Chemical modification of extracellular matrix by cold atmospheric plasma-generated reactive species affects chondrogenesis and bone formation.

The goal of this study was to investigate whether cold plasma generated by dielectric barrier discharge (DBD) modifies extracellular matrices (ECM) to influence chondrogenesis and endochondral ossification. Replacement of cartilage by bone during endochondral ossification is essential in fetal skeletal development, bone growth and fracture healing. Regulation of this process by the ECM occurs through matrix remodelling, involving a variety of cell attachment molecules and growth factors, which influence cell morphology and protein expression. The commercially available ECM, Matrigel, was treated with microsecond or nanosecond pulsed (μsp or nsp, respectively) DBD frequencies conditions at the equivalent frequencies (1 kHz) or power (~1 W). Recombinant human bone morphogenetic protein-2 was added and the mixture subcutaneously injected into mice to simulate ectopic endochondral ossification. Two weeks later, the masses were extracted and analysed by microcomputed tomography. A significant increase in bone formation was observed in Matrigel treated with μsp DBD compared with control, while a significant decrease in bone formation was observed for both nsp treatments. Histological and immunohistochemical analysis showed Matrigel treated with μsp plasma increased the number of invading cells, the amount of vascular endothelial growth factor and chondrogenesis while the opposite was true for Matrigel treated with nsp plasma. In support of the in vivo Matrigel study, 10 T1/2 cells cultured in vitro on μsp DBD-treated type I collagen showed increased expression of adhesion proteins and activation of survival pathways, which decreased with nsp plasma treatments. These results indicate DBD modification of ECM can influence cellular behaviours to accelerate or inhibit chondrogenesis and endochondral ossification. Copyright © 2016 John Wiley & Sons, Ltd

A 490 GHz planar circuit balanced Nb-Al2_\mathbf{2}O3_{\mathbf{3}}-Nb quasiparticle mixer for radio astronomy: Application to quantitative local oscillator noise determination

This article presents a heterodyne experiment which uses a 380-520 GHz planar circuit balanced Nb-$\mathrm{Al_2O_3}$-Nb superconductor-insulator-superconductor (SIS) quasiparticle mixer with 4-8 GHz instantaneous intermediate frequency (IF) bandwidth to quantitatively determine local oscillator (LO) noise. A balanced mixer is a unique tool to separate noise at the mixer's LO port from other noise sources. This is not possible in single-ended mixers. The antisymmetric IV characteristic of a SIS mixer further helps to simplify the measurements. The double-sideband receiver sensitivity of the balanced mixer is 2-4 times the quantum noise limit $h\nu/k_B$ over the measured frequencies with a maximum LO noise rejection of 15 dB. This work presents independent measurements with three different LO sources that produce the reference frequency but also an amount of near-carrier noise power which is quantified in the experiment as a function of the LO and IF frequency in terms of an equivalent noise temperature $T_{LO}$. In a second experiment we use only one of two SIS mixers of the balanced mixer chip, in order to verify the influence of near-carrier LO noise power on a single-ended heterodyne mixer measurement. We find an IF frequency dependence of near-carrier LO noise power. The frequency-resolved IF noise temperature slope is flat or slightly negative for the single-ended mixer. This is in contrast to the IF slope of the balanced mixer itself which is positive due to the expected IF roll-off of the mixer. This indicates a higher noise level closer to the LO's carrier frequency. Our findings imply that near-carrier LO noise has the largest impact on the sensitivity of a receiver system which uses mixers with a low IF band, for example superconducting hot-electron bolometer (HEB) mixers.Comment: 13 pages, 8 figures, 2 tables, see manuscript for complete abstrac

Brief mindfulness training enhances cognitive control in socioemotional contexts: Behavioral and neural evidence.

In social contexts, the dynamic nature of others' emotions places unique demands on attention and emotion regulation. Mindfulness, characterized by heightened and receptive moment-to-moment attending, may be well-suited to meet these demands. In particular, mindfulness may support more effective cognitive control in social situations via efficient deployment of top-down attention. To test this, a randomized controlled study examined effects of mindfulness training (MT) on behavioral and neural (event-related potentials [ERPs]) responses during an emotional go/no-go task that tested cognitive control in the context of emotional facial expressions that tend to elicit approach or avoidance behavior. Participants (N = 66) were randomly assigned to four brief (20 min) MT sessions or to structurally equivalent book learning control sessions. Relative to the control group, MT led to improved discrimination of facial expressions, as indexed by d-prime, as well as more efficient cognitive control, as indexed by response time and accuracy, and particularly for those evidencing poorer discrimination and cognitive control at baseline. MT also produced better conflict monitoring of behavioral goal-prepotent response tendencies, as indexed by larger No-Go N200 ERP amplitudes, and particularly so for those with smaller No-Go amplitude at baseline. Overall, findings are consistent with MT's potential to enhance deployment of early top-down attention to better meet the unique cognitive and emotional demands of socioemotional contexts, particularly for those with greater opportunity for change. Findings also suggest that early top-down attention deployment could be a cognitive mechanism correspondent to the present-oriented attention commonly used to explain regulatory benefits of mindfulness more broadly

Geographical inequalities in use of improved drinking water supply and sanitation across Sub-Saharan Africa: mapping and spatial analysis of cross-sectional survey data.

