Sample records for reduced barrier function
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LaDow, Kathy; Schumann, Brenda L; Luse, Nicole; Warshawsky, Dave; Pickens, William L; Hoath, Steven B; Talaska, Glenn
2011-12-01
The dermal route is important in many occupational exposures. Some materials may reduce the barrier function of the skin to enhance absorption and effect on internal organs. We have reported previously that kerosene cleaning following treatment with used engine oil increased DNA adduct levels in the lungs of mice compared with animals treated with used oil alone. To investigate what other physiological parameters might be affected by kerosene, we conducted in vitro and in vivo measurements of skin barrier function. We also topically applied (3)H-BAP(100 nM in 25 μL acetone) and washed half the mice with 25 μL kerosene 1 hr after carcinogen application. Groups of four mice were euthanized from 1 to 72 hr after treatment. Skin, lungs, and livers were harvested from each animal and stored separately. Kerosene application reduced the barrier function of the skin in vitro beyond the effect of the acetone vehicle and the vehicle plus BAP. In vivo studies indicated that kerosene treatment reduced the barrier function at 4 and 8 hr post application and that the barrier function recovered at 24 hr after a single treatment. The fraction of the radiolabel remaining in the skin of animals treated with (3)H-BAP and washed with kerosene was significantly less than those not washed, beginning at 24 hr (p< 0.05). Fractional distribution to the lungs and livers of these animals became significantly elevated at this time. Kerosene treatment compromises dermal barrier function and the ability of the skin to retain water, enhances carcinogen absorption, and alters organ distribution. This appears to contribute to the increase in BAP DNA adducts we reported earlier.
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Dudek, Steven M.; Chiang, Eddie T.; Camp, Sara M.; Guo, Yurong; Zhao, Jing; Brown, Mary E.; Singleton, Patrick A.; Wang, Lichun; Desai, Anjali; Arce, Fernando T.; Lal, Ratnesh; Van Eyk, Jennifer E.; Imam, Syed Z.
2010-01-01
Nonmuscle myosin light chain kinase (nmMLCK), a multi-functional cytoskeletal protein critical to vascular homeostasis, is highly regulated by tyrosine phosphorylation. We identified multiple novel c-Abl–mediated nmMLCK phosphorylation sites by mass spectroscopy analysis (including Y231, Y464, Y556, Y846) and examined their influence on nmMLCK function and human lung endothelial cell (EC) barrier regulation. Tyrosine phosphorylation of nmMLCK increased kinase activity, reversed nmMLCK-mediated inhibition of Arp2/3-mediated actin polymerization, and enhanced binding to the critical actin-binding phosphotyrosine protein, cortactin. EC challenge with sphingosine 1-phosphate (S1P), a potent barrier-enhancing agonist, resulted in c-Abl and phosphorylated nmMLCK recruitment into caveolin-enriched microdomains, rapid increases in Abl kinase activity, and spatial targeting of c-Abl to barrier-promoting cortical actin structures. Conversely, reduced c-Abl expression in EC (siRNA) markedly attenuated S1P-mediated cortical actin formation, reduced the EC modulus of elasticity (assessed by atomic force microscopy), reduced nmMLCK and cortactin tyrosine phosphorylation, and attenuated S1P-mediated barrier enhancement. These studies indicate an essential role for Abl kinase in vascular barrier regulation via posttranslational modification of nmMLCK and strongly support c-Abl-cortactin-nmMLCK interaction as a novel determinant of cortical actin-based cytoskeletal rearrangement critical to S1P-mediated EC barrier enhancement. PMID:20861316
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Standards for the Protection of Skin Barrier Function.
Giménez-Arnau, Ana
2016-01-01
The skin is a vital organ, and through our skin we are in close contact with the entire environment. If we lose our skin we lose our life. The barrier function of the skin is mainly driven by the sophisticated epidermis in close relationship with the dermis. The epidermal epithelium is a mechanically, chemically, biologically and immunologically active barrier submitted to continuous turnover. The barrier function of the skin needs to be protected and restored. Its own physiology allows its recovery, but many times this is not sufficient. This chapter is focused on the standards to restore, treat and prevent barrier function disruption. These standards were developed from a scientific, academic and clinical point of view. There is a lack of standardized administrative recommendations. Still, there is a walk to do that will help to reduce the social and economic burden of diseases characterized by an abnormal skin barrier function. © 2016 S. Karger AG, Basel.
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Cheng, You-Hong; Eby, Jonathan M; LaPorte, Heather M; Volkman, Brian F; Majetschak, Matthias
2017-01-01
Recent evidence suggests that chemokine CXCL12, the cognate agonist of chemokine receptors CXCR4 and ACKR3, reduces thrombin-mediated impairment of endothelial barrier function. A detailed characterization of the effects of CXCL12 on thrombin-mediated human lung endothelial hyperpermeability is lacking and structure-function correlations are not available. Furthermore, effects of other CXCR4/ACKR3 ligands on lung endothelial barrier function are unknown. Thus, we tested the effects of a panel of CXCR4/ACKR3 ligands (CXCL12, CXCL11, ubiquitin, AMD3100, TC14012) and compared the CXCR4/ACKR3 activities of CXCL12 variants (CXCL12α/β, CXCL12(3-68), CXCL121, CXCL122, CXCL12-S-S4V, CXCL12-R47E, CXCL12-K27A/R41A/R47A) with their effects on human lung endothelial barrier function in permeability assays. CXCL12α enhanced human primary pulmonary artery endothelial cell (hPPAEC) barrier function, whereas CXCL11, ubiquitin, AMD3100 and TC14012 were ineffective. Pre-treatment of hPPAEC with CXCL12α and ubiquitin reduced thrombin-mediated hyperpermeability. CXCL12α-treatment of hPPAEC after thrombin exposure reduced barrier function impairment by 70% (EC50 0.05-0.5nM), which could be antagonized with AMD3100; ubiquitin (0.03-3μM) was ineffective. In a human lung microvascular endothelial cell line (HULEC5a), CXCL12α and ubiquitin post-treatment attenuated thrombin-induced hyperpermeability to a similar degree. CXCL12(3-68) was inefficient to activate CXCR4 in Presto-Tango β-arrestin2 recruitment assays; CXCL12-S-S4V, CXCL12-R47E and CXCL12-K27A/R41A/R47A showed significantly reduced potencies to activate CXCR4. While the potencies of all proteins in ACKR3 Presto-Tango assays were comparable, the efficacy of CXCL12(3-68) to activate ACKR3 was significantly reduced. The potencies to attenuate thrombin-mediated hPPAEC barrier function impairment were: CXCL12α/β, CXCL121, CXCL12-K27A/R41A/R47A > CXCL12-S-S4V, CXCL12-R47E > CXCL122 > CXCL12(3-68). Our findings indicate that CXCR4 activation attenuates thrombin-induced lung endothelial barrier function impairment and suggest that protective effects of CXCL12 are dictated by its CXCR4 agonist activity and interactions of distinct protein moieties with heparan sulfate on the endothelial surface. These data may facilitate development of compounds with improved pharmacological properties to attenuate thrombin-induced vascular leakage in the pulmonary circulation.
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A framework for understanding semi-permeable barrier effects on migratory ungulates
Sawyer, Hall; Kauffman, Matthew J.; Middleton, Arthur D.; Morrison, Thomas A.; Nielson, Ryan M.; Wyckoff, Teal B.
2013-01-01
1. Impermeable barriers to migration can greatly constrain the set of possible routes and ranges used by migrating animals. For ungulates, however, many forms of development are semi-permeable, and making informed management decisions about their potential impacts to the persistence of migration routes is difficult because our knowledge of how semi-permeable barriers affect migratory behaviour and function is limited. 2. Here, we propose a general framework to advance the understanding of barrier effects on ungulate migration by emphasizing the need to (i) quantify potential barriers in terms that allow behavioural thresholds to be considered, (ii) identify and measure behavioural responses to semi-permeable barriers and (iii) consider the functional attributes of the migratory landscape (e.g. stopovers) and how the benefits of migration might be reduced by behavioural changes. 3. We used global position system (GPS) data collected from two subpopulations of mule deer Odocoileus hemionus to evaluate how different levels of gas development influenced migratory behaviour, including movement rates and stopover use at the individual level, and intensity of use and width of migration route at the population level. We then characterized the functional landscape of migration routes as either stopover habitat or movement corridors and examined how the observed behavioural changes affected the functionality of the migration route in terms of stopover use. 4. We found migratory behaviour to vary with development intensity. Our results suggest that mule deer can migrate through moderate levels of development without any noticeable effects on migratory behaviour. However, in areas with more intensive development, animals often detoured from established routes, increased their rate of movement and reduced stopover use, while the overall use and width of migration routes decreased. 5. Synthesis and applications. In contrast to impermeable barriers that impede animal movement, semi-permeable barriers allow animals to maintain connectivity between their seasonal ranges. Our results identify the mechanisms (e.g. detouring, increased movement rates, reduced stopover use) by which semi-permeable barriers affect the functionality of ungulate migration routes and emphasize that the management of semi-permeable barriers may play a key role in the conservation of migratory ungulate populations.
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Gehring, W; Gloor, M
2000-07-01
In a randomized, double-blind, placebo-controlled study the effect of topical dexpanthenol (CAS 81-13-0) formulated in two different lipophilic vehicles on epidermal barrier function in vivo was carried out. Seven days' treatment with dexpanthenol improved stratum corneum hydration and reduced transepidermal water loss. Active treatment was statistically different from the vehicle control on both measures. Our results suggest that topical dexpanthenol formulated in either lipophilic vehicle stabilizes the skin barrier function.
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In vitro models to estimate drug penetration through the compromised stratum corneum barrier.
Engesland, André; Škalko-Basnet, Nataša; Flaten, Gøril Eide
2016-11-01
The phospholipid vesicle-based permeation assay (PVPA) is a recently established in vitro stratum corneum model to estimate the permeability of intact and healthy skin. The aim here was to further evolve this model to mimic the stratum corneum in a compromised skin barrier by reducing the barrier functions in a controlled manner. To mimic compromised skin barriers, PVPA barriers were prepared with explicitly defined reduced barrier function and compared with literature data from both human and animal skin with compromised barrier properties. Caffeine, diclofenac sodium, chloramphenicol and the hydrophilic marker calcein were tested to compare the PVPA models with established models. The established PVPA models mimicking the stratum corneum in healthy skin showed good correlation with biological barriers by ranking drugs similar to those ranked by the pig ear skin model and were comparable to literature data on permeation through healthy human skin. The PVPA models provided reproducible and consistent results with a distinction between the barriers mimicking compromised and healthy skin. The trends in increasing drug permeation with an increasing degree of compromised barriers for the model drugs were similar to the literature data from other in vivo and in vitro models. The PVPA models have the potential to provide permeation predictions when investigating drugs or cosmeceuticals intended for various compromised skin conditions and can thus possibly reduce the time and cost of testing as well as the use of animal testing in the early development of drug candidates, drugs and cosmeceuticals.
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USDA-ARS?s Scientific Manuscript database
Threonine is an essential amino acid necessary for synthesis of intestinal (glyco)proteins such as mucin (MUC2) to maintain adequate gut barrier function. In premature infants, reduced barrier function may contribute to the development of necrotizing enterocolitis (NEC). Human milk protects against ...
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Acoustic design by topology optimization
NASA Astrophysics Data System (ADS)
Dühring, Maria B.; Jensen, Jakob S.; Sigmund, Ole
2008-11-01
To bring down noise levels in human surroundings is an important issue and a method to reduce noise by means of topology optimization is presented here. The acoustic field is modeled by Helmholtz equation and the topology optimization method is based on continuous material interpolation functions in the density and bulk modulus. The objective function is the squared sound pressure amplitude. First, room acoustic problems are considered and it is shown that the sound level can be reduced in a certain part of the room by an optimized distribution of reflecting material in a design domain along the ceiling or by distribution of absorbing and reflecting material along the walls. We obtain well defined optimized designs for a single frequency or a frequency interval for both 2D and 3D problems when considering low frequencies. Second, it is shown that the method can be applied to design outdoor sound barriers in order to reduce the sound level in the shadow zone behind the barrier. A reduction of up to 10 dB for a single barrier and almost 30 dB when using two barriers are achieved compared to utilizing conventional sound barriers.
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Shin, Hee Soon; Jung, Sun Young; Back, Su Yeon; Do, Jeong-Ryong; Shon, Dong-Hwa
2015-01-01
Fructus Arctii is used as a traditional herbal medicine to treat inflammatory diseases in oriental countries. This study aimed to investigate effect of F. Arctii extract on intestinal barrier function in human intestinal epithelial Caco-2 cells and to reveal the active component of F. Arctii. We measured transepithelial electrical resistance (TEER) value (as an index of barrier function) and ovalbumin (OVA) permeation (as an index of permeability) to observe the changes of intestinal barrier function. The treatment of F. Arctii increased TEER value and decreased OVA influx on Caco-2 cell monolayers. Furthermore, we found that arctigenin as an active component of F. Arctii increased TEER value and reduced permeability of OVA from apical to the basolateral side but not arctiin. In the present study, we revealed that F. Arctii could enhance intestinal barrier function, and its active component was an arctigenin on the functionality. We expect that the arctigenin from F. Arctii could contribute to prevention of inflammatory, allergic, and infectious diseases by reinforcing intestinal barrier function. PMID:26550018
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USDA-ARS?s Scientific Manuscript database
Study objectives were to evaluate the effects of intentionally reduced intestinal barrier function on productivity, metabolism, and inflammatory indices in otherwise healthy dairy cows. Fourteen lactating Holstein cows (parity 2.6 ± 0.3; 117 ± 18 days in milk) were enrolled in two experimental perio...
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Spindler, Volker; Waschke, Jens
2011-02-01
cAMP signaling within the endothelium is known to reduce paracellular permeability and to protect against loss of barrier functions under various pathological conditions. Because activation of β-adrenergic receptors elevates cellular cAMP, we tested whether β-adrenergic receptor signaling contributes to the maintenance of baseline endothelial barrier properties. We compared hydraulic conductivity of rat postcapillary venules in vivo with resistance measurements and with reorganization of endothelial adherens junctions in cultured microvascular endothelial cells downstream of β-adrenergic receptor-mediated changes of cAMP levels. Inhibition of β-adrenergic receptors by propranolol increased hydraulic conductivity, reduced both cAMP levels and TER of microvascular endothelial cell monolayers and induced fragmentation of VE-cadherin staining. In contrast, activation by epinephrine both increased cAMP levels and TER and resulted in linearized VE-cadherin distribution, however this was not sufficient to block barrier-destabilization by propranolol. Similarly, PDE inhibition did not prevent propranolol-induced TER reduction and VE-cadherin reorganization whereas increased cAMP formation by AC activation enhanced endothelial barrier functions under baseline conditions and under conditions of propranolol treatment. Our results indicate that generation of cAMP mediated by activation of β-adrenergic receptor signaling contributes to the maintenance of endothelial barrier properties under baseline conditions. © 2011 John Wiley & Sons Ltd.
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Alimperti, Stella; Mirabella, Teodelinda; Bajaj, Varnica; Polacheck, William; Pirone, Dana M; Duffield, Jeremy; Eyckmans, Jeroen; Assoian, Richard K; Chen, Christopher S
2017-08-15
The integrity of the endothelial barrier between circulating blood and tissue is important for blood vessel function and, ultimately, for organ homeostasis. Here, we developed a vessel-on-a-chip with perfused endothelialized channels lined with human bone marrow stromal cells, which adopt a mural cell-like phenotype that recapitulates barrier function of the vasculature. In this model, barrier function is compromised upon exposure to inflammatory factors such as LPS, thrombin, and TNFα, as has been observed in vivo. Interestingly, we observed a rapid physical withdrawal of mural cells from the endothelium that was accompanied by an inhibition of endogenous Rac1 activity and increase in RhoA activity in the mural cells themselves upon inflammation. Using a system to chemically induce activity in exogenously expressed Rac1 or RhoA within minutes of stimulation, we demonstrated RhoA activation induced loss of mural cell coverage on the endothelium and reduced endothelial barrier function, and this effect was abrogated when Rac1 was simultaneously activated. We further showed that N -cadherin expression in mural cells plays a key role in barrier function, as CRISPR-mediated knockout of N -cadherin in the mural cells led to loss of barrier function, and overexpression of N -cadherin in CHO cells promoted barrier function. In summary, this bicellular model demonstrates the continuous and rapid modulation of adhesive interactions between endothelial and mural cells and its impact on vascular barrier function and highlights an in vitro platform to study the biology of perivascular-endothelial interactions.
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A new DFT functional based on spin-states and SN2 barriers
NASA Astrophysics Data System (ADS)
Swart, M.; Solà, M.; Bickelhaupt, F. M.
2012-12-01
We recently reported a study into what causes the dramatic differences between OPBE and PBE for reaction barriers, spin-state energies, hydrogen-bonding and π-π stacking energies.1 It was achieved by smoothly switching from OPBE to PBE at a predefined point P of the reduced density gradient s. By letting the point P run as function of the reduced density gradient s, with values from s=0.1 to s=10, we could determine which part of the exchange functional determines its behavior for the different interactions. Based on the thus obtained results, we created a new exchange functional that showed the good results of OPBE for reaction barriers and spin-state energies, and combined it with the good (H-bonds) and reasonable (π-stacking) results of PBE for weak interactions. In other words, it combined the best of OPBE with the best of PBE. Encouraged by these good results, we have further improved the new exchange functional and fine-tuned its parameters.2 Similar to the switched functional from ref. 1, our new SSB functional2 works well for SN2 barriers (see e.g. ref. 3), spin states and H-bonding interactions. Moreover, by including Grimme's dispersion corrections4,5 (to give our final SSB-D functional) it also works well for π-π stacking interactions.2 In summary, we have constructed a new GGA exchange functional that when combined with the sPBE correlation functional6 gives the correct spin ground-state of iron complexes, and small deviations for SN2 barriers (2.7 kcalṡmol-1), geometries (0.005 Å), Hbond distances (0.012 Å), weak interactions (S22 set, 0.5 kcalṡmol-1), and transition-metal ligand distances (0.008 Å).
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Sundh, Henrik; Kvamme, Bjørn Olav; Fridell, Frode; Olsen, Rolf Erik; Ellis, Tim; Taranger, Geir Lasse; Sundell, Kristina
2010-11-09
Fish farmed under high intensity aquaculture conditions are subjected to unnatural environments that may cause stress. Therefore awareness of how to maintain good health and welfare of farmed fish is important. For Atlantic salmon held in sea cages, water flow, dissolved oxygen (DO) levels and temperature will fluctuate over time and the fish can at times be exposed to detrimentally low DO levels and high temperatures. This experimental study investigates primary and secondary stress responses of Atlantic salmon post smolts to long-term exposure to reduced and fluctuating DO levels and high water temperatures, mimicking situations in the sea cages. Plasma cortisol levels and cortisol release to the water were assessed as indicators of the primary stress response and intestinal barrier integrity and physiological functions as indicators of secondary responses to changes in environmental conditions. Plasma cortisol levels were elevated in fish exposed to low (50% and 60% saturation) DO levels and low temperature (9°C), at days 9, 29 and 48. The intestinal barrier function, measured as electrical resistance (TER) and permeability of mannitol at the end of the experiment, were reduced at 50% DO, in both proximal and distal intestine. When low DO levels were combined with high temperature (16°C), plasma cortisol levels were elevated in the cyclic 1:5 h at 85%:50% DO group and fixed 50% DO group compared to the control (85% DO) group at day 10 but not at later time points. The intestinal barrier function was clearly disturbed in the 50% DO group; TER was reduced in both intestinal regions concomitant with increased paracellular permeability in the distal region. This study reveals that adverse environmental conditions (low water flow, low DO levels at low and high temperature), that can occur in sea cages, elicits primary and secondary stress responses in Atlantic salmon post smolts. The intestinal barrier function was significantly affected by prolonged hypoxic stress even when no primary stress response was observed. This suggests that intestinal barrier function is a good experimental marker for evaluation of chronic stress and that it can be a valuable tool to study the impact of various husbandry conditions on health and welfare of farmed Atlantic salmon.
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2010-01-01
Background Fish farmed under high intensity aquaculture conditions are subjected to unnatural environments that may cause stress. Therefore awareness of how to maintain good health and welfare of farmed fish is important. For Atlantic salmon held in sea cages, water flow, dissolved oxygen (DO) levels and temperature will fluctuate over time and the fish can at times be exposed to detrimentally low DO levels and high temperatures. This experimental study investigates primary and secondary stress responses of Atlantic salmon post smolts to long-term exposure to reduced and fluctuating DO levels and high water temperatures, mimicking situations in the sea cages. Plasma cortisol levels and cortisol release to the water were assessed as indicators of the primary stress response and intestinal barrier integrity and physiological functions as indicators of secondary responses to changes in environmental conditions. Results Plasma cortisol levels were elevated in fish exposed to low (50% and 60% saturation) DO levels and low temperature (9°C), at days 9, 29 and 48. The intestinal barrier function, measured as electrical resistance (TER) and permeability of mannitol at the end of the experiment, were reduced at 50% DO, in both proximal and distal intestine. When low DO levels were combined with high temperature (16°C), plasma cortisol levels were elevated in the cyclic 1:5 h at 85%:50% DO group and fixed 50% DO group compared to the control (85% DO) group at day 10 but not at later time points. The intestinal barrier function was clearly disturbed in the 50% DO group; TER was reduced in both intestinal regions concomitant with increased paracellular permeability in the distal region. Conclusions This study reveals that adverse environmental conditions (low water flow, low DO levels at low and high temperature), that can occur in sea cages, elicits primary and secondary stress responses in Atlantic salmon post smolts. The intestinal barrier function was significantly affected by prolonged hypoxic stress even when no primary stress response was observed. This suggests that intestinal barrier function is a good experimental marker for evaluation of chronic stress and that it can be a valuable tool to study the impact of various husbandry conditions on health and welfare of farmed Atlantic salmon. PMID:21062437
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Gorbunova, Elena E.; Dalrymple, Nadine A.; Gavrilovskaya, Irina N.
2013-01-01
Abstract Background Hantaviruses in the Americas cause a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). Hantaviruses nonlytically infect microvascular and lymphatic endothelial cells and cause dramatic changes in barrier functions without disrupting the endothelium. Hantaviruses cause changes in the function of infected endothelial cells that normally regulate fluid barrier functions. The endothelium of arteries, veins, and lymphatic vessels are unique and central to the function of vast pulmonary capillary beds that regulate pulmonary fluid accumulation. Results We have found that HPS-causing hantaviruses alter vascular barrier functions of microvascular and lymphatic endothelial cells by altering receptor and signaling pathway responses that serve to permit fluid tissue influx and clear tissue edema. Infection of the endothelium provides several mechanisms for hantaviruses to cause acute pulmonary edema, as well as potential therapeutic targets for reducing the severity of HPS disease. Conclusions Here we discuss interactions of HPS-causing hantaviruses with the endothelium, roles for unique lymphatic endothelial responses in HPS, and therapeutic targeting of the endothelium as a means of reducing the severity of HPS disease. PMID:24024573
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Mackow, Erich R; Gorbunova, Elena E; Dalrymple, Nadine A; Gavrilovskaya, Irina N
2013-09-01
Hantaviruses in the Americas cause a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). Hantaviruses nonlytically infect microvascular and lymphatic endothelial cells and cause dramatic changes in barrier functions without disrupting the endothelium. Hantaviruses cause changes in the function of infected endothelial cells that normally regulate fluid barrier functions. The endothelium of arteries, veins, and lymphatic vessels are unique and central to the function of vast pulmonary capillary beds that regulate pulmonary fluid accumulation. We have found that HPS-causing hantaviruses alter vascular barrier functions of microvascular and lymphatic endothelial cells by altering receptor and signaling pathway responses that serve to permit fluid tissue influx and clear tissue edema. Infection of the endothelium provides several mechanisms for hantaviruses to cause acute pulmonary edema, as well as potential therapeutic targets for reducing the severity of HPS disease. Here we discuss interactions of HPS-causing hantaviruses with the endothelium, roles for unique lymphatic endothelial responses in HPS, and therapeutic targeting of the endothelium as a means of reducing the severity of HPS disease.
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Tight junction proteins contribute to barrier properties in human pleura.
Markov, Alexander G; Voronkova, Maria A; Volgin, George N; Yablonsky, Piotr K; Fromm, Michael; Amasheh, Salah
2011-03-15
The permeability of pleural mesothelium helps to control the volume and composition of the liquid lubricating pleural surfaces. Information on pleural barrier function in health and disease, however, is scarce. Tissue specimens of human pleura were mounted in Ussing chambers for measurement of transmesothelial resistance. Expression of tight junction (TJ) proteins was studied by Western blots and immune fluorescence confocal microscopy. Both visceral and parietal pleura showed barrier properties represented by transmesothelial resistance. Occludin, claudin-1, -3, -5, and -7, were detected in visceral pleura. In parietal pleura, the same TJ proteins were detected, except claudin-7. In tissues from patients with pleural inflammation these tightening claudins were decreased and in visceral pleura claudin-2, a paracellular channel former, became apparent. We report that barrier function in human pleura coincides with expression of claudins known to be key determinants of epithelial barrier properties. In inflamed tissue, claudin expression indicates a reduced barrier function. Copyright © 2010 Elsevier B.V. All rights reserved.
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Sundling, Catherine; Berglund, Birgitta; Nilsson, Mats E; Emardson, Ragne; Pendrill, Leslie R
2014-12-01
Elderly persons' perceived accessibility to railway traveling depends on their functional limitations/diseases, their functional abilities and their travel behaviors in interaction with the barriers encountered during whole trips. A survey was conducted on a random sample of 1000 city residents (65-85 years old; 57% response rate). The travels were perceived least accessible by respondents with severely reduced functional ability and by those with more than one functional limitation/disease (e.g., restricted mobility and chronic pain). Those who traveled "often", perceived the accessibility to be better than those who traveled less frequently. For travelers with high functional ability, the main barriers to more frequent traveling were travel costs and low punctuality. For those with low functional ability, one's own health was reported to be the main barrier. Our results clarify the links among existing functional limitations/functional abilities, the barriers encountered, the travel behavior, and the overall accessibility to traveling. By operationalizing the whole-trip concept as a chain of events, we deliver practical knowledge on vulnerable groups for decision-making to improve the transport environment for all.
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Hou, Maihua; Sun, Richard; Hupe, Melanie; Kim, Peggy L.; Park, Kyungho; Crumrine, Debra; Lin, Tzu-kai; Santiago, Juan Luis; Mauro, Theodora M.; Elias, Peter M.; Man, Mao-Qiang
2013-01-01
The beneficial effects of certain herbal medicines on cutaneous function have been appreciated for centuries. Among these agents, Chrysanthemum extract, apigenin, has been used for skin care, particularly in China, for millennia. However, the underlying mechanisms by which apigenin benefits the skin are not known. In the present study, we first determined whether topical apigenin positively influences permeability barrier homeostasis, and then the basis thereof. Hairless mice were treated topically with either 0.1% apigenin or vehicle alone twice-daily for 9 days. At the end of treatments, permeability barrier function was assessed with either an electrolytic water analyzer or a Tewameter. Our results show that topical apigenin significantly enhanced permeability barrier homeostasis after tape stripping, though basal permeability barrier function remained unchanged. Improved barrier function correlated with enhanced filaggrin expression and lamellar body production, which was paralleled by elevated mRNA levels for the epidermal ABCA12. The mRNA levels for key lipid synthetic enzymes also were up-regulated by apigenin. Finally, both CAMP and mBD3 immunostaining were increased by apigenin. We conclude that topical apigenin improves epidermal permeability barrier function by stimulating epidermal differentiation, lipid synthesis and secretion, as well as cutaneous antimicrobial peptide production. Apigenin could be useful for the prevention and treatment of skin disorders characterized by permeability barrier dysfunction, associated with reduced filaggrin levels, and impaired antimicrobial defenses, such as atopic dermatitis. PMID:23489424
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Wang, Hualin; Chen, Minmin; Jin, Chongyang; Niu, Baicheng; Jiang, Suwei; Li, Xingjiang; Jiang, Shaotong
2018-01-24
The objective of present work was to construct antibacterial [2-(methacryloyloxy) ethyl] trimethylammonium chloride functionalized reduced graphene oxide/poly(ethylene-co-vinyl alcohol) (MTAC-rGO/EVOH) multilayer barrier films by using layer-by-layer assembly under a parallel electric field. Besides barrier and mechanical properties, the antibacterial activities of the film and cytotoxicity of MTAC-rGO nanosheets were extensively investigated. The functionalization of rGO was achieved by grafting MTAC onto a graphene framework through C (sp 3 )-C bonds. The assembly of MTAC-rGO on the EVOH matrix not only significantly improved film mechanical strength, but also endowed the targeting film with outstanding moisture barrier even under a relative humidity of 99% (e.g., 0.019 g m -2 s -1 atm -1 for (MTAC-rGO/EVOH) 20 ) besides good oxygen barrier (e.g., 0.07 cm 3 m -2 d -1 atm -1 for (MTAC-rGO/EVOH) 20 ). Among the testing films, MTAC-rGO/EVOH film had the best antibacterial activity, and the activity against S. aureus was better than E. coli. Meanwhile, the cytotoxicity of MTAC-rGO nanosheets was very low. Results suggest that MTAC-rGO/EVOH film may have great potential in food active packaging.
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Sayedyahossein, Samar; Rudkouskaya, Alena; Leclerc, Valerie; Dagnino, Lina
2016-02-01
A functional permeability barrier is essential to prevent the passage of water and electrolytes, macromolecules, and pathogens through the epidermis. This is accomplished in terminally differentiated keratinocytes through formation of a cornified envelope and the assembly of tight intercellular junctions. Integrin-linked kinase (ILK) is a scaffold protein essential for hair follicle morphogenesis and epidermal attachment to the basement membrane. However, the biological functions of ILK in differentiated keratinocytes remain poorly understood. Furthermore, whether ILK is implicated in keratinocyte differentiation and intercellular junction formation has remained an unresolved issue. Here we describe a pivotal role for ILK in keratinocyte differentiation responses to increased extracellular Ca(2+), regulation of adherens and tight junction assembly, and the formation of an outside-in permeability barrier toward macromolecules. In the absence of ILK, the calcium sensing receptor, E-cadherin, and ZO-1 fail to translocate to the cell membrane, through mechanisms that involve abnormalities in microtubules and in RhoA activation. In situ, ILK-deficient epidermis exhibits reduced tight junction formation and increased outside-in permeability to a dextran tracer, indicating reduced barrier properties toward macromolecules. Therefore, ILK is an essential component of keratinocyte differentiation programs that contribute to epidermal integrity and the establishment of its barrier properties. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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Fink, Cornelia; Weigel, Roswitha; Hembes, Tanja; Lauke-Wettwer, Heidrun; Kliesch, Sabine; Bergmann, Martin; Brehm, Ralph H
2006-01-01
Abstract Carcinoma in situ (CIS) is the noninvasive precursor of most human testicular germ cell tumors. In normal seminiferous epithelium, specialized tight junctions between Sertoli cells constitute the major component of the blood-testis barrier. Sertoli cells associated with CIS exhibit impaired maturation status, but their functional significance remains unknown. The aim was to determine whether the blood-testis barrier is morphologically and/or functionally altered. We investigated the expression and distribution pattern of the tight junction proteins zonula occludens (ZO) 1 and 2 in normal seminiferous tubules compared to tubules showing CIS. In normal tubules, ZO-1 and ZO-2 immunostaining was observed at the blood-testis barrier region of adjacent Sertoli cells. Within CIS tubules, ZO-1 and ZO-2 immunoreactivity was reduced at the blood-testis barrier region, but spread to stain the Sertoli cell cytoplasm. Western blot analysis confirmed ZO-1 and ZO-2, and their respective mRNA were shown by RT-PCR. Additionally, we assessed the functional integrity of the blood-testis barrier by lanthanum tracer study. Lanthanum permeated tight junctions in CIS tubules, indicating disruption of the blood-testis barrier. In conclusion, Sertoli cells associated with CIS show an altered distribution of ZO-1 and ZO-2 and lose their blood-testis barrier function. PMID:17217619
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Shalumon, K T; Sheu, Chialin; Chen, Chih-Hao; Chen, Shih-Heng; Jose, Gils; Kuo, Chang-Yi; Chen, Jyh-Ping
2018-05-01
The possibility of endowing an electrospun anti-adhesive barrier membrane with multi-functionality, such as lubrication, prevention of fibroblast attachment and anti-infection and anti-inflammation properties, is highly desirable for the management of post-surgical tendon adhesion. To this end, we fabricated core-shell nanofibrous membranes (CSNMs) with embedded silver nanoparticles (Ag NPs) in the poly(ethylene glycol) (PEG)/poly(caprolactone) (PCL) shell and hyaluronic acid (HA)/ibuprofen in the core. HA imparted a lubrication effect for smooth tendon gliding and reduced fibroblast attachment, while Ag NPs and ibuprofen functioned as anti-infection and anti-inflammation agents, respectively. CSNMs with a PEG/PCL/Ag shell (PPA) and HA core containing 0% (H/PPA), 10% (HI10/PPA), 30% (HI30/PPA) and 50% (HI50/PPA) ibuprofen were fabricated through co-axial electrospinning and assessed through microscopic, spectroscopic, thermal, mechanical and drug release analyses. Considering nutrient passage through the barrier, the microporous CSNMs exerted the same barrier effect but drastically increased the mass transfer coefficients of bovine serum albumin compared with the commercial anti-adhesive membrane SurgiWrap®. Cell attachment/focal adhesion formation of fibroblasts revealed effective reduction of initial cell attachment on the CSNM surface with minimum cytotoxicity (except HI50/PPA). The anti-bacterial effect against both Gram-negative and Gram-positive bacteria was verified to be due to the Ag NPs in the membranes. In vivo studies using H/PPA and HI30/PPA CSNMs and SurgiWrap® in a rabbit flexor tendon rupture model demonstrated the improved efficacy of HI30/PPA CSNMs in reducing inflammation and tendon adhesion formation based on gross observation, histological analysis and functional assays. We conclude that HI30/PPA CSNMs can act as a multifunctional barrier membrane to prevent peritendinous adhesion after tendon surgery. A multi-functional anti-adhesion barrier membrane that could reduce fibroblasts attachment and penetration while simultaneously prevent post-surgical infection and inflammation is urgently needed. To this end, we prepared electrospun core-shell hyaluronic acid + ibuprofen/polyethylene glycol + polycaprolactone + Ag nanoparticles nanofibrous membranes by co-axial electrospinning as an ideal anti-adhesive membrane. The core-shell structure could meet the need of a desirable anti-adhesion barrier through release of ibuprofen and Ag nanoparticles to reduce infection and inflammation while hyaluronic acid can reduce fibroblasts adhesion. The superior performance of this multi-functional core-shell nanofibrous membrane in preventing peritendinous adhesion and post-surgical inflammation was demonstrated in a rabbit flexor tendon rupture model. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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Ewaschuk, Julia B; Murdoch, Gordon K; Johnson, Ian R; Madsen, Karen L; Field, Catherine J
2011-09-01
The weaning period is associated with an increased prevalence of gastrointestinal infection in many species. Glutamine (Gln) has been shown to improve intestinal barrier function and immune function in both in vivo and in vitro models. The objective of the present study was to determine the effect of dietary Gln supplementation on intestinal barrier function and intestinal cytokines in a model of Escherichia coli infection. We randomised 21-d-old piglets (n 20) to nutritionally complete isonitrogenous diets with or without Gln (4·4 %, w/w) for 2 weeks. Intestinal loops were isolated from anaesthetised pigs and inoculated with either saline or one of the two E. coli (K88AC or K88 wild-type)-containing solutions. Intestinal tissue was studied for permeability, cytokine expression, fluid secretion and tight-junction protein expression. Animals receiving Gln supplementation had decreased potential difference (PD) and short-circuit current (I(sc)) in E. coli-inoculated intestinal loops (PD 0·628 (SEM 0·151) mV; I(sc) 13·0 (SEM 3·07) μA/cm(2)) compared with control-fed animals (PD 1·36 (SEM 0·227) mV; I(sc) 22·4 (SEM 2·24) μA/cm(2)). Intestinal tissue from control, but not from Gln-supplemented, animals responded to E. coli with a significant increase in mucosal cytokine mRNA (IL-1β, IL-6, transforming growth factor-β and IL-10). Tight-junction protein expression (claudin-1 and occludin) was reduced with exposure to E. coli in control-fed animals and was not influenced in Gln-supplemented piglets. Gln supplementation may be useful in reducing the severity of weaning-related gastrointestinal infections, by reducing the mucosal cytokine response and altering intestinal barrier function.
