Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo.

Experiments were designed to study the effect of systemically administered IL-5 on local eosinophil accumulation induced by the intradermal injection of the chemokine eotaxin in the guinea pig. Intravenous interleukin-5 (IL-5) stimulated a rapid and dramatic increase in the numbers of accumulating eosinophils induced by i.d.-injected eotaxin and, for comparison, leukotriene B4. The numbers of locally accumulating eosinophils correlated directly with a rapid increase in circulating eosinophils: circulating eosinophil numbers were 13-fold higher 1 h after intravenous IL-5 (18.3 pmol/kg). This increase in circulating cells corresponded with a reduction in the number of displaceable eosinophils recovered after flushing out the femur bone marrow cavity. Intradermal IL-5, at the doses tested, did not induce significant eosinophil accumulation. We propose that these experiments simulate important early features of the tissue response to local allergen exposure in a sensitized individual, with eosinophil chemoattractant chemokines having an important local role in eosinophil recruitment from blood microvessels, and IL-5 facilitating this process by acting remotely as a hormone to stimulate the release into the circulation of a rapidly mobilizable pool of bone marrow eosinophils. This action of IL-5 would be complementary to the other established activities of IL-5 that operate over a longer time course

Airborne observations of the tropospheric CO2 distribution and its controlling factors over the South Pacific Basin

Highly precise measurements of CO2 mixing ratios were recorded aboard both the NASA DC-8 and P3-B aircraft during the Pacific Exploratory Mission-Tropics conducted in August-October 1996. Data were obtained at altitudes ranging from 0.1 to 12 km over a large portion of the South Pacific Basin representing the most geographically extensive CO2 data set recorded in this region. These data along with CO2 surface measurements from the National Oceanic and Atmospheric Administration/Climate Monitoring and Diagnostics Laboratory (NOAA/CMDL) and the National Institute of Water and Atmospheric Research (NIWA) were examined to establish vertical and meridional gradients. The CO2 spatial distribution in the southern hemisphere appeared to be largely determined by interhemispheric transport as air masses with depleted CO2 levels characteristic of northern hemispheric air were frequently observed south of the Intertropical Convergence Zone. However, regional processes also played a role in modulating background concentrations. Comparisons of CO2 with other trace gases indicated that CO2 values were influenced by continental sources. Large scale plumes from biomass burning activities produced enhanced CO2 mixing ratios within the lower to midtroposphere over portions of the remote Pacific. An apparent CO2 source was observed in the NOAA/ CMDL surface data between 15° N and 15° S and in the lower altitude flight data between 8° N and 8.5° S with a zone of intensity from 6.5° N to 1° S. Inferred from these data is the presence of a Southern Ocean sink from south of 15° S having two distinct zones seasonally out of phase with one another. Copyright 1999 by the American Geophysical Union

Hydrocode modeling of the Sierra Madera impact structure

We present the first hydrocode simulations of the formation of the Sierra Madera structure (west Texas, USA), which was caused by an impact into a thick sedimentary target sequence. We modeled Sierra Madera using the iSALE hydrocode, and here we present two best-fit models: 1) a crater with a rim (final crater) diameter of ~12 km, in agreement with previous authors interpretations of the original structure, and 2) a crater ~16 km in diameter with increased postimpact erosion. Both models fit some of the geologic observational data, but discrepancies with estimates of peak shock pressure, extent of deformation, and stratigraphic displacement remain. This study suggests that Sierra Madera may be a larger crater than previously reported and illustrates some of the challenges in simulating impact deformation of sedimentary lithologies. As many terrestrial craters possess some amount of sedimentary rocks in the target sequence, numerical models of impacts into sedimentary targets are essential to our understanding of target rock deformation and the mechanics of crater formation.The Meteoritics & Planetary Science archives are made available by the Meteoritical Society and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202

Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation.