BACKGROUND: Understanding geographic inequalities in coverage of drinking-water supply and sanitation (WSS) will help track progress towards universal coverage of water and sanitation by identifying marginalized populations, thus helping to control a large number of infectious diseases. This paper uses household survey data to develop comprehensive maps of WSS coverage at high spatial resolution for sub-Saharan Africa (SSA). Analysis is extended to investigate geographic heterogeneity and relative geographic inequality within countries. METHODS AND FINDINGS: Cluster-level data on household reported use of improved drinking-water supply, sanitation, and open defecation were abstracted from 138 national surveys undertaken from 1991-2012 in 41 countries. Spatially explicit logistic regression models were developed and fitted within a Bayesian framework, and used to predict coverage at the second administrative level (admin2, e.g., district) across SSA for 2012. Results reveal substantial geographical inequalities in predicted use of water and sanitation that exceed urban-rural disparities. The average range in coverage seen between admin2 within countries was 55% for improved drinking water, 54% for use of improved sanitation, and 59% for dependence upon open defecation. There was also some evidence that countries with higher levels of inequality relative to coverage in use of an improved drinking-water source also experienced higher levels of inequality in use of improved sanitation (rural populations r = 0.47, p = 0.002; urban populations r = 0.39, p = 0.01). Results are limited by the quantity of WSS data available, which varies considerably by country, and by the reliability and utility of available indicators. CONCLUSIONS: This study identifies important geographic inequalities in use of WSS previously hidden within national statistics, confirming the necessity for targeted policies and metrics that reach the most marginalized populations. The presented maps and analysis approach can provide a mechanism for monitoring future reductions in inequality within countries, reflecting priorities of the post-2015 development agenda. Please see later in the article for the Editors' Summary

TPN‐associated intestinal epithelial cell atrophy is modulated by TLR4/EGF signaling pathways

Recent studies suggest a close interaction between epidermal growth factor (EGF) and TLR signaling in the modulation of intestinal epithelial cell (IEC) proliferation; however, how these signaling pathways adjust IEC proliferation is poorly understood. We utilized a model of total parenteral nutrition (TPN), or enteral nutrient deprivation, to study this interaction as TPN results in mucosal atrophy due to decreased IEC proliferation and increased apoptosis. We identified the novel finding of decreased mucosal atrophy in TLR4 knockout (TLR4KO) mice receiving TPN. We hypothesized that EGF signaling is preserved in TLR4KO‐TPN mice and prevents mucosal atrophy. C57B1/6 and strain‐matched TLR4KO mice were provided either enteral feeding or TPN. IEC proliferation and apoptosis were measured. Cytokine and growth factor abundances were detected in both groups. To examine interdependence of these pathways, ErbB1 pharmacologic blockade was used. The marked decline in IEC proliferation with TPN was nearly prevented in TLR4KO mice, and intestinal length was partially preserved. EGF was significantly increased, and TNF‐α decreased in TLR4KO‐TPN versus wild‐type (WT)‐TPN mice. Apoptotic positive crypt cells were 15‐fold higher in WT‐TPN versus TLR4KO‐TPN mice. Bcl‐2 was significantly increased in TLR4KOTPN mice, while Bax decreased 10‐fold. ErbB1 blockade prevented this otherwise protective effect in TLR4KO‐sTPN mice. TLR4 blockade significantly prevented TPN‐associated atrophy by preserving proliferation and preventing apoptosis. This is driven by a reduction in TNF‐α abundance and increased EGF. Potential manipulation of this regulatory pathway may have significant clinical potential to prevent TPN‐associated atrophy.—Freeman, J. J., Feng, Y., Demehri, F. R., Dempsey, P. J., Teitelbaum, D. H. TPN‐associated intestinal epithelial cell atrophy is modulated by TLR4/EGF signaling pathways. FASEB J. 29, 2943‐2958 (2015). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154328/1/fsb2fj14269480.pd

Rapid, Semi-Automated Fractionation of Freshwater Dissolved Organic Carbon Using DAX 8 (XAD 8) and XAD 4 Resins in Tandem