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Sundling, Catherine; Berglund, Birgitta; Nilsson, Mats E.; Emardson, Ragne; Pendrill, Leslie R.
2014-01-01
Elderly persons’ perceived accessibility to railway traveling depends on their functional limitations/diseases, their functional abilities and their travel behaviors in interaction with the barriers encountered during whole trips. A survey was conducted on a random sample of 1000 city residents (65–85 years old; 57% response rate). The travels were perceived least accessible by respondents with severely reduced functional ability and by those with more than one functional limitation/disease (e.g., restricted mobility and chronic pain). Those who traveled “often”, perceived the accessibility to be better than those who traveled less frequently. For travelers with high functional ability, the main barriers to more frequent traveling were travel costs and low punctuality. For those with low functional ability, one’s own health was reported to be the main barrier. Our results clarify the links among existing functional limitations/functional abilities, the barriers encountered, the travel behavior, and the overall accessibility to traveling. By operationalizing the whole-trip concept as a chain of events, we deliver practical knowledge on vulnerable groups for decision-making to improve the transport environment for all. PMID:25514149
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Using FLIM in the study of permeability barrier function of aged and young skin
NASA Astrophysics Data System (ADS)
Xu, P.; Choi, E. H.; Man, M. Q.; Crumrine, D.; Mauro, T.; Elias, P.
2006-02-01
Aged skin commonly is afflicted by inflammatory skin diseases or xerosis/eczema that can be triggered or exacerbated by impaired epidermal permeability barrier homeostasis. It has been previously described a permeability barrier defect in humans of advanced age (> 75 years), which in a murine analog >18 mos, could be attributed to reduced lipid synthesis synthesis. However, the functional abnormality in moderately aged mice is due not to decreased lipid synthesis, but rather to a specific defect in stratum corneum (SC) acidification causing impaired lipid processing processing. Endogenous Na +/H + antiporter (NHE1) level was found declined in moderately aged mouse epidermis. This acidification defect leads to perturbed permeability barrier homeostasis through more than one pathways, we addressed suboptimal activation of the essential, lipid-processing enzyme, β-glucocerebrosidase (BGC) is linked to elevated SC pH. Finally, the importance of the epidermis acidity is shown by the normalization of barrier function after exogenous acidification of moderately aged skin.
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Electron Excess Doping and Effective Schottky Barrier Reduction on the MoS2/h-BN Heterostructure.
Joo, Min-Kyu; Moon, Byoung Hee; Ji, Hyunjin; Han, Gang Hee; Kim, Hyun; Lee, Gwanmu; Lim, Seong Chu; Suh, Dongseok; Lee, Young Hee
2016-10-12
Layered hexagonal boron nitride (h-BN) thin film is a dielectric that surpasses carrier mobility by reducing charge scattering with silicon oxide in diverse electronics formed with graphene and transition metal dichalcogenides. However, the h-BN effect on electron doping concentration and Schottky barrier is little known. Here, we report that use of h-BN thin film as a substrate for monolayer MoS 2 can induce ∼6.5 × 10 11 cm -2 electron doping at room temperature which was determined using theoretical flat band model and interface trap density. The saturated excess electron concentration of MoS 2 on h-BN was found to be ∼5 × 10 13 cm -2 at high temperature and was significantly reduced at low temperature. Further, the inserted h-BN enables us to reduce the Coulombic charge scattering in MoS 2 /h-BN and lower the effective Schottky barrier height by a factor of 3, which gives rise to four times enhanced the field-effect carrier mobility and an emergence of metal-insulator transition at a much lower charge density of ∼1.0 × 10 12 cm -2 (T = 25 K). The reduced effective Schottky barrier height in MoS 2 /h-BN is attributed to the decreased effective work function of MoS 2 arisen from h-BN induced n-doping and the reduced effective metal work function due to dipole moments originated from fixed charges in SiO 2 .
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Xu, Dabo; Gao, Jun; Gillilland, Merritt; Wu, Xiaoyin; Song, Il; Kao, John Y.; Owyang, Chung
2014-01-01
Background & Aims Rifaximin is used to treat patients with functional gastrointestinal disorders, but little is known about its therapeutic mechanism. We propose that rifaximin modulates the ileal bacterial community, reduces subclinical inflammation of the intestinal mucosa, and improves gut barrier function to reduce visceral hypersensitivity. Methods We induced visceral hyperalgesia in rats, via chronic water avoidance or repeat restraint stressors, and investigated whether rifaximin altered the gut microbiota, prevented intestinal inflammation, and improved gut barrier function. Quantitative polymerase chain reaction and 454 pyrosequencing were used to analyze bacterial 16S rRNA in ileal contents from the rats. Reverse transcription, immunoblot, and histologic analyses were used to evaluate levels of cytokines, the tight junction protein occludin, and mucosal inflammation, respectively. Intestinal permeability and rectal sensitivity were measured. Results Water avoidance and repeat restraint stress each led to visceral hyperalgesia, accompanied by mucosal inflammation and impaired mucosal barrier function. Oral rifaximin altered the composition of bacterial communities in the ileum (Lactobacillus species became the most abundant) and prevented mucosal inflammation, impairment to intestinal barrier function, and visceral hyperalgesia in response to chronic stress. Neomycin also changed the composition of the ileal bacterial community (Proteobacteria became the most abundant species). Neomycin did not prevent intestinal inflammation or induction of visceral hyperalgesia induced by water avoidance stress. Conclusions Rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus. These changes prevent intestinal abnormalities and visceral hyperalgesia in response to chronic psychological stress. PMID:24161699
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Smith, I M; Baker, A; Arneborg, N; Jespersen, L
2015-11-01
The human gastrointestinal epithelium makes up the largest barrier separating the body from the external environment. Whereas invasive pathogens cause epithelial barrier disruption, probiotic micro-organisms modulate tight junction regulation and improve epithelial barrier function. In addition, probiotic strains may be able to reduce epithelial barrier disruption caused by pathogenic species. The aim of this study was to explore non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Benchmarking against established probiotic strains, we evaluated the ability of four nonpathogenic yeast species to modulate transepithelial electrical resistance (TER) across a monolayer of differentiated human colonocytes (Caco-2 cells). Further, we assessed yeast modulation of a Salmonella Typhimurium-induced epithelial cell barrier function insult. Our findings demonstrate distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function. While the established probiotic yeast Saccharomyces boulardii increased TER across a Caco-2 monolayer by 30%, Kluyveromyces marxianus exhibited significantly stronger properties of TER enhancement (50% TER increase). In addition, our data demonstrate significant yeast-mediated modulation of Salmonella-induced epithelial cell barrier disruption and identify K. marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study demonstrates distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Further, our data demonstrate significant yeast-mediated modulation of Salmonella Typhimurium-induced epithelial cell barrier disruption and identify Kluyveromyces marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study is the first to demonstrate significant non-Saccharomyces yeast-mediated epithelial cell barrier protection from Salmonella invasion, thus encouraging future efforts aimed at confirming the observed effects in vivo and driving further strain development towards novel yeast probiotics. © 2015 The Society for Applied Microbiology.
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Assessing theoretical uncertainties in fission barriers of superheavy nuclei
Agbemava, S. E.; Afanasjev, A. V.; Ray, D.; ...
2017-05-26
Here, theoretical uncertainties in the predictions of inner fission barrier heights in superheavy elements have been investigated in a systematic way for a set of state-of-the-art covariant energy density functionals which represent major classes of the functionals used in covariant density functional theory. They differ in basic model assumptions and fitting protocols. Both systematic and statistical uncertainties have been quantified where the former turn out to be larger. Systematic uncertainties are substantial in superheavy elements and their behavior as a function of proton and neutron numbers contains a large random component. The benchmarking of the functionals to the experimental datamore » on fission barriers in the actinides allows to reduce the systematic theoretical uncertainties for the inner fission barriers of unknown superheavy elements. However, even then they on average increase on moving away from the region where benchmarking has been performed. In addition, a comparison with the results of non-relativistic approaches is performed in order to define full systematic theoretical uncertainties over the state-of-the-art models. Even for the models benchmarked in the actinides, the difference in the inner fission barrier height of some superheavy elements reaches $5-6$ MeV. This uncertainty in the fission barrier heights will translate into huge (many tens of the orders of magnitude) uncertainties in the spontaneous fission half-lives.« less
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A homolog of Drosophila grainy head is essential for epidermal integrity in mice.
Ting, Stephen B; Caddy, Jacinta; Hislop, Nikki; Wilanowski, Tomasz; Auden, Alana; Zhao, Lin-Lin; Ellis, Sarah; Kaur, Pritinder; Uchida, Yoshikazu; Holleran, Walter M; Elias, Peter M; Cunningham, John M; Jane, Stephen M
2005-04-15
The Drosophila cuticle is essential for maintaining the surface barrier defenses of the fly. Integral to cuticle resilience is the transcription factor grainy head, which regulates production of the enzyme required for covalent cross-linking of the cuticular structural components. We report that formation and maintenance of the epidermal barrier in mice are dependent on a mammalian homolog of grainy head, Grainy head-like 3. Mice lacking this factor display defective skin barrier function and deficient wound repair, accompanied by reduced expression of transglutaminase 1, the key enzyme involved in cross-linking the structural components of the superficial epidermis. These findings suggest that the functional mechanisms involving protein cross-linking that maintain the epidermal barrier and induce tissue repair are conserved across 700 million years of evolution.
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López-Carballo, Gracia; Cava, David; Lagarón, Jose M; Catalá, Ramón; Gavara, Rafael
2005-09-07
The ethylene-vinyl alcohol copolymers (EVOHs) are well-known high oxygen barrier materials that are being used successfully in the design of packaging structures for oxygen-sensitive food or pharmaceutical products. Recently, there has been increasing interest in using EVOH materials to provide a high barrier to organic compounds as a means to reduce food aroma scalping. However, the barrier function of this family of materials diminishes significantly in humid environments, and it is supposed that so does the organic vapor barrier. In this work, a new sorption-based method to characterize the interaction between food aroma and polymer films for packaging as a function of relative humidity is presented and is used to determine the barrier to ethyl butyrate and alpha-pinene of EVOH at 23 degrees C. The results show that although EVOH is an excellent barrier to food aroma when dry, a property that even improves at low relative humidity (RH), the solubility and diffusivity of the compounds tested increase dramatically with humidity at medium to high water activities. However, even in the worst case (100% RH), EVOH outperforms low-density polyethylene (LDPE) as a barrier to organic vapors at least 500,000-fold.
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Angelova-Fischer, I; Fischer, T W; Abels, C; Zillikens, D
2018-03-25
Increased skin surface pH is an important host-related factor for deteriorated barrier function in the aged. We investigated whether restoration of the skin pH through topical application of a water-in-oil (w/o) emulsion with pH 4 improved the barrier homeostasis in aged skin and compared the effects to an identical galenic formulation with pH 5.8. The effects of the test formulations on the barrier recovery were investigated by repeated measurements of transepidermal water loss (TEWL) and skin pH 3 h, 6 h and 24 h after acetone-induced impairment of the barrier function in aged skin. The long-term effects of the pH 4 and pH 5.8 emulsions were analyzed by investigation of the barrier integrity/cohesion, the skin surface pH and the skin roughness and scaliness before and after a 4-week, controlled application of the formulations. The application of the pH 4 emulsion accelerated the barrier recovery in aged skin: 3 h and 6 h after acetone-induced barrier disruption the differences in the TEWL recovery between the pH4-treated and acetone control field were significant. Furthermore, the long-term application of the pH 4 formulation resulted in significantly decreased skin pH, enhanced barrier integrity and reduced skin surface roughness and scaliness. At the same time points, the pH 5.8 formulation exerted only minor effects on the barrier function parameters. Exogenous acidification through topical application of a w/o emulsion with pH 4 leads to improvement of the barrier function and maintenance of the barrier homeostasis in aged skin. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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Potential Applications of Phyto-Derived Ceramides in Improving Epidermal Barrier Function.
Tessema, Efrem N; Gebre-Mariam, Tsige; Neubert, Reinhard H H; Wohlrab, Johannes
2017-01-01
The outer most layer of the skin, the stratum corneum, consists of corneocytes which are coated by a cornified envelope and embedded in a lipid matrix of ordered lamellar structure. It is responsible for the skin barrier function. Ceramides (CERs) are the backbone of the intercellular lipid membranes. Skin diseases such as atopic dermatitis and psoriasis and aged skin are characterized by dysfunctional skin barrier and dryness which are associated with reduced levels of CERs. Previously, the effectiveness of supplementation of synthetic and animal-based CERs in replenishing the depleted natural skin CERs and restoring the skin barrier function have been investigated. Recently, however, the barrier function improving effect of plant-derived CERs has attracted much attention. Phyto-derived CERs (phytoCERs) are preferable due to their assumed higher safety as they are mostly isolated from dietary sources. The beneficial effects of phytoCER-based oral dietary supplements for skin hydration and skin barrier reinforcement have been indicated in several studies involving animal models as well as human subjects. Ingestible dietary supplements containing phytoCERs are also widely available on the market. Nonetheless, little effort has been made to investigate the potential cosmetic applications of topically administered phytoCERs. Therefore, summarizing the foregoing investigations and identifying the gap in the scientific data on plant-derived CERs intended for skin-health benefits are of paramount importance. In this review, an attempt is made to synthesize the information available in the literature regarding the effects of phytoCER-based oral dietary supplements on skin hydration and barrier function with the underlying mechanisms. © 2017 S. Karger AG, Basel.
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Xu, Dabo; Gao, Jun; Gillilland, Merritt; Wu, Xiaoyin; Song, Il; Kao, John Y; Owyang, Chung
2014-02-01
Rifaximin is used to treat patients with functional gastrointestinal disorders, but little is known about its therapeutic mechanism. We propose that rifaximin modulates the ileal bacterial community, reduces subclinical inflammation of the intestinal mucosa, and improves gut barrier function to reduce visceral hypersensitivity. We induced visceral hyperalgesia in rats, via chronic water avoidance or repeat restraint stressors, and investigated whether rifaximin altered the gut microbiota, prevented intestinal inflammation, and improved gut barrier function. Quantitative polymerase chain reaction (PCR) and 454 pyrosequencing were used to analyze bacterial 16S ribosomal RNA in ileal contents from the rats. Reverse transcription, immunoblot, and histologic analyses were used to evaluate levels of cytokines, the tight junction protein occludin, and mucosal inflammation, respectively. Intestinal permeability and rectal sensitivity were measured. Water avoidance and repeat restraint stress each led to visceral hyperalgesia, accompanied by mucosal inflammation and impaired mucosal barrier function. Oral rifaximin altered the composition of bacterial communities in the ileum (Lactobacillus species became the most abundant) and prevented mucosal inflammation, impairment to intestinal barrier function, and visceral hyperalgesia in response to chronic stress. Neomycin also changed the composition of the ileal bacterial community (Proteobacteria became the most abundant species). Neomycin did not prevent intestinal inflammation or induction of visceral hyperalgesia induced by water avoidance stress. Rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus. These changes prevent intestinal abnormalities and visceral hyperalgesia in response to chronic psychological stress. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
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Müller-Redetzky, Holger Christian; Kummer, Wolfgang; Pfeil, Uwe; Hellwig, Katharina; Will, Daniel; Paddenberg, Renate; Tabeling, Christoph; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin
2012-01-01
Background Even protective ventilation may aggravate or induce lung failure, particularly in preinjured lungs. Thus, new adjuvant pharmacologic strategies are needed to minimize ventilator-induced lung injury (VILI). Intermedin/Adrenomedullin-2 (IMD) stabilized pulmonary endothelial barrier function in vitro. We hypothesized that IMD may attenuate VILI-associated lung permeability in vivo. Methodology/Principal Findings Human pulmonary microvascular endothelial cell (HPMVEC) monolayers were incubated with IMD, and transcellular electrical resistance was measured to quantify endothelial barrier function. Expression and localization of endogenous pulmonary IMD, and its receptor complexes composed of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs) 1–3 were analyzed by qRT-PCR and immunofluorescence in non ventilated mouse lungs and in lungs ventilated for 6 h. In untreated and IMD treated mice, lung permeability, pulmonary leukocyte recruitment and cytokine levels were assessed after mechanical ventilation. Further, the impact of IMD on pulmonary vasoconstriction was investigated in precision cut lung slices (PCLS) and in isolated perfused and ventilated mouse lungs. IMD stabilized endothelial barrier function in HPMVECs. Mechanical ventilation reduced the expression of RAMP3, but not of IMD, CRLR, and RAMP1 and 2. Mechanical ventilation induced lung hyperpermeability, which was ameliorated by IMD treatment. Oxygenation was not improved by IMD, which may be attributed to impaired hypoxic vasoconstriction due to IMD treatment. IMD had minor impact on pulmonary leukocyte recruitment and did not reduce cytokine levels in VILI. Conclusions/Significance IMD may possibly provide a new approach to attenuate VILI. PMID:22563471
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Douwes, Jeroen; Slater, Tania; Shanthakumar, Mathangi; McLean, Dave; Firestone, Ridvan Tua; Judd, Lissa; Pearce, Neil
2017-04-01
This study assessed the risk of dermatitis, urticaria and loss of skin barrier function in 425 cleaners and 281 reference workers (retail workers and bus drivers). Symptoms, atopy and skin barrier function were assessed by questionnaire, skin prick tests, and measurement of transepidermal water loss. Cleaners had an increased risk of current (past 3 months) hand/arm dermatitis (14.8% vs. 10.0%; OR = 1.9, p < 0.05) and urticaria (11% vs. 5.3%; OR = 2.4, p < 0.05) and were more likely to have dermatitis as adults (17.6% vs. 11.4%; OR = 1.8, p < 0.05). The risk of atopy was not increased, but associations with symptoms were more pronounced in atopics. Transepidermal water loss was significantly higher in cleaners. Wet-work was a significant risk factor for dermatitis and hand washing and drying significantly reduced the risk of urticaria. In conclusion, cleaners have an increased risk of hand/arm dermatitis, urticaria and loss of skin barrier function.
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Simultaneous assessment of glomerular filtration and barrier function in live zebrafish
Kotb, Ahmed M.; Müller, Tobias; Xie, Jing; Anand-Apte, Bela; Endlich, Nicole
2014-01-01
The zebrafish pronephros is a well-established model to study glomerular development, structure, and function. A few methods have been described to evaluate glomerular barrier function in zebrafish larvae so far. However, there is a need to assess glomerular filtration as well. In the present study, we extended the available methods by simultaneously measuring the intravascular clearances of Alexa fluor 647-conjugated 10-kDa dextran and FITC-conjugated 500-kDa dextran as indicators of glomerular filtration and barrier function, respectively. After intravascular injection of the dextrans, mean fluorescence intensities of both dextrans were measured in the cardinal vein of living zebrafish (4 days postfertilization) by confocal microscopy over time. We demonstrated that injected 10-kDa dextran was rapidly cleared from the circulation, became visible in the lumen of the pronephric tubule, quickly accumulated in tubular cells, and was detectably excreted at the cloaca. In contrast, 500-kDa dextran could not be visualized in the tubule at any time point. To check whether alterations in glomerular function can be quantified by our method, we injected morpholino oligonucleotides (MOs) against zebrafish nonmuscle myosin heavy chain IIA (zMyh9) or apolipoprotein L1 (zApol1). While glomerular filtration was reduced in zebrafish nonmuscle myosin heavy chain IIA MO-injected larvae, glomerular barrier function remained intact. In contrast, in zebrafish apolipoprotein L1 MO-injected larvae, glomerular barrier function was compromised as 500-kDa dextran disappeared from the circulation and became visible in tubular cells. In summary, we present a novel method that allows to simultaneously assess glomerular filtration and barrier function in live zebrafish. PMID:25298528
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Current-induced changes of migration energy barriers in graphene and carbon nanotubes
NASA Astrophysics Data System (ADS)
Obodo, J. T.; Rungger, I.; Sanvito, S.; Schwingenschlögl, U.
2016-05-01
An electron current can move atoms in a nanoscale device with important consequences for the device operation and breakdown. We perform first principles calculations aimed at evaluating the possibility of changing the energy barriers for atom migration in carbon-based systems. In particular, we consider the migration of adatoms and defects in graphene and carbon nanotubes. Although the current-induced forces are large for both the systems, in graphene the force component along the migration path is small and therefore the barrier height is little affected by the current flow. In contrast, the same barrier is significantly reduced in carbon nanotubes as the current increases. Our work also provides a real-system numerical demonstration that current-induced forces within density functional theory are non-conservative.An electron current can move atoms in a nanoscale device with important consequences for the device operation and breakdown. We perform first principles calculations aimed at evaluating the possibility of changing the energy barriers for atom migration in carbon-based systems. In particular, we consider the migration of adatoms and defects in graphene and carbon nanotubes. Although the current-induced forces are large for both the systems, in graphene the force component along the migration path is small and therefore the barrier height is little affected by the current flow. In contrast, the same barrier is significantly reduced in carbon nanotubes as the current increases. Our work also provides a real-system numerical demonstration that current-induced forces within density functional theory are non-conservative. Electronic supplementary information (ESI) available. See DOI: 10.1039/C6NR00534A
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Kim, Doyoon; Lee, Byeongdu; Thomopoulos, Stavros; Jun, Young-Shin
2018-03-06
Mineralization of collagen is critical for the mechanical functions of bones and teeth. Calcium phosphate nucleation in collagenous structures follows distinctly different patterns in highly confined gap regions (nanoscale confinement) than in less confined extrafibrillar spaces (microscale confinement). Although the mechanism(s) driving these differences are still largely unknown, differences in the free energy for nucleation may explain these two mineralization behaviors. Here, we report on experimentally obtained nucleation energy barriers to intra- and extrafibrillar mineralization, using in situ X-ray scattering observations and classical nucleation theory. Polyaspartic acid, an extrafibrillar nucleation inhibitor, increases interfacial energies between nuclei and mineralization fluids. In contrast, the confined gap spaces inside collagen fibrils lower the energy barrier by reducing the reactive surface area of nuclei, decreasing the surface energy penalty. The confined gap geometry, therefore, guides the two-dimensional morphology and structure of bioapatite and changes the nucleation pathway by reducing the total energy barrier.
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Schlegel, Nicolas; Baumer, Yvonne; Drenckhahn, Detlev; Waschke, Jens
2009-05-01
To determine whether cyclic adenosine monophosphate (cAMP) is critically involved in lipopolysaccharide (LPS)-induced breakdown of endothelial barrier functions in vivo and in vitro. Experimental laboratory research. Research laboratory. Wistar rats and cultured human microvascular endothelial cells. Permeability measurements in single postcapillary venules in vivo and permeability measurements and cell biology techniques in vitro. We demonstrate that within 120 minutes LPS increased endothelial permeability in rat mesenteric postcapillary venules in vivo and caused a barrier breakdown in human dermal microvascular endothelial cells in vitro. This was associated with the formation of large intercellular gaps and fragmentation of vascular endothelial cadherin immunostaining. Furthermore, claudin 5 immunostaining at cell borders was drastically reduced after LPS treatment. Interestingly, activity of the small GTPase Rho A, which has previously been suggested to mediate the LPS-induced endothelial barrier breakdown, was not increased after 2 hours. However, activity of Rac 1, which is known to be important for maintenance of endothelial barrier functions, was significantly reduced to 64 +/- 8% after 2 hours. All LPS-induced changes of endothelial cells were blocked by a forskolin-mediated or rolipram-mediated increase of cAMP. Consistently, enzyme-linked immunosorbent assay-based measurements demonstrated that LPS significantly decreased intracellular cAMP. In summary, our data demonstrate that LPS disrupts endothelial barrier properties by decreasing intracellular cAMP. This mechanism may involve inactivation of Rac 1 rather than activation of Rho A.
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Fingolimod promotes blood-nerve barrier properties in vitro.
Nishihara, Hideaki; Maeda, Toshihiko; Sano, Yasuteru; Ueno, Maho; Okamoto, Nana; Takeshita, Yukio; Shimizu, Fumitaka; Koga, Michiaki; Kanda, Takashi
2018-04-01
The main effect of fingolimod is thought to be functional antagonism of lymphocytic S1P1 receptors and the prevention of lymphocyte egress from lymphoid tissues, thereby reducing lymphocyte infiltration into the nervous system. However, a growing number of reports suggest that fingolimod also has a direct effect on several cell types in the nervous system. Although we previously reported that fingolimod enhances blood-brain barrier (BBB) functions, there have been no investigations regarding the blood-nerve barrier (BNB). In this study, we examine how fingolimod affects the BNB. An immortalized human peripheral nerve microvascular endothelial cell line (HPnMEC) was used to evaluate BNB barrier properties. We examined tight junction proteins and barrier functions of HPnMECs in conditioned medium with or without fingolimod-phosphate and blood sera from patients with typical chronic inflammatory demyelinating polyneuropathy (CIDP). Incubation with fingolimod-phosphate increased levels of claudin-5 mRNA and protein as well as TEER values in HPnMECs. Conversely, typical CIDP sera decreased claudin-5 mRNA/protein levels and TEER values in HPnMECs; however, pretreatment with fingolimod-phosphate inhibited the effects of the typical CIDP sera. Fingolimod-phosphate directly modifies the BNB and enhances barrier properties. This mechanism may be a viable therapeutic target for CIDP, and fingolimod may be useful in patients with typical CIDP who have severe barrier disruption.
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Bors, Luca; Tóth, Kinga; Tóth, Estilla Zsófia; Bajza, Ágnes; Csorba, Attila; Szigeti, Krisztián; Máthé, Domokos; Perlaki, Gábor; Orsi, Gergely; Tóth, Gábor K; Erdő, Franciska
2018-05-01
Decreased beta-amyloid clearance in Alzheimer's disease and increased blood-brain barrier permeability in aged subjects have been reported in several articles. However, morphological and functional characterization of blood-brain barrier and its membrane transporter activity have not been described in physiological aging yet. The aim of our study was to explore the structural changes in the brain microvessels and possible functional alterations of P-glycoprotein at the blood-brain barrier with aging. Our approach included MR imaging for anatomical orientation in middle aged rats, electronmicroscopy and immunohistochemistry to analyse the alterations at cellular level, dual or triple-probe microdialysis and SPECT to test P-glycoprotein functionality in young and middle aged rats. Our results indicate that the thickness of basal lamina increases, the number of tight junctions decreases and the size of astrocyte endfeet extends with advanced age. On the basis of microdialysis and SPECT results the P-gp function is reduced in old rats. With our multiparametric approach a complex regulation can be suggested which includes elements leading to increased permeability of blood-brain barrier by enhanced paracellular and transcellular transport, and factors working against it. To verify the role of P-gp pumps in brain aging further studies are warranted. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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Metformin Improves Ileal Epithelial Barrier Function in Interleukin-10 Deficient Mice
Xue, Yansong; Zhang, Hanying; Sun, Xiaofei; Zhu, Mei-Jun
2016-01-01
Background and aims The impairment of intestinal epithelial barrier is the main etiologic factor of inflammatory bowel disease. The proper intestinal epithelial proliferation and differentiation is crucial for maintaining intestinal integrity. Metformin is a common anti-diabetic drug. The objective is to evaluate the protective effects of metformin on ileal epithelial barrier integrity using interleukin-10 deficient (IL10KO) mice. Methods Wild-type and IL10KO mice were fed with/without metformin for 6 weeks and then ileum was collected for analyses. The mediatory role of AMP-activated protein kinase (AMPK) was further examined by gain and loss of function study in vitro. Results Compared to wild-type mice, IL10KO mice had increased proliferation, reduced goblet cell and Paneth cell lineage differentiation in the ileum tissue, which was accompanied with increased crypt expansion. Metformin supplementation mitigated intestinal cell proliferation, restored villus/crypt ratio, increased goblet cell and Paneth cell differentiation and improved barrier function. In addition, metformin supplementation in IL10KO mice suppressed macrophage pro-inflammatory activity as indicated by reduced M1 macrophage abundance and decreased pro-inflammatory cytokine IL-1β, TNF-α and IFN-γ expressions. As a target of metformin, AMPK phosphorylation was enhanced in mice treated with metformin, regardless of mouse genotypes. In correlation, the mRNA level of differentiation regulator including bmp4, bmpr2 and math1 were also increased in IL10KO mice supplemented with metformin, which likely explains the enhanced epithelial differentiation in IL10KO mice with metformin. Consistently, in Caco-2 cells, metformin promoted claudin-3 and E-cadherin assembly and mitigated TNF-α-induced fragmentation of tight junction proteins. Gain and loss of function assay also demonstrated AMPK was correlated with epithelial differentiation and proliferation. Conclusions Metformin supplementation promotes secretory cell lineage differentiation, suppresses inflammation and improves epithelial barrier function in IL10KO mice likely through activation of AMPK, showing its beneficial effects on gut epithelial. PMID:28002460
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The modulation of Schottky barriers of metal-MoS2 contacts via BN-MoS2 heterostructures.
Su, Jie; Feng, Liping; Zhang, Yan; Liu, Zhengtang
2016-06-22
Using first-principles calculations within density functional theory, we systematically studied the effect of BN-MoS2 heterostructure on the Schottky barriers of metal-MoS2 contacts. Two types of FETs are designed according to the area of the BN-MoS2 heterostructure. Results show that the vertical and lateral Schottky barriers in all the studied contacts, irrespective of the work function of the metal, are significantly reduced or even vanish when the BN-MoS2 heterostructure substitutes the monolayer MoS2. Only the n-type lateral Schottky barrier of Au/BN-MoS2 contact relates to the area of the BN-MoS2 heterostructure. Notably, the Pt-MoS2 contact with n-type character is transformed into a p-type contact upon substituting the monolayer MoS2 by a BN-MoS2 heterostructure. These changes of the contact natures are ascribed to the variation of Fermi level pinning, work function and charge distribution. Analysis demonstrates that the Fermi level pinning effects are significantly weakened for metal/BN-MoS2 contacts because no gap states dominated by MoS2 are formed, in contrast to those of metal-MoS2 contacts. Although additional BN layers reduce the interlayer interaction and the work function of the metal, the Schottky barriers of metal/BN-MoS2 contacts still do not obey the Schottky-Mott rule. Moreover, different from metal-MoS2 contacts, the charges transfer from electrodes to the monolayer MoS2, resulting in an increment of the work function of these metals in metal/BN-MoS2 contacts. These findings may prove to be instrumental in the future design of new MoS2-based FETs with ohmic contact or p-type character.
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DiGuilio, K M; Valenzano, M C; Rybakovsky, E; Mullin, J M
2018-01-05
Elevation of the transcription factor HIF-1 is a prominent mediator of not only processes that accompany hypoxia, but also the tumor microenvironment and tissue regeneration. This study uses mediators of "chemical hypoxia" to ask the question whether HIF-1α elevation in a healthy epithelial cell layer leads to leakiness in its tight junctional seals. Transepithelial electrical resistance and transepithelial diffusion of 14 C-D-mannitol and other radiolabeled probes are used as indicators of transepithelial barrier function of CaCo-2 BBe human gastrointestinal epithelial cell layers cultured on permeable supports. Western immunoblot analyses of integral tight junctional proteins (occludin and claudins) are used as further indicators of barrier function change. Cobalt, an inhibitor of the prolyl hydroxylase enzymes governing HIF-1α breakdown in the cell, induces transepithelial leakiness in CaCo-2 BBe cell layers in a time and concentration-dependent manner. This increased leakiness is accompanied by significant changes in certain specific integral tight junctional (TJ) proteins such as a decreased level of occludin and increased level of claudin-5. Similar results regarding barrier function compromise also occur with other chemical inhibitors of HIF-1α breakdown, namely ciclopiroxolamine (CPX) and dimethyloxalylglycine (DMOG). The increased leak is manifested by both decreased transepithelial electrical resistance (R t ) and increased paracellular diffusion of D-mannitol (J m ). The induced transepithelial leak shows significant size selectivity, consistent with induced effects on TJ permeability. Less-differentiated cell layers were significantly more affected than well-differentiated cell layers regarding induced transepithelial leak. A genetically modified CaCo-2 variant with reduced levels of HIF-1β, showed reduced transepithelial leak in response to cobalt exposure, further indicating that elevation of HIF-1α levels induced by agents of "chemical hypoxia" is responsible for the compromised barrier function of the CaCo-2 BBe cell layers. Exposure to inducers of chemical hypoxia elevated HIF-1α levels and increased transepithelial leak. The degree of epithelial differentiation has significant effects on this action, possibly explaining the varying effects of HIF-1 modulation in epithelial and endothelial barrier function in different physiological and pathophysiological conditions.
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DFT studies on the heterogeneous oxidation of SO2 by oxygen functional groups on graphene.
He, Guangzhi; He, Hong
2016-11-23
The heterogeneous oxidation of SO 2 has been the subject of intense scrutiny in atmospheric chemistry because of the adverse effects of sulfate particles. Although it has been found that the soot particles with a graphene-like structure play an important role in the oxidation of SO 2 , little is known about the atomic-level mechanism involved. Here, we studied the oxidation of SO 2 on oxygen-functionalized graphene using density functional theory (DFT) calculation. The results showed that SO 2 is oxidized by the epoxide group via a two-step mechanism, where the C-O bond away from the SO 2 is broken first, followed by the breaking of the other C-O bond and the synchronous formation of a new S-O bond. The energy barriers are significantly decreased when solvation free energies are involved, suggesting that humidity is favorable for promoting the oxidation by reducing the reaction barrier. The energy barriers for H 2 SO 3 oxidation are much higher than that for SO 2 oxidation, indicating that the direct conversion of SO 2 to SO 3 is the main pathway for the oxidation of SO 2 by oxygen-functionalized graphene sheets in both the gas phase and solution. The reduced density gradient (RDG) analysis showed that the hydrogen bond formed between H 2 SO 3 and epoxide groups enhances the stability of the reaction complex, and is responsible for the high energy barrier that has to be overcome for the reaction to proceed. These atomistic studies proposed a two-step mechanism for the oxidation of SO 2 on the oxygen-functionalized graphene-like carbonaceous surfaces under ambient conditions.
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Evidence for the effects of yogurt on gut health and obesity.
Pei, Ruisong; Martin, Derek A; DiMarco, Diana M; Bolling, Bradley W
2017-05-24
Obesity is associated with increased risk for chronic diseases, and affects both developed and developing nations. Yogurt is a nutrient-dense food that may benefit individuals with lactose intolerance, constipation and diarrheal diseases, hypertension, cardiovascular diseases, diabetes, and certain types of cancer. Emerging evidence suggests that yogurt consumption might also improve the health of obese individuals. Obesity is often accompanied by chronic, low-grade inflammation perpetuated by adipose tissue and the gut. In the gut, obesity-associated dysregulation of microbiota and impaired gut barrier function may increase endotoxin exposure. Intestinal barrier function can be compromised by pathogens, inflammatory cytokines, endocannabinoids, diet, exercise, and gastrointestinal peptides. Yogurt consumption may improve gut health and reduce chronic inflammation by enhancing innate and adaptive immune responses, intestinal barrier function, lipid profiles, and by regulating appetite. While this evidence suggests that yogurt consumption is beneficial for obese individuals, randomized-controlled trials are needed to further support this hypothesis.
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Olsson, P Olof; Kalamajski, Sebastian; Maccarana, Marco; Oldberg, Åke; Rubin, Kristofer
2017-01-01
Tumor barrier function in carcinoma represents a major challenge to treatment and is therefore an attractive target for increasing drug delivery. Variables related to tumor barrier include aberrant blood vessels, high interstitial fluid pressure, and the composition and structure of the extracellular matrix. One of the proteins associated with dense extracellular matrices is fibromodulin, a collagen fibrillogenesis modulator expressed in tumor stroma but scarce in normal loose connective tissues. Here, we investigated the effects of fibromodulin on stroma ECM in a syngeneic murine colon carcinoma model. We show that fibromodulin deficiency decreased collagen fibril thickness but glycosaminoglycan content and composition were unchanged. Furthermore, vascular density, pericyte coverage and macrophage amount were unaffected. Fibromodulin can therefore be a unique effector of dense collagen matrix assembly in tumor stroma and, without affecting other major matrix components or the cellular composition, can function as a main agent in tumor barrier function.
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Preservation of the gut by preoperative carbohydrate loading improves postoperative food intake.