Eosinophil accumulation is a prominent feature of allergic inflammatory reactions, such as those occurring in the lung of the allergic asthmatic, but the endogenous chemoattractants involved have not been identified. We have investigated this in an established model of allergic inflammation, using in vivo systems both to generate and assay relevant activity. Bronchoalveolar lavage (BAL) fluid was taken from sensitized guinea pigs at intervals after aerosol challenge with ovalbumin. BAL fluid was injected intradermally in unsensitized assay guinea pigs and the accumulation of intravenously injected 111In-eosinophils was measured. Activity was detected at 30 min after allergen challenge, peaking from 3 to 6 h and declining to low levels by 24 h. 3-h BAL fluid was purified using high performance liquid chromatography techniques in conjunction with the skin assay. Microsequencing revealed a novel protein from the C-C branch of the platelet factor 4 superfamily of chemotactic cytokines. The protein, eotaxin, exhibits homology of 53% with human MCP-1, 44% with guinea pig MCP-1, 31% with human MIP-1α, and 26% with human RANTES. Laser desorption time of flight mass analysis gave four different signals (8.15, 8.38, 8.81, and 9.03 kD), probably reflecting differential O-glycosylation. Eotaxin was highly potent, inducing substantial 111In-eosinophil accumulation at a 1-2-pmol dose in the skin, but did not induce significant 111In-neutrophil accumulation. Eotaxin was a potent stimulator of both guinea pig and human eosinophils in vitro. Human recombinant RANTES, MIP-1α, and MCP-1 were all inactive in inducing 111In-eosinophil accumulation in guinea pig skin; however, evidence was obtained that eotaxin shares a binding site with RANTES on guinea pig eosinophils. This is the first description of a potent eosinophil chemoattractant cytokine generated in vivo and suggests the possibility that similar molecules may be important in the human asthmatic lung

Near wall hemodynamics: Modelling the glycocalyx and the endothelial surface

This paper was presented at the 3rd Micro and Nano Flows Conference (MNF2011), which was held at the Makedonia Palace Hotel, Thessaloniki in Greece. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, Aristotle University of Thessaloniki, University of Thessaly, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute.In this paper a coarse-grained model for blood flow in small arteries is presented. Blood is modelled as a two-component incompressible fluid: the plasma and corpuscular elements dispersed in it. The latter are modelled as deformable liquid droplets having greater density and viscosity. Interfacial surface tension and membrane effects are present to mimic key properties and to avoid droplets’ coalescence. The mesoscopic model also includes the presence of the wavy wall, due to the endothelial cells and incorporates a representation of the glycocalyx, covering the vessel wall. The glycocalyx is modelled as a porous medium, the droplets being subjected to a repulsive elastic force when approaching it, during their transit. Preliminary simulations are intended to show the influence of the undulation on the wall together with that of the glycocalyx

Aerobic Fitness and Playing Experience Protect Against Spikes in Workload: The Role of the Acute:Chronic Workload Ratio on Injury Risk in Elite Gaelic Football.

PURPOSE: To examine the association between combined session-RPE workload measures and injury risk in elite Gaelic footballers. METHODS: Thirty-seven elite Gaelic footballers (mean ± SD age of 24.2 ± 2.9 yr) from one elite squad were involved in a single season study. Weekly workload (session-RPE multiplied by duration) and all time-loss injuries (including subsequent week injuries) were recorded during the period. Rolling weekly sums and week-to-week changes in workload were measured, allowing for the calculation of the 'acute:chronic workload ratio' that was calculated by dividing acute workload (i.e. 1-week workload) by chronic workload (i.e. rolling average 4-weekly workload). Workload measures were then modelled against all injury data sustained using a logistic regression model. Odds ratios (OR) were reported against a reference group. RESULTS: High 1-weekly workloads (≥2770 AU, OR = 1.63 - 6.75) were associated with significantly higher risk of injury compared to a low training load reference group (1.5), players with 1 year experience had a higher risk of injury (OR = 2.22) and players with 2-3 (OR = 0.20) and 4-6 years (OR = 0.24) of experience had a lower risk of injury. Players with poorer aerobic fitness (estimated from a 1 km time trial) had a higher injury risk compared to players with higher aerobic fitness (OR = 1.50-2.50). An acute:chronic workload ratio of (≥2.0) demonstrated the greatest risk of injury. CONCLUSIONS: These findings highlight an increased risk of injury for elite Gaelic football players with high (>2.0) acute:chronic workload ratios and high weekly workloads. A high aerobic capacity and playing experience appears to offer injury protection against rapid changes in workload and high acute:chronic workload ratios. Moderate workloads, coupled with moderate-high changes in the acute:chronic workload ratio appear to be protective for Gaelic football players

