of the TEXTOR machine. During decommissioning all plasma-facing components (PFCs) became available for surface studies. Detailed mapping of Mo deposition was performed in order to determine its migration on global scale. The concentration of Mo on PFC decays exponentially with distance from the source. The decay length is of the order of 0.1m on the main PFC and 1m on the receded components. Also the decay lengths modelled with the ERO code are between 0.15–1.3m, depending on the anomalous cross-field diffusion coefficient. The inner bumper limiter is found to be the major repository for Mo. Material balance measurements show that only up to 22% of the injected Mo was detected on all the PFCs thus indicating that a large fraction of injected Mo may have been pumped out before being deposited. Keywords: Global transport, Material migration, High-Z metals, TEXTOR, Plasma-facing components, Molybdenum

An overview of diagnostic tools – test limiters and collector probes – used over the years for material migration studies in the TEXTOR tokamak is presented. Probe transfer systems are shown and their technical capabilities are described. This is accompanied by a brief presentation of selected results and conclusions from the research on material erosion – deposition processes including tests of candidate materials (e.g. W, Mo, carbon-based composites) for plasma-facing components in controlled fusion devices. The use of tracer techniques and methods for analysis of materials retrieved from the tokamak are summarized. The impact of research on the reactor wall technology is addressed.

Peptidoglycan (PGN) recognition proteins (PGLYRPs) are a highly conserved group of host defense proteins in insects and mammals that sense bacterial cell wall PGN and act bactericidally or cleave PGN by amidase function. Streptococcus (S.) pneumoniae is one of the top five killers worldwide and causes, e.g., pneumonia, endocarditis, meningitis and sepsis. S. pneumoniae accounts for approximately 1.5–2 million deaths every year. The risk of antibiotic resistance and a general poor prognosis in young children and elderly people have led to the need for new treatment approaches. To the best of our knowledge, there is no report on the relevance of PGLYRP2 in lung infections. Therefore, we infected mice deficient for PGLYRP2 transnasally with S. pneumoniae and examined the innate immune response in comparison to WT animals. As expected, PGLYRP2-KO animals had to be sacrificed earlier than their WT counterparts, and this was due to higher bacteremia. The higher bacterial load in the PGLYRP2-KO mice was accomplished with lower amounts of proinflammatory cytokines in the lungs. This led to an abolished recruitment of neutrophils into the lungs, the spread of bacteria and the subsequent aggravated course of the disease and early mortality of the PGLYRP2-KO mice. These data suggest a substantial role of PGLYRP2 in the early defense against S. pneumoniae infection, and PGLYRP2 might also affect other infections in the lungs.

High-resolution in situ balloon measurements of water vapour, aerosol, methane and temperature in the upper tropical tropopause layer (TTL) and lower stratosphere are used to evaluate the processes affecting the stratospheric water budget: horizontal transport (in-mixing) and hydration by cross-tropopause overshooting updrafts. The obtained in situ evidence of these phenomena are analysed using satellite observations by Aura MLS (Microwave Limb Sounder) and CALIPSO (Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation) together with trajectory and transport modelling performed using CLaMS (Chemical Lagrangian Model of the Stratosphere) and HYSPLIT (Hybrid Single-Particle Lagrangian Integrated Trajectory) model. Balloon soundings were conducted during March 2012 in Bauru, Brazil (22.3° S) in the frame of the TRO-Pico campaign for studying the impact of convective overshooting on the stratospheric water budget. The balloon payloads included two stratospheric hygrometers: FLASH-B (Fluorescence Lyman-Alpha Stratospheric Hygrometer for Balloon) and Pico-SDLA instrument as well as COBALD (Compact Optical Backscatter Aerosol Detector) sondes, complemented by Vaisala RS92 radiosondes. Water vapour vertical profiles obtained independently by the two stratospheric hygrometers are in excellent agreement, ensuring credibility of the vertical structures observed. A signature of in-mixing is inferred from a series of vertical profiles, showing coincident enhancements in water vapour (of up to 0.5 ppmv) and aerosol at the 425 K (18.5 km) level. Trajectory analysis unambiguously links these features to intrusions from the Southern Hemisphere extratropical stratosphere, containing more water and aerosol, as demonstrated by MLS and CALIPSO global observations. The in-mixing is successfully reproduced by CLaMS simulations, showing a relatively moist filament extending to 20° S. A signature of local cross-tropopause transport of water is observed in a particular sounding, performed on a convective day and revealing water vapour enhancements of up to 0.6 ppmv as high as the 404 K (17.8 km) level. These are shown to originate from convective overshoots upwind detected by an S-band weather radar operating locally in Bauru. The accurate in situ observations uncover two independent moisture pathways into the tropical lower stratosphere, which are hardly detectable by space-borne sounders. We argue that the moistening by horizontal transport is limited by the weak meridional gradients of water, whereas the fast convective cross-tropopause transport, largely missed by global models, can have a substantial effect, at least at a regional scale.