Luttikhold, Joanna; Oosting, Annemarie; van den Braak, Claudia C M; van Norren, Klaske; Rijna, Herman; van Leeuwen, Paul A M; Bouritius, Hetty
2013-08-01
A carbohydrate (CHO) drink given preoperatively changes the fasted state into a fed state. The ESPEN guidelines for perioperative care include preoperative CHO loading and re-establishment of oral feeding as early as possible after surgery. An intestinal ischaemia reperfusion (IR) animal model was used to investigate whether preoperative CHO loading increases spontaneous postoperative food intake, intestinal barrier function and the catabolic response. Male Wistar rats (n = 65) were subjected to 16 h fasting with ad libitum water and: A) sham laparotomy (Sham fasted, n = 24); B) intestinal ischaemia (IR fasted, n = 27); and C) intestinal ischaemia with preoperatively access to a CHO drink (IR CHO, n = 14). Spontaneous food intake, intestinal barrier function, insulin sensitivity, intestinal motility and plasma amino acids were measured after surgery. The IR CHO animals started eating significantly earlier and also ate significantly more than the IR fasted animals. Furthermore, preoperative CHO loading improved the intestinal barrier function, functional enterocyte metabolic mass measured by citrulline and reduced muscle protein catabolism, as indicated by normalization of the biomarker 3-methylhistidine. Preoperative CHO loading improves food intake, preserves the GI function and reduces the catabolic response in an IR animal model. These findings suggest that preoperative CHO loading preserves the intestinal function in order to accelerate recovery and food intake. If this effect is caused by overcoming the fasted state or CHO loading remains unclear. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
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Kulmuni, J; Westram, A M
2017-06-01
The possibility of intrinsic barriers to gene flow is often neglected in empirical research on local adaptation and speciation with gene flow, for example when interpreting patterns observed in genome scans. However, we draw attention to the fact that, even with gene flow, divergent ecological selection may generate intrinsic barriers involving both ecologically selected and other interacting loci. Mechanistically, the link between the two types of barriers may be generated by genes that have multiple functions (i.e., pleiotropy), and/or by gene interaction networks. Because most genes function in complex networks, and their evolution is not independent of other genes, changes evolving in response to ecological selection can generate intrinsic barriers as a by-product. A crucial question is to what extent such by-product barriers contribute to divergence and speciation-that is whether they stably reduce gene flow. We discuss under which conditions by-product barriers may increase isolation. However, we also highlight that, depending on the conditions (e.g., the amount of gene flow and the strength of selection acting on the intrinsic vs. the ecological barrier component), the intrinsic incompatibility may actually destabilize barriers to gene flow. In practice, intrinsic barriers generated as a by-product of divergent ecological selection may generate peaks in genome scans that cannot easily be interpreted. We argue that empirical studies on divergence with gene flow should consider the possibility of both ecological and intrinsic barriers. Future progress will likely come from work combining population genomic studies, experiments quantifying fitness and molecular studies on protein function and interactions. © 2017 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.
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G3X-K theory: A composite theoretical method for thermochemical kinetics
NASA Astrophysics Data System (ADS)
da Silva, Gabriel
2013-02-01
A composite theoretical method for accurate thermochemical kinetics, G3X-K, is described. This method is accurate to around 0.5 kcal mol-1 for barrier heights and 0.8 kcal mol-1 for enthalpies of formation. G3X-K is a modification of G3SX theory using the M06-2X density functional for structures and zero-point energies and parameterized for a test set of 223 heats of formation and 23 barrier heights. A reduced perturbation-order variant, G3X(MP3)-K, is also developed, providing around 0.7 kcal mol-1 accuracy for barrier heights and 0.9 kcal mol-1 accuracy for enthalpies, at reduced computational cost. Some opportunities to further improve Gn composite methods are identified and briefly discussed.
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Coated article and method of making
NASA Technical Reports Server (NTRS)
Wang, Hongyu (Inventor); Lee, Kang Neung (Inventor)
2003-01-01
An article includes a silicon-containing substrate and a modified mullite coating. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating. The article can further comprise a thermal barrier coating applied to the modified mullite coating. The modified mullite coating functions as a bond coating between the external environmental/thermal barrier coating and the silicon-containing substrate. In a method of forming an article, a silicon-containing substrate is formed and a modified mullite coating is applied. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating.
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Coated article and method of making
NASA Technical Reports Server (NTRS)
Wang, Hongyu (Inventor); Lee, Kang Neung (Inventor)
2002-01-01
An article includes a silicon-containing substrate and a modified mullite coating. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating. The article can further comprise a thermal barrier coating applied to the modified mullite coating. The modified mullite coating functions as a bond coating between the external environmental/thermal barrier coating and the silicon-containing substrate. In a method of forming an article, a silicon-containing substrate is formed and a modified mullite coating is applied. The modified mullite coating comprises mullite and a modifier component that reduces cracks in the modified mullite coating.
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Sugiura, Ayumi; Nomura, Tsuyoshi; Mizuno, Atsuko; Imokawa, Genji
2014-07-01
Atopic dermatitis is characterized by disruption of the cutaneous barrier due to reduced ceramide levels even in non-lesional dry skin. Following further acute barrier disruption by repeated tape strippings, we re-characterized the non-lesional dry skin of subjects with atopic dermatitis, which shows significantly reduced levels of barrier function and ceramide but not of beta-glucocerebrosidase activity. For the first time, we report an abnormal trans-epidermal water loss homeostasis in which delayed recovery kinetics of trans-epidermal water loss occurred on the first day during the 4 days after acute barrier disruption compared with healthy control skin. Interestingly, whereas the higher ceramide level in the stratum corneum of healthy control skin was further significantly up-regulated at 4 days post-tape stripping, the lower ceramide level in the stratum corneum of subjects with atopic dermatitis was not significantly changed. In a parallel study, whereas beta-glucocerebrosidase activity at 4 days post-tape stripping was significantly up-regulated in healthy control skin compared with before tape stripping, the level of that activity remained substantially unchanged in atopic dermatitis. These findings indicate that subjects with atopic dermatitis have a defect in sphingolipid-metabolic processing that generates ceramide in the interface between the stratum corneum and the epidermis. The results also support the notion that the continued disruption of barrier function in atopic dermatitis non-lesional skin is associated with the impaired homeostasis of a ceramide-generating process, which underscores an atopy-specific inflammation-triggered ceramide deficiency that is distinct from other types of dermatitis.
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Wang, Jing; Ghosh, Siddhartha S; Ghosh, Shobha
2017-04-01
Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as type 2 diabetes and atherosclerosis) has shifted the focus from high-fat high-cholesterol containing Western-type diet (WD)-induced changes in gut microbiota per se to release of gut bacteria-derived products (e.g., LPS) into circulation due to intestinal barrier dysfunction as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. We demonstrated earlier that oral supplementation with curcumin attenuates WD-induced development of type 2 diabetes and atherosclerosis. Poor bioavailability of curcumin has precluded the establishment of a causal relationship between oral supplementation and it is in vivo effects. We hypothesized that curcumin attenuates WD-induced chronic inflammation and associated metabolic diseases by modulating the function of intestinal epithelial cells (IECs) and the intestinal barrier function. The objective of the present study was to delineate the underlying mechanisms. The human IEC lines Caco-2 and HT-29 were used for these studies and modulation of direct as well as indirect effects of LPS on intracellular signaling as well as tight junctions were examined. Pretreatment with curcumin significantly attenuated LPS-induced secretion of master cytokine IL-1β from IECs and macrophages. Furthermore, curcumin also reduced IL-1β-induced activation of p38 MAPK in IECs and subsequent increase in expression of myosin light chain kinase involved in the phosphorylation of tight junction proteins and ensuing disruption of their normal arrangement. The major site of action of curcumin is, therefore, likely the IECs and the intestinal barrier, and by reducing intestinal barrier dysfunction, curcumin modulates chronic inflammatory diseases despite poor bioavailability. Copyright © 2017 the American Physiological Society.
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Nagasawa, Kunihiko; Chiba, Hideki; Fujita, Hiroki; Kojima, Takashi; Saito, Tsuyoshi; Endo, Toshiaki; Sawada, Norimasa
2006-07-01
Gap-junction plaques are often observed with tight-junction strands of vascular endothelial cells but the molecular interaction and functional relationships between these two junctions remain obscure. We herein show that gap-junction proteins connexin40 (Cx40) and Cx43 are colocalized and coprecipitated with tight-junction molecules occludin, claudin-5, and ZO-1 in porcine blood-brain barrier (BBB) endothelial cells. Gap junction blockers 18beta-glycyrrhetinic acid (18beta-GA) and oleamide (OA) did not influence expression of Cx40, Cx43, occludin, claudin-5, junctional adhesion molecule (JAM)-A, JAM-B, JAM-C, or ZO-1, or their subcellular localization in the porcine BBB endothelial cells. In contrast, these gap-junction blocking agents inhibited the barrier function of tight junctions in cells, determined by measurement of transendothelial electrical resistance and paracellular flux of mannitol and inulin. 18beta-GA also significantly reduced the barrier property in rat lung endothelial (RLE) cells expressing doxycycline-induced claudin-1, but did not change the interaction between Cx43 and either claudin-1 or ZO-1, nor their expression levels or subcellular distribution. These findings suggest that Cx40- and/or Cx43-based gap junctions might be required to maintain the endothelial barrier function without altering the expression and localization of the tight-junction components analyzed. Copyright 2006 Wiley-Liss, Inc.
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Effects of human rhinovirus on epithelial barrier integrity and function in children with asthma.
Looi, K; Buckley, A G; Rigby, P J; Garratt, L W; Iosifidis, T; Zosky, G R; Larcombe, A N; Lannigan, F J; Ling, K-M; Martinovich, K M; Kicic-Starcevich, E; Shaw, N C; Sutanto, E N; Knight, D A; Kicic, A; Stick, S M
2018-05-01
Bronchial epithelial tight junctions (TJ) have been extensively assessed in healthy airway epithelium. However, no studies have yet assessed the effect of human rhinovirus (HRV) infection on the expression and resultant barrier function in epithelial tight junctions (TJ) in childhood asthma. To investigate the impact of HRV infection on airway epithelial TJ expression and barrier function in airway epithelial cells (AECs) of children with and without asthma. Furthermore, to test the hypothesis that barrier integrity and function is compromised to a greater extent by HRV in AECs from asthmatic children. Primary AECs were obtained from children with and without asthma, differentiated into air-liquid interface (ALI) cultures and infected with rhinovirus. Expression of claudin-1, occludin and zonula occluden-1 (ZO-1) was assessed via qPCR, immunocytochemistry (ICC), in-cell western (ICW) and confocal microscopy. Barrier function was assessed by transepithelial electrical resistance (TER; R T ) and permeability to fluorescent dextran. Basal TJ gene expression of claudin-1 and occludin was significantly upregulated in asthmatic children compared to non-asthmatics; however, no difference was seen with ZO-1. Interestingly, claudin-1, occludin and ZO-1 protein expression was significantly reduced in AEC of asthmatic children compared to non-asthmatic controls suggesting possible post-transcriptional inherent differences. HRV infection resulted in a transient dissociation of TJ and airway barrier integrity in non-asthmatic children. Although similar dissociation of TJ was observed in asthmatic children, a significant and sustained reduction in TJ expression concurrent with both a significant decrease in TER and an increase in permeability in asthmatic children was observed. This study demonstrates novel intrinsic differences in TJ gene and protein expression between AEC of children with and without asthma. Furthermore, it correlates directly the relationship between HRV infection and the resultant dissociation of epithelial TJ that causes a continued altered barrier function in children with asthma. © 2018 John Wiley & Sons Ltd.
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Li, Jiajia; Zhang, Rong; Wang, Caixia; Wang, Xin; Xu, Man; Ma, Jingxue; Shang, Qingli
2018-03-30
Choroidal neovascularization (CNV) is a common vision-threatening complication associated with many fundus diseases. The retinal pigment epithelial (RPE) cell junction barrier has critical functions in preventing CNV, and oxidative stress can cause compromise of barrier integrity and induce angiogenesis. Rap1, a small guanosine triphosphatase (GTPase), is involved in regulating endothelial and epithelial cell junctions. In this work, we explored the function and mechanism of Rap1 in CNV in vivo. A laser-induced rat CNV model was developed. Rap1 was activated through intravitreal injection of the Rap1 activator 8CPT-2'-O-Me-cAMP (8CPT). At 14 days after laser treatment, CNV size in RPE/choroid flat mounts was measured by fluorescein isothiocyanate-dextran staining. Expression of vascular endothelial growth factor (VEGF) and cell junction proteins in RPE/choroid tissues were analyzed by western blots and quantitative real-time PCR assays. Reactive oxygen species (ROS) in RPE cells were detectedbydichloro-dihydro-fluorescein diacetate assays. The antioxidant apocynin was intraperitoneally injected into rats. Activating Rap1 by 8CPT significantly reduced CNV size and VEGF expression in the rat CNV model. Rap1 activation enhanced protein and mRNA levels of ZO-1 and occludin, two tight junction proteins in the RPE barrier. In addition, reducing ROS generation by injection of apocynin, a NADPH oxidase inhibitor, inhibited CNV formation. Rap1 activation reduced ROS generation and expression of NADPH oxidase 4. Rap1 activation inhibits CNV through regulating barrier integrity and ROS generation of RPE in vivo, and selectively activating Rap1 may be a way to reduce vision loss from CNV.
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Long-Term Drainage from the Riprap Side Slope of a Surface Barrier
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Zhuanfang
Surface barriers designed to isolate underground nuclear waste in place are expected to function for at least 1000 years. To achieve this long design life, such barriers need to be protected with side slopes against wind- and water-induced erosion and damage by natural or human activities. However, the side slopes are usually constructed with materials coarser than the barrier. Their hydrological characteristics must be understood so that any drainage from them is considered in the barrier design and will not compromise the barrier function. The Prototype Hanford Barrier, an evapotranspiration-capillary (ETC) barrier, was constructed in 1994 at the Hanford Sitemore » in southeastern Washington state, with a gravel side slope and a riprap side slope. The soil water content in the gravel side slope and drainage from both side slopes have been monitored since the completion of construction. The monitoring results show that under natural precipitation the annual drainage rates from the two types of side slopes were very similar and about 5 times the typical recharge from local soil with natural vegetation and 40 times the barrier design criterion. The higher recharge from the side slopes results in some of the drainage migrating laterally to the region beneath the ETC barrier. This edge effect of the enhanced drainage was evaluated for a period of 1000 years by numerical simulation. The edge effect was quantified by the amount of water across the barrier edges and the affecting distance of the barrier edges. These results indicate that design features can be adjusted to reduce the edge effect when necessary.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Doyoon; Lee, Byeongdu; Thomopoulos, Stavros
Mineralization of collagen is critical for the mechanical functions of bones and teeth. Calcium phosphate nucleation in collagenous structures follows distinctly different patterns in highly confined gap regions (nanoscale confinement) than in less confined extrafibrillar spaces (microscale confinement). Although the mechanism(s) driving these differences are still largely unknown, differences in the free energy for nucleation may explain these two mineralization behaviors. Here, we report on experimentally obtained nucleation energy barriers to intra- and extrafibrillar mineralization, using in situ X-ray scattering observations and classical nucleation theory. Polyaspartic acid, an extrafibrillar nucleation inhibitor, increases interfacial energies between nuclei and mineralization fluids. Inmore » contrast, the confined gap spaces inside collagen fibrils lower the energy barrier by reducing the reactive surface area of nuclei, decreasing the surface energy penalty. The confined gap geometry, therefore, guides the two-dimensional morphology and structure of bioapatite and changes the nucleation pathway by reducing the total energy barrier.« less
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Kim, Doyoon; Lee, Byeongdu; Thomopoulos, Stavros; ...
2018-03-06
Mineralization of collagen is critical for the mechanical functions of bones and teeth. Calcium phosphate nucleation in collagenous structures follows distinctly different patterns in highly confined gap regions (nanoscale confinement) than in less confined extrafibrillar spaces (microscale confinement). Although the mechanism(s) driving these differences are still largely unknown, differences in the free energy for nucleation may explain these two mineralization behaviors. Here, we report on experimentally obtained nucleation energy barriers to intra- and extrafibrillar mineralization, using in situ X-ray scattering observations and classical nucleation theory. Polyaspartic acid, an extrafibrillar nucleation inhibitor, increases interfacial energies between nuclei and mineralization fluids. Inmore » contrast, the confined gap spaces inside collagen fibrils lower the energy barrier by reducing the reactive surface area of nuclei, decreasing the surface energy penalty. The confined gap geometry, therefore, guides the two-dimensional morphology and structure of bioapatite and changes the nucleation pathway by reducing the total energy barrier.« less
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Giantsos-Adams, Kristina; Lopez-Quintero, Veronica; Kopeckova, Pavla; Kopecek, Jindrich; Tarbell, John M.; Dull, Randal
2015-01-01
Pulmonary edema and the associated increases in vascular permeability continue to represent a significant clinical problem in the intensive care setting, with no current treatment modality other than supportive care and mechanical ventilation. Therapeutic compound(s) capable of attenuating changes in vascular barrier function would represent a significant advance in critical care medicine. We have previously reported the development of HPMA-based copolymers, targeted to endothelial glycocalyx that are able to enhance barrier function. In this work, we report the refinement of copolymer design and extend our physiological studies todemonstrate that the polymers: 1) reduce both shear stress and pressure-mediated increase in hydraulic conductivity, 2) reduce nitric oxide production in response to elevated hydrostatic pressure and, 3) reduce the capillary filtration coefficient (Kfc) in an isolated perfused mouse lung model. These copolymers represent an important tool for use in mechanotransduction research and a novel strategy for developing clinically useful copolymers for the treatment of vascular permeability. PMID:20932573
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Li, Yihang; Song, Zehe; Kerr, Katelyn A.; Moeser, Adam J.
2017-01-01
Psychosocial stress is a major factor driving gastrointestinal (GI) pathophysiology and disease susceptibility in humans and animals. The mechanisms governing susceptibility to stress-induced GI disease remain poorly understood. In the present study, we investigated the influence of chronic social stress (CSS) in pigs, induced by 7 d of chronic mixing/crowding stress, on intestinal barrier and nutrient transport function, corticotropin releasing factor (CRF) signaling and immunological responses. Results from this study showed that CSS resulted in a significant impairment of ileal and colonic barrier function indicated by reduced transepithelial electrical resistance (TER) in the ileum and increased FD4 flux in the ileum (by 0.8 fold) and colon (by 0.7 fold). Ileal sodium glucose linked transporter 1 (SGLT-1) function, measured as glucose-induced changes in short-circuit current (Isc), was diminished (by 52%) in CSS pigs, associated with reduced body weight gain and feed efficiency. Although reductions in SGLT-1 function were observed in CSS pigs, mRNA expression for SGLT-1, villus heights were increased in CSS pigs. Corticotropin releasing factor (CRF) mRNA was upregulated (by 0.9 fold) in the ileum of CSS pigs but not in the colon. Urocortin 2 (Ucn2) mRNA was upregulated (by 1.5 fold) in the colon of CSS pigs, but not in the ileum. In CSS pigs, a downregulation of pro-inflammatory cytokines mRNA (IL1B, TNFA, IL8, and IL6) was observed in both ileum and colon, compared with controls. In contrast CSS induced a marked upregulation of mRNA for IL10 and mast cell chymase gene (CMA1) in the ileum and colon. Together, these data demonstrate that chronic stress in pigs results in significant alterations in intestinal barrier and nutrient transport function and neuro-immune mediator and receptor expression. PMID:28170426
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Lysosomal storage diseases and the blood-brain barrier.
Begley, David J; Pontikis, Charles C; Scarpa, Maurizio
2008-01-01
The blood-brain barrier becomes a crucial issue in neuronopathic lysosomal storage diseases for three reasons. Firstly, the function of the blood-brain barrier may be compromised in many of the lysosomal storage diseases and this barrier dysfunction may contribute to the neuropathology seen in the diseases and accelerate cell death. Secondly, the substrate reduction therapies, which successfully reduce peripheral lysosomal storage, because of the blood-brain barrier may not have as free an access to brain cells as they do to peripheral cells. And thirdly, enzyme replacement therapy appears to have little access to the central nervous system as the mannose and mannose-6-phosphate receptors involved in their cellular uptake and transport to the lysosome do not appear to be expressed at the adult blood-brain barrier. This review will discuss in detail these issues and their context in the development of new therapeutic strategies.
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Tokudome, Yoshihiro; Masutani, Noriomi; Uchino, Shohei; Fukai, Hisano
2017-10-27
Purified glucosylceramide from beet extract (beet GlcCer) and beet extract containing an equal amount of GlcCer were administered orally to ultra violet B (UVB)-irradiated mice, and differences in the protective effects against skin barrier dysfunction caused by UVB irradiation were compared. In the beet GlcCer group, epidermal thickening and the decrease in stratum corneum (SC) ceramide content caused by UVB irradiation were reduced. In the group that was orally administered beet extract containing glucosylceramide, effects similar to those in the beet GlcCer group were observed. Oral administration of beet GlcCer had no obvious effects against an increase in TEWL or decrease in SC water content after UVB irradiation, but there was improvement in the beet extract group. Oral administration of beet GlcCer is effective in improving skin barrier function in UVB-irradiated mice. Beet extract contains constituents other than GlcCer that are also effective in improving skin barrier function.
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Portegijs, Erja; Rantakokko, Merja; Viljanen, Anne; Rantanen, Taina; Iwarsson, Susanne
We studied whether entrance-related environmental barriers, perceived and objectively recorded, were associated with moving out-of-home daily in older people with and without limitations in lower extremity performance. Cross-sectional analyses of the "Life-space mobility in old age" cohort including 848 community-dwelling 75-90-year-old of central Finland. Participants reported their frequency of moving out-of-home (daily vs. 0-6 times/week) and perceived entrance-related environmental barriers (yes/no). Lower extremity performance was assessed (Short Physical Performance Battery) and categorized as poorer (score 0-9) or good (score 10-12). Environmental barriers at entrances and in exterior surroundings were objectively registered (Housing Enabler screening tool) and divided into tertiles. Logistic regression analyses were adjusted for age, sex, number of chronic diseases, cognitive function, month of assessment, type of neighborhood, and years lived in the current home. At home entrances a median of 6 and in the exterior surroundings 5 environmental barriers were objectively recorded, and 20% of the participants perceived entrance-related barriers. The odds for moving out-of-home less than daily increased when participants perceived entrance-related barrier(s) or when they lived in homes with higher numbers of objectively recorded environmental barriers at entrances. Participants with limitations in lower extremity performance were more susceptible to these environmental barriers. Objectively recorded environmental barriers in the exterior surroundings did not compromise out-of-home mobility. Entrance-related environmental barriers may hinder community-dwelling older people to move out-of-home daily especially when their functional capacity is compromised. Potentially, reducing entrance-related barriers may help to prevent confinement to the home. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Wu, Xiaowu; Dubick, Michael A; Schwacha, Martin G; Cap, Andrew P; Darlington, Daniel N
2017-04-01
Severe trauma, hemorrhage, and resuscitation can lead to a trauma-related acute lung injury that involves rapid infiltration of immune cells and platelets. This infiltration involves exymatic degradation of matrix proteins, including plasmin, and causes loss of barrier function. Since tranexamic acid (TXA) inhibits plasminogen/ plasmin binding to target substrates, it may attenuate loss of barrier function after severe trauma, hemorrhage, and resuscitation. Sprague-Dawley rats were subjected to polytrauma (laparotomy, and trauma to intestines, liver, right leg skeletal muscle, and right femur fracture), then bled 40% of their blood volume. One hour after completion of polytrauma and hemorrhage, resuscitation was begun with fresh whole blood (FWB) or FWB with prior bolus administration of TXA (10 mg/kg in 0.2 mL). Polytrauma, hemorrhage, and resuscitation with FWB led to an elevation in lung water content that was significantly reduced with TXA administration. Polytrauma and hemorrhage led to rise in the number of neutrophils/monocytes and platelets in the lungs, and a rise in myeloperoxidase (MPO), neutrophil elastase and complement C5a content. While resuscitation with FWB significantly reduced the cellular infiltrate and MPO, FWB/TXA further reduced the levels of neutrophil/monocytes, neutrophil elastase, and complement C5a. Polytrauma and hemorrhage led to rise in lung plasmin activity that was significantly reduced with either FWB or FWB/TXA resuscitation. Severe trauma and hemorrhage leads to increases in lung water content, and immune cell, platelets, MPO, elastase, and C5a content in lung tissue, all markers of inflammation and acute lung injury. The addition of TXA to FWB resuscitation markedly attenuated the rise in these parameters suggesting its utility in treating acute lung injury.
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Zhang, Shishuang; Zhi, Yongle; Li, Fei; Huang, Shan; Gao, Huabin; Han, Zhaoli; Ge, Xintong; Li, Dai; Chen, Fanglian; Kong, Xiaodong; Lei, Ping
2018-04-15
To date, the pathogenesis of Alzheimer's disease (AD) remains unclear. It is well-known that excessive deposition of Aβ in the brain is a crucial part of the pathogenesis of AD. In recent years, the AD neurovascular unit hypothesis has attracted much attention. Impairment of the blood-brain barrier (BBB) leads to abnormal amyloid-β (Aβ) transport, and chronic cerebral hypoperfusion causes Aβ deposition throughout the onset and progression of AD. Endothelial progenitor cells (EPCs) are the universal cells for repairing blood vessels. Our previous studies have shown that a reduced number of EPCs in the peripheral blood results in cerebral vascular repair disorder, cerebral hypoperfusion and neurodegeneration, which might be related to the cognitive dysfunction of AD patients. This study was designed to confirm whether EPCs transplantation could repair the blood-brain barrier, stimulate angiogenesis and reduce Aβ deposition in AD. The expression of ZO-1, Occludin and Claudin-5 was up-regulated in APP/PS1 transgenic mice after hippocampal transplantation of EPCs. Consistent with previous studies, EPC transplants also increased the microvessel density. We observed that Aβ senile plaque deposition was decreased and hippocampal cell apoptosis was reduced after EPCs transplantation. The Morris water maze test showed that spatial learning and memory functions were significantly improved in mice transplanted with EPCs. Consequently, EPCs could up-regulate the expression of tight junction proteins, repair BBB tight junction function, stimulate angiogenesis, promote Aβ clearance, and decrease neuronal loss, ultimately improve cognitive function. Taken together, these data demonstrate EPCs may play an important role in the therapeutic implications for vascular dysfunction in AD. Copyright © 2018 Elsevier B.V. All rights reserved.
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Foote, A P; Penner, G B; Walpole, M E; Klotz, J L; Brown, K R; Bush, L P; Harmon, D L
2014-07-01
Ergot alkaloids in endophyte-infected (Neotyphodium coenophialum) tall fescue (Lolium arundinaceum) have been shown to cause a reduction in blood flow to the rumen epithelium as well as a decrease in volatile fatty acids (VFA) absorption from the washed rumen of steers. Previous data also indicates that incubating an extract of endophyte-infected tall fescue seed causes an increase in the amount of VFA absorbed per unit of blood flow, which could result from an alteration in the absorptive or barrier function of the rumen epithelium. An experiment was conducted to determine the acute effects of an endophyte-infected tall fescue seed extract (EXT) on total, passive or facilitated acetate and butyrate flux across the isolated bovine rumen as well as the barrier function measured by inulin flux and tissue conductance (G t ). Flux of ergovaline across the rumen epithelium was also evaluated. Rumen tissue from the caudal dorsal sac of Holstein steers (n=6), fed a common diet, was collected and isolated shortly after slaughter and mounted between two halves of Ussing chambers. In vitro treatments included vehicle control (80% methanol, 0.5% of total volume), Low EXT (50 ng ergovaline/ml) and High EXT (250 ng ergovaline/ml). Results indicate that there is no effect of acute exposure to ergot alkaloids on total, passive or facilitated flux of acetate or butyrate across the isolate bovine rumen epithelium (P>0.51). Inulin flux (P=0.16) and G t (P>0.17) were not affected by EXT treatment, indicating no alteration in barrier function due to acute ergot alkaloid exposure. Ergovaline was detected in the serosal buffer of the High EXT treatment indicating that the flux rate is ~0.25 to 0.44 ng/cm2 per hour. Data indicate that specific pathways for VFA absorption and barrier function of the rumen epithelium are not affected by acute exposure to ergot alkaloids from tall fescue at the concentrations tested. Ergovaline has the potential to be absorbed from the rumen of cattle that could contribute to reduced blood flow and motility and lead to reduced growth rates of cattle.
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Chen, Kang; Zhou, Xiao-Qiu; Jiang, Wei-Dan; Wu, Pei; Liu, Yang; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Feng, Lin
2018-03-01
In aquaculture, the occurrence of enteritis has increased and dietary nutrition is considered as one of the major strategies to solve this problem. In the present study, we assume that dietary phosphorus might enhance intestinal immune barrier and physical barrier function to reduce the occurrence of enteritis in fish. To test this assumption, a total of 540 grass carp (Ctenopharyngodon idella) were investigated by feeding graded levels of available phosphorus (0.95-8.75 g/kg diet) and then infection with Aeromonas hydrophila. The results firstly showed that phosphorus deficiency decreased the ability to combat enteritis, which might be related to the impairment of intestinal immune barrier and physical barrier function. Compared with optimal phosphorus level, phosphorus deficiency decreased fish intestinal antimicrobial substances activities or contents and down-regulated antimicrobial peptides mRNA levels leading to the impairment of intestinal immune response. Phosphorus deficiency down-regulated fish intestinal anti-inflammatory cytokines mRNA levels and up-regulated the mRNA levels of pro-inflammatory cytokines [except IL-1β and IL-12p35 in distal intestine (DI) and IL-12p40] causing aggravated of intestinal inflammatory responses, which might be related to the signalling molecules target of rapamycin and nuclear factor kappa B. In addition, phosphorus deficiency disturbed fish intestinal tight junction function and induced cell apoptosis as well as oxidative damage leading to impaired of fish intestinal physical barrier function, which might be partially associated with the signalling molecules myosin light chain kinase, c-Jun N-terminal protein kinase and NF-E2-related factor 2, respectively. Finally, based on the ability to combat enteritis, dietary available phosphorus requirement for grass carp (254.56-898.23 g) was estimated to be 4.68 g/kg diet. Copyright © 2017. Published by Elsevier Ltd.
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Riggs, G H; Schweitzer, L
1994-01-01
Various studies have suggested that glycoconjugates may influence connectivity and lamination in the developing central nervous system and may function as barriers to neuritic extension. It has been proposed that the peanut agglutinin lectin labels a glycoconjugate subserving a barrier function. We chose to investigate the distribution of this peanut-agglutinin-labelled glycoconjugate in the dorsal cochlear nucleus of the developing hamster since the development of the dorsal cochlear nucleus is well characterised and its axons obey laminar boundaries. The distribution of peanut agglutinin label throughout the cochlear nucleus delineated zones that cochlear axons fail to invade. In the dorsal cochlear nucleus, laminar differences were reduced on postnatal d 13 and virtually disappearing by postnatal d 23. Label in the molecular layer dissipated as axons and dendrites grew into this layer. These patterns of peanut agglutinin binding correspond to axonal ingrowth and are consistent with a barrier function for glycoconjugates in the molecular layer. Images Fig. 1 Fig. 2 Fig. 4 PMID:7961144
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Piqué, Núria; Gómez-Guillén, María Del Carmen; Montero, María Pilar
2018-02-27
Disruption of the epithelial barrier function has been recently associated with a variety of diseases, mainly at intestinal level, but also affecting the respiratory epithelium and other mucosal barriers. Non-pharmacological approaches such as xyloglucan, with demonstrated protective barrier properties, are proposed as new alternatives for the management of a wide range of diseases, for which mucosal disruption and, particularly, tight junction alterations, is a common characteristic. Xyloglucan, a natural polysaccharide derived from tamarind seeds, possesses a "mucin-like" molecular structure that confers mucoadhesive properties, allowing xyloglucan formulations to act as a barrier capable of reducing bacterial adherence and invasion and to preserve tight junctions and paracellular flux, as observed in different in vitro and in vivo studies. In clinical trials, xyloglucan has been seen to reduce symptoms of gastroenteritis in adults and children, nasal disorders and dry eye syndrome. Similar mucosal protectors containing reticulated proteins have also been useful for the treatment of irritable bowel syndrome and urinary tract infections. The role of xyloglucan in other disorders with mucosal disruption, such as dermatological or other infectious diseases, deserves further research. In conclusion, xyloglucan, endowed with film-forming protective barrier properties, is a safe non-pharmacological alternative for the management of different diseases, such as gastrointestinal and nasal disorders.
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Gómez-Guillén, María del Carmen; Montero, María Pilar
2018-01-01
Disruption of the epithelial barrier function has been recently associated with a variety of diseases, mainly at intestinal level, but also affecting the respiratory epithelium and other mucosal barriers. Non-pharmacological approaches such as xyloglucan, with demonstrated protective barrier properties, are proposed as new alternatives for the management of a wide range of diseases, for which mucosal disruption and, particularly, tight junction alterations, is a common characteristic. Xyloglucan, a natural polysaccharide derived from tamarind seeds, possesses a “mucin-like” molecular structure that confers mucoadhesive properties, allowing xyloglucan formulations to act as a barrier capable of reducing bacterial adherence and invasion and to preserve tight junctions and paracellular flux, as observed in different in vitro and in vivo studies. In clinical trials, xyloglucan has been seen to reduce symptoms of gastroenteritis in adults and children, nasal disorders and dry eye syndrome. Similar mucosal protectors containing reticulated proteins have also been useful for the treatment of irritable bowel syndrome and urinary tract infections. The role of xyloglucan in other disorders with mucosal disruption, such as dermatological or other infectious diseases, deserves further research. In conclusion, xyloglucan, endowed with film-forming protective barrier properties, is a safe non-pharmacological alternative for the management of different diseases, such as gastrointestinal and nasal disorders. PMID:29495535
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NASA Astrophysics Data System (ADS)
Kuntze, Thomas; Wollmann, Philipp; Klotzbach, Udo; Fledderus, Henri
2017-03-01
The proper long term operation of organic electronic devices like organic photovoltaics OPV depends on their resistance to environmental influences such as permeation of water vapor. Major efforts are spent to encapsulate OPV. State of the art is sandwich-like encapsulation between two ultra-barrier foils. Sandwich encapsulation faces two major disadvantages: high costs ( 1/3 of total costs) and parasitic intrinsic water (sponge effects of the substrate foil). To fight these drawbacks, a promising approach is to use the OPV substrate itself as barrier by integration of an ultra-barrier coating, followed by alternating deposition and structuring of OPV functional layers. In effect, more functionality will be integrated into less material, and production steps are reduced in number. All processing steps must not influence the underneath barrier functionality, while all electrical functionalities must be maintained. As most reasonable structuring tool, short and ultrashort pulsed lasers USP are used. Laser machining applies to three layers: bottom electrode made of transparent conductive materials (P1), organic photovoltaic operative stack (P2) and top electrode (P3). In this paper, the machining of functional 110…250 nm layers of flexible OPV by USP laser systems is presented. Main focus is on structuring without damaging the underneath ultra-barrier layer. The close-to-process machining quality characterization is performed with the analysis tool "hyperspectral imaging" (HSI), which is checked crosswise with the "gold standard" Ca-test. It is shown, that both laser machining and quality controlling, are well suitable for R2R production of OPV.
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Rebamipide ameliorates radiation-induced intestinal injury in a mouse model.
Shim, Sehwan; Jang, Hyo-Sun; Myung, Hyun-Wook; Myung, Jae Kyung; Kang, Jin-Kyu; Kim, Min-Jung; Lee, Seung Bum; Jang, Won-Suk; Lee, Sun-Joo; Jin, Young-Woo; Lee, Seung-Sook; Park, Sunhoo
2017-08-15
Radiation-induced enteritis is a major side effect in cancer patients undergoing abdominopelvic radiotherapy. Radiation exposure produces an uncontrolled inflammatory cascade and epithelial cell loss leading to impaired epithelial barrier function. The goal of this study was to determine the effect of rebamipide on regeneration of the intestinal epithelia after radiation injury. The abdomens of C57BL/6 mice were exposed to 13Gy of irradiation (IR) and then the mice were treated with rebamipide. Upon IR, intestinal epithelia were destroyed structurally at the microscopic level and bacterial translocation was increased. The intestinal damage reached a maximum level on day 6 post-IR and intestinal regeneration occurred thereafter. We found that rebamipide significantly ameliorated radiation-induced intestinal injury. In mice treated with rebamipide after IR, intestinal barrier function recovered and expression of the tight junction components of the intestinal barrier were upregulated. Rebamipide administration reduced radiation-induced intestinal mucosal injury. The levels of proinflammatory cytokines and matrix metallopeptidase 9 (MMP9) were significantly reduced upon rebamipide administration. Intestinal cell proliferation and β-catenin expression also increased upon rebamipide administration. These data demonstrate that rebamipide reverses impairment of the intestinal barrier by increasing intestinal cell proliferation and attenuating the inflammatory response by inhibiting MMP9 and proinflammatory cytokine expression in a murine model of radiation-induced enteritis. Copyright © 2017 Elsevier Inc. All rights reserved.
