Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

Metabonomics and Intensive Care

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2016. Other selected articles can be found online at http://www.biomedcentral.com/collections/annualupdate2016. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901

Semi-parametric benchmark dose analysis with monotone additive models.

Benchmark dose analysis aims to estimate the level of exposure to a toxin associated with a clinically significant adverse outcome and quantifies uncertainty using the lower limit of a confidence interval for this level. We develop a novel framework for benchmark dose analysis based on monotone additive dose-response models. We first introduce a flexible approach for fitting monotone additive models via penalized B-splines and Laplace-approximate marginal likelihood. A reflective Newton method is then developed that employs de Boor's algorithm for computing splines and their derivatives for efficient estimation of the benchmark dose. Finally, we develop a novel approach for calculating benchmark dose lower limits based on an approximate pivot for the nonlinear equation solved by the estimated benchmark dose. The favorable properties of this approach compared to the Delta method and a parameteric bootstrap are discussed. We apply the new methods to make inferences about the level of prenatal alcohol exposure associated with clinically significant cognitive defects in children using data from six NIH-funded longitudinal cohort studies. Software to reproduce the results in this paper is available online and makes use of the novel semibmd  R package, which implements the methods in this paper

Laser clad and HVOF sprayed Stellite 6 coating in chlorine rich environment with KCI at 700 °C

Laser clads and HVOF coatings from a stellite 6 alloy (Co–Cr–W–C alloy) on 304 stainless steel substrates were exposed both bare and with KCl deposits in 500 ppm HCl with 5% O2 for 250 h at 700 C. SEM/EDX and PXRD analyses with Rietveld refinement were used for assessment of the attack and for analysis of the scales. The bare samples suffered from scale spallation and the scale was mostly composed of Cr2O3, CoCr2O4 and CoO, although due to dilution haematite (Fe2O3) was detected in the scale formed on the laser clad sample. A small amount of hydrated HCl was detected in bare samples. While the corrosion of the bare surfaces was limited to comparatively shallow depths and manifested by g and M7C3 carbide formation, the presence of KCl on the surface led to severe Cr depletion from the HVOF coating (to 1 wt%). Both inward and outward diffusion of elements occurred in the HVOF coating resulting in Kirdendall voids at the coating–steel interface. The laser clad sample performed significantly better in conditions of the KCl deposit-induced corrosion. In addition to the oxides, CoCl2 was detected in the HVOF sample and K3CrO4 was detected in the laser clad sample. Thermodynamic calculations and kinetic simulations were carried out to interpret the oxidation and diffusion behaviours of coatings

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Entanglements of faith: Discourses, practices of care and homeless people in an Italian City of Saints

This is the author accepted manuscript. The final version is available from SAGE via http://dx.doi.org/10.1177/0042098013514620This paper investigates how Catholic-inspired services for homeless people are delivered in Turin, Italy. The purpose is to critically interrogate particular faith-based organisations’ moral discourses on homelessness, and to show how they are enacted through practices of care directed at the homeless subject. The paper contributes to the geographical literature on faith-based organisations addressing its shortcomings – namely the lack of critical and contextual focus on faith-based organisations’ ‘love for the poor’. To address this point, the paper takes a vitalist perspective on the urban and introduces the notion of the ‘entanglements of faith’, which allows an integrated and grounded perspective on faith-based organisations’ interventions. The outcomes of the work suggest that these faith-based organisations propose standardised services that, producing particular assemblages and affective atmospheres, have deep emotional and relational effects on their recipients. Further lines of research are sketched in the conclusions

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Land cover change across the major proglacial regions of the sub-Antarctic islands, Antarctic Peninsula, and McMurdo Dry Valleys, during the 21st century

Land cover information is essential for understanding Earth surface processes and ecosystems. Here, we use K-means clustering to classify Landsat 8 Operational Land Imager (OLI) images covering six proglacial sites of sub-Antarctic islands, the Antarctic Peninsula, and the McMurdo Dry Valleys at 30-m resolution. We quantify spatial patterns of water, bedrock, vegetation, and sediments to an accuracy of 77 percent. Vegetation is most abundant on South Georgia (7 percent of the proglacial area) and the South Shetland Islands (1 to 2 percent). Furthermore, we use change vector analysis (CVA) to discriminate landcover change in the twenty-first century. A latitudinal pattern is evident in ice loss and proglacial landscape change; for example, loss of ice on South Georgia and proglacial landcover change is two orders of magnitude greater than in the McMurdo Dry Valleys. Four of the studied sites had similar landscape stability (64 to 68 percent unchanged), with Alexander Island an exception (50 percent change) due to recent enhanced glacier melt. Overall, we show how landcover of proglacial regions of the climaticallysensitive sub-Antarctic and Antarctica has changed since 2000, with a CVA accuracy of 80 percent. These findings inform understanding of geomorphological activity and sediment and nutrient fluxes and hence terrestrial and marine ecosystems

Coincident evolution of glaciers and ice-marginal proglacial lakes across the Southern Alps, New Zealand: Past, present and future

Global glacier mass loss is causing expansion of proglacial landscapes and producing meltwater that can become impounded as lakes within natural topographic depressions or ‘overdeepenings’. It is important to understand the evolution of these proglacial landscapes for water resources, natural hazards and ecosystem services. In this study we (i) overview contemporary loss of glacier ice across the Southern Alps of New Zealand, (ii) analyse ice-marginal lake development since the 1980s, (iii) utilise modelled glacier ice thickness to suggest the position and size of future lakes, and (iv) employ a large-scale glacier evolution model to suggest the timing of future lake formation and future lake expansion rate. In recent decades, hundreds of Southern Alps glaciers have been lost and those remaining have fragmented both by separation of tributaries and by detachment of ablation zones. Glaciers with ice-contact margins in proglacial lakes (n > 0.1 km2 = 20 in 2020) have experienced the greatest terminus retreat and typically twice as negative mass balance compared to similar-sized land-terminating glaciers. Our analysis indicates a positive relationship between mean glacier mass balance and rate of lake growth (R2 = 0.34) and also with length of an ice-contact lake boundary (R2 = 0.44). We project sustained and relatively homogenous glacier volume loss for east-draining basins but in contrast a heterogeneous pattern of volume loss for west-draining basins. Our model results show that ice-marginal lakes will increase in combined size by ~150% towards 2050 and then decrease to 2100 as glaciers disconnect from them. Overall, our findings should inform (i) glacier evolution models into which ice-marginal lake effects need incorporating, (ii) studies of rapid landscape evolution and especially of meltwater and sediment delivery, and (iii) considerations of future meltwater supply and water quality