Natural dissolved organic carbon (DOC) consists of different bio-molecular classes of compounds that are currently very difficult and time-consuming to isolate as individual compounds. However, it is possible to separate natural DOC into hydrophobic and hydrophilic fractions. Such characterisation approaches are becoming increasingly important because, over the past 20 years natural DOC concentrations have been rising rapidly in many parts of the world, most likely influenced by climate change. Higher DOC concentrations in drinking water catchments present a serious problem for the water industry because DOC can form disinfection by-products DBPs during water treatment (e.g. chlorination). Hence, there is an urgent need to better characterise natural DOC before, during and after water treatment. However, current DOC fractionation procedures are extremely laborious requiring days and continual manual monitoring to separate sufficient quantities of DOC for subsequent analysis. This seriously limits sample throughput and the parameter space which can be studied. In this paper, we propose a much more rapid semi-automated method (12.5 hours/litre/sample) which utilises readily available equipment, i.e., HPLC pump or similar and sequential columns of Amberlite DAX 8 and XAD 4 resins. The method reduces the manual input from continual attention to minutes. This paper describes the development of the method and its application in the fractionation of natural DOC from reservoir and lake samples fed from upland peat-land catchments. Recoveries are found to be comparable to those using the manual technique, with the dominant component being hydrophobic acid accounting for 35% - 40% of the natural DOC with the second largest, being hydrophilic acid at 20% - 27%

Sustained Thromboresistant Bioactivity with Reduced Intimal Hyperplasia of Heparin-Bonded PTFE Propaten Graft in a Chronic Canine Femoral Artery Bypass Model

Background: Bypass graft thrombosis remains a significant mode of failure in prosthetic graft revascularization. The purpose of this investigation was to evaluate the long-term thromboresistant effect of heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft using Carmeda BioActive Surface technology in a canine model. Methods: Bilateral femorofemoral artery bypass grafts with ePTFE grafts were performed in 25 adult grayhound dogs. In each animal, a heparin-bonded ePTFE graft (Propaten, WL Gore) was placed on one side, whereas a control nonheparin graft was placed on the contralateral side. The graft patency was assessed at 1, 6, 12, 18, and 24 months (n = 5 per group) following the bypass. Heparin bioactivity of the graft material was analyzed. The effect of intimal hyperplasia was also assessed. Results: All bypass grafts were patent at 1 month. Significantly greater patency rates were noted in the Propaten group compared to the control group at 12, 18, and 24 months, which were 84%, 80%, and 80% vs. 55%, 35%, and 20%, respectively (P 0.05). Conclusions: Heparin-bonded ePTFE graft provides a thromboresistant surface and reduced anastomotic intimal hyperplasia at 2 years. The stable heparin bioactivity of the Propaten graft confers an advantage in long-term graft patency

Plasma homocyst(e)ine concentration, but not MTHFR genotype, is associated with variation in carotid plaque area

Background and Purpose - Elevated plasma homocyst(e)ine [H(e)] concentration is associated with premature atherosclerosis. A common cause of elevated plasma H(e) concentration is a thermolabile mutation (677T) in the gene encoding methylenetetrahydrofolate reductase (MTHFR). We sought to determine whether plasma H(e) concentration or MTHFR genotype would be more strongly associated with carotid plaque area (CPA), a potential intermediate phenotype of atherosclerosis. Methods - In 307 subjects who were ascertained through a premature atherosclerosis clinic, we measured CPA with 2- dimensional ultrasound and also determined traditional atherosclerosis risk factors, in addition to plasma H(e) concentration and MTHFR genotypes. Results - We found that the frequency of the MTHFR 677T allele was 0.363 in this sample. Mean plasma H(e) concentration was significantly higher in 677T/T homozygotes than in 677T/C heterozygotes and 677C/C homozygotes (17.1±13.7 versus 13.5±6.1 versus 12.6±5.9 μmol/L, respectively, P\u3c0.001). Analysis of variance showed that CPA was significantly associated with age, sex, smoking, diabetes, hypertension, and hyperlipidemia (each P\u3c0.05). When plasma H(e) concentration was included in the model, it was significantly associated with CPA (P\u3c0.05). However, when the MTHFR genotype was included in the model, it was not associated with CPA (P=0.50). Furthermore, there was a significant correlation of CPA with plasma H(e) (r=0.23, P\u3c0.0001). However, the mean CPA did not differ between subjects according to genotype. Conclusions - Thus, plasma H(e), but not MTHFR genotype, is significantly associated with carotid atherosclerosis, suggesting that the biochemical test may be sufficient to identify patients who may be at increased risk of atherosclerosis through this mechanism

Stakeholder Theory and Marketing: Moving from a Firm-Centric to a Societal Perspective

This essay is inspired by the ideas and research examined in the special section on “Stakeholder Marketing” of the Journal of Public Policy & Marketing in 2010. The authors argue that stakeholder marketing is slowly coalescing with the broader thinking that has occurred in the stakeholder management and ethics literature streams during the past quarter century. However, the predominant view of stakeholders that many marketers advocate is still primarily pragmatic and company centric. The position advanced herein is that stronger forms of stakeholder marketing that reflect more normative, macro/societal, and network-focused orientations are necessary. The authors briefly explain and justify these characteristics in the context of the growing “prosociety” and “proenvironment” perspectives—orientations that are also in keeping with the public policy focus of this journal. Under the “hard form” of stakeholder theory, which the authors endorse, marketing managers must realize that serving stakeholders sometimes requires sacrificing maximum profits to mitigate outcomes that would inflict major damage on other stakeholders, especially society