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Moeser, Adam-J; Nighot, Prashant-K; Roerig, Birgit; Ueno, Ryuji; Blikslager, Anthony-T
2008-10-21
To investigate the effects of lubiprostone and Polyethylene Glycol 3350 (PEG) on mucosal barrier repair in ischemic-injured porcine intestine. Ileum from 6 piglets (approximately 15 kg body weight) was subjected to ischemic conditions by occluding the local mesenteric circulation for 45 min in vivo. Ileal tissues from each pig were then harvested and mounted in Ussing chambers and bathed in oxygenated Ringer's solution in vitro. Intestinal barrier function was assessed by measuring transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of (3)H-mannitol and (14)C-inulin. Statistical analyses of data collected over a 120-min time course included 2-way ANOVA for the effects of time and treatment on indices of barrier function. Application of 1 micromol/L lubiprostone to the mucosal surface of ischemic-injured ileum in vitro induced significant elevations in TER compared to non-treated tissue. Lubiprostone also reduced mucosal-to-serosal fluxes of (3)H-mannitol and (14)C-inulin. Alternatively, application of a polyethylene laxative (PEG, 20 mmol/L) to the mucosal surface of ischemic tissues significantly increased flux of (3)H-mannitol and (14)C-inulin. This experiment demonstrates that lubiprostone stimulates recovery of barrier function in ischemic intestinal tissues whereas the PEG laxative had deleterious effects on mucosal repair. These results suggest that, unlike osmotic laxatives, lubiprostone stimulates repair of the injured intestinal barrier.
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Moeser, Adam J; Nighot, Prashant K; Roerig, Birgit; Ueno, Ryuji; Blikslager, Anthony T
2008-01-01
AIM: To investigate the effects of lubiprostone and Polyethylene Glycol 3350 (PEG) on mucosal barrier repair in ischemic-injured porcine intestine. METHODS: Ileum from 6 piglets (approximately 15 kg body weight) was subjected to ischemic conditions by occluding the local mesenteric circulation for 45 min in vivo. Ileal tissues from each pig were then harvested and mounted in Ussing chambers and bathed in oxygenated Ringer’s solution in vitro. Intestinal barrier function was assessed by measuring transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of 3H-mannitol and 14C-inulin. Statistical analyses of data collected over a 120-min time course included 2-way ANOVA for the effects of time and treatment on indices of barrier function. RESULTS: Application of 1 μmol/L lubiprostone to the mucosal surface of ischemic-injured ileum in vitro induced significant elevations in TER compared to non-treated tissue. Lubiprostone also reduced mucosal-to-serosal fluxes of 3H-mannitol and 14C-inulin. Alternatively, application of a polyethylene laxative (PEG, 20 mmol/L) to the mucosal surface of ischemic tissues significantly increased flux of 3H-mannitol and 14C-inulin. CONCLUSION: This experiment demonstrates that lubiprostone stimulates recovery of barrier function in ischemic intestinal tissues whereas the PEG laxative had deleterious effects on mucosal repair. These results suggest that, unlike osmotic laxatives, lubiprostone stimulates repair of the injured intestinal barrier. PMID:18932279
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Sutton, Jonathan E.; Beste, Ariana; Steven H. Overbury
2015-10-12
In this study, we use density functional theory to explain the preferred structure of partially reduced CeO 2(111). Low-energy ordered structures are formed when the vacancies are isolated (maximized intervacancy separation) and the size of the Ce 3+ ions is minimized. Both conditions help minimize disruptions to the lattice around the vacancy. The stability of the ordered structures suggests that isolated vacancies are adequate for modeling more complex (e.g., catalytic) systems. Oxygen diffusion barriers are predicted to be low enough that O diffusion between vacancies is thermodynamically controlled at room temperature. The O-diffusion-reaction energies and barriers are decreased when onemore » Ce f electron hops from a nearest-neighbor Ce cation to a next-nearest-neighbor Ce cation, with a barrier that has been estimated to be slightly less than the barrier to O diffusion in the absence of polaron hopping. In conculsion, this indicates that polaron hopping plays a key role in facilitating the overall O diffusion process, and depending on the relative magnitudes of the polaron hopping and O diffusion barriers, polaron hopping may be the kinetically limiting process.« less
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[Advances in the research of effects of glutamine on immune function of burn patients].
Liu, Y H; Guo, P F; Chen, G Y; Bo, Y C; Ma, Y; Cui, Z J
2018-04-20
Glutamine is the most abundant amino acid found in plasma and cells. It is the preferred fuel for enterocytes in the small intestine, macrophages, and lymphocytes. After serious burn, increased requirement of glutamine by the gastrointestinal tract, kidney and lymphocytes, and relatively insufficient self synthesis likely contribute to the rapid decline of glutamine in circulation and cells. Glutamine supplementation can not only protect intestinal mucosa, maintain normal intestinal barrier function, reduce bacterial translocation, and enhance the intestinal immune function, but also increase the number of lymphocytes, enhance the phagocytic function of macrophage, promote the synthesis of immunoglobulin, and reduce the body's inflammatory response, so as to enhance the immune function. Therefore, glutamine supplementation can improve and enhance the immune function, reduce complications and promote the prognosis of severely burned patients.
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Ramezanpour, Mahnaz; Murphy, Jae; Smith, Jason L P; Vreugde, Sarah; Psaltis, Alkis James
2017-12-01
Carrageenans have shown to reduce the viral load in nasal secretions and lower the incidence of secondary infections in children with common cold. Despite the widespread use of carrageenans in topical applications, the effect of carrageenans on the sinonasal epithelial barrier has not been elucidated. We investigate the effect of different carrageenans on the sinonasal epithelial barrier and inflammatory response in vitro. Iota and Kappa carrageenan delivered in saline irrigation solutions applied to air-liquid interface (ALI) cultures of primary human nasal epithelial cells from chronic rhinosinusitis patients and controls. Epithelial barrier structure was assessed by measuring the transepithelial electrical resistance (TEER) and immunolocalization of F actin. Ciliary beat frequency (CBF), toxicity, and inflammatory response was studied. Kappa or Iota carrageenan in the different solutions was not toxic, did not have detrimental effects on epithelial barrier structure and CBF. Rather, application of Kappa carrageenan significantly increased TEER and suppressed interleukin 6 (IL-6) secretion in ALI cultures from CRS patients. Kappa or Iota carrageenan solution was safe and did not negatively affect epithelial barrier function. Kappa carrageenan increased TEER and decreased IL-6 production in CRS patients, indicating positive effects on epithelial barrier function in vitro. © 2017 ARS-AAOA, LLC.
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Optimal design of wind barriers using 3D computational fluid dynamics simulations
NASA Astrophysics Data System (ADS)
Fang, H.; Wu, X.; Yang, X.
2017-12-01
Desertification is a significant global environmental and ecological problem that requires human-regulated control and management. Wind barriers are commonly used to reduce wind velocity or trap drifting sand in arid or semi-arid areas. Therefore, optimal design of wind barriers becomes critical in Aeolian engineering. In the current study, we perform 3D computational fluid dynamics (CFD) simulations for flow passing through wind barriers with different structural parameters. To validate the simulation results, we first inter-compare the simulated flow field results with those from both wind-tunnel experiments and field measurements. Quantitative analyses of the shelter effect are then conducted based on a series of simulations with different structural parameters (such as wind barrier porosity, row numbers, inter-row spacing and belt schemes). The results show that wind barriers with porosity of 0.35 could provide the longest shelter distance (i.e., where the wind velocity reduction is more than 50%) thus are recommended in engineering designs. To determine the optimal row number and belt scheme, we introduce a cost function that takes both wind-velocity reduction effects and economical expense into account. The calculated cost function show that a 3-row-belt scheme with inter-row spacing of 6h (h as the height of wind barriers) and inter-belt spacing of 12h is the most effective.
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Liu, Chunyu; Zhang, Dezhong; Li, Zhiqi; Zhang, Xinyuan; Guo, Wenbin; Zhang, Liu; Ruan, Shengping; Long, Yongbing
2017-07-05
To overcome drawbacks of the electron transport layer, such as complex surface defects and unmatched energy levels, we successfully employed a smart semiconductor-metal interfacial nanojunciton in organic solar cells by evaporating an ultrathin Al interlayer onto annealing-free ZnO electron transport layer, resulting in a high fill factor of 73.68% and power conversion efficiency of 9.81%. The construction of ZnO-Al nanojunction could effectively fill the surface defects of ZnO and reduce its work function because of the electron transfer from Al to ZnO by Fermi level equilibrium. The filling of surface defects decreased the interfacial carrier recombination in midgap trap states. The reduced surface work function of ZnO-Al remodulated the interfacial characteristics between ZnO and [6,6]-phenyl C71-butyric acid methyl ester (PC 71 BM), decreasing or even eliminating the interfacial barrier against the electron transport, which is beneficial to improve the electron extraction capacity. The filled surface defects and reduced interfacial barrier were realistically observed by photoluminescence measurements of ZnO film and the performance of electron injection devices, respectively. This work provides a simple and effective method to simultaneously solve the problems of surface defects and unmatched energy level for the annealing-free ZnO or other metal oxide semiconductors, paving a way for the future popularization in photovoltaic devices.
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Wan Saudi, Wan Salman
2017-01-01
Alcohol disrupts the intestinal mucosal barrier by inducing metabolic and functional changes in epithelial cells. Recently, we showed that neuropeptide S (NPS) decreases duodenal motility and increases mucosal paracellular permeability, suggesting a role of NPS in the pathogenesis of disorders and dysfunctions in the small intestine. The aim of the present study was to investigate the effects of NPS on ethanol- and HCl-induced changes of duodenal mucosal barrier function and motility. Rats were anaesthetized with thiobarbiturate, and a 30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ. The effects on duodenal bicarbonate secretion, the blood-to-lumen clearance of 51Cr-EDTA, motility and transepithelial net fluid flux were investigated. Intravenous (i.v.) administration of NPS significantly reduced duodenal mucosal bicarbonate secretion and stimulated mucosal transepithelial fluid absorption, mechanisms dependent on nitrergic signaling. NPS dose-dependently reduced ethanol-induced increases in duodenal motility. NPS (83 pmol·kg-1·min-1, i.v.) reduced the bicarbonate and fluid secretory response to luminal ethanol, whereas a 10-fold higher dose stimulated fluid secretion but did not influence bicarbonate secretion. In NPS-treated animals, duodenal perfusion of acid (pH 3) induced greater bicarbonate secretory rates than in controls. Pre-treating animals with Nω-nitro-L-arginine methyl ester (L-NAME) inhibited the effect of NPS on bicarbonate secretion. In response to luminal acid, NPS-treated animals had significantly higher paracellular permeability compared to controls, an effect that was abolished by L-NAME. Our findings demonstrate that NPS reduces basal and ethanol-induced increases in duodenal motility. In addition, NPS increases luminal alkalinization and mucosal permeability in response to luminal acid via mechanisms that are dependent on nitric oxide signaling. The data support a role for NPS in neurohumoral regulation of duodenal mucosal barrier function and motility. PMID:28384243
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Liu, Hao-Yu; Roos, Stefan; Jonsson, Hans; Ahl, David; Dicksved, Johan; Lindberg, Jan Erik; Lundh, Torbjörn
2015-01-01
Heat shock proteins (HSPs) are a set of highly conserved proteins that can serve as intestinal gate keepers in gut homeostasis. Here, effects of a probiotic, Lactobacillus rhamnosus GG (LGG), and two novel porcine isolates, Lactobacillus johnsonii strain P47-HY and Lactobacillus reuteri strain P43-HUV, on cytoprotective HSP expression and gut barrier function, were investigated in a porcine IPEC-J2 intestinal epithelial cell line model. The IPEC-J2 cells polarized on a permeable filter exhibited villus-like cell phenotype with development of apical microvilli. Western blot analysis detected HSP expression in IPEC-J2 and revealed that L. johnsonii and L. reuteri strains were able to significantly induce HSP27, despite high basal expression in IPEC-J2, whereas LGG did not. For HSP72, only the supernatant of L. reuteri induced the expression, which was comparable to the heat shock treatment, which indicated that HSP72 expression was more stimulus specific. The protective effect of lactobacilli was further studied in IPEC-J2 under an enterotoxigenic Escherichia coli (ETEC) challenge. ETEC caused intestinal barrier destruction, as reflected by loss of cell–cell contact, reduced IPEC-J2 cell viability and transepithelial electrical resistance, and disruption of tight junction protein zonula occludens-1. In contrast, the L. reuteri treatment substantially counteracted these detrimental effects and preserved the barrier function. L. johnsonii and LGG also achieved barrier protection, partly by directly inhibiting ETEC attachment. Together, the results indicate that specific strains of Lactobacillus can enhance gut barrier function through cytoprotective HSP induction and fortify the cell protection against ETEC challenge through tight junction protein modulation and direct interaction with pathogens. PMID:25847917
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Wang, Jing-Jing; Wei, Zheng-Kai; Zhang, Xu; Wang, Ya-Nan; Fu, Yun-He; Yang, Zheng-Tao
2017-11-01
Short-chain fatty acids are fermentation end products produced by gut bacteria, which have been shown to ameliorate inflammatory bowel diseases and allergic asthma. However, the mechanism involved remains largely unknown. Here, we investigate the protective effects and mechanisms of sodium butyrate (SB) on LPS-induced mastitis model. Effects of increasing doses of SB on blood-milk barrier function and inflammation are studied in BALB/c mice with LPS-induced mastitis. The underlying mechanisms of anti-inflammatory effects of SB were further investigated in LPS-stimulated mouse mammary epithelial cells (mMECs). The results show that SB decreased LPS-induced disruption in mammary tissues, infiltration of inflammatory cells and the levels of TNF-α, IL-6 and IL-1β. SB up-regulated the tight junction proteins occludin and claudin-3 and reduced blood-milk barrier permeability in LPS-induced mastitis. Studies in vitro revealed that SB inhibited LPS-induced inflammatory response by inhibition of the NF-κB signalling pathway and histone deacetylases in LPS-stimulated mMECs. In our model, SB protected against LPS-induced mastitis by preserving blood-milk barrier function and depressing pro-inflammatory responses, suggesting the potential use of SB as a prophylactic agent to protect blood-milk barrier function in mastitis. © 2017 The British Pharmacological Society.
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Ghosh, Siddhartha S.; Bie, Jinghua; Wang, Jing; Ghosh, Shobha
2014-01-01
Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as Type 2 Diabetes and atherosclerosis) has shifted the focus from Western diet-induced changes in gut microbiota per se to release of gut bacteria-derived products into circulation as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. Under physiological conditions, an intact intestinal barrier prevents this release of LPS underscoring the importance of examining and modulating the direct effects of Western diet on intestinal barrier function. In the present study we evaluated two strategies, namely selective gut decontamination and supplementation with oral curcumin, to modulate Western-diet (WD) induced changes in intestinal barrier function and subsequent development of glucose intolerance and atherosclerosis. LDLR−/− mice were fed WD for 16 weeks and either received non-absorbable antibiotics (Neomycin and polymyxin) in drinking water for selective gut decontamination or gavaged daily with curcumin. WD significantly increased intestinal permeability as assessed by in vivo translocation of FITC-dextran and plasma LPS levels. Selective gut decontamination and supplementation with curcumin significantly attenuated the WD-induced increase in plasma LPS levels (3.32 vs 1.90 or 1.51 EU/ml, respectively) and improved intestinal barrier function at multiple levels (restoring intestinal alkaline phosphatase activity and expression of tight junction proteins, ZO-1 and Claudin-1). Consequently, both these interventions significantly reduced WD-induced glucose intolerance and atherosclerosis in LDLR−/− mice. Activation of macrophages by low levels of LPS (50 ng/ml) and its exacerbation by fatty acids is likely the mechanism by which release of trace amounts of LPS into circulation due to disruption of intestinal barrier function induces the development of these diseases. These studies not only establish the important role of intestinal barrier function, but also identify oral supplementation with curcumin as a potential therapeutic strategy to improve intestinal barrier function and prevent the development of metabolic diseases. PMID:25251395
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Electron transport in electrically biased inverse parabolic double-barrier structure
NASA Astrophysics Data System (ADS)
M, Bati; S, Sakiroglu; I, Sokmen
2016-05-01
A theoretical study of resonant tunneling is carried out for an inverse parabolic double-barrier structure subjected to an external electric field. Tunneling transmission coefficient and density of states are analyzed by using the non-equilibrium Green’s function approach based on the finite difference method. It is found that the resonant peak of the transmission coefficient, being unity for a symmetrical case, reduces under the applied electric field and depends strongly on the variation of the structure parameters.
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Nitrogen-doped fullerene as a potential catalyst for hydrogen fuel cells.
Gao, Feng; Zhao, Guang-Lin; Yang, Shizhong; Spivey, James J
2013-03-06
We examine the possibility of nitrogen-doped C60 fullerene (N-C60) as a cathode catalyst for hydrogen fuel cells. We use first-principles spin-polarized density functional theory calculations to simulate the electrocatalytic reactions on N-C60. The first-principles results show that an O2 molecule can be adsorbed and partially reduced on the N-C complex sites (Pauling sites) of N-C60 without any activation barrier. Through a direct pathway, the partially reduced O2 can further react with H(+) and additional electrons and complete the water formation reaction (WFR) with no activation energy barrier. In the indirect pathway, reduced O2 reacts with H(+) and additional electrons to form H2O molecules through a transition state (TS) with a small activation barrier (0.22-0.37 eV). From an intermediate state to a TS, H(+) can obtain a kinetic energy of ∼0.95-3.68 eV, due to the Coulomb electric interaction, and easily overcome the activation energy barrier during the WFR. The full catalytic reaction cycles can be completed energetically, and N-C60 fullerene recovers to its original structure for the next catalytic reaction cycle. N-C60 fullerene is a potential cathode catalyst for hydrogen fuel cells.
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Local Variability of the Peierls Barrier of Screw Dislocations in Ta-10W.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Foiles, Stephen M.
2017-10-01
It is well know that the addition of substitutional elements changes the mechanical behavior of metals, a effect referred to solid solution hardening. For body-centered-cubic (BCC) metals, screw dislocation play a key role in the mechanical properties. Here the detailed modification of the Peierls barrier for screw dislocation motion in Ta with W substitutional atoms is computing using density functional theory (DFT). A reduced order model (ROM) of the influence of W substitution on the Peierls barrier is developed. The mean field change in the Peierls barrier for a Ta10W alloy is determined and shown to be larger than anticipatedmore » based on simple elasticity considerations. The ROM could be used in future calculations to determine the local variability of the Peierls barrier and the resultant influence on the motion of screw dislocation in this alloy.« less
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Defect kinetics and resistance to amorphization in zirconium carbide
NASA Astrophysics Data System (ADS)
Zheng, Ming-Jie; Szlufarska, Izabela; Morgan, Dane
2015-02-01
To better understand the radiation response of zirconium carbide (ZrC), and in particular its excellent resistance to amorphization, we have used density functional theory methods to study the kinetics of point defects in ZrC. The migration barriers and recombination barriers of the simple point defects are calculated using the ab initio molecular dynamics simulation and the nudged elastic band method. These barriers are used to estimate C and Zr interstitial and vacancy diffusion and Frenkel pair recombination rates. A significant barrier for C Frenkel pair recombination is found but it is shown that a large concentration of C vacancies reduces this barrier dramatically, allowing facile healing of radiation damage. The mechanisms underlying high resistance to amorphization of ZrC were analyzed from the perspectives of structural, thermodynamic, chemical and kinetic properties. This study provides insights into the amorphization resistance of ZrC as well as a foundation for understanding general radiation damage in this material.
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Current-induced changes of migration energy barriers in graphene and carbon nanotubes.
Obodo, J T; Rungger, I; Sanvito, S; Schwingenschlögl, U
2016-05-21
An electron current can move atoms in a nanoscale device with important consequences for the device operation and breakdown. We perform first principles calculations aimed at evaluating the possibility of changing the energy barriers for atom migration in carbon-based systems. In particular, we consider the migration of adatoms and defects in graphene and carbon nanotubes. Although the current-induced forces are large for both the systems, in graphene the force component along the migration path is small and therefore the barrier height is little affected by the current flow. In contrast, the same barrier is significantly reduced in carbon nanotubes as the current increases. Our work also provides a real-system numerical demonstration that current-induced forces within density functional theory are non-conservative.
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Konya, Viktoria; Üllen, Andreas; Kampitsch, Nora; Theiler, Anna; Philipose, Sonia; Parzmair, Gerald P; Marsche, Gunther; Peskar, Bernhard A; Schuligoi, Rufina; Sattler, Wolfgang; Heinemann, Akos
2013-02-01
Increased vascular permeability is a fundamental characteristic of inflammation. Substances that are released during inflammation, such as prostaglandin (PG) E(2), can counteract vascular leakage, thereby hampering tissue damage. In this study we investigated the role of PGE(2) and its receptors in the barrier function of human pulmonary microvascular endothelial cells and in neutrophil trafficking. Endothelial barrier function was determined based on electrical impedance measurements. Neutrophil recruitment was assessed based on adhesion and transendothelial migration. Morphologic alterations are shown by using immunofluorescence microscopy. We observed that activation of E-type prostanoid (EP) 4 receptor by PGE(2) or an EP4-selective agonist (ONO AE1-329) enhanced the barrier function of human microvascular lung endothelial cells. EP4 receptor activation prompted similar responses in pulmonary artery and coronary artery endothelial cells. These effects were reversed by an EP4 antagonist (ONO AE3-208), as well as by blocking actin polymerization with cytochalasin B. The EP4 receptor-induced increase in barrier function was independent of the classical cyclic AMP/protein kinase A signaling machinery, endothelial nitric oxide synthase, and Rac1. Most importantly, EP4 receptor stimulation showed potent anti-inflammatory activities by (1) facilitating wound healing of pulmonary microvascular endothelial monolayers, (2) preventing junctional and cytoskeletal reorganization of activated endothelial cells, and (3) impairing neutrophil adhesion to endothelial cells and transendothelial migration. The latter effects could be partially attributed to reduced E-selectin expression after EP4 receptor stimulation. These data indicate that EP4 agonists as anti-inflammatory agents represent a potential therapy for diseases with increased vascular permeability and neutrophil extravasation. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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Sherwood, Cara L.; Liguori, Andrew E.; Olsen, Colin E.; Lantz, R. Clark; Burgess, Jefferey L.; Boitano, Scott
2013-01-01
Arsenic is a lung toxicant that can lead to respiratory illness through inhalation and ingestion, although the most common exposure is through contaminated drinking water. Lung effects reported from arsenic exposure include lung cancer and obstructive lung disease, as well as reductions in lung function and immune response. As part of their role in innate immune function, airway epithelial cells provide a barrier that protects underlying tissue from inhaled particulates, pathogens, and toxicants frequently found in inspired air. We evaluated the effects of a five-day exposure to environmentally relevant levels of arsenic {<4μM [~300 μg/L (ppb)] as NaAsO2} on airway epithelial barrier function and structure. In a primary mouse tracheal epithelial (MTE) cell model we found that both micromolar (3.9 μM) and submicromolar (0.8 μM) arsenic concentrations reduced transepithelial resistance, a measure of barrier function. Immunofluorescent staining of arsenic-treated MTE cells showed altered patterns of localization of the transmembrane tight junction proteins claudin (Cl) Cl-1, Cl-4, Cl-7 and occludin at cell-cell contacts when compared with untreated controls. To better quantify arsenic-induced changes in tight junction transmembrane proteins we conducted arsenic exposure experiments with an immortalized human bronchial epithelial cell line (16HBE14o-). We found that arsenic exposure significantly increased the protein expression of Cl-4 and occludin as well as the mRNA levels of Cl-4 and Cl-7 in these cells. Additionally, arsenic exposure resulted in altered phosphorylation of occludin. In summary, exposure to environmentally relevant levels of arsenic can alter both the function and structure of airway epithelial barrier constituents. These changes likely contribute to the observed arsenic-induced loss in basic innate immune defense and increased infection in the airway. PMID:24349408
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Notman, Rebecca; Anwar, Jamshed; Briels, W J; Noro, Massimo G; den Otter, Wouter K
2008-11-15
Transmembrane pore formation is central to many biological processes such as ion transport, cell fusion, and viral infection. Furthermore, pore formation in the ceramide bilayers of the stratum corneum may be an important mechanism by which penetration enhancers such as dimethylsulfoxide (DMSO) weaken the barrier function of the skin. We have used the potential of mean constraint force (PMCF) method to calculate the free energy of pore formation in ceramide bilayers in both the innate gel phase and in the DMSO-induced fluidized state. Our simulations show that the fluid phase bilayers form archetypal water-filled hydrophilic pores similar to those observed in phospholipid bilayers. In contrast, the rigid gel-phase bilayers develop hydrophobic pores. At the relatively small pore diameters studied here, the hydrophobic pores are empty rather than filled with bulk water, suggesting that they do not compromise the barrier function of ceramide membranes. A phenomenological analysis suggests that these vapor pores are stable, below a critical radius, because the penalty of creating water-vapor and tail-vapor interfaces is lower than that of directly exposing the strongly hydrophobic tails to water. The PMCF free energy profile of the vapor pore supports this analysis. The simulations indicate that high DMSO concentrations drastically impair the barrier function of the skin by strongly reducing the free energy required for pore opening.
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Notman, Rebecca; Anwar, Jamshed; Briels, W. J.; Noro, Massimo G.; den Otter, Wouter K.
2008-01-01
Transmembrane pore formation is central to many biological processes such as ion transport, cell fusion, and viral infection. Furthermore, pore formation in the ceramide bilayers of the stratum corneum may be an important mechanism by which penetration enhancers such as dimethylsulfoxide (DMSO) weaken the barrier function of the skin. We have used the potential of mean constraint force (PMCF) method to calculate the free energy of pore formation in ceramide bilayers in both the innate gel phase and in the DMSO-induced fluidized state. Our simulations show that the fluid phase bilayers form archetypal water-filled hydrophilic pores similar to those observed in phospholipid bilayers. In contrast, the rigid gel-phase bilayers develop hydrophobic pores. At the relatively small pore diameters studied here, the hydrophobic pores are empty rather than filled with bulk water, suggesting that they do not compromise the barrier function of ceramide membranes. A phenomenological analysis suggests that these vapor pores are stable, below a critical radius, because the penalty of creating water-vapor and tail-vapor interfaces is lower than that of directly exposing the strongly hydrophobic tails to water. The PMCF free energy profile of the vapor pore supports this analysis. The simulations indicate that high DMSO concentrations drastically impair the barrier function of the skin by strongly reducing the free energy required for pore opening. PMID:18708461
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Scott, Kevin G-E; Meddings, Jonathon B; Kirk, David R; Lees-Miller, Susan P; Buret, André G
2002-10-01
Giardiasis causes malabsorptive diarrhea, and symptoms can be present in the absence of any significant morphologic injury to the intestinal mucosa. The effects of giardiasis on epithelial permeability in vivo remain unknown, and the role of T cells and myosin light chain kinase (MLCK) in altered intestinal barrier function is unclear. This study was conducted to determine whether Giardia spp. alters intestinal permeability in vivo, to assess whether these abnormalities are dependent on T cells, and to assess the role of MLCK in altered epithelial barrier function. Immunocompetent and isogenic athymic mice were inoculated with axenic Giardia muris trophozoites or sterile vehicle (control), then assessed for trophozoite colonization and gastrointestinal permeability. Mechanistic studies using nontransformed human duodenal epithelial monolayers (SCBN) determined the effects of Giardia on myosin light chain (MLC) phosphorylation, transepithelial fluorescein isothiocyanate-dextran fluxes, cytoskeletal F-actin, tight junctional zonula occludens-1 (ZO-1), and MLCK. Giardia infection caused a significant increase in small intestinal, but not gastric or colonic, permeability that correlated with trophozoite colonization in both immunocompetent and athymic mice. In vitro, Giardia increased permeability and phosphorylation of MLC and reorganized F-actin and ZO-1. These alterations were abolished with an MLCK inhibitor. Disruption of small intestinal barrier function is T cell independent, disappears on parasite clearance, and correlates with reorganization of cytoskeletal F-actin and tight junctional ZO-1 in an MLCK-dependent fashion.
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Glutamate-Mediated Blood-Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery.
Vazana, Udi; Veksler, Ronel; Pell, Gaby S; Prager, Ofer; Fassler, Michael; Chassidim, Yoash; Roth, Yiftach; Shahar, Hamutal; Zangen, Abraham; Raccah, Ruggero; Onesti, Emanuela; Ceccanti, Marco; Colonnese, Claudio; Santoro, Antonio; Salvati, Maurizio; D'Elia, Alessandro; Nucciarelli, Valter; Inghilleri, Maurizio; Friedman, Alon
2016-07-20
The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders. Copyright © 2016 the authors 0270-6474/16/367727-13$15.00/0.
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Glutamate-Mediated Blood–Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery
Vazana, Udi; Veksler, Ronel; Pell, Gaby S.; Prager, Ofer; Fassler, Michael; Chassidim, Yoash; Roth, Yiftach; Shahar, Hamutal; Zangen, Abraham; Raccah, Ruggero; Onesti, Emanuela; Ceccanti, Marco; Colonnese, Claudio; Santoro, Antonio; Salvati, Maurizio; D'Elia, Alessandro; Nucciarelli, Valter; Inghilleri, Maurizio
2016-01-01
The blood–brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood–brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood–brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo. Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood–brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood–brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT In this study, we reveal a new mechanism that governs blood–brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders. PMID:27445149
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Vikström, Elena; Magnusson, Karl-Eric; Vécsey-Semjén, Beatrix; Colque-Navarro, Patricia; Möllby, Roland
2012-01-01
Increased microvascular permeability is a hallmark of sepsis and septic shock. Intestinal mucosal dysfunction may allow translocation of bacteria and their products, thereby promoting sepsis and inflammation. Although Staphylococcus aureus alpha-toxin significantly contributes to sepsis and perturbs the endothelial barrier function, little is known about possible effects of S. aureus alpha-toxin on human epithelial barrier functions. We hypothesize that S. aureus alpha-toxin in the blood can impair the intestinal epithelial barrier and thereby facilitate the translocation of luminal bacteria into the blood, which may in turn aggravate a septic condition. Here, we showed that staphylococcal alpha-toxin disrupts the barrier integrity of human intestinal epithelial Caco-2 cells as evidenced by decreased transepithelial electrical resistance (TER) and reduced cellular levels of junctional proteins, such as ZO-1, ZO-3, and E-cadherin. The Caco-2 cells also responded to alpha-toxin with an elevated cytosolic calcium ion concentration ([Ca2+]i), elicited primarily by calcium influx from the extracellular environment, as well as with a significant reduction in TER, which was modulated by intracellular calcium chelation. Moreover, a significantly larger reduction in TER and amounts of the junctional proteins, viz., ZO-3 and occludin, was achieved by basolateral than by apical application of the alpha-toxin. These experimental findings thus support the hypothesis that free staphylococcal alpha-toxin in the bloodstream may cause intestinal epithelial barrier dysfunction and further aggravate the septic condition by promoting the release of intestinal bacteria into the underlying tissues and the blood. PMID:22354024
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Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract
Arnold, Kelly; Romas, Laura; Westmacott, Garrett; McCorrister, Stuart; McKinnon, Lyle R.; Cohen, Craig R.; Mackelprang, Romel; Lingappa, Jairam; Lauffenburger, Doug A.; Klatt, Nichole R.; Burgener, Adam D.
2016-01-01
The mechanism(s) by which bacterial communities impact susceptibility to infectious diseases, such as HIV, and maintain female genital tract (FGT) health are poorly understood. Evaluation of FGT bacteria has predominantly been limited to studies of species abundance, but not bacterial function. We therefore sought to examine the relationship of bacterial community composition and function with mucosal epithelial barrier health in the context of bacterial vaginosis (BV) using metaproteomic, metagenomic, and in vitro approaches. We found highly diverse bacterial communities dominated by Gardnerella vaginalis associated with host epithelial barrier disruption and enhanced immune activation, and low diversity communities dominated by Lactobacillus species that associated with lower Nugent scores, reduced pH, and expression of host mucosal proteins important for maintaining epithelial integrity. Importantly, proteomic signatures of disrupted epithelial integrity associated with G. vaginalis-dominated communities in the absence of clinical BV diagnosis. Because traditional clinical assessments did not capture this, it likely represents a larger underrepresented phenomenon in populations with high prevalence of G. vaginalis. We finally demonstrated that soluble products derived from G. vaginalis inhibited wound healing, while those derived from L. iners did not, providing insight into functional mechanisms by which FGT bacterial communities affect epithelial barrier integrity. PMID:27656899
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Tfayli, Ali; Bonnier, Franck; Farhane, Zeineb; Libong, Danielle; Byrne, Hugh J; Baillet-Guffroy, Arlette
2014-06-01
The use of animals for scientific research is increasingly restricted by legislation, increasing the demand for human skin models. These constructs present comparable bulk lipid content to human skin. However, their permeability is significantly higher, limiting their applicability as models of barrier function, although the molecular origins of this reduced barrier function remain unclear. This study analyses the stratum corneum (SC) of one such commercially available reconstructed skin model (RSM) compared with human SC by spectroscopic imaging and chromatographic profiling. Total lipid composition was compared by chromatographic analysis (HPLC). Raman spectroscopy was used to evaluate the conformational order, lateral packing and distribution of lipids in the surface and skin/RSM sections. Although HPLC indicates that all SC lipid classes are present, significant differences are observed in ceramide profiles. Raman imaging demonstrated that the RSM lipids are distributed in a non-continuous matrix, providing a better understanding of the limited barrier function. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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RNase L Interacts with Filamin A To Regulate Actin Dynamics and Barrier Function for Viral Entry
Siddiqui, Mohammad Adnan; Dayal, Shubham; Naji, Merna; Ezelle, Heather J.; Zeng, Chun; Zhou, Aimin; Hassel, Bret A.
2014-01-01
ABSTRACT The actin cytoskeleton and its network of associated proteins constitute a physical barrier that viruses must circumvent to gain entry into cells for productive infection. The mechanisms by which the physical signals of infection are sensed by the host to activate an innate immune response are not well understood. The antiviral endoribonuclease RNase L is ubiquitously expressed in a latent form and activated upon binding 2-5A, a unique oligoadenylate produced during viral infections. We provide evidence that RNase L in its inactive form interacts with the actin-binding protein Filamin A to modulate the actin cytoskeleton and inhibit virus entry. Cells lacking either RNase L or Filamin A displayed increased virus entry which was exacerbated in cells lacking both proteins. RNase L deletion mutants that reduced Filamin A interaction displayed a compromised ability to restrict virus entry, supporting the idea of an important role for the RNase L-Filamin A complex in barrier function. Remarkably, both the wild type and a catalytically inactive RNase L mutant were competent to reduce virus entry when transfected into RNase L-deficient cells, indicating that this novel function of RNase L is independent of its enzymatic activity. Virus infection and RNase L activation disrupt its association with Filamin A and release RNase L to mediate its canonical nuclease-dependent antiviral activities. The dual functions of RNase L as a constitutive component of the actin cytoskeleton and as an induced mediator of antiviral signaling and effector functions provide insights into its mechanisms of antiviral activity and opportunities for the development of novel antiviral agents. PMID:25352621
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Theory of dynamic barriers, activated hopping, and the glass transition in polymer melts
NASA Astrophysics Data System (ADS)
Schweizer, Kenneth S.; Saltzman, Erica J.
2004-07-01
A statistical mechanical theory of collective dynamic barriers, slow segmental relaxation, and the glass transition of polymer melts is developed by combining, and in some aspects extending, methods of mode coupling, density functional, and activated hopping transport theories. A coarse-grained description of polymer chains is adopted and the melt is treated as a liquid of segments. The theory is built on the idea that collective density fluctuations on length scales considerably longer than the local cage scale are of primary importance in the deeply supercooled regime. The barrier hopping or segmental relaxation time is predicted to be a function primarily of a single parameter that is chemical structure, temperature, and pressure dependent. This parameter depends on the material-specific dimensionless amplitude of thermal density fluctuations (compressibility) and a reduced segmental density determined by the packing length and backbone characteristic ratio. Analytic results are derived for a crossover temperature Tc, collective barrier, and glass transition temperature Tg. The relation of these quantities to structural and thermodynamic properties of the polymer melt is established. A universal power-law scaling behavior of the relaxation time below Tc is predicted based on identification of a reduced temperature variable that quantifies the breadth of the supercooled regime. Connections between the ratio Tc/Tg, two measures of dynamic fragility, and the magnitude of the local relaxation time at Tg logically follow. Excellent agreement with experiment is found for these generic aspects, and the crucial importance of the experimentally observed near universality of the dynamic crossover time is established. Extensions of the theory to treat the full chain dynamics, heterogeneity, barrier fluctuations, and nonpolymeric thermal glass forming liquids are briefly discussed.
