Bleomycin increases neutrophil adhesion to human vascular endothelial cells independently of upregulation of ICAM-1 and E-selectin

© 2016 Taylor & Francis. Aim of the Study: Bleomycin-induced lung disease is a serious complication of therapy characterized by alveolar injury, cytokine release, inflammatory cell recruitment, and eventually pulmonary fibrosis. The mechanisms underlying bleomycin-induced pulmonary fibrosis may be relevant to other progressive scarring diseases of the lungs. Pulmonary vascular endothelial cells are critically involved in immune cell extravasation at sites of injury through adhesion molecule expression and cytokine release. We sought to determine the effects of bleomycin on adhesion molecule expression and cytokine release by pulmonary vascular endothelial cells, and their functional relevance to inflammatory cell recruitment. Materials and Methods: The effects of pharmacologically relevant concentrations of bleomycin on adhesion molecule expression and cytokine release by human vascular endothelial cells in vitro were studied by flow cytometry, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay. A flow chamber model was used to assess the functional consequences on adhesion of flowing human neutrophils to endothelial cell monolayers. Results: Bleomycin increased intercellular adhesion molecule 1 (ICAM-1; CD54), vascular cell adhesion molecule (VCAM-1; CD106), and E-selectin (CD62E) expression, and increased monocyte chemoattractant protein (MCP-1) and interleukin (IL-8) release by endothelial cells. Increases in protein expression were accompanied by increased mRNA transcription. In contrast, there was no direct effect of bleomycin on the profibrotic cytokines transforming growth factor-beta (TGF-β), platelet-derived growth factor-BB (PDGF-BB), or endothelin-1. Under flow conditions, endothelial cells exposed to bleomycin supported increased neutrophil adhesion which was independent of ICAM-1 or E-selectin. Conclusion: Our findings demonstrate that bleomycin promotes endothelial-mediated inflammation and neutrophil adhesion. These mechanisms may contribute to the development of pulmonary fibrosis by supporting immune cell recruitment in the lungs

The Relationship between Marital Status and Psychological Resilience in Chronic Pain

We examined the relationship between marital status and a 2-stage model of pain-related effect, consisting of pain unpleasantness and suffering. We studied 1914 chronic pain patients using multivariate analysis of covariance (MANCOVA) to clarify whether marital status was a determinant factor in the emotional or ideational suffering associated with chronic pain after controlling for pain sensation intensity, age, and ethnicity. Marital status was unrelated to immediate unpleasantness (). We found a strong association with emotional suffering () but not with negative illness beliefs (). Interestingly, widowed subjects experienced significantly less frustration, fear, and anger than all other groups (married, divorced, separated, or single). A final MANCOVA including sex as a covariate revealed that the emotional response to pain was the same for both widow and widower. Only those individuals whose spouse died experienced less emotional turmoil in the face of a condition threatening their lifestyle. These data suggest that after experiencing the death of a spouse, an individual may derive some “emotional inoculation” against future lifestyle threat

The effects of extended public transport operating hours and venue lockout policies on drinking-related harms in Melbourne, Australia: Results from SimDrink, an agent-based simulation model.

Background: The late-night accessibility of entertainment precincts is a contributing factor to acute drinking-related harms. Using computer simulation we test the effects of improved public transport (PT) and venue lockouts on verbal aggression, consumption-related harms and transport-related harms among a population of young adults engaging in heavy drinking in Melbourne. Methods: Using an agent-based model we implemented: a two-hour PT extension/24-hour PT; 1 am/3 am venue lockouts; and combinations of both. Outcomes determined for outer-urban (OU) and inner-city (IC) residents were: the number of incidents of verbal aggression inside public and private venues; the number of people ejected from public venues for being intoxicated; and the percentage of people experiencing verbal aggression, consumption-related harms and transport-related harms. Results: All-night PT reduced verbal aggression in the model by 21% but displaced some incidents among OU residents from private to public settings. Comparatively, 1 am lockouts reduced verbal aggression in the model by 19% but led to IC residents spending more time in private rather than public venues where their consumption-related harms increased. Extending PT by 2 h had similar outcomes to 24-hour PT except with fewer incidents of verbal aggression displaced. Although 3 am lockouts were inferior to 1 am lockouts, when modelled in combination with any extension of PT both policies were similar. Conclusions: A two-hour extension of PT is likely to be more effective in reducing verbal aggression and consumption-related harms than venue lockouts. Modelling a further extension of PT to 24 h had minimal additional benefits but the potential to displace incidents of verbal aggression among OU residents from private to public venues