High chronic training loads and exposure to bouts of maximal velocity running reduce injury risk in elite Gaelic football.

OBJECTIVES: To examine the relationship between chronic training loads, number of exposures to maximal velocity, the distance covered at maximal velocity, percentage of maximal velocity in training and match-play and subsequent injury risk in elite Gaelic footballers. DESIGN: Prospective cohort design. METHODS: Thirty-seven elite Gaelic footballers from one elite squad were involved in a one-season study. Training and game loads (session-RPE multiplied by duration in min) were recorded in conjunction with external match and training loads (using global positioning system technology) to measure the distance covered at maximal velocity, relative maximal velocity and the number of player exposures to maximal velocity across weekly periods during the season. Lower limb injuries were also recorded. Training load and GPS data were modelled against injury data using logistic regression. Odds ratios (OR) were calculated based on chronic training load status, relative maximal velocity and number of exposures to maximal velocity with these reported against the lowest reference group for these variables. RESULTS: Players who produced over 95% maximal velocity on at least one occasion within training environments had lower risk of injury compared to the reference group of 85% maximal velocity on at least one occasion (OR: 0.12, p=0.001). Higher chronic training loads (≥4750AU) allowed players to tolerate increased distances (between 90 to 120m) and exposures to maximal velocity (between 10 to 15 exposures), with these exposures having a protective effect compared to lower exposures (OR: 0.22 p=0.026) and distance (OR=0.23, p=0.055). CONCLUSIONS: Players who had higher chronic training loads (≥4750AU) tolerated increased distances and exposures to maximal velocity when compared to players exposed to low chronic training loads (≤4750AU). Under- and over-exposure of players to maximal velocity events (represented by a U-shaped curve) increased the risk of injury

Can the workload–injury relationship be moderated by improved strength, speed and repeated-sprint qualities?

Objectives The aim of this study was to investigate potential moderators (i.e. lower body strength, repeated-sprint ability [RSA] and maximal velocity) of injury risk within a team-sport cohort. Design Observational Cohort Study. Methods Forty male amateur hurling players (age: 26.2 ± 4.4 yr, height: 184.2 ± 7.1 cm, mass: 82.6 ± 4.7 kg) were recruited. During a two-year period, workload (session RPE x duration), injury and physical qualities were assessed. Specific physical qualities assessed were a three-repetition maximum Trapbar deadlift, 6 × 35-m repeated-sprint (RSA) and 5-, 10- and 20-m sprint time. All derived workload and physical quality measures were modelled against injury data using regression analysis. Odds ratios (OR) were reported against a reference group. Results Moderate weekly loads between ≥ 1400 AU and ≤ 1900 AU were protective against injury during both the pre-season (OR: 0.44, 95%CI: 0.18–0.66) and in-season periods (OR: 0.59, 95% CI: 0.37–0.82) compared to a low load reference group (≤ 1200 AU). When strength was considered as a moderator of injury risk, stronger athletes were better able to tolerate the given workload at a reduced risk. Stronger athletes were also better able to tolerate larger week-to-week changes ( > 550 AU to 1000 AU) in workload than weaker athletes (OR = 2.54–4.52). Athletes who were slower over 5-m (OR: 3.11, 95% CI: 2.33–3.87), 10-m (OR: 3.45, 95% CI: 2.11–4.13) and 20-m (OR: 3.12, 95% CI: 2.11–4.13) were at increased risk of injury compared to faster athletes. When repeated-sprint total time (RSAt) was considered as a moderator of injury risk at a given workload (≥ 1750 AU), athletes with better RSAt were at reduced risk compared to those with poor RSAt (OR: 5.55, 95%: 3.98–7.94). Conclusions These findings demonstrate that well-developed lower-body strength, RSA and speed are associated with better tolerance to higher workloads and reduced risk of injury in team-sport athletes