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Brufau, M Teresa; Campo-Sabariz, Joan; Carné, Sergi; Ferrer, Ruth; Martín-Venegas, Raquel
2017-03-01
Mannan-oligosaccharides (MOSs) are mannose-rich substrates with several intestinal health-promoting properties. The aim of this study was to investigate the potential capacity of Salmosan (S-βGM), a β-galactomannan-rich MOS product, to restore epithelial barrier function independently from its capacity to reduce bacterial invasion. In addition, the combination of S-βGM with the proven probiotic Lactobacillus plantarum (LP) was also tested. Paracellular permeability was assessed by transepithelial electrical resistance (TER) in co-cultures of Caco-2 cells and macrophages (differentiated from THP-1 cells) stimulated with LPS of Salmonella Enteritidis and in Caco-2 cell cultures stimulated with TNF-α in the absence or presence of 500 μg/ml S-βGM, LP (MOI 10) or a combination of both. In both culture models, TER was significantly reduced up to 25% by LPS or TNF-α stimulation, and the addition of S-βGM or LP alone did not modify TER, whereas the combination of both restored TER to values of nonstimulated cells. Under LPS stimulation, TNF-α production was significantly increased by 10-fold, whereas IL-10 and IL-6 levels were not modified. The combination of S-βGM and LP reduced TNF-α production to nonstimulated cell values and significantly increased IL-10 and IL-6 levels (5- and 7.5-fold, respectively). Moreover, S-βGM has the capacity to induce an increase of fivefold in LP growth. In conclusion, we have demonstrated that S-βGM in combination with LP protects epithelial barrier function by modulation of cytokine secretion, thus giving an additional value to this MOS as a potential symbiotic. Copyright © 2016 Elsevier Inc. All rights reserved.
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Orellano-Colón, Elsa M.; Mann, William C.; Rivero, Marta; Torres, Mayra; Jutai, Jeff; Santiago, Angélica; Varas, Nelson
2016-01-01
Assistive technologies (AT) are tools that enhance the independence, safety, and quality of life of older people with functional limitations. While AT may extend independence in ageing, there are racial and ethnic disparities in late-life AT use, with lower rates reported among Hispanic older populations. The aim of this study was to identify barriers experienced by Hispanic community-living older adults for using AT. Sixty Hispanic older adults (70 years and older) with functional limitations participated in this study. A descriptive qualitative research design was used guided by the principles of the Human Activity Assistive Technology Model to gain in-depth understanding of participants’ perspectives regarding barriers to using AT devices. Individual in-depth semi-structure interviews were conducted, using the Assistive Technology Devices Cards (ATDC) assessment as a prompt to facilitate participants’ qualitative responses. Data analysis included descriptive statistics and rigorous thematic content analysis. Lack of AT awareness and information, cost of AT, limited coverage of AT by heath care plans, and perceived complexity of AT were the predominant barriers experienced by the participants. A multi-level approach is required for a better understanding of the barriers for using AT devices. The personal, contextual, and activity-based barriers found in this study can be used to develop culturally sensitive AT interventions to reduce existent disparities in independent living disabilities among older Hispanics. PMID:27294762
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Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice.
Cheng, Zhuo; Wang, Liping; Qu, Meijie; Liang, Huaibin; Li, Wanlu; Li, Yongfang; Deng, Lidong; Zhang, Zhijun; Yang, Guo-Yuan
2018-05-03
Ischemic stroke induced matrixmetallo-proteinase-9 (MMP-9) upregulation, which increased blood-brain barrier permeability. Studies demonstrated that mesenchymal stem cell therapy protected blood-brain barrier disruption from several cerebrovascular diseases. However, the underlying mechanism was largely unknown. We therefore hypothesized that mesenchymal stem cells reduced blood-brain barrier destruction by inhibiting matrixmetallo-proteinase-9 and it was related to intercellular adhesion molecule-1 (ICAM-1). Adult ICR male mice (n = 118) underwent 90-min middle cerebral artery occlusion and received 2 × 10 5 mesenchymal stem cell transplantation. Neurobehavioral outcome, infarct volume, and blood-brain barrier permeability were measured after ischemia. The relationship between myeloperoxidase (MPO) activity and ICAM-1 release was further determined. We found that intracranial injection of mesenchymal stem cells reduced infarct volume and improved behavioral function in experimental stroke models (p < 0.05). IgG leakage, tight junction protein loss, and inflammatory cytokines IL-1β, IL-6, and TNF-α reduced in mesenchymal stem cell-treated mice compared to the control group following ischemia (p < 0.05). After transplantation, MMP-9 was decreased in protein and activity levels as compared with controls (p < 0.05). Furthermore, myeloperoxidase-positive cells and myeloperoxidase activity were decreased in mesenchymal stem cell-treated mice (p < 0.05). The results showed that mesenchymal stem cell therapy attenuated blood-brain barrier disruption in mice after ischemia. Mesenchymal stem cells attenuated the upward trend of MMP-9 and potentially via downregulating ICAM-1 in endothelial cells. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway may influence MMP-9 expression of neutrophils and resident cells, and ICAM-1 acted as a key factor in the paracrine actions of mesenchymal stem cell.
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Low dose Naltrexone for induction of remission in inflammatory bowel disease patients.
Lie, Mitchell R K L; van der Giessen, Janine; Fuhler, Gwenny M; de Lima, Alison; Peppelenbosch, Maikel P; van der Ent, Cokkie; van der Woude, C Janneke
2018-03-09
Around 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. Novel treatments are called for, and low dose Naltrexone (LDN) may provide a safe, easily accessible alternative treatment option for these patients. We investigated the potential of LDN to induce clinical response in therapy refractory IBD patients, and investigated its direct effects on epithelial barrier function. Patients not in remission and not responding to conventional therapy were offered to initiate LDN as a concomitant treatment. In total 47 IBD patients prescribed LDN were followed prospectively for 12 weeks. Where available, endoscopic remission data, serum and biopsies were collected. Further the effect of Naltrexone on wound healing (scratch assay), cytokine production and endoplasmic reticulum (ER) stress (GRP78 and CHOP western blot analysis, immunohistochemistry) were investigated in HCT116 and CACO2 intestinal epithelial cells, human IBD intestinal organoids and patient samples. Low dose Naltrexone induced clinical improvement in 74.5%, and remission in 25.5% of patients. Naltrexone improved wound healing and reduced ER stress induced by Tunicamycin, lipopolysaccharide or bacteria in epithelial barriers. Inflamed mucosa from IBD patients showed high ER stress levels, which was reduced in patients treated with LDN. Cytokine levels in neither epithelial cells nor serum from IBD patients were affected. Naltrexone directly improves epithelial barrier function by improving wound healing and reducing mucosal ER stress levels. Low dose Naltrexone treatment is effective and safe, and could be considered for the treatment of therapy refractory IBD patients.
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Jin, Younggeon; Pridgen, Tiffany A; Blikslager, Anthony T
2015-12-01
We have previously reported that the ClC-2 chloride channel has an important role in regulation of tight junction barrier function during experimental colitis, and the pharmaceutical ClC-2 activator lubiprostone initiates intestinal barrier repair in ischemic-injured intestine. Thus, we hypothesized that pharmaceutical ClC-2 activation would have a protective and therapeutic effect in murine models of colitis, which would be absent in ClC-2 mice. We administered lubiprostone to wild-type or ClC-2 mice with dextran sulfate sodium (DSS) or 2, 4, 5-trinitrobenzene sulfonic acid-induced colitis. We determined the severity of colitis and assessed intestinal permeability. Selected tight junction proteins were analyzed by Western blotting and immunofluorescence/confocal microscopy, whereas proliferative and differentiated cells were examined with special staining and immunohistochemistry. Oral preventive or therapeutic administration of lubiprostone significantly reduced the severity of colitis and reduced intestinal permeability in both DSS and trinitrobenzene sulfonic acid-induced colitis. Preventive treatment with lubiprostone induced significant recovery of the expression and distribution of selected sealing tight junction proteins in mice with DSS-induced colitis. In addition, lubiprostone reduced crypt proliferation and increased the number of differentiated epithelial cells. Alternatively, when lubiprostone was administered to ClC-2 mice, the protective effect against DSS colitis was limited. This study suggests a central role for ClC-2 in restoration of barrier function and tight junction architecture in experimental murine colitis, which can be therapeutically targeted with lubiprostone.
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Duplan, Hélène; Questel, Emmanuel; Hernandez-Pigeon, Hélène; Galliano, Marie Florence; Caruana, Antony; Ceruti, Isabelle; Ambonati, Marco; Mejean, Carine; Damour, Odile; Castex-Rizzi, Nathalie; Bessou-Touya, Sandrine; Schmitt, Anne-Marie
2011-01-01
10-Hydroxy-2-decenoic acid, a natural fatty acid only found in royal jelly, may be of value in correcting skin barrier dysfunction. We evaluated the activity of Hydroxydecine(®), its synthetic counterpart, in vitro on the regulation of epidermal differentiation markers, ex vivo on the inflammatory response and restoration of skin barrier function, and in vivo on UV-induced xerosis in healthy human volunteers. In cultured normal human keratinocytes, Hydroxydecine(®) induced involucrin, transglutaminase-1 and filaggrin protein production. In topically Hydroxydecine(®)-treated skin equivalents, immunohistochemical analysis revealed an increase in involucrin, transglutaminase-1 and filaggrin staining. In a model of thymic stromal lymphopoietin (TSLP)-induced inflamed epidermis, a Hydroxydecine(®)-containing emulsion inhibited TSLP release. In a model of inflammation and barrier impairment involving human skin explants maintained alive, Hydroxydecine(®) balm restored stratum corneum cohesion and significantly increased filaggrin expression, as shown by immunohistochemistry. It also decreased pro-inflammatory cytokine secretion (IL-4, IL-5 and IL-13). In healthy volunteers with UV-induced xerosis, the hydration index increased by +28.8% (p<0.01) and +60.4% (p<0.001) after 7 and 21 days of treatment with Hydroxydecine(®) cream, respectively. Hydroxydecine(®) thus proved its efficacy in activating keratinocyte differentiation processes in vitro, restoring skin barrier function and reducing inflammation ex vivo, and hydrating dry skin in vivo.
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Heinemann, Allen W; Lai, Jin-Shei; Wong, Alex; Dashner, Jessica; Magasi, Susan; Hahn, Elizabeth A; Carlozzi, Noelle E; Tulsky, David S; Jerousek, Sara; Semik, Patrick; Miskovic, Ana; Gray, David B
2016-11-01
To develop a measure of natural environment and human-made change features (Chapter 2 of the international classification of functioning, disability, and health) and evaluate the influence of perceived barriers on health-related quality of life. A sample of 570 adults with stroke, spinal cord injury, and traumatic brain injury residing in community settings reported their functioning in home, outdoor, and community settings (mean age = 47.0 years, SD = 16.1). They rated 18 items with a 5-point rating scale to describe the influence of barriers to moving around, seeing objects, hearing sounds, hearing conversations, feeling safe, and regulating temperature and indicated whether any difficulties were due to environmental features. We used Rasch analysis to identify misfitting items and evaluate differential item functioning (DIF) across impairment groups. We computed correlations between barriers and patient-reported outcomes measurement information system (PROMIS) social domain measures and community participation indicators (CPI) measures. The 18 items demonstrated person reliability of .70, discriminating nearly three levels of barriers. All items fit the Rasch model; impairment-related DIF was negligible. Ceiling effects were negligible, but 25 % of the respondents were at the floor, indicating that they did not experience barriers that they attributed to the built and natural environment. As anticipated, barriers correlated moderately with PROMIS and CPI variables, suggesting that although this new item bank measures a construct that is related to participation and health-related quality of life, it also captures something unique. Known-groups validity was supported by wheelchair users reporting a higher level of barriers than did ambulatory respondents. Preliminary evidence supports the reliability and validity of this new measure of barriers to the built and natural environment. This measure allows investigators and clinicians to measure perceptions of the natural environment and human-made changes, providing information that can guide interventions to reduce barriers. Moderate relationships between barriers and PROMIS and CPI variables provide support for the measurement and theory of environmental influences on social health and participation.
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Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye
Bauskar, Aditi; Mack, Wendy J.; Mauris, Jerome; Argüeso, Pablo; Heur, Martin; Nagel, Barbara A.; Kolar, Grant R.; Gleave, Martin E.; Nakamura, Takahiro; Kinoshita, Shigeru; Moradian-Oldak, Janet; Panjwani, Noorjahan; Pflugfelder, Stephen C.; Wilson, Mark R.; Fini, M. Elizabeth; Jeong, Shinwu
2015-01-01
Dry eye is a common disorder caused by inadequate hydration of the ocular surface that results in disruption of barrier function. The homeostatic protein clusterin (CLU) is prominent at fluid-tissue interfaces throughout the body. CLU levels are reduced at the ocular surface in human inflammatory disorders that manifest as severe dry eye, as well as in a preclinical mouse model for desiccating stress that mimics dry eye. Using this mouse model, we show here that CLU prevents and ameliorates ocular surface barrier disruption by a remarkable sealing mechanism dependent on attainment of a critical all-or-none concentration. When the CLU level drops below the critical all-or-none threshold, the barrier becomes vulnerable to desiccating stress. CLU binds selectively to the ocular surface subjected to desiccating stress in vivo, and in vitro to the galectin LGALS3, a key barrier component. Positioned in this way, CLU not only physically seals the ocular surface barrier, but it also protects the barrier cells and prevents further damage to barrier structure. These findings define a fundamentally new mechanism for ocular surface protection and suggest CLU as a biotherapeutic for dry eye. PMID:26402857
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Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye.
Bauskar, Aditi; Mack, Wendy J; Mauris, Jerome; Argüeso, Pablo; Heur, Martin; Nagel, Barbara A; Kolar, Grant R; Gleave, Martin E; Nakamura, Takahiro; Kinoshita, Shigeru; Moradian-Oldak, Janet; Panjwani, Noorjahan; Pflugfelder, Stephen C; Wilson, Mark R; Fini, M Elizabeth; Jeong, Shinwu
2015-01-01
Dry eye is a common disorder caused by inadequate hydration of the ocular surface that results in disruption of barrier function. The homeostatic protein clusterin (CLU) is prominent at fluid-tissue interfaces throughout the body. CLU levels are reduced at the ocular surface in human inflammatory disorders that manifest as severe dry eye, as well as in a preclinical mouse model for desiccating stress that mimics dry eye. Using this mouse model, we show here that CLU prevents and ameliorates ocular surface barrier disruption by a remarkable sealing mechanism dependent on attainment of a critical all-or-none concentration. When the CLU level drops below the critical all-or-none threshold, the barrier becomes vulnerable to desiccating stress. CLU binds selectively to the ocular surface subjected to desiccating stress in vivo, and in vitro to the galectin LGALS3, a key barrier component. Positioned in this way, CLU not only physically seals the ocular surface barrier, but it also protects the barrier cells and prevents further damage to barrier structure. These findings define a fundamentally new mechanism for ocular surface protection and suggest CLU as a biotherapeutic for dry eye.
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High-fat enteral nutrition reduces intestinal mucosal barrier damage after peritoneal air exposure.
Tan, Shan-Jun; Yu, Chao; Yu, Zhen; Lin, Zhi-Liang; Wu, Guo-Hao; Yu, Wen-Kui; Li, Jie-Shou; Li, Ning
2016-05-01
Peritoneal air exposure is needed in open abdominal surgery, but long-time exposure could induce intestinal mucosal barrier dysfunction followed by many postoperative complications. High-fat enteral nutrition can ameliorate intestinal injury and improve intestinal function in many gastrointestinal diseases. In the present study, we investigated the effect of high-fat enteral nutrition on intestinal mucosal barrier after peritoneal air exposure and the underlying mechanism. Male adult rats were administrated saline, low-fat or high-fat enteral nutrition via gavage before and after peritoneal air exposure for 3 h. Rats undergoing anesthesia without laparotomy received saline as control. Twenty four hours after surgery, samples were collected to assess intestinal mucosal barrier changes in serum D-lactate levels, intestinal permeability, intestinal tight junction protein ZO-1 and occludin levels, and intestinal histopathology. The levels of malondialdehyde and the activity of superoxide dismutase in the ileum tissue were also measured to assess the status of intestinal oxidative stress. High-fat enteral nutrition significantly decreased the serum D-lactate level and increased the intestinal tight junction protein ZO-1 level when compared to the group treated with low-fat enteral nutrition (P < 0.05). Meanwhile, histopathologic findings showed that the intestinal mucosal injury assessed by the Chiu's score and the intestinal epithelial tight junction were also improved much more in the high-fat enteral nutrition-treated group (P < 0.05). In addition, the intestinal malondialdehyde level was lower, and the intestinal superoxide dismutase activity was higher in the high-fat enteral nutrition-treated group than that in the low-fat enteral nutrition-treated group (P < 0.05). These results suggest that high-fat enteral nutrition could reduce intestinal mucosal barrier damage after peritoneal air exposure, and the underlying mechanism may be associated with its antioxidative action. Perioperative administration of high-fat enteral nutrition may be a promising intervention to preserve intestinal mucosal barrier function in open abdominal surgery. Copyright © 2016 Elsevier Inc. All rights reserved.
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Pratt-Chapman, Mandi; Simon, Melissa A.; Patterson, Angela; Risendal, Betsy C.; Patierno, Steven
2013-01-01
Survivorship navigation is a relatively new concept in the field of patient navigation, but an important one. This paper highlights the essential functions of the survivorship navigator and defines core outcomes and measures for navigation in the survivorship period. Barriers to access to care experienced by patients during active cancer treatment can continue into the post-treatment period, affecting quality follow-up care for survivors. These barriers to care can be particularly acute for non-English speakers, immigrants, the uninsured, the underinsured and other vulnerable populations. The survivorship navigator can help reduce barriers and facilitate access to survivorship care and services through communication and information exchange for patients. Survivorship navigation may improve appropriate health care utilization through education and care coordination, potentially improving health outcomes and quality of life of survivors while reducing cost to the health care system. Survivorship navigators can also educate survivors on how to improve their overall wellness, thereby directly impacting the health of a growing population of cancer survivors. PMID:21780092
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Memon, Zahid; Zaidi, Shehla; Riaz, Atif
2016-01-01
Low utilization of maternal and child care services in rural areas has constrained Pakistan from meeting targets of Millennium Development Goals (MDGs) 4 and 5. This study explores community barriers in accessing Maternal and Child Health (MCH) services in ten remote rural districts of Pakistan. It further presents how the barriers differ across a range of MCH services, and also whether the presence of Community Health Workers (CHWs) reduces client barriers. Qualitative methods were used involving altogether sixty focus group discussions with mothers, their spouses and community health workers. Low awareness, formidable distances, expense, and poorly functional services were the main barriers reported, while cultural and religious restrictions were lesser reported. For preventive services including antenatal care (ANC), facility deliveries, postnatal care (PNC), childhood immunization and family planning, the main barrier was low awareness. Conversely, formidable distances and poorly functional services were the main reported constraints in the event of maternal complications and acute child illnesses. The study also found that clients residing in areas served by CHWs had better awareness only of ANC and family planning, while other MCH services were overlooked by the health worker program. The paper highlights that traditional policy emphasis on health facility infrastructure expansion is not likely to address poor utilization rates in remote rural areas. Preventive MCH services require concerted attention to building community awareness, task shifting from facility to community for services provision, and re-energization of CHW program. For maternal and child emergencies there is strong community demand to utilize health facilities, but this will require catalytic support for transport networks and functional health care centers. PMID:26925902
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Harford, Terri J.; Linfield, Debra T.; Altawallbeh, Ghaith; Midura, Ronald J.; Ivanov, Andrei I.; Piedimonte, Giovanni
2017-01-01
Airway epithelium forms a barrier to the outside world and has a crucial role in susceptibility to viral infections. Cyclic adenosine monophosphate (cAMP) is an important second messenger acting via two intracellular signaling molecules: protein kinase A (PKA) and the guanidine nucleotide exchange factor, Epac. We sought to investigate effects of increased cAMP level on the disruption of model airway epithelial barrier caused by RSV infection and the molecular mechanisms underlying cAMP actions. Human bronchial epithelial cells were infected with RSV-A2 and treated with either cAMP releasing agent, forskolin, or cAMP analogs. Structure and functions of the Apical Junctional Complex (AJC) were evaluated by measuring transepithelial electrical resistance and permeability to FITC-dextran, and determining localization of AJC proteins by confocal microscopy. Increased intracellular cAMP level significantly attenuated RSV-induced disassembly of AJC. These barrier-protective effects of cAMP were due to the activation of PKA signaling and did not involve Epac activity. Increased cAMP level reduced RSV-induced reorganization of the actin cytoskeleton, including apical accumulation of an essential actin-binding protein, cortactin, and inhibited expression of the RSV F protein. These barrier-protective and antiviral-function of cAMP signaling were evident even when cAMP level was increased after the onset of RSV infection. Taken together, our study demonstrates that cAMP/PKA signaling attenuated RSV-induced disruption of structure and functions of the model airway epithelial barrier by mechanisms involving the stabilization of epithelial junctions and inhibition of viral biogenesis. Improving our understanding of the mechanisms involved in RSV-induced epithelial dysfunction and viral pathogenesis will help to develop novel anti-viral therapeutic approaches. PMID:28759570
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Z. Fred
A surface barrier (or cover) is a commonly used technology for subsurface remediation. A key function of the barrier is to reduce or eliminate the movement of meteoric precipitation into the underlying waste zone, where it could mobilize and transport contaminants. Surface barriers are expected to perform for centuries to millennia, yet there are very few examples of performance for periods longer than a decade. The Prototype Hanford Barrier was constructed in 1994 over an existing waste site to demonstrate its long-term performance for a design period of 1000 years. This barrier is a field-scale evapotranspiration-capillary (ETC) barrier. In thismore » design, the storage layer consists of 2-m-thick silt loam. The 19-year monitoring results show that the store-and-release mechanism for the ETC barrier worked efficiently as the storage layer was recharged in the winter season (November to March) and the stored water was released to the atmosphere in the summer season (April to October) via soil evaporation and plant transpiration. The capillary break functioned normally in improving the storage capacity and minimizing drainage. The maximum drainage observed through the ET barrier at any of the monitoring stations was only 0.178 mm yr-1 (under an enhanced precipitation condition), which is less than the design criterion. A very small amount (2.0 mm yr-1 on average) of runoff was observed during the 19-year monitoring period. The observed storage capacity of the storage layer was considerably (39%) larger than the estimated value based on the method of equilibrium of water pressure. After a controlled fire in 2008, the newly grown vegetation (primarily shallow-rooted grasses) could still release the stored water and summer precipitation to the atmosphere via transpiration. The findings are useful for predicting water storage and ET under different precipitation conditions and for the design of future barriers.« less
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Gentle cleansing and moisturizing for patients with atopic dermatitis and sensitive skin.
Cheong, Wai Kwong
2009-01-01
Atopic dermatitis is a common condition characterized by pruritus, inflammation, and dryness of the skin. Inflammation disrupts the barrier function of the stratum corneum, predisposing the skin to be dry, and increases susceptibility to irritants and secondary bacterial infection. Sensitive skin is common, reported by 40-50% of women and 30% of men in the US, Europe, and Japan. Basic requirements in managing eczema and sensitive skin include effective cleansers that do not compromise skin barrier integrity, alleviation of skin dryness, and restoration of skin barrier function through the use of therapeutic moisturizers. The selection of a skin cleanser is therefore an important part of managing these conditions. Studies have reported clinical improvement with the use of soap-free cleansers in combination with topical treatments. While topical corticosteroids and immunosuppressive agents are mainstays of treatment for atopic dermatitis, therapeutic moisturizers are important adjuncts. Moisturizers improve skin hydration, reduce susceptibility to irritation, restore the integrity of the stratum corneum, and enhance the efficacy of topical corticosteroids.
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Monk, Jennifer M; Lepp, Dion; Zhang, Claire P; Wu, Wenqing; Zarepoor, Leila; Lu, Jenifer T; Pauls, K Peter; Tsao, Rong; Wood, Geoffrey A; Robinson, Lindsay E; Power, Krista A
2016-02-01
Common beans are rich in phenolic compounds and nondigestible fermentable components, which may help alleviate intestinal diseases. We assessed the gut health priming effect of a 20% cranberry bean flour diet from two bean varieties with differing profiles of phenolic compounds [darkening (DC) and nondarkening (NDC) cranberry beans vs. basal diet control (BD)] on critical aspects of gut health in unchallenged mice, and during dextran sodium sulfate (DSS)-induced colitis (2% DSS wt/vol, 7 days). In unchallenged mice, NDC and DC increased (i) cecal short-chain fatty acids, (ii) colon crypt height, (iii) crypt goblet cell number and mucus content and (iv) Muc1, Klf4, Relmβ and Reg3γ gene expression vs. BD, indicative of enhanced microbial activity and gut barrier function. Fecal 16S rRNA sequencing determined that beans reduced abundance of the Lactobacillaceae (Ruminococcus gnavus), Clostridiaceae (Clostridium perfringens), Peptococcaceae, Peptostreptococcaceae, Rikenellaceae and Pophyromonadaceae families, and increased abundance of S24-7 and Prevotellaceae. During colitis, beans reduced (i) disease severity and colonic histological damage, (ii) increased gene expression of barrier function promoting genes (Muc1-3, Relmβ, and Reg3γ) and (iii) reduced colonic and circulating inflammatory cytokines (IL-1β, IL-6, IFNγ and TNFα). Therefore, prior to disease induction, bean supplementation enhanced multiple concurrent gut health promoting parameters that translated into reduced colitis severity. Moreover, both bean diets exerted similar effects, indicating that differing phenolic content did not influence the endpoints assessed. These data demonstrate a proof-of-concept regarding the gut-priming potential of beans in colitis, which could be extended to mitigate the severity of other gut barrier-associated pathologies. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.
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Quantum Chemical Calculations of Amine-Catalyzed Polymerization of Silanol
NASA Astrophysics Data System (ADS)
Gu, Hongyu; Xu, Wenbin; Zhang, Jinlin; Qi, Zhenyi; Zhang, Tao; Song, Lixin
2018-03-01
Because of the technical importance of organosilicon materials, insight into the related synthetic processes is significantly essential. In this paper, the amine-catalyzed polymerization of silanol has been investigated by the density functional theory (DFT) method. Our data have shown that amines can catalytically promote the hydrogen transfer process by substantially reducing the energy barrier. The activation barrier via hydrogen transfer with catalysis is 38.32 kJ/mol, much lower than that of catalysis-free process (120.88 kJ/mol). The lower energy barrier is in agreement with the much more intense polymerization of silanols with amine catalysts. Based on the above results, amines and other catalysts capable of assisting hydrogen transfer are expected to be used as catalysts for silanol polymerization.
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Causality, apparent ``superluminality,'' and reshaping in barrier penetration
NASA Astrophysics Data System (ADS)
Sokolovski, D.
2010-04-01
We consider tunneling of a nonrelativistic particle across a potential barrier. It is shown that the barrier acts as an effective beam splitter which builds up the transmitted pulse from the copies of the initial envelope shifted in the coordinate space backward relative to the free propagation. Although along each pathway causality is explicitly obeyed, in special cases reshaping can result an overall reduction of the initial envelope, accompanied by an arbitrary coordinate shift. In the case of a high barrier the delay amplitude distribution (DAD) mimics a Dirac δ function, the transmission amplitude is superoscillatory for finite momenta and tunneling leads to an accurate advancement of the (reduced) initial envelope by the barrier width. In the case of a wide barrier, initial envelope is accurately translated into the complex coordinate plane. The complex shift, given by the first moment of the DAD, accounts for both the displacement of the maximum of the transmitted probability density and the increase in its velocity. It is argued that analyzing apparent “superluminality” in terms of spacial displacements helps avoid contradiction associated with time parameters such as the phase time.
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Liu, Hao-Yu; Roos, Stefan; Jonsson, Hans; Ahl, David; Dicksved, Johan; Lindberg, Jan Erik; Lundh, Torbjörn
2015-04-01
Heat shock proteins (HSPs) are a set of highly conserved proteins that can serve as intestinal gate keepers in gut homeostasis. Here, effects of a probiotic, Lactobacillus rhamnosus GG (LGG), and two novel porcine isolates, Lactobacillus johnsonii strain P47-HY and Lactobacillus reuteri strain P43-HUV, on cytoprotective HSP expression and gut barrier function, were investigated in a porcine IPEC-J2 intestinal epithelial cell line model. The IPEC-J2 cells polarized on a permeable filter exhibited villus-like cell phenotype with development of apical microvilli. Western blot analysis detected HSP expression in IPEC-J2 and revealed that L. johnsonii and L. reuteri strains were able to significantly induce HSP27, despite high basal expression in IPEC-J2, whereas LGG did not. For HSP72, only the supernatant of L. reuteri induced the expression, which was comparable to the heat shock treatment, which indicated that HSP72 expression was more stimulus specific. The protective effect of lactobacilli was further studied in IPEC-J2 under an enterotoxigenic Escherichia coli (ETEC) challenge. ETEC caused intestinal barrier destruction, as reflected by loss of cell-cell contact, reduced IPEC-J2 cell viability and transepithelial electrical resistance, and disruption of tight junction protein zonula occludens-1. In contrast, the L. reuteri treatment substantially counteracted these detrimental effects and preserved the barrier function. L. johnsonii and LGG also achieved barrier protection, partly by directly inhibiting ETEC attachment. Together, the results indicate that specific strains of Lactobacillus can enhance gut barrier function through cytoprotective HSP induction and fortify the cell protection against ETEC challenge through tight junction protein modulation and direct interaction with pathogens. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
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Jin, Rong; Xiao, Adam Y; Chen, Rui; Granger, D Neil; Li, Guohong
2017-12-01
Inflammation and thrombosis currently are recognized as critical contributors to the pathogenesis of ischemic stroke. CD147 (cluster of differentiation 147), also known as extracellular matrix metalloproteinase inducer, can function as a key mediator of inflammatory and immune responses. CD147 expression is increased in the brain after cerebral ischemia, but its role in the pathogenesis of ischemic stroke remains unknown. In this study, we show that CD147 acts as a key player in ischemic stroke by driving thrombotic and inflammatory responses. Focal cerebral ischemia was induced in C57BL/6 mice by a 60-minute transient middle cerebral artery occlusion. Animals were treated with anti-CD147 function-blocking antibody (αCD147) or isotype control antibody. Blood-brain barrier permeability, thrombus formation, and microvascular patency were assessed 24 hours after ischemia. Infarct size, neurological deficits, and inflammatory cells invaded in the brain were assessed 72 hours after ischemia. CD147 expression was rapidly increased in ischemic brain endothelium after transient middle cerebral artery occlusion. Inhibition of CD147 reduced infarct size and improved functional outcome on day 3 after transient middle cerebral artery occlusion. The neuroprotective effects were associated with (1) prevented blood-brain barrier damage, (2) decreased intravascular fibrin and platelet deposition, which in turn reduced thrombosis and increased cerebral perfusion, and (3) reduced brain inflammatory cell infiltration. The underlying mechanism may include reduced NF-κB (nuclear factor κB) activation, MMP-9 (matrix metalloproteinase-9) activity, and PAI-1 (plasminogen activator inhibitor-1) expression in brain microvascular endothelial cells. Inhibition of CD147 ameliorates acute ischemic stroke by reducing thromboinflammation. CD147 might represent a novel and promising therapeutic target for ischemic stroke and possibly other thromboinflammatory disorders. © 2017 American Heart Association, Inc.
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Investigation of ionic transport in sodium scandium phosphate (NSP) and related compounds
NASA Astrophysics Data System (ADS)
Bhat, Kaustubh; Blügel, Stefan; Lustfeld, Hans
Sodium ionic conductors offer significant advantages for application in large scale energy storage systems. In this study, we investigate the different pathways available for sodium ion conduction in NSP and calculate energy barriers for ionic transport using Density Functional Theory (DFT) and the Nudged Elastic Band Method. We identify the structural parameters that reduce the energy barrier, by calculating the influence of positive and negative external pressure on the energy barrier. Lattice strain can be introduced by cation or anion substitution within the NASICON structure. We substitute the scandium atom with other trivalent atoms such as aluminium and yttrium, and calculate the resulting energy barriers. Sodium thiophosphate (Na3PS4) has previously shown about two orders of magnitude higher ionic conductivity than sodium phosphate (Na3PO4). We investigate the effect of substituting oxygen with sulphur in NSP. We acknowledge discussions with our experimental colleagues F. Tietz and M. Guin toward this work
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Homoepitaxial graphene tunnel barriers for spin transport (Presentation Recording)
NASA Astrophysics Data System (ADS)
Friedman, Adam L.
2015-09-01
Tunnel barriers are key elements for both charge-and spin-based electronics, offering devices with reduced power consumption and new paradigms for information processing. Such devices require mating dissimilar materials, raising issues of heteroepitaxy, interface stability, and electronic states that severely complicate fabrication and compromise performance. Graphene is the perfect tunnel barrier. It is an insulator out-of-plane, possesses a defect-free, linear habit, and is impervious to interdiffusion. Nonetheless, true tunneling between two stacked graphene layers is not possible in environmental conditions (magnetic field, temperature, etc.) usable for electronics applications. However, two stacked graphene layers can be decoupled using chemical functionalization. Here, we demonstrate homoepitaxial tunnel barrier devices in which graphene serves as both the tunnel barrier and the high mobility transport channel. Beginning with multilayer graphene, we fluorinate or hydrogenate the top layer to decouple it from the bottom layer, so that it serves as a single monolayer tunnel barrier for both charge and spin injection into the lower graphene transport channel. We demonstrate successful tunneling by measuring non-linear IV curves, and a weakly temperature dependent zero bias resistance. We perform lateral transport of spin currents in non-local spin-valve structures and determine spin lifetimes with the non-local Hanle effect to be commensurate with previous studies (~200 ps). However, we also demonstrate the highest spin polarization efficiencies (~45%) yet measured in graphene-based spin devices [1]. [1] A.L. Friedman, et al., Homoepitaxial tunnel barriers with functionalized graphene-on-graphene for charge and spin transport, Nat. Comm. 5, 3161 (2014).
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Janette Williams, S; Huang, Han-Hung; Kover, Karen; Moore, Wayne; Berkland, Cory; Singh, Milind; Smirnova, Irina V; MacGregor, Ronal
2010-01-01
For people with type 1 diabetes and severe hypoglycemic unawareness, islet transplants offer hope for improving the quality of life. However, islet cell death occurs quickly during or after transplantation, requiring large quantities of islets per transplant. The purpose of this study was to determine whether poor function demonstrated in large islets was a result of diffusion barriers and if removing those barriers could improve function and transplantation outcomes. Islets were isolated from male DA rats and measured for cell viability, islet survival, glucose diffusion and insulin secretion. Modeling of diffusion barriers was completed using dynamic partial differential equations for a sphere. Core cell death occurred in 100% of the large islets (diameter >150 µm), resulting in poor survival within 7 days after isolation. In contrast, small islets (diameter <100 µm) exhibited good survival rates in culture (91%). Glucose diffusion into islets was tracked with 2-NBDG; 4.2 µm/min in small islets and 2.8 µm/min in large islets. 2-NBDG never permeated to the core cells of islets larger than 150 µm diameter. Reducing the diffusion barrier in large islets improved their immediate and long-term viability in culture. However, reduction of the diffusion barrier in large islets failed to improve their inferior in vitro insulin secretion compared to small islets, and did not return glucose control to diabetic animals following transplantation. Thus, diffusion barriers lead to low viability and poor survival for large islets, but are not solely responsible for the inferior insulin secretion or poor transplantation outcomes of large versus small islets. PMID:20885858
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Xing, Weiyi; Yang, Wei; Yang, Wenjie; Hu, Qihang; Si, Jingyu; Lu, Hongdian; Yang, Benhong; Song, Lei; Hu, Yuan; Yuen, Richard K K
2016-10-05
Aminated multiwalled carbon nanotubes (A-MWCNT) were reacted with diphenylphosphinic chloride (DPP-Cl) to prepare the functionalized MWCNT (DPPA-MWCNT). A-MWCNT and DPPA-MWCNT were respectively mixed with polystyrene (PS) to obtain composites through the melt compounding method. SEM observations demonstrated that the DPPA-MWCNT nanofillers were more uniformly distributed within the PS matrix than A-MWCNT. PS/DPPA-MWCNT showed improved thermal stability, glass transition temperature, and tensile strength in comparison with PS/A-MWCNT, resulting from good dispersion and interfacial interactions between DPPA-MWCNT and PS matrix. The incorporation of DPPA-MWCNT to PS significantly reduced peak heat release rate, smoke production rate, and carbon monoxide and carbon dioxide release in cone calorimeter tests. The enhanced fire-retardant properties should be ascribed to the barrier effect of carbon nanotubes, which could provide enough time for DPPA-MWCNT and its functionalized groups to trap the degrading polymer radicals to catalyze char formation. The char layer served as an efficient insulating barrier to reduce the exposure of polymer matrix to an external heat source as well as retarding the flammable gases from feeding the flame.