Tensor-reduced atomic density representations

Density based representations of atomic environments that are invariant under Euclidean symmetries have become a widely used tool in the machine learning of interatomic potentials, broader data-driven atomistic modelling and the visualisation and analysis of materials datasets.The standard mechanism used to incorporate chemical element information is to create separate densities for each element and form tensor products between them. This leads to a steep scaling in the size of the representation as the number of elements increases. Graph neural networks, which do not explicitly use density representations, escape this scaling by mapping the chemical element information into a fixed dimensional space in a learnable way. We recast this approach as tensor factorisation by exploiting the tensor structure of standard neighbour density based descriptors. In doing so, we form compact tensor-reduced representations whose size does not depend on the number of chemical elements, but remain systematically convergeable and are therefore applicable to a wide range of data analysis and regression tasks.Comment: 8 pages, 4 figure

Regional astrocyte IFN signaling restricts pathogenesis during neurotropic viral infection

Type I IFNs promote cellular responses to viruses, and IFN receptor (IFNAR) signaling regulates the responses of endothelial cells of the blood-brain barrier (BBB) during neurotropic viral infection. However, the role of astrocytes in innate immune responses of the BBB during viral infection of the CNS remains to be fully elucidated. Here, we have demonstrated that type I IFNAR signaling in astrocytes regulates BBB permeability and protects the cerebellum from infection and immunopathology. Mice with astrocyte-specific loss of IFNAR signaling showed decreased survival after West Nile virus infection. Accelerated mortality was not due to expanded viral tropism or increased replication. Rather, viral entry increased specifically in the hindbrain of IFNAR-deficient mice, suggesting that IFNAR signaling critically regulates BBB permeability in this brain region. Pattern recognition receptors and IFN-stimulated genes had higher basal and IFN-induced expression in human and mouse cerebellar astrocytes than did cerebral cortical astrocytes, suggesting that IFNAR signaling has brain region–specific roles in CNS immune responses. Taken together, our data identify cerebellar astrocytes as key responders to viral infection and highlight the existence of distinct innate immune programs in astrocytes from evolutionarily disparate regions of the CNS

The Algorithm Theoretical Basis Document for the GLAS Atmospheric Data Products

The purpose of this document is to present a detailed description of the algorithm theoretical basis for each of the GLAS data products. This will be the final version of this document. The algorithms were initially designed and written based on the authors prior experience with high altitude lidar data on systems such as the Cloud and Aerosol Lidar System (CALS) and the Cloud Physics Lidar (CPL), both of which fly on the NASA ER-2 high altitude aircraft. These lidar systems have been employed in many field experiments around the world and algorithms have been developed to analyze these data for a number of atmospheric parameters. CALS data have been analyzed for cloud top height, thin cloud optical depth, cirrus cloud emittance (Spinhirne and Hart, 1990) and boundary layer depth (Palm and Spinhirne, 1987, 1998). The successor to CALS, the CPL, has also been extensively deployed in field missions since 2000 including the validation of GLAS and CALIPSO. The CALS and early CPL data sets also served as the basis for the construction of simulated GLAS data sets which were then used to develop and test the GLAS analysis algorithms

Ocean Chlorophyll Studies From a U-2 Aircraft Platform

Chlorophyll gradient maps of large ocean areas were generated from U-2/OCS data obtained over test sites in the Pacific and the Atlantic Oceans. The delineation of oceanic features using the upward radiant intensity relies on an analysis method which presupposes that radiation backscattered from the atmosphere and the ocean surface can be properly modeled by using a measurement made at 778 nm. The calculation of atmospheric radiance was performed by using a method developed by J.V. Dave. An estimation of the chlorophyll concentration is performed by properly ratioing radiances measured at 472 and 548 nm after removing the atmospheric effects. The correlation between the remotely sensed data and the in situ surface chlorophyll measurements has been validated in two sets of data. The results show that the correlation between the in situ measured chlorophyll and the derived quantity is a negative exponential function, and the correlation coefficient was calculated to be -0.965