Combinatorial Synthesis of Structurally Diverse Triazole-Bridged Flavonoid Dimers and Trimers

Flavonoids are a large family of compounds associated with a broad range of biologically useful properties. In recent years, synthetic compounds that contain two flavonoid units linked together have attracted attention in drug discovery and development projects. Numerous flavonoid dimer systems, incorporating a range of monomers attached via different linkers, have been reported to exhibit interesting bioactivities. From a medicinal chemistry perspective, the 1,2,3-triazole ring system has been identified as a particularly attractive linker moiety in dimeric derivatives (owing to several favourable attributes including proven biological relevance and metabolic stability) and triazole-bridged flavonoid dimers possessing anticancer and antimalarial activities have recently been reported. However, there are relatively few examples of libraries of triazole-bridged flavonoid dimers and the diversity of flavonoid subunits present within these is typically limited. Thus, this compound type arguably remains underexplored within drug discovery. Herein, we report a modular strategy for the synthesis of novel and biologically interesting triazole-bridged flavonoid heterodimers and also very rare heterotrimers from readily available starting materials. Application of this strategy has enabled step-efficient and systematic access to a library of structurally diverse compounds of this sort, with a variety of monomer units belonging to six different structural subclasses of flavonoid successfully incorporated.Cambridge Commonwealth Trust, European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013)/ERC grant agreement No. [279337/DOS], AstraZeneca, European Union, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Medical Research Council, Wellcome Trus

Homogeneous catalysis under ultra-dilute conditions: TAML/NaClO oxidation of persistent metaldehyde

This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Journal of the American Chemical Society, copyright © American Chemical Society after peer review. To access the final edited and published work see https://doi.org/10.1021/jacs.6b11145TAML activators enable homogenous oxidation catalysis where the catalyst and substrate (S) are ultra-dilute (pM–low μM) and the oxidant is very dilute (high nM–low mM). Water contamination by exceptionally persistent micropollutants (MPs), including metaldehyde (Met), provides an ideal space for determining the characteristics and utilitarian limits of this ultradilute catalysis. The low MP concentrations decrease throughout catalysis with S oxidation (kII) and catalyst inactivation (ki) competing for the active catalyst. The percentage of substrate converted (%Cvn) can be increased by discovering methods to increase kII/ki. Here we show that NaClO extends catalyst lifetime to increase the Met turnover number (TON) threefold compared with H2O2, highlighting the importance of oxidant choice as a design tool in TAML systems. Met oxidation studies (pH 7, D2O, 0.01 M phosphate, 25 °C) monitored by 1H NMR spectroscopy show benign acetic acid as the only significant product. Analysis of TAML/NaClO treated Met solutions employing successive identical catalyst doses revealed that the processes can be modeled by the recently published relationship between the initial and final [S] (S0 and S∞, respectively), the initial [catalyst] (FeTot) and kII/ki. Consequently, this study establishes that S is proportional to S0 and that the %Cvn is conserved across all catalyst doses in multicatalyst-dose processes because the rate of the kII process depends on [S] while that of the ki process does not. A general tool for determining the FeTot required to effect a desired %Cvn is presented. Examination of the dependence of TON on kII/ki and FeTot at a fixed S0 indicates that for any TAML process employing FeTot < 1 10-6 M, small catalyst doses are not more efficient than one large dose.T.J.C thanks the Heinz Endowments for funding. NMR instrumentation at CMU was partially supported by NSF (CHE-0130903 and CHE-1039870)