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Kim, Yeojung; Kessler, Sean P; Obery, Dana R; Homer, Craig R; McDonald, Christine; de la Motte, Carol A
2017-10-01
Maintaining a healthy intestinal barrier, the primary physical barrier between intestinal microbiota and the underlying lamina propria, is critical for optimal health. Epithelial integrity is essential for the prevention of the entrance of luminal contents, such as bacteria and their products, through the large intestinal barrier. In this study, we investigated the protective functions of biosynthetic, specific sized, hyaluronan around 35kDa (HA35) on intestinal epithelium in healthy mice, as well as mice infected Citrobacter rodentium, an established model that mimics infection with a serious human pathogen, enteropathogenic E. coli (EPEC). Our results reveal that treatment with HA35 protects mice from Citrobacter infection and enhances the epithelial barrier function. In particular, we have found that HA35 induces the expression of tight junction protein zonula occludens (ZO)-1 in both healthy and Citrobacter infected mice, as demonstrated by immunoflurorescence and Western blot analyses. Furthermore, we determined that HA35 treatment enhances ZO-1 expression and reduces intestinal permeability at the early stages of dextran sulfate sodium (DSS)-induced colitis in mice. Together, our data demonstrate that the expression and functionality of tight junctions, are increased by HA35 treatment, suggesting a novel mechanism for the protection from Citrobacter infection. Copyright © 2016 Elsevier B.V. All rights reserved.
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Wu, Liping; Oshima, Tadayuki; Tomita, Toshihiko; Ohda, Yoshio; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto
2016-11-01
Serotonin regulates gastrointestinal function, and mast cells are a potential nonneuronal source of serotonin in the esophagus. Tight junction (TJ) proteins in the esophageal epithelium contribute to the barrier function, and the serotonin signaling pathway may contribute to epithelial leakage in gastroesophageal reflux disease. Therefore, the aim of this study was to investigate the role of serotonin on barrier function, TJ proteins, and related signaling pathways. Normal primary human esophageal epithelial cells were cultured with use of an air-liquid interface system. Serotonin was added to the basolateral compartment, and transepithelial electrical resistance (TEER) was measured. The expression of TJ proteins and serotonin receptor 7 (5-HT 7 ) was assessed by Western blotting. The involvement of 5-HT 7 was assessed with use of an antagonist and an agonist. The underlying cellular signaling pathways were examined with use of specific blockers. Serotonin decreased TEER and reduced the expression of TJ proteins ZO-1, occludin, and claudin 1, but not claudin 4. A 5-HT 7 antagonist blocked the serotonin-induced decrease in TEER, and a 5-HT 7 agonist decreased TEER. Inhibition of p38 mitogen-activated protein kinase (MAPK) reduced the serotonin-induced decrease in TEER. Inhibition of p38 MAPK blocked the decrease of ZO-1 levels, whereas extracellular-signal-regulated kinase (ERK) inhibition blocked the decrease in occludin levels. Cell signaling pathway inhibitors had no effect on serotonin-induced alterations in claudin 1 and claudin 4 levels. Serotonin induced phosphorylation of p38 MAPK and ERK, and a 5-HT 7 antagonist partially blocked serotonin-induced phosphorylation of p38 MAPK but not that of ERK. Serotonin disrupted esophageal squamous epithelial barrier function by modulating the levels of TJ proteins. Serotonin signaling pathways may mediate the pathogenesis of gastroesophageal reflux disease.
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Hawkins, Brian T; Grego, Sonia; Sellgren, Katelyn L
2015-05-22
Blood-brain barrier (BBB) function is regulated by dynamic interactions among cell types within the neurovascular unit, including astrocytes and endothelial cells. Co-culture models of the BBB typically involve astrocytes seeded on two-dimensional (2D) surfaces, which recent studies indicate cause astrocytes to express a phenotype similar to that of reactive astrocytes in situ. We hypothesized that the culture conditions of astrocytes would differentially affect their ability to modulate BBB function in vitro. Brain endothelial cells were grown alone or in co-culture with astrocytes. Astrocytes were grown either as conventional (2D) monolayers, or in a collagen-based gel which allows them to grow in a three-dimensional (3D) construct. Astrocytes were viable in 3D conditions, and displayed a marked reduction in their expression of glial fibrillary acidic protein (GFAP), suggesting reduced activation. Stimulation of astrocytes with transforming growth factor (TGF)β1 decreased transendothelial electrical resistance (TEER) and reduced expression of claudin-5 in co-cultures, whereas treatment of endothelial cells in the absence of astrocytes was without effect. The effect of TGFβ1 on TEER was significantly more pronounced in endothelial cells cultured with 3D astrocytes compared to 2D astrocytes. These results demonstrate that astrocyte culture conditions differentially affect their ability to modulate brain endothelial barrier function, and suggest a direct relationship between reactive gliosis and BBB permeability. Moreover, these studies demonstrate the potential importance of physiologically relevant culture conditions to in vitro modeling of disease processes that affect the neurovascular unit. Copyright © 2015 Elsevier B.V. All rights reserved.
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High Fat Diets Induce Colonic Epithelial Cell Stress and Inflammation that is Reversed by IL-22
Gulhane, Max; Murray, Lydia; Lourie, Rohan; Tong, Hui; Sheng, Yong H.; Wang, Ran; Kang, Alicia; Schreiber, Veronika; Wong, Kuan Yau; Magor, Graham; Denman, Stuart; Begun, Jakob; Florin, Timothy H.; Perkins, Andrew; Cuív, Páraic Ó.; McGuckin, Michael A.; Hasnain, Sumaira Z.
2016-01-01
Prolonged high fat diets (HFD) induce low-grade chronic intestinal inflammation in mice, and diets high in saturated fat are a risk factor for the development of human inflammatory bowel diseases. We hypothesized that HFD-induced endoplasmic reticulum (ER)/oxidative stress occur in intestinal secretory goblet cells, triggering inflammatory signaling and reducing synthesis/secretion of proteins that form the protective mucus barrier. In cultured intestinal cells non-esterified long-chain saturated fatty acids directly increased oxidative/ER stress leading to protein misfolding. A prolonged HFD elevated the intestinal inflammatory cytokine signature, alongside compromised mucosal barrier integrity with a decrease in goblet cell differentiation and Muc2, a loss in the tight junction protein, claudin-1 and increased serum endotoxin levels. In Winnie mice, that develop spontaneous colitis, HFD-feeding increased ER stress, further compromised the mucosal barrier and increased the severity of colitis. In obese mice IL-22 reduced ER/oxidative stress and improved the integrity of the mucosal barrier, and reversed microbial changes associated with obesity with an increase in Akkermansia muciniphila. Consistent with epidemiological studies, our experiments suggest that HFDs are likely to impair intestinal barrier function, particularly in early life, which partially involves direct effects of free-fatty acids on intestinal cells, and this can be reversed by IL-22 therapy. PMID:27350069
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MacEachern, Sarah J.; Patel, Bhavik A.; Keenan, Catherine M.; Dicay, Michael; Chapman, Kevin; McCafferty, Donna-Marie; Savidge, Tor C.; Beck, Paul L.; MacNaughton, Wallace K.; Sharkey, Keith A.
2015-01-01
Background & Aims Disturbances in the control of ion transport lead to epithelial barrier dysfunction in patients with colitis. Enteric glia regulate intestinal barrier function and colonic ion transport. However, it is not clear whether enteric glia are involved in the epithelial hypo-responsiveness. We investigated enteric glial regulation of ion transport in mice with trinitrobenzene sulphonic acid- or dextran sodium sulfate-induced colitis and in Il10−/− mice. Methods Electrically-evoked ion transport was measured in full-thickness segments of colon from CD1 and Il10−/− mice with or without colitis in Ussing chambers. Nitric oxide (NO) production was assessed using amperometry. Bacterial translocation was investigated in the liver, spleen and blood of mice. Results Electrical stimulation of the colon evoked a tetrodotoxin-sensitive chloride secretion. In mice with colitis, ion transport almost completely disappeared. Inhibiting inducible NO synthase (NOS2), but not neuronal NOS (NOS1), partially restored the evoked secretory response. Blocking glial function with fluoroacetate, which is not a NOS2 inhibitor, also partially restored ion transport. Combined NOS2 inhibition and fluoroacetate administration fully restored secretion. Epithelial responsiveness to vasoactive intestinal peptide was increased after enteric glial function was blocked in mice with colitis. In colons of mice without colitis, NO was produced in the myenteric plexus almost completely via NOS1. NO production was increased in mice with colitis, compared to mice without colitis; a substantial proportion of NOS2 was blocked by fluoroacetate administration. Inhibition of enteric glial function in vivo reduced the severity of trinitrobenzene sulphonic acid -induced colitis and associated bacterial translocation. Conclusions Increased production of NOS2 in enteric glia contributes to the dysregulation of intestinal ion transport in mice with colitis. Blocking enteric glial function in these mice restores epithelial barrier function and reduces bacterial translocation. PMID:25865048
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MacEachern, Sarah J; Patel, Bhavik A; Keenan, Catherine M; Dicay, Michael; Chapman, Kevin; McCafferty, Donna-Marie; Savidge, Tor C; Beck, Paul L; MacNaughton, Wallace K; Sharkey, Keith A
2015-08-01
Disturbances in the control of ion transport lead to epithelial barrier dysfunction in patients with colitis. Enteric glia regulate intestinal barrier function and colonic ion transport. However, it is not clear whether enteric glia are involved in epithelial hyporesponsiveness. We investigated enteric glial regulation of ion transport in mice with trinitrobenzene sulfonic acid- or dextran sodium sulfate-induced colitis and in Il10(-/-) mice. Electrically evoked ion transport was measured in full-thickness segments of colon from CD1 and Il10(-/-) mice with or without colitis in Ussing chambers. Nitric oxide (NO) production was assessed using amperometry. Bacterial translocation was investigated in the liver, spleen, and blood of mice. Electrical stimulation of the colon evoked a tetrodotoxin-sensitive chloride secretion. In mice with colitis, ion transport almost completely disappeared. Inhibiting inducible NO synthase (NOS2), but not neuronal NOS (NOS1), partially restored the evoked secretory response. Blocking glial function with fluoroacetate, which is not a NOS2 inhibitor, also partially restored ion transport. Combined NOS2 inhibition and fluoroacetate administration fully restored secretion. Epithelial responsiveness to vasoactive intestinal peptide was increased after enteric glial function was blocked in mice with colitis. In colons of mice without colitis, NO was produced in the myenteric plexus almost completely via NOS1. NO production was increased in mice with colitis, compared with mice without colitis; a substantial proportion of NOS2 was blocked by fluoroacetate administration. Inhibition of enteric glial function in vivo reduced the severity of trinitrobenzene sulfonic acid-induced colitis and associated bacterial translocation. Increased production of NOS2 in enteric glia contributes to the dysregulation of intestinal ion transport in mice with colitis. Blocking enteric glial function in these mice restores epithelial barrier function and reduces bacterial translocation. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
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Khemis, A; Duteil, L; Tillet, Y; Dereure, O; Ortonne, J-P
2014-09-01
Topical or systemic antiviral drugs reduce the duration of genital herpes recurrences but may not always alleviate functional symptoms. To assess the efficacy and safety of oxygenated glycerol triesters-based CS21 barrier genital gel(®) vs. topical aciclovir and placebo (vehicle) in resolving functional symptoms and in healing of genital herpes recurrences. A prospective randomized controlled, investigator-blinded trial of CS21 barrier genital gel(®) vs. topical aciclovir (reference treatment) and placebo (vehicle) was designed. The primary endpoint was the cumulative score of four herpes-related functional symptoms (pain, burning, itching and tingling sensations). Secondary endpoints included objective skin changes (erythema, papules, vesicles, oedema, erosion/ulceration, crusts), time to heal, local tolerance and overall acceptability of the treatment as reported by a self-administered questionnaire. Overall, 61 patients were included. CS 21 barrier genital gel(®) was significantly more efficient than topical aciclovir and vehicle for subjective symptoms and pain relief in genital herpes recurrences; additionally, time to heal was significantly shorter with CS 21 than with vehicle, whereas no significantly difference was observed between patients receiving topical aciclovir and vehicle. The treatments under investigation were well tolerated and the adverse events were comparable in the three treatment groups. Overall, these results support the interest of using of CS 21 barrier genital gel(®) in symptomatic genital herpes recurrences. Accordingly, this product offers a valuable alternative in topical management of recurrent genital herpes. © 2013 European Academy of Dermatology and Venereology.
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T Tank Farm Interim Surface Barrier Demonstration - Vadose Zone Monitoring FY09 Report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Z. F.; Strickland, Christopher E.; Field, Jim G.
2010-01-01
DOE’s Office of River Protection constructed a temporary surface barrier over a portion of the T Tank Farm as part of the T Farm Interim Surface Barrier Demonstration Project. As part of the demonstration effort, vadose zone moisture is being monitored to assess the effectiveness of the barrier at reducing soil moisture. A solar-powered system was installed to continuously monitor soil water conditions at four locations (i.e., instrument Nests A, B, C, and D) beneath the barrier and outside the barrier footprint as well as site meteorological conditions. Nest A is placed in the area outside the barrier footprint andmore » serves as a control, providing subsurface conditions outside the influence of the surface barrier. Nest B provides subsurface measurements to assess surface-barrier edge effects. Nests C and D are used to assess changes in soil-moisture conditions beneath the interim surface barrier. Each instrument nest is composed of a capacitance probe (CP) with multiple sensors, multiple heat-dissipation units (HDUs), and a neutron probe (NP) access tube. The monitoring results in FY09 are summarized below. The solar panels functioned normally and could provide sufficient power to the instruments. The CP in Nest C after September 20, 2009, was not functional. The CP sensors in Nest B after July 13 and the 0.9-m CP sensor in Nest D before June 10 gave noisy data. Other CPs were functional normally. All the HDUs were functional normally but some pressure-head values measured by HDUs were greater than the upper measurement-limit. The higher-than-upper-limit values might be due to the very wet soil condition and/or measurement error but do not imply the malfunction of the sensors. Similar to FY07 and FY08, in FY09, the soil under natural conditions (Nest A) was generally recharged during the winter period (October-March) and discharged during the summer period (April-September). Soil water conditions above about 1.5-m to 2-m depth from all three types of measurements (i.e., CP, NP and HDU) showed relatively large variation during the seasonal wetting-drying cycle. For the soil below 2-m depth, the seasonal variation of soil water content was relatively small. The construction of the surface barrier was completed in April 2008. In the soil below the surface barrier (Nests C and D), the CP measurements showed that water content at the soil between 0.6-m and 2.3-m depths was very stable, indicating no climatic impacts on soil water condition beneath the barrier. The NP-measured water content showed that soil water drainage seemed occurring in the soil between about 3.4 m (11 ft) and 9.1 m (30 ft) in FY09. The HDU-measured water pressure decreased consistently in the soil above 5-m depth, indicating soil water drainage at these depths of the soil. In the soil below the edge of the surface barrier (Nest B), the CP-measured water content was relatively stable through the year except at the 0.9-m depth; the NP-measured water content showed that soil water drainage was occurring in the soil between about 3.4 m (11 ft) and 9.1 m (30 ft) but at a slightly smaller magnitude than those in Nests C and D; the HDU-measurements show that the pressure head changes in FY09 in Nest B were less than those for C and D but more than those for A. The soil-water-pressure head was more sensitive to soil water regime changes under dry conditions. In the soil beneath the barrier, the theoretical steady-state values of pressure head is equal to the negative of the distance to groundwater table. Hence, it is expected that, in the future, while the water content become stable, the pressure head will keep decreasing for a long time (e.g., many years). These results indicate that the T Tank Farm surface barrier was performing as expected by intercepting the meteoric water from infiltrating into the soil and the soil was becoming drier gradually. The barrier also has some effects on the soil below the barrier edge but at a reduced magnitude.« less
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The barrier function of organotypic non-melanoma skin cancer models.
Zoschke, Christian; Ulrich, Martina; Sochorová, Michaela; Wolff, Christopher; Vávrová, Kateřina; Ma, Nan; Ulrich, Claas; Brandner, Johanna M; Schäfer-Korting, Monika
2016-07-10
Non-melanoma skin cancer (NMSC) is the most frequent human cancer with continuously rising incidences worldwide. Herein, we investigated the molecular basis for the impaired skin barrier function of organotypic NMSC models. We unraveled disturbed epidermal differentiation by reflectance confocal microscopy and histopathological evaluation. While the presence of claudin-4 and occludin were distinctly reduced, zonula occludens protein-1 was more wide-spread, and claudin-1 was heterogeneously distributed within the NMSC models compared with normal reconstructed human skin. Moreover, the cancer altered stratum corneum lipid packing and profile with decreased cholesterol content, increased phospholipid amount, and altered ceramide subclasses. These alterations contributed to increased surface pH and to 1.5 to 2.6-fold enhanced caffeine permeability of the NMSC models. Three topical applications of ingenol mebutate gel (0.015%) caused abundant epidermal cell necrosis, decreased Ki-67 indices, and increased lactate dehydrogenase activity. Taken together, our study provides new biological insights into the microenvironment of organotypic NMSC models, improves the understanding of the disease model by revealing causes for impaired skin barrier function in NMSC models at the molecular level, and fosters human cell-based approaches in preclinical drug evaluation. Copyright © 2016 Elsevier B.V. All rights reserved.
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Forteza, Rosanna Malbran; Casalino-Matsuda, S. Marina; Falcon, Nieves S.; Valencia Gattas, Monica; Monzon, Maria E.
2012-01-01
Cigarette smoke (CigS) exposure is associated with increased bronchial epithelial permeability and impaired barrier function. Primary cultures of normal human bronchial epithelial cells exposed to CigS exhibit decreased E-cadherin expression and reduced transepithelial electrical resistance. These effects were mediated by hyaluronan (HA) because inhibition of its synthesis with 4-methylumbelliferone prevented these effects, and exposure to HA fragments of <70 kDa mimicked these effects. We show that the HA receptor layilin is expressed apically in human airway epithelium and that cells infected with lentivirus expressing layilin siRNAs were protected against increased permeability triggered by both CigS and HA. We identified RhoA/Rho-associated protein kinase (ROCK) as the signaling effectors downstream layilin. We conclude that HA fragments generated by CigS bind to layilin and signal through Rho/ROCK to inhibit the E-cadherin gene and protein expression, leading to a loss of epithelial cell-cell contact. These studies suggest that HA functions as a master switch protecting or disrupting the epithelial barrier in its high versus low molecular weight form and that its depolymerization is a first and necessary step triggering the inflammatory response to CigS. PMID:23048036
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Effects of glyceryl glucoside on AQP3 expression, barrier function and hydration of human skin.
Schrader, A; Siefken, W; Kueper, T; Breitenbach, U; Gatermann, C; Sperling, G; Biernoth, T; Scherner, C; Stäb, F; Wenck, H; Wittern, K-P; Blatt, T
2012-01-01
Aquaporins (AQPs) present in the epidermis are essential hydration-regulating elements controlling cellular water and glycerol transport. In this study, the potential of glyceryl glucoside [GG; alpha-D-glucopyranosyl-alpha-(1->2)-glycerol], an enhanced glycerol derivative, to increase the expression of AQP3 in vitro and ex vivo was evaluated. In vitro studies with real-time RT-PCR and FACS measurements were performed to test the induction by GG (3% w/v) of AQP3 mRNA and protein in cultured human keratinocytes. GG-containing formulations were applied topically to volunteer subjects and suction blister biopsies were analyzed to assess whether GG (5%) could penetrate the epidermis of intact skin, and subsequently upregulate AQP3 mRNA expression and improve barrier function. AQP3 mRNA and protein levels were significantly increased in cultured human keratinocytes. In the studies on volunteer subjects, GG significantly increased AQP3 mRNA levels in the skin and reduced transepidermal water loss compared with vehicle-controlled areas. GG promotes AQP3 mRNA and protein upregulation and improves skin barrier function, and may thus offer an effective treatment option for dehydrated skin. Copyright © 2012 S. Karger AG, Basel.
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Impact of humidity on functionality of on-paper printed electronics.
Bollström, Roger; Pettersson, Fredrik; Dolietis, Peter; Preston, Janet; Osterbacka, Ronald; Toivakka, Martti
2014-03-07
A multilayer coated paper substrate, combining barrier and printability properties was manufactured utilizing a pilot-scale slide curtain coating technique. The coating structure consists of a thin mineral pigment layer coated on top of a barrier layer. The surface properties, i.e. smoothness and surface porosity, were adjusted by the choice of calendering parameters. The influence of surface properties on the fine line printability and conductivity of inkjet-printed silver lines was studied. Surface roughness played a significant role when printing narrow lines, increasing the risk of defects and discontinuities, whereas for wider lines the influence of surface roughness was less critical. A smooth, calendered surface resulted in finer line definition, i.e. less edge raggedness. Dimensional stability and its influence on substrate surface properties as well as on the functionality of conductive tracks and transistors were studied by exposure to high/low humidity cycles. The barrier layer of the multilayer coated paper reduced the dimensional changes and surface roughness increase caused by humidity and helped maintain the conductivity of the printed tracks. Functionality of a printed transistor during a short, one hour humidity cycle was maintained, but a longer exposure to humidity destroyed the non-encapsulated transistor.
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Han, Seung Hoon; Park, Ji Woong
2017-11-01
The presence of long-standing hyperglycemic conditions has been suggested to lead to many skin problems associated with an impaired skin barrier function. However, the relationship between impaired skin barrier status and altered peripheral nervous system function has not yet been determined. The purpose of this study was to investigate the water evaporation rate as a measure of the permeability barrier function of diabetic skin and its relationship to diabetic sensorimotor polyneuropathy (DSPN) and peripheral autonomic neuropathy (PAN) using well-controlled confounding variables.This case-control study included 42 participants with chronic diabetes and 43 matched healthy controls. The diabetic group underwent a nerve conduction study and sympathetic skin response (SSR) test to confirm the presence of DSPN and PAN, respectively. Different skin regions were analyzed using the noninvasive Tewameter instrument (Courage + Khazaka Electronic GmbH, Cologne, Germany). The impacts of PAN, DSPN, age, and diabetes duration on the values of transepidermal water loss (TEWL) were each analyzed and compared between the groups.Regardless of the presence of DSPN or PAN, the TEWL values as measured on the distal extremities were significantly lower in the diabetic group than in the control group. In the diabetic group, participants with abnormal SSR test results showed decreased TEWL values in the finger, sole, and first toe, as compared with participants with normal SSR test results. In the control group, age showed a negative correlation with the TEWL values with respect to some measured regions. However, in the diabetic group, there was no significant correlation between either patient age or diabetes duration and TEWL values.The presence of a long-term hyperglycemic state can reduce the permeability barrier function of the skin, a phenomenon that might be related to the presence of an impaired peripheral sympathetic nervous system, rather than peripheral sensorimotor denervation.
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Pan, Yijun; Short, Jennifer L; Choy, Kwok H C; Zeng, Annie X; Marriott, Philip J; Owada, Yuji; Scanlon, Martin J; Porter, Christopher J H; Nicolazzo, Joseph A
2016-11-16
Fatty acid-binding protein 5 (FABP5) at the blood-brain barrier contributes to the brain uptake of docosahexaenoic acid (DHA), a blood-derived polyunsaturated fatty acid essential for maintenance of cognitive function. Given the importance of DHA in cognition, the aim of this study was to investigate whether deletion of FABP5 results in cognitive dysfunction and whether this is associated with reduced brain endothelial cell uptake of exogenous DHA and subsequent attenuation in the brain levels of endogenous DHA. Cognitive function was assessed in male and female FABP5 +/+ and FABP5 -/- mice using a battery of memory paradigms. FABP5 -/- mice exhibited impaired working memory and short-term memory, and these cognitive deficits were associated with a 14.7 ± 5.7% reduction in endogenous brain DHA levels. The role of FABP5 in the blood-brain barrier transport of DHA was assessed by measuring 14 C-DHA uptake into brain endothelial cells and capillaries isolated from FABP5 +/+ and FABP5 -/- mice. In line with a crucial role of FABP5 in the brain uptake of DHA, 14 C-DHA uptake into brain endothelial cells and brain capillaries of FABP5 -/- mice was reduced by 48.4 ± 14.5% and 14.0 ± 4.2%, respectively, relative to those of FABP5 +/+ mice. These results strongly support the hypothesis that FABP5 is essential for maintaining brain endothelial cell uptake of DHA, and that cognitive deficits observed in FABP5 -/- mice are associated with reduced CNS access of DHA. Genetic deletion of fatty acid-binding protein 5 (FABP5) in mice reduces uptake of exogenous docosahexaenoic acid (DHA) into brain endothelial cells and brain capillaries and reduces brain parenchymal levels of endogenous DHA. Therefore, FABP5 in the brain endothelial cell is a crucial contributor to the brain levels of DHA. Critically, lowered brain DHA levels in FABP5 -/- mice occurred in tandem with cognitive deficits in a battery of memory paradigms. This study provides evidence of a critical role for FABP5 in the maintenance of cognitive function via regulating the brain uptake of DHA, and suggests that upregulation of FABP5 in neurodegenerative diseases, where brain DHA levels are possibly diminished (e.g., Alzheimer's disease), may provide a novel therapeutic approach for restoring cognitive function. Copyright © 2016 the authors 0270-6474/16/3611756-13$15.00/0.
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NASA Astrophysics Data System (ADS)
Kirley, M. P.; Novakovic, B.; Sule, N.; Weber, M. J.; Knezevic, I.; Booske, J. H.
2012-03-01
We report experiments and analysis of field emission from metallic knife-edge cathodes, which are sputter-coated with thin films of lanthanum hexaboride (LaB6), a low-work function material. The emission current is found to depend sensitively on the thickness of the LaB6 layer. We find that films thinner than 10 nm greatly enhance the emitted current. However, cathodes coated with a thicker layer of LaB6 are observed to emit less current than the uncoated metallic cathode. This result is unexpected due to the higher work function of the bare metal cathode. We show, based on numerical calculation of the electrostatic potential throughout the structure, that the external (LaB6/vacuum) barrier is reduced with respect to uncoated samples for both thin and thick coatings. However, this behavior is not exhibited at the internal (metal/LaB6) barrier. In thinly coated samples, electrons tunnel efficiently through both the internal and external barrier, resulting in current enhancement with respect to the uncoated case. In contrast, the thick internal barrier in thickly coated samples suppresses current below the value for uncoated samples in spite of the lowered external barrier. We argue that this coating thickness variation stems from a relatively low (no higher than 1018 cm-3) free carrier density in the sputtered polycrystalline LaB6.
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Zou, Yaotian; Tarko, Andrew P; Chen, Erdong; Romero, Mario A
2014-11-01
Roadway departure crashes tend to be severe, especially when the roadside exposes the occupants of errant vehicles to excessive injury hazards. As a cost-effective method when the clear zone width is insufficient, road barriers are often installed to prevent errant vehicles from colliding with dangerous obstacles or traversing steep slopes. This paper focuses on the safety performance of road barriers in Indiana in reducing the risk of injury. The objective of the study presented here is to compare the risk of injury among different hazardous events faced by an occupant in a single-vehicle crash. The studied hazardous events include rolling over, striking three types of barriers (guardrails, concrete barrier walls, and cable barriers) with different barrier offsets to the edge of the travelled way, and striking various roadside objects. A total of 2124 single-vehicle crashes (3257 occupants) that occurred between 2008 and 2012 on 517 pair-matched homogeneous barrier and non-barrier segments were analyzed. A binary logistic regression model with mixed effects was estimated for vehicle occupants. The segment pairing process and the use of random effects were able to handle the commonality within the same segment pair as well as the heterogeneity across segment pairs. The modeling results revealed that hitting a barrier is associated with lower risk of injury than a high-hazard event (hitting a pole, rollover, etc.). The odds of injury are reduced by 39% for median concrete barrier walls offset 15-18ft from the travelled way, reduced by 65% for a guardrail face offset 5-55ft, reduced by 85% for near-side median cable barriers (offset between 10ft and 29ft), and reduced by 78% with far-side median cable barriers (offset at least 30ft). Comparing different types of barriers is useful where some types of barriers can be used alternatively. This study found that the odds of injury are 43% lower when striking a guardrail instead of a median concrete barrier offset 15-18ft and 65% lower when striking a median concrete barrier offset 7-14ft. The odds of injury when striking a near-side median cable barrier is 57% lower than the odds for a guardrail face. This reduction for a far side median cable barrier is 37%. Thus, a guardrail should be preferred over a concrete wall and a cable barrier should be preferred over a guardrail where the road and traffic conditions allow. In the light of the results, installing median cable barriers on both sides of the median to reduce their lateral offset is beneficial for safety. The study also found that the unexplained heterogeneity across vehicles is much larger than it was across matched segment pairs. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Guha, Madhumita; Gao, Xuan; Jayaraman, Shobini; Gursky, Olga
2008-11-04
High-density lipoproteins (HDLs) are protein-lipid assemblies that remove excess cell cholesterol and prevent atherosclerosis. HDLs are stabilized by kinetic barriers that decelerate protein dissociation and lipoprotein fusion. We propose that similar barriers modulate metabolic remodeling of plasma HDLs; hence, changes in particle composition that destabilize HDLs and accelerate their denaturation may accelerate their metabolic remodeling. To test this notion, we correlate existing reports on HDL-mediated cell cholesterol efflux and esterification, which are obligatory early steps in cholesterol removal, with our kinetic studies of HDL stability. The results support our hypothesis and show that factors accelerating cholesterol efflux and esterification in model discoidal lipoproteins (including reduced protein size, reduced fatty acyl chain length, and/or increased level of cis unsaturation) destabilize lipoproteins and accelerate their fusion and apolipoprotein dissociation. Oxidation studies of plasma spherical HDLs show a similar trend: mild oxidation by Cu(2+) or OCl(-) accelerates cell cholesterol efflux, protein dissociation, and HDL fusion, while extensive oxidation inhibits these reactions. Consequently, moderate destabilization may be beneficial for HDL functions by facilitating insertion of cholesterol and lipophilic enzymes, promoting dissociation of lipid-poor apolipoproteins, which are primary acceptors of cell cholesterol, and thereby accelerating HDL metabolism. Therefore, HDL stability must be delicately balanced to maintain the structural integrity of the lipoprotein assembly and ensure structural specificity necessary for interactions of HDL with its metabolic partners, while facilitating rapid HDL remodeling and turnover at key junctures of cholesterol transport. The inverse correlation between HDL stability and remodeling illustrates the functional importance of structural disorder in macromolecular assemblies stabilized by kinetic barriers.
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Pathophysiological consequences of VEGF-induced vascular permeability
NASA Astrophysics Data System (ADS)
Weis, Sara M.; Cheresh, David A.
2005-09-01
Although vascular endothelial growth factor (VEGF) induces angiogenesis, it also disrupts vascular barrier function in diseased tissues. Accordingly, VEGF expression in cancer and ischaemic disease has unexpected pathophysiological consequences. By uncoupling endothelial cell-cell junctions VEGF causes vascular permeability and oedema, resulting in extensive injury to ischaemic tissues after stroke or myocardial infarction. In cancer, VEGF-mediated disruption of the vascular barrier may potentiate tumour cell extravasation, leading to widespread metastatic disease. Therefore, by blocking the vascular permeability promoting effects of VEGF it may be feasible to reduce tissue injury after ischaemic disease and minimize the invasive properties of circulating tumour cells.
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Preventable hospitalizations, barriers to care, and disability.
Pezzin, Liliana E; Bogner, Hillary R; Kurichi, Jibby E; Kwong, Pui L; Streim, Joel E; Xie, Dawei; Na, Ling; Hennessy, Sean
2018-05-01
The AHRQ's Prevention Quality Indicators assume inpatient hospitalizations for certain conditions, referred as ambulatory-care sensitive (ACS) conditions, are potentially preventable and may indicate reduced access to and a lower quality of ambulatory care. Using a cohort drawn from the Medicare Current Beneficiary Survey (MCBS) linked to Medicare claims, we examined the extent to which barriers to healthcare are associated with ACS hospitalizations and related costs, and whether these associations differ by beneficiaries' disability status. Our results indicate that the regression-adjusted cost of ACS hospitalizations for elderly Medicare beneficiaries with no disabilities was $799. This cost increased six-fold, by $5148, among beneficiaries with mild disability, by $9045 for beneficiaries with moderate disability, by $5513 for those with severe disability, and by $8557 for persons with complete disability (P < 0.001). Persons reporting having foregone or delayed needed medical care because of financial difficulties (+$2082, P = .05), those experiencing low satisfaction with care coordination (+$1714, P = .01), and those reporting low satisfaction with access to care (+$1237, P = .02) also incurred significant excess ACS hospitalization costs relative to persons reporting no such barriers. This pattern held true for those with and without a disability, but were especially marked among persons with no functional limitations. These findings suggest that a better understanding of how public policy might effectively improve care coordination and reduce financial barriers to care is essential to formulating programs that reduce excess hospitalizations among the large and growing number of elderly Medicare beneficiaries.
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Cancer Cells Regulate Biomechanical Properties of Human Microvascular Endothelial Cells*
Mierke, Claudia Tanja
2011-01-01
Metastasis is a key event of malignant tumor progression. The capability to metastasize depends on the ability of the cancer cell to migrate into connective tissue, adhere, and possibly transmigrate through the endothelium. Previously we reported that the endothelium does not generally act as barrier for cancer cells to migrate in three-dimensional extracellular matrices (3D-ECMs). Instead, the endothelium acts as an enhancer or a promoter for the invasiveness of certain cancer cells. How invasive cancer cells diminish the endothelial barrier function still remains elusive. Therefore, this study investigates whether invasive cancer cells can decrease the endothelial barrier function through alterations of endothelial biomechanical properties. To address this, MDA-MB-231 breast cancer cells were used that invade deeper and more numerous into 3D-ECMs when co-cultured with microvascular endothelial cells. Using magnetic tweezer measurements, MDA-MB-231 cells were found to alter the mechanical properties of endothelial cells by reducing endothelial cell stiffness. Using spontaneous bead diffusion, actin cytoskeletal remodeling dynamics were shown to be increased in endothelial cells co-cultured with MDA-MB-231 cells compared with mono-cultured endothelial cells. In addition, knockdown of the α5 integrin subunit in highly transmigrating α5β1high cells derived from breast, bladder, and kidney cancer cells abolished the endothelial invasion-enhancing effect comparable with the inhibition of myosin light chain kinase. These results indicate that the endothelial invasion-enhancing effect is α5β1 integrin-dependent. Moreover, inhibition of Rac-1, Rho kinase, MEK kinase, and PI3K reduced the endothelial invasion-enhancing effect, indicating that signaling via small GTPases may play a role in the endothelial facilitated increased invasiveness of cancer cells. In conclusion, decreased stiffness and increased cytoskeletal remodeling dynamics of endothelial cells may account for the breakdown of endothelial barrier function, suggesting that biomechanical alterations are sufficient to facilitate the transmigration and invasion of invasive cancer cells into 3D-ECMs. PMID:21940631
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Berardesca, Enzo; Mortillo, Susan; Cameli, Norma; Ardigo, Marco; Mariano, Maria
2018-05-10
Atopic dermatitis is a chronic, pruritic inflammatory skin disease that adversely affects quality of life. The current study evaluates the efficacy of a shower cream and a lotion, each with skin-identical lipids and emollients, in the treatment of atopic dry skin of subjects with a history of atopic condition. In all, 40 healthy females with clinically dry skin on the lower legs were enrolled in the study and underwent 4 weeks of daily use of the shower cream and 2 additional weeks of both the shower cream and the body lotion. Subjects were evaluated at day 0, week 4, and week 6. Skin barrier function was assessed by Tewameter ® , skin hydration by Corneometer ® , smoothness and desquamation by Visioscan ® , and stratum corneum architecture by reflectance confocal microscopy (RCM). The investigator assessed the degree of dryness, roughness, redness, cracks, tingling and itch, and subjective self-assessment evaluated the perception of skin soothing, smoothness, and softness. Skin barrier function and skin moisture maintenance were significantly improved using the shower cream. The lotion with physiological lipids, together with the shower cream, also improved skin barrier function and moisture. Both the shower cream and the body lotion reduced clinical dryness, roughness, redness, cracks, tingling and itch, according to the dermatologist, and increased soothing, smoothness, and softness, according to the subjects of the study. The combination of a shower cream and a lotion with physiological lipids efficiently restores skin barrier function and increases skin hydration, becoming an effective skin-care option for patients with atopic dry skin. © 2018 Wiley Periodicals, Inc.
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Wiltshire, Rachael; Nelson, Vicky; Kho, Dan Ting; Angel, Catherine E; O'Carroll, Simon J; Graham, E Scott
2016-01-27
Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors.
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Mineral oil barrier sequential polymer treatment for recycled paper products in food packaging
NASA Astrophysics Data System (ADS)
Paul, Uttam C.; Fragouli, Despina; Bayer, Ilker S.; Mele, Elisa; Conchione, Chiara; Cingolani, Roberto; Moret, Sabrina; Athanassiou, Athanassia
2017-01-01
Recycled cellulosic paperboards may include mineral oils after the recycle process, which together with their poor water resistance limit their use as food packaging materials. In this work, we demonstrate that a proper functionalization of the recycled paper with two successive polymer treatments, imposes a mineral oil migration barrier and simultaneously renders it waterproof and grease resistant, making it an ideal material for food contact. The first poly (methyl methacrylate) treatment penetrates the paper network and creates a protective layer around every fiber, permitting thus the transformation of the paperboard to a hydrophobic material throughout its thickness, reducing at the same time the mineral oil migration. Subsequently, the second layer with a cyclic olefin copolymer fills the open pores of the surface, and reduces the mineral oil hydrocarbons migration at levels below those proposed by the BMEL. Online liquid chromatography-gas chromatography coupled with flame ionization detection quantitatively demonstrate that this dual functional treatment prevents the migration of both saturated (mineral oil saturated hydrocarbons) and aromatic hydrocarbon (mineral oil aromatic hydrocarbons) mineral oils from the recycled paperboard to a dry food simulant.
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Miyata, Ryo; Nomura, Kazuaki; Kakuki, Takuya; Takano, Ken-Ichi; Kohno, Takayuki; Konno, Takumi; Sawada, Norimasa; Himi, Tetsuo; Kojima, Takashi
2015-04-01
The airway epithelium of the human nasal mucosa acts as the first physical barrier that protects against inhaled substances and pathogens. Irsogladine maleate (IM) is an enhancer of gastric mucosal protective factors via upregulation of gap junctional intercellular communication (GJIC). GJIC is thought to participate in the formation of functional tight junctions. However, the effects of IM on GJIC and the epithelial barrier in human nasal epithelial cells (HNECs) remain unknown. To investigate the effects of IM on GJIC and the tight junctional barrier in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were treated with IM and the GJIC inhibitors oleamide and 18β-GA. Some cells were pretreated with IM before treatment with TLR3 ligand poly(I:C) to examine whether IM prevented the changes via TLR3-mediated signal pathways. In hTERT-HNECs, GJIC blockers reduced the expression of tight junction molecules claudin-1, -4, -7, occludin, tricellulin, and JAM-A. IM induced GJIC activity and enhanced the expression of claudin-1, -4, and JAM-A at the protein and mRNA levels with an increase of barrier function. GJIC blockers prevented the increase of the tight junction proteins induced by IM. Furthermore, IM prevented the reduction of JAM-A but not induction of IL-8 and TNF-α induced by poly(I:C). In conclusion, IM can maintain the GJIC-dependent tight junctional barrier via regulation of GJIC in upper airway nasal epithelium. Therefore, it is possible that IM may be useful as a nasal spray to prevent the disruption of the epithelial barrier by viral infections and exposure to allergens in human nasal mucosa.
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The effect of urothelial damage on ureteric motility. An ultrastructural and functional study.
Ugaily-Thulesius, L; Thulesius, O; Sabha, M
1988-07-01
Evidence of a leaky urothelial barrier in bilharzial uropathy is presented. The ultrastructural basis of this concept is demonstrated together with its functional consequences. The study was conducted on 4 ureters obtained at surgery from patients with non-functioning kidneys due to chronic bilharzial infections. Six normal ureters from kidney donors served as controls. Light and electron microscopic studies showed a reduced thickness of the transitional epithelium together with localised disruption of intercellular junctions and infiltration of red blood cells. The functional studies involved in vitro demonstration of stable phasic peristaltic contractions which were fundamentally altered by the addition of urine. The changes in motility included increase in contractile frequency and elevation of basal tone, inducing a state of hypermotility which could be equated with ureteric spasm. These changes were partly reversible upon administration of the histamine l-blocker, mepyramine. Evidence is presented to show that these changes might be induced in vivo by histamine released from mast cells triggered by urine leaking through a damaged urothelial barrier. The functional consequences (pain, spasm) are discussed.
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Infrasonic wind-noise reduction by barriers and spatial filters.
Hedlin, Michael A H; Raspet, Richard
2003-09-01
This paper reports experimental observations of wind speed and infrasonic noise reduction inside a wind barrier. The barrier is compared with "rosette" spatial filters and with a reference site that uses no noise reduction system. The barrier is investigated for use at International Monitoring System (IMS) infrasound array sites where spatially extensive noise-reducing systems cannot be used because of a shortage of suitable land. Wind speed inside a 2-m-high 50%-porous hexagonal barrier coated with a fine wire mesh is reduced from ambient levels by 90%. If the infrasound wind-noise level reductions are all plotted versus the reduced frequency given by f*L/v, where L is the characteristic size of the array or barrier, f is the frequency, and v is the wind speed, the reductions at different wind speeds are observed to collapse into a single curve for each wind-noise reduction method. The reductions are minimal below a reduced frequency of 0.3 to 1, depending on the device, then spatial averaging over the turbulence structure leads to increased reduction. Above the reduced corner frequency, the barrier reduces infrasonic noise by up to 20 to 25 dB. Below the corner frequency the barrier displays a small reduction of about 4 dB. The rosettes display no reduction below the corner frequency. One other advantage of the wind barrier over rosette spatial filters is that the signal recorded inside the barrier enters the microbarometer from free air and is not integrated, possibly out of phase, after propagation through a system of narrow pipes.
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Kim, Chang-Hyun; Cheong, Kyung Ah; Lee, Ai-Young
2013-11-01
Light emitting diode (LED) phototherapy is an effective alternative for the treatment of inflammatory skin disorders. Tacrolimus (FK-506) is a potent immunomodulating agent, which has been used to treat AD. Combination therapy is often used in the treatment of AD to improve therapeutic efficacy or to reduce the dose of each drug. To investigate the therapeutic efficacy of monotherapy with either 850nm LED phototherapy or low-dose FK-506, and combination therapy in Dermatophagoides farina (Df)-induced AD-like skin lesions in NC/Nga mice. The Df-induced NC/Nga mice with a clinical score of 7 were used for treatment with LED (10 and 25J/cm(2)) alone, low-dose FK-506 (1mg/kg) or in combination. The synergistic effects of combined therapy were evaluated by dermatitis scores, skin histology, skin barrier function, and immunological parameters, such as IgE, NO, Th2-mediated cytokines and chemokines. Combination therapy with 850nm (25J/cm(2)) LED and low-dose FK-506 showed a significant reduction in the severity of skin lesions. Combined therapy decreased in the serum level of IgE, NO, and in the splenic level of Th2-mediated cytokines and chemokines. Combination therapy significantly also reduced the inflammatory cellular infiltrate into the skin lesions. Moreover, combination therapy led to recovery of skin barrier function in the skin lesions. The use of combination of LED phototherapy and low-dose immunosuppressant improved Df-induced AD-like skin lesions in an NC/Nga mouse model by dominantly reducing IgE, NO, suppressing Th2-mediated immune responses, and inhibiting inflammatory cells, as well as improving skin barrier function. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
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Centromeric Barrier Disruption Leads to Mitotic Defects in Schizosaccharomyces pombe
Gaither, Terilyn L.; Merrett, Stephanie L.; Pun, Matthew J.; Scott, Kristin C.
2014-01-01
Centromeres are cis-acting chromosomal domains that direct kinetochore formation, enabling faithful chromosome segregation and preserving genome stability. The centromeres of most eukaryotic organisms are structurally complex, composed of nonoverlapping, structurally and functionally distinct chromatin subdomains, including the specialized core chromatin that underlies the kinetochore and pericentromeric heterochromatin. The genomic and epigenetic features that specify and preserve the adjacent chromatin subdomains critical to centromere identity are currently unknown. Here we demonstrate that chromatin barriers regulate this process in Schizosaccharomyces pombe. Reduced fitness and mitotic chromosome segregation defects occur in strains that carry exogenous DNA inserted at centromere 1 chromatin barriers. Abnormal phenotypes are accompanied by changes in the structural integrity of both the centromeric core chromatin domain, containing the conserved CENP-ACnp1 protein, and the flanking pericentric heterochromatin domain. Barrier mutant cells can revert to wild-type growth and centromere structure at a high frequency after the spontaneous excision of integrated exogenous DNA. Our results reveal a previously undemonstrated role for chromatin barriers in chromosome segregation and in the prevention of genome instability. PMID:24531725
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Homoepitaxial graphene tunnel barriers for spin transport
NASA Astrophysics Data System (ADS)
Friedman, Adam L.; van't Erve, Olaf M. J.; Robinson, Jeremy T.; Whitener, Keith E.; Jonker, Berend T.
2016-05-01
Tunnel barriers are key elements for both charge-and spin-based electronics, offering devices with reduced power consumption and new paradigms for information processing. Such devices require mating dissimilar materials, raising issues of heteroepitaxy, interface stability, and electronic states that severely complicate fabrication and compromise performance. Graphene is the perfect tunnel barrier. It is an insulator out-of-plane, possesses a defect-free, linear habit, and is impervious to interdiffusion. Nonetheless, true tunneling between two stacked graphene layers is not possible in environmental conditions usable for electronics applications. However, two stacked graphene layers can be decoupled using chemical functionalization. Here, we demonstrate that hydrogenation or fluorination of graphene can be used to create a tunnel barrier. We demonstrate successful tunneling by measuring non-linear IV curves and a weakly temperature dependent zero-bias resistance. We demonstrate lateral transport of spin currents in non-local spin-valve structures, and determine spin lifetimes with the non-local Hanle effect. We compare the results for hydrogenated and fluorinated tunnel and we discuss the possibility that ferromagnetic moments in the hydrogenated graphene tunnel barrier affect the spin transport of our devices.
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Edaravone Protects against Methylglyoxal-Induced Barrier Damage in Human Brain Endothelial Cells
Tóth, Andrea E.; Walter, Fruzsina R.; Bocsik, Alexandra; Sántha, Petra; Veszelka, Szilvia; Nagy, Lajos; Puskás, László G.; Couraud, Pierre-Olivier; Takata, Fuyuko; Dohgu, Shinya; Kataoka, Yasufumi; Deli, Mária A.
2014-01-01
Background Elevated level of reactive carbonyl species, such as methylglyoxal, triggers carbonyl stress and activates a series of inflammatory responses leading to accelerated vascular damage. Edaravone is the active substance of a Japanese medicine, which aids neurological recovery following acute brain ischemia and subsequent cerebral infarction. Our aim was to test whether edaravone can exert a protective effect on the barrier properties of human brain endothelial cells (hCMEC/D3 cell line) treated with methylglyoxal. Methodology Cell viability was monitored in real-time by impedance-based cell electronic sensing. The barrier function of the monolayer was characterized by measurement of resistance and flux of permeability markers, and visualized by immunohistochemistry for claudin-5 and β-catenin. Cell morphology was also examined by holographic phase imaging. Principal Findings Methylglyoxal exerted a time- and dose-dependent toxicity on cultured human brain endothelial cells: a concentration of 600 µM resulted in about 50% toxicity, significantly reduced the integrity and increased the permeability of the barrier. The cell morphology also changed dramatically: the area of cells decreased, their optical height significantly increased. Edaravone (3 mM) provided a complete protection against the toxic effect of methylglyoxal. Co-administration of edaravone restored cell viability, barrier integrity and functions of brain endothelial cells. Similar protection was obtained by the well-known antiglycating molecule, aminoguanidine, our reference compound. Conclusion These results indicate for the first time that edaravone is protective in carbonyl stress induced barrier damage. Our data may contribute to the development of compounds to treat brain endothelial dysfunction in carbonyl stress related diseases. PMID:25033388
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Cheng, Jian; Zhang, Lin; Dai, Weiqi
Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys{sup 3}]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and alsomore » prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation.« less
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Chen, Xiaodi; Threlkeld, Steven W.; Cummings, Erin E.; Juan, Ilona; Makeyev, Oleksandr; Besio, Walter G.; Gaitanis, John; Banks, William A.; Sadowska, Grazyna B.; Stonestreet, Barbara S.
2012-01-01
The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (Ki) and tight junction proteins by Western immunoblot in fetal sheep at 127 days-of-gestation without ischemia, and 4-, 24-, or 48-h after ischemia. The largest increase in Ki (P<0.05) was 4-h after ischemia. Occludin and claudin-5 expressions decreased at 4-h, but returned toward control levels 24- and 48-h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between Ki and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (Ki) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4-h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24- and 48- than 4-h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia. PMID:22986172
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Jensen, Lone Donbæk; Maribo, Thomas; Schiøttz-Christensen, Berit; Madsen, Finn Hjorth; Gonge, Bigitte; Christensen, Michael; Frost, Poul
2012-01-01
To assess if counselling by an occupational physician (OP) addressing experienced workplace barriers and physical activity integrated as a part of low-back pain (LBP) outpatient treatment influences pain, function and sick leave. Randomised controlled trial in the secondary healthcare sector with 3 months' follow-up. The participants were LBP patients who, independently of sick-leave status, expressed concerns about the ability to maintain their current job. Patients referred for surgery were excluded. The intervention consisted of two counselling sessions conducted by an OP addressing both workplace barriers and leisure-time physical activity. A workplace visit was performed if required. Pain, function and duration of sick leave due to LBP were primary outcomes. A reduction in bodily pain and improvement in physical function both measured by the 36-item short-form health survey questionnaire in favour of the intervention group was found. The change in pain score was found to be clinically relevant. The risk of sick leave for at least 8 weeks due to LBP was significantly reduced in the intervention group. Two secondary outcomes, Fear Avoidance Beliefs about physical activity and maximum oxygen uptake, supported compliance and adherence to the part of the intervention focusing on enhanced physical activity. Two short counselling sessions by an OP combining advice on meeting workplace barriers and enhancing physical activity had a substantial effect on important prognostic factors for LBP patients with moderate to severe symptoms diagnosed in outpatient rheumatological clinics. Current Controlled Trials ISRCTN13071157.
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Regulation of endothelial barrier function by p120-catenin∙VE-cadherin interaction
Garrett, Joshua P.; Lowery, Anthony M.; Adam, Alejandro P.; Kowalczyk, Andrew P.; Vincent, Peter A.
2017-01-01
Endothelial p120-catenin (p120) maintains the level of vascular endothelial cadherin (VE-Cad) by inhibiting VE-Cad endocytosis. Loss of p120 results in a decrease in VE-Cad levels, leading to the formation of monolayers with decreased barrier function (as assessed by transendothelial electrical resistance [TEER]), whereas overexpression of p120 increases VE-Cad levels and promotes a more restrictive monolayer. To test whether reduced endocytosis mediated by p120 is required for VE-Cad formation of a restrictive barrier, we restored VE-Cad levels using an endocytic-defective VE-Cad mutant. This endocytic-defective mutant was unable to rescue the loss of TEER associated with p120 or VE-Cad depletion. In contrast, the endocytic-defective mutant was able to prevent sprout formation in a fibrin bead assay, suggesting that p120•VE-Cad interaction regulates barrier function and angiogenic sprouting through different mechanisms. Further investigation found that depletion of p120 increases Src activity and that loss of p120 binding results in increased VE-Cad phosphorylation. In addition, expression of a Y658F–VE-Cad mutant or an endocytic-defective Y658F–VE-Cad double mutant were both able to rescue TEER independently of p120 binding. Our results show that in addition to regulating endocytosis, p120 also allows the phosphorylated form of VE-Cad to participate in the formation of a restrictive monolayer. PMID:27852896
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Thermal acclimation mitigates cold-induced paracellular leak from the Drosophila gut.
MacMillan, Heath A; Yerushalmi, Gil Y; Jonusaite, Sima; Kelly, Scott P; Donini, Andrew
2017-08-18
Chill susceptible insects suffer tissue damage and die at low temperatures. The mechanisms that cause chilling injury are not well understood but a growing body of evidence suggests that a cold-induced loss of ion and water homeostasis leads to hemolymph hyperkalemia that depolarizes cells, leading to cell death. The apparent root of this cascade is the net leak of osmolytes down their concentration gradients in the cold. Many insects, however, are capable of adjusting their thermal physiology, and cold-acclimated Drosophila can maintain homeostasis and avoid injury better than warm-acclimated flies. Here, we test whether chilling causes a loss of epithelial barrier function in female adult Drosophila, and provide the first evidence of cold-induced epithelial barrier failure in an invertebrate. Flies had increased rates of paracellular leak through the gut epithelia at 0 °C, but cold acclimation reduced paracellular permeability and improved cold tolerance. Improved barrier function was associated with changes in the abundance of select septate junction proteins and the appearance of a tortuous ultrastructure in subapical intercellular regions of contact between adjacent midgut epithelial cells. Thus, cold causes paracellular leak in a chill susceptible insect and cold acclimation can mitigate this effect through changes in the composition and structure of transepithelial barriers.
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Diels-Alder reactions onto fluorinated and hydrogenated graphene
NASA Astrophysics Data System (ADS)
Denis, Pablo A.
2017-09-01
We studied Diels-Alder (DA) reactions onto functionalized graphene. When fluorine, hydrogen or oxygen functional groups are present on one side of the sheet, the DA cycloadditions become significantly more exergonic when performed on the opposite side. Hydrogen is more effective than fluorine and oxygen to promote these cycloadditions. In contrast with the results obtained for perfect graphene, the functionalization with H, F or O turns the DA reactions exergonic, with ΔG°298 = -127.2 kcal/mol. The reaction barriers are expected to be considerably lowered with respect to perfect graphene because the functional groups significantly reduce the distortion energy.
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Russell, K. L.; Berman, N. E. J.; Gregg, P. R. A.; Levant, B.
2014-01-01
SUMMARY The effects of an oral fish oil treatment regimen on sensorimotor, blood-brain barrier, and biochemical outcomes of traumatic brain injury (TBI) were investigated in a juvenile rat model. Seventeen-day old Long-Evans rats were given a 15 mL/kg fish oil (2.01 g/kg EPA, 1.34 g/kg DHA) or soybean oil dose via oral gavage 30 minutes prior to being subjected to a controlled cortical impact injury or sham surgery, followed by daily doses for seven days. Fish oil treatment resulted in less severe hindlimb deficits after TBI as assessed with the beam walk test, decreased cerebral IgG infiltration, and decreased TBI-induced expression of the Mmp9h gene one day after injury. These results indicate that fish oil improved functional outcome after TBI resulting, at least in part from decreased disruption of the blood-brain barrier through a mechanism that includes attenuation of TBI-induced expression of Mmp9. PMID:24342130
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Russell, K L; Berman, N E J; Gregg, P R A; Levant, B
2014-01-01
The effects of an oral fish oil treatment regimen on sensorimotor, blood-brain barrier, and biochemical outcomes of traumatic brain injury (TBI) were investigated in a juvenile rat model. Seventeen-day old Long-Evans rats were given a 15mL/kg fish oil (2.01g/kg EPA, 1.34g/kg DHA) or soybean oil dose via oral gavage 30min prior to being subjected to a controlled cortical impact injury or sham surgery, followed by daily doses for seven days. Fish oil treatment resulted in less severe hindlimb deficits after TBI as assessed with the beam walk test, decreased cerebral IgG infiltration, and decreased TBI-induced expression of the Mmp9 gene one day after injury. These results indicate that fish oil improved functional outcome after TBI resulting, at least in part from decreased disruption of the blood-brain barrier through a mechanism that includes attenuation of TBI-induced expression of Mmp9. © 2013 Elsevier Ltd. All rights reserved.
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Fernández-Martín, Laura; Marcos-Ramiro, Beatriz; Bigarella, Carolina L; Graupera, Mariona; Cain, Robert J; Reglero-Real, Natalia; Jiménez, Anaïs; Cernuda-Morollón, Eva; Correas, Isabel; Cox, Susan; Ridley, Anne J; Millán, Jaime
2012-08-01
Endothelial cells provide a barrier between the blood and tissues, which is reduced during inflammation to allow selective passage of molecules and cells. Adherens junctions (AJ) play a central role in regulating this barrier. We aim to investigate the role of a distinctive 3-dimensional reticular network of AJ found in the endothelium. In endothelial AJ, vascular endothelial-cadherin recruits the cytoplasmic proteins β-catenin and p120-catenin. β-catenin binds to α-catenin, which links AJ to actin filaments. AJ are usually described as linear structures along the actin-rich intercellular contacts. Here, we show that these AJ components can also be organized in reticular domains that contain low levels of actin. Reticular AJ are localized in areas where neighboring cells overlap and encompass the cell adhesion receptor platelet endothelial cell adhesion molecule-1 (PECAM-1). Superresolution microscopy revealed that PECAM-1 forms discrete structures distinct from and distributed along AJ, within the voids of reticular domains. Inflammatory tumor necrosis factor-α increases permeability by mechanisms that are independent of actomyosin-mediated tension and remain incompletely understood. Reticular AJ, but not actin-rich linear AJ, were disorganized by tumor necrosis factor-α. This correlated with PECAM-1 dispersal from cell borders. PECAM-1 inhibition with blocking antibodies or small interfering RNA specifically disrupted reticular AJ, leaving linear AJ intact. This disruption recapitulated typical tumor necrosis factor-α-induced alterations of barrier function, including increased β-catenin phosphorylation, without altering the actomyosin cytoskeleton. We propose that reticular AJ act coordinately with PECAM-1 to maintain endothelial barrier function in regions of low actomyosin-mediated tension. Selective disruption of reticular AJ contributes to permeability increase in response to tumor necrosis factor-α.
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Suitability of polystyrene as a functional barrier layer in coloured food contact materials.
Genualdi, Susan; Addo Ntim, Susana; Begley, Timothy
2015-01-01
Functional barriers in food contact materials (FCMs) are used to prevent or reduce migration from inner layers in multilayer structures to food. The effectiveness of functional barrier layers was investigated in coloured polystyrene (PS) bowls due to their intended condition of use with hot liquids such as soups or stew. Migration experiments were performed over a 10-day period using USFDA-recommended food simulants (10% ethanol, 50% ethanol, corn oil and Miglyol) along with several other food oils. At the end of the 10 days, solvent dyes had migrated from the PS bowls at 12, 1 and 31,000 ng cm(-)(2) into coconut oil, palm kernel oil and Miglyol respectively, and in coconut oil and Miglyol the colour change was visible to the human eye. Scanning electron microscope (SEM) images revealed that the functional barrier was no longer intact for the bowls exposed to coconut oil, palm kernel oil, Miglyol, 10% ethanol, 50% ethanol and goat's milk. Additional tests showed that 1-dodecanol, a lauryl alcohol derived from palm kernel oil and coconut oil, was present in the PS bowls at an average concentration of 11 mg kg(-1). This compound is likely to have been used as a dispersing agent for the solvent dye and aided the migration of the solvent dye from the PS bowl into the food simulant. The solvent dye was not found in the 10% ethanol, 50% ethanol and goat's milk food simulants above their respective limits of detection, which is likely to be due to its insolubility in aqueous solutions. A disrupted barrier layer is of concern because if there are unregulated materials in the inner layers of the laminate, they may migrate to food, and therefore be considered unapproved food additives resulting in the food being deemed adulterated under the Federal Food Drug and Cosmetic Act.
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Potential barrier classification by short-time measurement
NASA Astrophysics Data System (ADS)
Granot, Er'El; Marchewka, Avi
2006-03-01
We investigate the short-time dynamics of a delta-function potential barrier on an initially confined wave packet. There are mainly two conclusions: (A) At short times the probability density of the first particles that passed through the barrier is unaffected by it. (B) When the barrier is absorptive (i.e., its potential is imaginary) it affects the transmitted wave function at shorter times than a real potential barrier. Therefore, it is possible to distinguish between an imaginary and a real potential barrier by measuring its effect at short times only on the transmitting wave function.
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Voronoi Tessellation for reducing the processing time of correlation functions
NASA Astrophysics Data System (ADS)
Cárdenas-Montes, Miguel; Sevilla-Noarbe, Ignacio
2018-01-01
The increase of data volume in Cosmology is motivating the search of new solutions for solving the difficulties associated with the large processing time and precision of calculations. This is specially true in the case of several relevant statistics of the galaxy distribution of the Large Scale Structure of the Universe, namely the two and three point angular correlation functions. For these, the processing time has critically grown with the increase of the size of the data sample. Beyond parallel implementations to overcome the barrier of processing time, space partitioning algorithms are necessary to reduce the computational load. These can delimit the elements involved in the correlation function estimation to those that can potentially contribute to the final result. In this work, Voronoi Tessellation is used to reduce the processing time of the two-point and three-point angular correlation functions. The results of this proof-of-concept show a significant reduction of the processing time when preprocessing the galaxy positions with Voronoi Tessellation.
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Barrier Requirements as the Evolutionary “Driver” of Epidermal Pigmentation in Humans
ELIAS, PETER M.; MENON, GOPINATHAN; WETZEL, BRUCE K.; WILLIAMS, JOHN (JACK) W.
2011-01-01
Current explanations for the development of epidermal pigmentation during human evolution are not tenable as stand-alone hypotheses. Accordingly, we assessed instead whether xeric- and UV-B-induced stress to the epidermal permeability barrier, critical to survival in a terrestrial environment, could have “driven” the development of epidermal pigmentation. (1) Megadroughts prevailed in central Africa when hominids expanded into open savannahs [≈1.5–0.8 million years ago], resulting in sustained exposure to both extreme aridity and erythemogenic UV-B, correlating with genetic evidence that pigment developed ≈1.2 million years ago. (2) Pigmented skin is endowed with enhanced permeability barrier function, stratum corneum integrity/cohesion, and a reduced susceptibility to infections. The enhanced function of pigmented skin can be attributed to the lower pH of the outer epidermis, likely due to the persistence of (more-acidic) melanosomes into the outer epidermis, as well as the conservation of genes associated with eumelanin synthesis and melanosome acidification (e.g., TYR, OCA2 [p protein], SLC24A5, SLC45A2, MATP) in pigmented populations. Five keratinocyte-derived signals (stem cell factor⇒KIT; FOXn1⇒FGF2; IL-1α, NGF, and p53) are potential candidates to have stimulated the sequential development of epidermal pigmentation in response to stress to the barrier. We summarize evidence here that epidermal interfollicular pigmentation in early hominids likely evolved in response to stress to the permeability barrier. PMID:20209486
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Chemical Vapor Deposition of Turbine Thermal Barrier Coatings
NASA Technical Reports Server (NTRS)
Haven, Victor E.
1999-01-01
Ceramic thermal barrier coatings extend the operating temperature range of actively cooled gas turbine components, therefore increasing thermal efficiency. Performance and lifetime of existing ceram ic coatings are limited by spallation during heating and cooling cycles. Spallation of the ceramic is a function of its microstructure, which is determined by the deposition method. This research is investigating metalorganic chemical vapor deposition (MOCVD) of yttria stabilized zirconia to improve performance and reduce costs relative to electron beam physical vapor deposition. Coatings are deposited in an induction-heated, low-pressure reactor at 10 microns per hour. The coating's composition, structure, and response to the turbine environment will be characterized.
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Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines.
Hu, Lizhi; Mauro, Theodora M; Dang, Erle; Man, George; Zhang, Jing; Lee, Dale; Wang, Gang; Feingold, Kenneth R; Elias, Peter M; Man, Mao-Qiang
2017-06-01
Even though elderly populations lack visible or other clinical signs of inflammation, their serum cytokine and C-reactive protein levels typically are elevated. However, the origin of age-associated systemic inflammation is unknown. Our previous studies showed that abnormalities in epidermal function provoke cutaneous inflammation, and because intrinsically aged skin displays compromised permeability barrier homeostasis and reduced stratum corneum hydration, we hypothesized here that epidermal dysfunction could contribute to the elevations in serum cytokines in the elderly. Our results show first that acute disruption of the epidermal permeability barrier in young mice leads not only to a rapid increase in cutaneous cytokine mRNA expression but also an increase in serum cytokine levels. Second, cytokine levels in both the skin and serum increase in otherwise normal, aged mice (>12 months). Third, expression of tumor necrosis factor-α and amyloid A mRNA levels increased in the epidermis, but not in the liver, in parallel with a significant elevation in serum levels of cytokines. Fourth, disruption of the permeability barrier induced similar elevations in epidermal and serum cytokine levels in normal and athymic mice, suggesting that T cells play a negligible role in the elevations in cutaneous and serum inflammatory cytokines induced by epidermal dysfunction. Fifth, correction of epidermal function significantly reduced cytokine levels not only in the skin but also in the serum of aged mice. Together, these results indicate that the sustained abnormalities in epidermal function in chronologically aged skin contribute to the elevated serum levels of inflammatory cytokines, potentially predisposing the elderly to the subsequent development or exacerbation of chronic inflammatory disorders. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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Choi, Hyeongwon; Kim, Dong-Jin; Nam, Seungwoo; Lim, Sunki; Hwang, Jae-Sung; Park, Ki Sook; Hong, Hyun Sook; Won, Younsun; Shin, Min Kyung; Chung, Eunkyung; Son, Youngsook
2018-03-01
Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense pruritus and eczematous lesion. Substance P (SP) is an 11-amino-acid endogenous neuropeptide that belongs to the tachykinin family and several reports recently have supported the anti-inflammatory and tissue repairing roles of SP. In this study, we investigated whether SP can improve AD symptoms, especially the impaired skin barrier function, in 2, 4, 6-trinitrochlorobenzene (TNCB)-induced chronic dermatitis of NC/Nga mice or not. AD-like dermatitis was induced in NC/Nga mice by repeated sensitization with TNCB for 5 weeks. The experimental group designations and topical treatments were as follows: vehicle group (AD-VE); SP group (AD-SP); and SP with NK1R antagonist CP99994 (AD-SP-A) group. Histological analysis was performed to evaluate epidermal differentiation, dermal integrity, and epidermal nerve innervation in AD-like lesions. The skin barrier functions and pruritus of NC/Nga mice were evaluated by measuring transepidermal water loss (TEWL) and scratching behavior, respectively. Topical SP treatment resulted in significant down-regulation of Ki67 and the abnormal-type keratins (K) K6, K16, and K17, restoration of filaggrin and claudin-1, marked reduction of TEWL, and restoration of basement membrane and dermal collagen deposition, even under continuous sensitization of low dose TNCB. In addition, SP significantly reduced innervation of itch-evoking nerve fibers, gelatinase activity and nerve growth factor (NGF) expression in the epidermis but upregulated semaphorin-3A (Sema3A) expression in the epidermis, along with reduced scratching behavior in TNCB-treated NC/Nga mice. All of these effects were completely reversed by co-treatment with the NK1R antagonist CP99994. In cultured human keratinocytes, SP treatment reduced expression of TGF-α, but upregulated TGF-β and Sema3A. Topically administered SP can restore normal skin barrier function, reduce epidermal infiltration of itch-evoking nerve fibers in the AD-like skin lesions, and alleviate scratching behavior. Thus, SP may be proposed as a potential medication for chronic dermatitis and AD. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
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Design and performance evaluation of a 1000-year evapotranspiration-capillary surface barrier
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Zhuanfang Fred; Strickland, Christopher E.; Link, Steven O.
Surface barrier technology is used to isolate radioactive waste and to reduce or eliminate recharge water to the waste zone for 1000 years or longer. However, the design and evaluation of such a barrier is challenging because of the extremely long design life. The Prototype Hanford Barrier (PHB) was designed as a 1000-year barrier with pre-determined design and performance objectives and demonstrated in field from 1994 to present. The barrier was tested to evaluate surface-barrier design and performance at the field scale under conditions of enhanced and natural precipitation and of no vegetation. The monitoring data demonstrate that the barriermore » satisfied nearly all key objectives. The PHB far exceeded the Resource Conservation and Recovery Act criteria, functioned in Hanford’s semiarid climate, limited drainage to well below the 0.5 mm yr-1 performance criterion, limited runoff, and minimized erosion. Given the two-decade record of successful performance and consideration of all the processes and mechanisms that could degrade the stability and hydrology in the future, the results suggest the PHB is very likely to perform for its 1000-year design life. This conclusion is based on two assumptions: (1) the exposed subgrade receives protection against erosion and (2) institutional controls prevent inadvertent human activity at the barrier. The PHB design can serve as the base for site-specific barriers over waste sites containing underground nuclear waste, uranium mine tailings, and hazardous mine waste.« less
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NASA Astrophysics Data System (ADS)
Lee, Eon S.; Ranasinghe, Dilhara R.; Ahangar, Faraz Enayati; Amini, Seyedmorteza; Mara, Steven; Choi, Wonsik; Paulson, Suzanne; Zhu, Yifang
2018-02-01
Traffic-related air pollutants are a significant public health concern, particularly near freeways. Previous studies have suggested either soundwall or vegetation barriers might reduce the near-freeway air pollution. This study aims to investigate the effectiveness of a combination of both soundwall and vegetation barrier for reducing ultrafine particles (UFPs, diameter ≤ 100 nm) and PM2.5 (diameter ≤ 2.5 μm) concentrations. Concurrent data collection was carried out at both upwind and downwind fixed locations approximately 10-15 m away from the edge of two major freeways in California. This study observed that the reduction of UFP and PM2.5 was generally greater with the combination barrier than with either soundwall or vegetation alone. Since there were no non-barrier sites at the study locations, the reductions reported here are all in relative terms. The soundwall barrier was more effective for reducing PM2.5 (25-53%) than UFPs (0-5%), and was most effective (51-53% for PM2.5) when the wind speed ranged between 1 and 2 m/s. Under the same range of wind speed, the vegetation barrier had little effect (0-5%) on reducing PM2.5; but was effective at reducing UFP (up to 50%). For both types of roadside barrier, decreasing wind speed resulted in greater net reduction of UFPs (i.e., total number particle concentrations; inversely proportional). This trend was observed, however, only within specific particle size ranges (i.e., diameter < 20 nm for the soundwall barrier and 12-60 nm for the vegetation barrier). Out of these size ranges, the reduction of UFP concentration was proportional to increasing wind speed. Overall findings of this study support positive effects of soundwall and vegetation barriers for near-freeway air pollution mitigation.
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Ibrahim, Marwa K.; Barnes, Jeffrey L.; Anstead, Gregory M.; Jimenez, Fabio; Travi, Bruno L.; Peniche, Alex G.; Osorio, E. Yaneth; Ahuja, Seema S.; Melby, Peter C.
2013-01-01
In a murine model of moderate childhood malnutrition we found that polynutrient deficiency led to a 4–5-fold increase in early visceralization of L. donovani (3 days post-infection) following cutaneous infection and a 16-fold decrease in lymph node barrier function (p<0.04 for all). To begin to understand the mechanistic basis for this malnutrition-related parasite dissemination we analyzed the cellularity, architecture, and function of the skin-draining lymph node. There was no difference in the localization of multiple cell populations in the lymph node of polynutrient deficient (PND) mice, but there was reduced cellularity with fewer CD11c+dendritic cells (DCs), fibroblastic reticular cells (FRCs), MOMA-2+ macrophages, and CD169+ subcapsular sinus macrophage (p<0.05 for all) compared to the well-nourished (WN) mice. The parasites were equally co-localized with DCs associated with the lymph node conduit network in the WN and PND mice, and were found in the high endothelial venule into which the conduits drain. When a fluorescent low molecular weight (10 kD) dextran was delivered in the skin, there was greater efflux of the marker from the lymph node conduit system to the spleens of PND mice (p<0.04), indicating that flow through the conduit system was altered. There was no evidence of disruption of the conduit or subcapsular sinus architecture, indicating that the movement of parasites into the subcortical conduit region was due to an active process and not from passive movement through a leaking barrier. These results indicate that the impaired capacity of the lymph node to act as a barrier to dissemination of L. donovani infection is associated with a reduced number of lymph node phagocytes, which most likely leads to reduced capture of parasites as they transit through the sinuses and conduit system. PMID:23967356
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Brunse, Anders; Abbaspour, Afrouz; Sangild, Per Torp
2018-06-06
Necrotizing enterocolitis (NEC) increases the risk of brain injury and impaired neurodevelopment. Rapid brain maturation prior to birth may explain why preterm brains are particularly vulnerable to serious infections. Using pigs as models, we hypothesized that preterm birth was associated with altered blood-cerebrospinal fluid (CSF) barrier (BCSFB) function and cerebral structural deficits, and that NEC was associated with systemic inflammation, BCSFB disruption, and neuroinflammation. First, cesarean-delivered preterm and term pigs (n = 43-44) were euthanized at birth to investigate BCSFB function and markers of brain structural maturation, or on day 5 to measure markers of blood-brain barrier maturation in the hippocampus and striatum (experiment 1). Next, preterm pigs (n = 162) were fed increasing volumes of infant formula to assess NEC lesions, systemic inflammation, BCSFB permeability, cerebral histopathology, hippocampal micro-glial density, and cytokine levels on day 5 (experiments 2 and 3). In experiment 1, preterm newborns had increased CSF-plasma ratios of albumin and raffinose, reduced CSF glucose levels, as well as increased cerebral hydration and reduced white matter myelination compared with term animals. We observed lower hippocampal (but not striatal) perivascular astrocyte coverage for the first 5 days after preterm birth, accompanied by altered cell junction protein levels. In experiments 2 and- 3, piglets with severe NEC lesions showed reduced blood thrombocytes and increased plasma C-reactive protein and interleukin-6 levels. NEC was associated with increased CSF-plasma albumin and raffinose ratios, reduced CSF leukocyte numbers, and increased cerebral hydration. In the hippocampus, NEC was associated with pyramidal neuron loss and increased interleukin-6 levels. In the short term, NEC did not affect cerebral myelination or microglia density. In conclusion, altered BCSFB properties and brain structural deficits were observed in pigs after preterm birth. Acute gastrointestinal NEC lesions were associated with systemic inflammation, increased BCSFB permeability and region-specific neuronal damage. The results demonstrate the importance of early interventions against NEC to prevent brain injury in preterm infants. © 2018 S. Karger AG, Basel.
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Low temperature barriers with heat interceptor wells for in situ processes
McKinzie, II, Billy John
2008-10-14
A system for reducing heat load applied to a frozen barrier by a heated formation is described. The system includes heat interceptor wells positioned between the heated formation and the frozen barrier. Fluid is positioned in the heat interceptor wells. Heat transfers from the formation to the fluid to reduce the heat load applied to the frozen barrier.
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Nasseau, M; Boublik, Y; Meier, W; Winterhalter, M; Fournier, D
2001-12-05
How can enzymes be protected against denaturation and proteolysis while keeping them in a fully functional state? One solution is to encapsulate the enzymes into liposomes, which enhances their stability against denaturation and proteases. However, the permeability barrier of the lipid membrane drastically reduces the activity of enzyme entrapped in the liposome by reducing the internal concentration of the substrate. To overcome this problem, we permeabilized the wall of the liposome by reconstitution of a porin from Escherichia coli. In this way, we recovered the full functionality of the enzyme while retaining the protection against denaturation and proteolytic enzymes. Copyright 2001 John Wiley & Sons, Inc.
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Chen, X; Threlkeld, S W; Cummings, E E; Juan, I; Makeyev, O; Besio, W G; Gaitanis, J; Banks, W A; Sadowska, G B; Stonestreet, B S
2012-12-13
The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (K(i)) and tight junction proteins by Western immunoblot in fetal sheep at 127 days of gestation without ischemia, and 4, 24, or 48 h after ischemia. The largest increase in K(i) (P<0.05) was 4 h after ischemia. Occludin and claudin-5 expressions decreased at 4 h, but returned toward control levels 24 and 48 h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between K(i) and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (K(i)) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4 h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24 and 48 than 4 h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
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NASA Technical Reports Server (NTRS)
Nash, Stephen G.; Polyak, R.; Sofer, Ariela
1994-01-01
When a classical barrier method is applied to the solution of a nonlinear programming problem with inequality constraints, the Hessian matrix of the barrier function becomes increasingly ill-conditioned as the solution is approached. As a result, it may be desirable to consider alternative numerical algorithms. We compare the performance of two methods motivated by barrier functions. The first is a stabilized form of the classical barrier method, where a numerically stable approximation to the Newton direction is used when the barrier parameter is small. The second is a modified barrier method where a barrier function is applied to a shifted form of the problem, and the resulting barrier terms are scaled by estimates of the optimal Lagrange multipliers. The condition number of the Hessian matrix of the resulting modified barrier function remains bounded as the solution to the constrained optimization problem is approached. Both of these techniques can be used in the context of a truncated-Newton method, and hence can be applied to large problems, as well as on parallel computers. In this paper, both techniques are applied to problems with bound constraints and we compare their practical behavior.
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Erickson, Michelle A.
2018-01-01
Central nervous system (CNS) barriers predominantly mediate the immune-privileged status of the brain, and are also important regulators of neuroimmune communication. It is increasingly appreciated that communication between the brain and immune system contributes to physiologic processes, adaptive responses, and disease states. In this review, we discuss the highly specialized features of brain barriers that regulate neuroimmune communication in health and disease. In section I, we discuss the concept of immune privilege, provide working definitions of brain barriers, and outline the historical work that contributed to the understanding of CNS barrier functions. In section II, we discuss the unique anatomic, cellular, and molecular characteristics of the vascular blood–brain barrier (BBB), blood–cerebrospinal fluid barrier, and tanycytic barriers that confer their functions as neuroimmune interfaces. In section III, we consider BBB-mediated neuroimmune functions and interactions categorized as five neuroimmune axes: disruption, responses to immune stimuli, uptake and transport of immunoactive substances, immune cell trafficking, and secretions of immunoactive substances. In section IV, we discuss neuroimmune functions of CNS barriers in physiologic and disease states, as well as pharmacological interventions for CNS diseases. Throughout this review, we highlight many recent advances that have contributed to the modern understanding of CNS barriers and their interface functions. PMID:29496890
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[Recent studies on corneal epithelial barrier function].
Liu, F F; Li, W; Liu, Z G; Chen, W S
2016-08-01
Corneal epithelium, the outermost layer of eyeball, is the main route for foreign materials to enter the eye. Under physiological conditions, the corneal epithelial superficial cells form a functionally selective permeability barrier. Integral corneal epithelial barrier function not only ensures the enrolling of nutrients which is required for regular metabolism, but also prevents foreign bodies, or disease-causing microorganism invasion. Recently, a large number of clinical and experimental studies have shown that abnormal corneal epithelial barrier function is the pathological basis for many ocular diseases. In addition, some study found that corneal epithelial barrier constitutes a variety of proteins involved in cell proliferation, differentiation, apoptosis, and a series of physiological and pathological processes. This paper reviewed recent studies specifically on the corneal epithelial barrier, highlights of its structure, function and influence factors. (Chin J Ophthalmol, 2016, 52: 631-635).
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang Kunzhong; Tian Yeping; Yin Liangjie
2011-09-01
Purpose: Epidermal keratinocytes, which can be severely damaged after ionizing radiation (IR), are rapid turnover cells that function as a barrier, protecting the host from pathogenic invasion and fluid loss. We tested fibroblast growth factor-peptide (FGF-P), a small peptide derived from the receptor-binding domain of FGF-2, as a potential mitigator of radiation effects via proliferation and the barrier function of keratinocytes. Methods and Materials: Keratinocytes isolated from neonatal foreskin were grown on transwells. After being exposed to 0, 5, or 10 Gy IR, the cells were treated with a vehicle or FGF-P. The permeability of IR cells was assessed bymore » using transepithelial electrical resistance (TEER) and a paracellular tracer flux of fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) with Ussing chambers. The cell proliferation was measured with yellow tetrazolium salt (MTT) and tritiated thymidine ([{sup 3}H]-TdR) assays. The phosphorylation of extracellular signal-regulated kinases (ERK) was measured in an enzyme-linked immunosorbent (ELISA)-like assay, and the proteins related to tight junctions (TJ) and adherens junctions (AJ) were examined with Western blotting. We used a mouse model to assess the ability of FGF-P to promote the healing of skin {beta} burns created with a strontium applicator. Results: We found (1) FGF-P reduced the permeability of irradiated keratinocytes, as evidenced by increased TEER and decreased diffusion of FITC-BSA, both associated with the regulation of different proteins and levels of TJ and AJ; and (2) FGF-P enhanced the proliferation of irradiated keratinocytes, as evidenced by increased MTT activity and [{sup 3}H]-TdR incorporation, which was associated with activation of the ERK pathway; and (3) FGF-P promoted the healing of skin {beta} burns. Conclusions: FGF-P enhances the barrier function, including up-regulation of TJ proteins, increases proliferation of human keratinocytes, and accelerates the healing of skin {beta} burns. FGF-P is a promising mitigator that improves the proliferation and barrier function of keratinocytes after IR.« less
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Ban, Yuriko; Cooper, Leanne J; Fullwood, Nigel J; Nakamura, Takahiro; Tsuzuki, Masakatsu; Koizumi, Noriko; Dota, Atsuyoshi; Mochida, Chikako; Kinoshita, Shigeru
2003-06-01
To evaluate the usefulness of the air-lifting technique for culturing corneal limbal epithelial cells on amniotic membrane (AM) for use in ocular surface reconstruction. A cultured sheet that has a good barrier function should be better for this purpose. In corneal epithelium, tight junctions (TJ) play a vital role in the barrier function. The TJ complex includes the integral transmembrane proteins occludin and the claudins, and some membrane-associated proteins such as ZO-1. In this paper, we investigated the barrier function and the expression of TJ related proteins. Corneal limbal epithelium obtained from donor corneas and cultivated on acellular AM was divided into two groups. These were the non-air-lifting (Non-AL) group, which was continuously submerged in medium, and the air-lifting (AL) group, which was submerged in medium for 3 weeks, then exposed to air by lowering the medium level. Morphology and the permeability to horseradish peroxidase (HRP) were determined by electron microscopy. Tight junction (TJ)-related protein and mRNA expression changes were assessed by immunoblotting and reverse transcription-polymerase chain reaction. The cultures of both groups formed 4-5-layer-thick, well-stratified epithelium. The AL cultures had tightly packed epithelial cells with all the HRP/diaminobenzidine (DAB) reaction product accumulated on the apical surface of the superficial cells. The Non-AL culture, by contrast, had more loosely packed epithelial cells with larger intercellular spaces. The HRP/DAB reaction product penetrated the intercellular space to a depth of 3-4 cell layers. Statistically, there was a significant difference in intercellular spaces and desmosome count in the superficial cells between the groups. With AL, TJ-related proteins localized at the apical portion of the lateral membrane. TJ-related protein and mRNA amounts were not changed by AL while claudin subtype expression became more consistent and closer to that of in vivo corneal epithelium. The AL technique reduces intercellular spaces in the superficial cells and promotes the formation of the barrier function. It is useful in culturing corneal epithelial cells for use in ocular surface reconstruction.
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Taylor, C T; Murphy, A; Kelleher, D; Baird, A W
1997-01-01
BACKGROUND: Elements of the mucosal immune system may play an important part in regulating epithelial barrier function in the intestinal tract. Intraepithelial lymphocytes (IELs) represent a subtype of immunocyte which is strategically placed to regulate epithelial function at most mucosal sites. AIMS AND METHODS: An IEL derived cell line (SC1) was used to examine its effects on the model epithelium T84--a tumour derived cell line which retains the phenotype of colonic crypt cells. Transepithelial electrical resistance (TER) was used as a marker of epithelial integrity. RESULTS: Coculture of T84 cells with SC1 produced a significant fall in TER as did exposure of T84 monolayers to IEL derived supernatant. Recombinant interferon-gamma (rIFN gamma) also reduced TER in T84 monolayers. Cycloheximide prevented the effects of IEL supernatant and of rIFN gamma on TER. The fall in TER in response to rIFN gamma was attenuated by blocking antibodies, which did not alter the fall in resistance induced by IEL supernatant. Fractions of IEL supernatant, separated on the basis of size, evoked temporally distinct changes in TER. Ultrastructural studies support the hypothesis that the slow onset but severe fall in TER indicates catastrophic effects on the monolayer. The more rapid onset fall in TER was not associated with gross changes in monolayer morphology. Reduction of TER by IEL supernatant was not influenced by inhibitors of tyrosine phosphatase or of protein kinase C. Although herbimycin did reduce the rapid onset change in TER, the tyrosine kinase inhibitor genistein did not alter responses to IEL supernatant. CONCLUSIONS: Mucosal T cells may influence barrier function by a process involving new protein synthesis by epithelial cells. This model may have relevance in some inflammatory conditions of the gastrointestinal tract. Images PMID:9203943
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Khemis, A; Duteil, L; Coudert, A C; Tillet, Y; Dereure, O; Ortonne, J P
2012-10-01
Topical or systemic antiviral drugs reduce the duration of herpes simplex virus 1 (HSV-1) recurrences but may not alleviate functional symptoms. To assess the efficacy and safety of CS20 (Acura 24(®) ) protective barrier gel versus topical aciclovir and placebo in resolving functional symptoms in HSV-1 labial recurrences. A prospective, randomized, single-centre, assessor-blinded study of CS20 versus topical aciclovir or placebo. The primary endpoint was the total score of four herpes-related functional symptoms (pain, burning, itching, and tingling sensations), evaluated by visual analogue scale (VAS). Secondary endpoints encompassed objective skin changes (oedema, crusting and erythema), evaluated by specific clinical scores. In a study of 106 patients, compared with placebo, a significant improvement in total functional symptom score was observed after 1 day of treatment in the CS20 group, but only after 7 days of treatment in the topical aciclovir group. Burning sensations were significantly reduced by CS20 compared with aciclovir (Days 1-2) or placebo (Days 1-7). Compared to placebo, CS20 significantly reduced pain intensity on Days 1-6. CS20 induced significant and early improvements in the clinical scores for oedema and crusting compared with placebo. Time to cure was similar for CS20 and aciclovir. The treatments were well tolerated and adverse events were comparable in the three treatment groups. Limitations The single-centre and single-blind design of the study and the preselection of patients. CS20 showed superior effectiveness against functional symptoms (pain and burning) associated with HSV-1 labial recurrences and was similar to aciclovir for time to cure. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.
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Tinkum, Kelsey L; Stemler, Kristina M; White, Lynn S; Loza, Andrew J; Jeter-Jones, Sabrina; Michalski, Basia M; Kuzmicki, Catherine; Pless, Robert; Stappenbeck, Thaddeus S; Piwnica-Worms, David; Piwnica-Worms, Helen
2015-12-22
Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to high-dose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing demonstrated that multiple SI stem cell populations, marked by Lgr5, Bmi1, or HopX expression, contributed to fasting-induced survival. DNA repair and DNA damage response genes were elevated in SI stem/progenitor cells of fasted etoposide-treated mice, which importantly correlated with faster resolution of DNA double-strand breaks and less apoptosis. Thus, fasting preserved SI stem cell viability as well as SI architecture and barrier function suggesting that fasting may reduce host toxicity in patients undergoing dose intensive chemotherapy.
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The effect of aging on brain barriers and the consequences for Alzheimer's disease development.
Gorlé, Nina; Van Cauwenberghe, Caroline; Libert, Claude; Vandenbroucke, Roosmarijn E
2016-08-01
Life expectancy has increased in most developed countries, which has led to an increase in the proportion of elderly people in the world's population. However, this increase in life expectancy is not accompanied by a lengthening of the health span since aging is characterized with progressive deterioration in cellular and organ functions. The brain is particularly vulnerable to disease, and this is reflected in the onset of age-related neurodegenerative diseases such as Alzheimer's disease. Research shows that dysfunction of two barriers in the central nervous system (CNS), the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB), plays an important role in the progression of these neurodegenerative diseases. The BBB is formed by the endothelial cells of the blood capillaries, whereas the BCSFB is formed by the epithelial cells of the choroid plexus (CP), both of which are affected during aging. Here, we give an overview of how these barriers undergo changes during aging and in Alzheimer's disease, thereby disturbing brain homeostasis. Studying these changes is needed in order to gain a better understanding of the mechanisms of aging at the brain barriers, which might lead to the development of new therapies to lengthen the health span (including mental health) and reduce the chances of developing Alzheimer's disease.
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In vitro effects of preserved and unpreserved anti-allergic drugs on human corneal epithelial cells.
Guzman-Aranguez, Ana; Calvo, Patricia; Ropero, Inés; Pintor, Jesús
2014-11-01
Treatment with topical eye drops for long-standing ocular diseases like allergy can induce detrimental side effects. The purpose of this study was to investigate in vitro cytotoxicity of commercially preserved and unpreserved anti-allergic eye drops on the viability and barrier function of monolayer and stratified human corneal-limbal epithelial cells. Cells were treated with unpreserved ketotifen solution, benzalkonium chloride (BAC)-containing anti-allergic drugs (ketotifen, olopatadine, levocabastine) as well as BAC alone. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to determine cell viability. Effects of compounds on barrier function were analyzed measuring transepithelial electrical resistance (TEER) to determine paracellular permeability and rose bengal assays to evaluate transcellular barrier formation. The BAC-preserved anti-allergic formulations and BAC alone significantly reduced cell viability, monolayer cultures being more sensitive to damage by these solutions. Unpreserved ketotifen induced the least diminution in cell viability. The extent of decrease of cell viability was clearly dependent of BAC presence, but it was also affected by the different types of drugs when the concentration of BAC was low and the short time of exposure. Treatment with BAC-containing anti-allergic drugs and BAC alone resulted in increased paracellular permeability and loss of transcellular barrier function as indicated by TEER measurement and rose bengal assays. The presence of the preservative BAC in anti-allergic eye drop formulations contributes importantly to the cytotoxic effects induced by these compounds. Stratified cell cultures seem to be a more relevant model for toxicity evaluation induced on the ocular surface epithelia than monolayer cultures.
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USDA-ARS?s Scientific Manuscript database
Protein p40, a Lactobacillus rhamnosus GG (LGG)-derived soluble protein, ameliorates intestinal injury and colitis, reduces apoptosis and preserves barrier function by activation of EGF receptor (EGFR) in intestinal epithelial cells. The aim of this study was to determine the mechanisms by which p40...
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Simal-Gándara, J; Sarria-Vidal, M; Koorevaar, A; Rijk, R
2000-08-01
The advent of the functional barrier concept in food packaging has brought with it a requirement for fast tests of permeation through potential barrier materials. In such tests it would be convenient for both foodstuffs and materials below the functional barrier (sub-barrier materials) to be represented by standard simulants. By means of inverse gas chromatography, liquid paraffin spiked with appropriate permeants was considered as a potential simulant of sub-barrier materials based on polypropylene (PP) or similar polyolefins. Experiments were performed to characterize the kinetics of the permeation of low molecular weight model permeants (octene, toluene and isopropanol) from liquid paraffin, through a surrogate potential functional barrier (25 microns-thick oriented PP) into the food stimulants olive oil and 3% (w/v) acetic acid. These permeation results were interpreted in terms of three permeation kinetic models regarding the solubility of a particular model permeant in the post-barrier medium (i.e. the food simulant). The results obtained justify the development and evaluation of liquid sub-barrier simulants that would allow flexible yet rigorous testing of new laminated multilayer packaging materials.
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A Lagrange multiplier and Hopfield-type barrier function method for the traveling salesman problem.
Dang, Chuangyin; Xu, Lei
2002-02-01
A Lagrange multiplier and Hopfield-type barrier function method is proposed for approximating a solution of the traveling salesman problem. The method is derived from applications of Lagrange multipliers and a Hopfield-type barrier function and attempts to produce a solution of high quality by generating a minimum point of a barrier problem for a sequence of descending values of the barrier parameter. For any given value of the barrier parameter, the method searches for a minimum point of the barrier problem in a feasible descent direction, which has a desired property that lower and upper bounds on variables are always satisfied automatically if the step length is a number between zero and one. At each iteration, the feasible descent direction is found by updating Lagrange multipliers with a globally convergent iterative procedure. For any given value of the barrier parameter, the method converges to a stationary point of the barrier problem without any condition on the objective function. Theoretical and numerical results show that the method seems more effective and efficient than the softassign algorithm.
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Dang, C; Xu, L
2001-03-01
In this paper a globally convergent Lagrange and barrier function iterative algorithm is proposed for approximating a solution of the traveling salesman problem. The algorithm employs an entropy-type barrier function to deal with nonnegativity constraints and Lagrange multipliers to handle linear equality constraints, and attempts to produce a solution of high quality by generating a minimum point of a barrier problem for a sequence of descending values of the barrier parameter. For any given value of the barrier parameter, the algorithm searches for a minimum point of the barrier problem in a feasible descent direction, which has a desired property that the nonnegativity constraints are always satisfied automatically if the step length is a number between zero and one. At each iteration the feasible descent direction is found by updating Lagrange multipliers with a globally convergent iterative procedure. For any given value of the barrier parameter, the algorithm converges to a stationary point of the barrier problem without any condition on the objective function. Theoretical and numerical results show that the algorithm seems more effective and efficient than the softassign algorithm.
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Regulation of Endothelial Barrier Function by Cyclic Nucleotides: The Role of Phosphodiesterases
Surapisitchat, James
2014-01-01
The endothelium plays an important role in maintaining normal vascular function. Endothelial barrier dysfunction leading to increased permeability and vascular leakage is associated with several pathological conditions such as edema and sepsis. Thus, the development of drugs that improve endothelial barrier function is an active area of research. In this chapter, the current knowledge concerning the signaling pathways regulating endothelial barrier function is discussed with a focus on cyclic nucleotide second messengers (cAMP and cGMP) and cyclic nucleotide phosphodiesterases (PDEs). Both cAMP and cGMP have been shown to have differential effects on endothelial permeability in part due to the various effector molecules, crosstalk, and compartmentalization of cyclic nucleotide signaling. PDEs, by controlling the amplitude, duration, and localization of cyclic nucleotides, have been shown to play a critical role in regulating endothelial barrier function. Thus, PDEs are attractive drug targets for the treatment of disease states involving endothelial barrier dysfunction. PMID:21695641
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Regulation of endothelial barrier function by cyclic nucleotides: the role of phosphodiesterases.
Surapisitchat, James; Beavo, Joseph A
2011-01-01
The endothelium plays an important role in maintaining normal vascular function. Endothelial barrier dysfunction leading to increased permeability and vascular leakage is associated with several pathological conditions such as edema and sepsis. Thus, the development of drugs that improve endothelial barrier function is an active area of research. In this chapter, the current knowledge concerning the signaling pathways regulating endothelial barrier function is discussed with a focus on cyclic nucleotide second messengers (cAMP and cGMP) and cyclic nucleotide phosphodiesterases (PDEs). Both cAMP and cGMP have been shown to have differential effects on endothelial permeability in part due to the various effector molecules, crosstalk, and compartmentalization of cyclic nucleotide signaling. PDEs, by controlling the amplitude, duration, and localization of cyclic nucleotides, have been shown to play a critical role in regulating endothelial barrier function. Thus, PDEs are attractive drug targets for the treatment of disease states involving endothelial barrier dysfunction.
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Spray particle drift mitigation using field corn (Zea mays L.) as a drift barrier.
Vieira, Bruno C; Butts, Thomas R; Rodrigues, Andre O; Golus, Jeffrey A; Schroeder, Kasey; Kruger, Greg R
2018-04-24
Herbicide particle drift reduces application efficacy and can cause severe impacts on nearby vegetation depending on the herbicide mode-of-action, exposure level, and tolerance to the herbicide. A particle drift mitigation effort placing windbreaks or barriers on the field boundaries to reduce off-target movement of spray particles has been utilized in the past. The objective of this research was to evaluate the effectiveness of field corn (Zea mays L.) at different heights as a particle drift barrier. Applications with a non-air inclusion flat fan nozzle (ER11004) resulted in greater particle drift when compared to an air inclusion nozzle (TTI11004). Eight rows of corn were used as barriers (0.91, 1.22, and 1.98 m height) which reduced the particle drift for both nozzles, especially at shorter downwind distances. Applications with the ER11004 nozzle without corn barriers had 1% of the applied rate (D 99 ) predicted to deposit at 14.8 m downwind, whereas this distance was reduced (up to 7-fold) when applications were performed with corn barriers. The combination of corn drift barriers and nozzle selection (TTI11004) provided satisfactory particle drift reduction when the D 99 estimates were compared to applications with the ER11004 nozzle without corn barriers (up to 10-fold difference). The corn drift barriers were effective in reducing particle drift from applications with the ER11004 and the TTI11004 nozzles (Fine and Ultra Coarse spray classifications, respectively). The corn drift barrier had appropriate porosity and width as the airborne spray was captured within its canopy instead of deflecting up and over it. This article is protected by copyright. All rights reserved.
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Dash, Surjya Narayan; Lehtonen, Eero; Wasik, Anita A; Schepis, Antonino; Paavola, Jere; Panula, Pertti; Nelson, W James; Lehtonen, Sanna
2014-04-01
The conserved septin family of filamentous small GTPases plays important roles in mitosis, cell migration and cell morphogenesis by forming scaffolds and diffusion barriers. Recent studies in cultured cells in vitro indicate that a septin complex of septin 2, 7 and 9 is required for ciliogenesis and cilia function, but septin function in ciliogenesis in vertebrate organs in vivo is not understood. We show that sept7b is expressed in ciliated cells in different tissues during early zebrafish development. Knockdown of sept7b by using morpholino antisense oligonucleotides caused misorientation of basal bodies and cilia, reduction of apical actin and the shortening of motile cilia in Kupffer's vesicle and pronephric tubules. This resulted in pericardial and yolk sac edema, body axis curvature and hydrocephaly. Notably, in sept7b morphants we detected strong left-right asymmetry defects in the heart and lateral plate mesoderm (situs inversus), reduced fluid flow in the kidney, the formation of kidney cysts and loss of glomerular filtration barrier function. Thus, sept7b is essential during zebrafish development for pronephric function and ciliogenesis, and loss of expression of sept7b results in defects that resemble human ciliopathies.
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Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E.; Dagnino, Lina
2012-01-01
Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function. PMID:22574216
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Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E; Dagnino, Lina
2012-01-01
Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.
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Batarseh, Yazan S; Bharate, Sonali S; Kumar, Vikas; Kumar, Ajay; Vishwakarma, Ram A; Bharate, Sandip B; Kaddoumi, Amal
2017-08-16
Crocus sativus, commonly known as saffron or Kesar, is used in Ayurveda and other folk medicines for various purposes as an aphrodisiac, antispasmodic, and expectorant. Previous evidence suggested that Crocus sativus is linked to improving cognitive function in Alzheimer's disease (AD) patients. The aim of this study was to in vitro and in vivo investigate the mechanism(s) by which Crocus sativus exerts its positive effect against AD. The effect of Crocus sativus extract on Aβ load and related toxicity was evaluated. In vitro results showed that Crocus sativus extract increases the tightness of a cell-based blood-brain barrier (BBB) model and enhances transport of Aβ. Further in vivo studies confirmed the effect of Crocus sativus extract (50 mg/kg/day, added to mice diet) on the BBB tightness and function that was associated with reduced Aβ load and related pathological changes in 5XFAD mice used as an AD model. Reduced Aβ load could be explained, at least in part, by Crocus sativus extract effect to enhance Aβ clearance pathways including BBB clearance, enzymatic degradation and ApoE clearance pathway. Furthermore, Crocus sativus extract upregulated synaptic proteins and reduced neuroinflammation associated with Aβ pathology in the brains of 5XFAD mice. Crocin, a major active constituent of Crocus sativus and known for its antioxidant and anti-inflammatory effect, was also tested separately in vivo in 5XFAD mice. Crocin (10 mg/kg/day) was able to reduce Aβ load but to a lesser extent when compared to Crocus sativus extract. Collectively, findings from this study support the positive effect of Crocus sativus against AD by reducing Aβ pathological manifestations.
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Design and performance evaluation of a 1000-year evapotranspiration-capillary surface barrier.
Zhang, Zhuanfang Fred; Strickland, Christopher E; Link, Steven O
2017-02-01
Surface barrier technology is used to isolate radioactive waste and to reduce or eliminate recharge water to the waste zone for 1000 years or longer. However, the design and evaluation of such a barrier is challenging because of the extremely long design life. After establishing a set of design and performance objectives, a package of design solutions was developed for 1000-year surface barriers over nuclear waste sites. The Prototype Hanford Barrier (PHB) was then constructed in 1994 in the field over an existing waste site as a demonstration. The barrier was tested to evaluate surface-barrier design and performance at the field scale under conditions of enhanced and natural precipitation and of no vegetation. The monitoring data demonstrate that the barrier satisfied nearly all objectives in the past two decades. The PHB far exceeded the Resource Conservation and Recovery Act criteria, functioned in Hanford's semiarid climate, limited drainage to well below the 0.5 mm yr -1 performance criterion, limited runoff, and minimized erosion and bio-intrusion. Given the two-decade record of successful performance and consideration of the processes and mechanisms that could affect barrier stability and hydrology in the future, the results suggest the PHB is very likely to perform for its 1000-year design life. This conclusion is based on two assumptions: (1) the exposed subgrade receives protection against erosion and (2) institutional controls prevent inadvertent human activity at the barrier. The PHB design can serve as the basis for site-specific barriers over waste sites containing underground nuclear waste, uranium mine tailings, and hazardous mine waste. Copyright © 2016 Elsevier Ltd. All rights reserved.
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The rate of the reaction between CN and C2H2 at interstellar temperatures.
Woon, D E; Herbst, E
1997-03-01
The rate coefficient for the important interstellar reaction between CN and C2H2 has been calculated as a function of temperature between 10 and 300 K. The potential surface for this reaction has been determined through ab initio quantum chemical techniques; the potential exhibits no barrier in the entrance channel but does show a small exit channel barrier, which lies below the energy of reactants. Phase-space calculations for the reaction dynamics, which take the exit channel barrier into account, show the same unusual temperature dependence as determined by experiment, in which the rate coefficient at first increases as the temperature is reduced below room temperature and then starts to decrease as the temperature drops below 50-100 K. The agreement between theory and experiment provides strong confirmation that the reaction occurs appreciably at cool interstellar temperatures.
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NASA Astrophysics Data System (ADS)
Cho, Hongseok; Lee, Hwa-Youn; Han, Mun; Choi, Jong-Ryul; Ahn, Sanghyun; Lee, Taekwan; Chang, Yongmin; Park, Juyoung
2016-08-01
Multi-drug resistant efflux transporters found in Blood-Brain Barrier (BBB) acts as a functional barrier, by pumping out most of the drugs into the blood. Previous studies showed focused ultrasound (FUS) induced microbubble oscillation can disrupt the BBB by loosening the tight junctions in the brain endothelial cells; however, no study was performed to investigate its impact on the functional barrier of the BBB. In this study, the BBB in rat brains were disrupted using the MRI guided FUS and microbubbles. The immunofluorescence study evaluated the expression of the P-glycoprotein (P-gp), the most dominant multi-drug resistant protein found in the BBB. Intensity of the P-gp expression at the BBB disruption (BBBD) regions was significantly reduced (63.2 ± 18.4%) compared to the control area. The magnitude of the BBBD and the level of the P-gp down-regulation were significantly correlated. Both the immunofluorescence and histologic analysis at the BBBD regions revealed no apparent damage in the brain endothelial cells. The results demonstrate that the FUS and microbubbles can induce a localized down-regulation of P-gp expression in rat brain. The study suggests a clinically translation of this method to treat neural diseases through targeted delivery of the wide ranges of brain disorder related drugs.
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Surface pre-treatment for barrier coatings on polyethylene terephthalate
NASA Astrophysics Data System (ADS)
Bahre, H.; Bahroun, K.; Behm, H.; Steves, S.; Awakowicz, P.; Böke, M.; Hopmann, Ch; Winter, J.
2013-02-01
Polymers have favourable properties such as light weight, flexibility and transparency. Consequently, this makes them suitable for food packaging, organic light-emitting diodes and flexible solar cells. Nonetheless, raw plastics do not possess sufficient barrier functionality against oxygen and water vapour, which is of paramount importance for most applications. A widespread solution is to deposit thin silicon oxide layers using plasma processes. However, silicon oxide layers do not always fulfil the requirements concerning adhesion and barrier performance when deposited on films. Thus, plasma pre-treatment is often necessary. To analyse the influence of a plasma-based pre-treatment on barrier performance, different plasma pre-treatments on three reactor setups were applied to a very smooth polyethylene terephthalate film before depositing a silicon oxide barrier layer. In this paper, the influence of oxygen and argon plasma pre-treatments towards the barrier performance is discussed examining the chemical and topological change of the film. It was observed that a short one-to-ten-second plasma treatment can reduce the oxygen transmission rate by a factor of five. The surface chemistry and the surface topography change significantly for these short treatment times, leading to an increased surface energy. The surface roughness rises slowly due to the development of small spots in the nanometre range. For very long treatment times, surface roughness of the order of the barrier layer's thickness results in a complete loss of barrier properties. During plasma pre-treatment, the trade-off between surface activation and roughening of the surface has to be carefully considered.
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Li, Fengxue; Xu, Dingguo
2015-08-01
Hyaluronan lyase from Streptococcus pneumoniae can degrade hyaluronic acid, which is one of the major components in the extracellular matrix. Hyaluronan can regulate water balance, osmotic pressure, and act as an ion exchange resin. Followed by our recent work on the catalytic reaction mechanism and substrate binding mode, we in this work further investigate the functional role of active site arginine residue, R462, in the degradation of hyaluronan. The site directed mutagenesis simulation of R462A and R462Q were modeled using a combined quantum mechanical and molecular mechanical method. The overall substrate binding features upon mutations do not have significant changes. The energetic profiles for the reaction processes are essentially the same as that in wild type enzyme, but significant activation barrier height changes can be observed. Both mutants were shown to accelerate the overall enzymatic activity, e.g., R462A can reduce the barrier height by about 2.8 kcal mol(-1), while R462Q reduces the activation energy by about 2.9 kcal mol(-1). Consistent with the active site model calculated using density functional theory, our results can support that the positive charge on R462 guanidino side chain group plays a negative role in the catalysis. Finally, the functional role of R462 was proposed to facilitate the formation of initial enzyme-substrate complex, but not in the subsequent catalytic degradation reaction. Graphical Abstract Degradation of hyaluronan catalyzed by hyaluronate lyase from Streptococcus pneumoniae.
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Haag, S F; Tscherch, K; Arndt, S; Kleemann, A; Gersonde, I; Lademann, J; Rohn, S; Meinke, M C
2014-02-01
Hyperforin is well-known for its anti-inflammatory, anti-tumor, anti-bacterial, and antioxidant properties. The application of a hyperforin-rich verum cream could strengthen the skin barrier function by reducing radical formation and stabilizing stratum corneum lipids. Here, it was investigated whether topical treatment with a hyperforin-rich cream increases the radical protection of the skin during VIS/NIR irradiation. Skin lipid profile was investigated applying HPTLC on skin lipid extracts. Furthermore, the absorption- and scattering coefficients, which influence radical formation, were determined. 11 volunteers were included in this study. After a single cream application, VIS/NIR-induced radical formation could be completely inhibited by both verum and placebo showing an immediate protection. After an application period of 4weeks, radical formation could be significantly reduced by 45% following placebo application and 78% after verum application showing a long-term protection. Furthermore, the skin lipids in both verum and placebo groups increased directly after a single cream application but only significantly for ceramide [AP], [NP1], and squalene. After long-term cream application, concentration of cholesterol and the ceramides increased, but no significance was observed. These results indicate that regular application of the hyperforin-rich cream can reduce radical formation and can stabilize skin lipids, which are responsible for the barrier function. Copyright © 2013 Elsevier B.V. All rights reserved.
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The impact of aging on epithelial barriers.
Parrish, Alan R
2017-10-02
The epithelium has many critical roles in homeostasis, including an essential responsibility in establishing tissue barriers. In addition to the fundamental role in separating internal from external environment, epithelial barriers maintain nutrient, fluid, electrolyte and metabolic waste balance in multiple organs. While, by definition, barrier function is conserved, the structure of the epithelium varies across organs. For example, the skin barrier is a squamous layer of cells with distinct structural features, while the lung barrier is composed of a very thin single cell to minimize diffusion space. With the increased focus on age-dependent alterations in organ structure and function, there is an emerging interest in the impact of age on epithelial barriers. This review will focus on the impact of aging on the epithelial barrier of several organs, including the skin, lung, gastrointestinal tract and the kidney, at a structural and functional level.
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NASA Astrophysics Data System (ADS)
O'Rourke, Conn; Morgan, Benjamin J.
2018-04-01
The (Li,Al)-codoped magnesium spinel (LixMg1 -2 xAl2 +xO4 ) is a solid lithium-ion electrolyte with potential use in all-solid-state lithium-ion batteries. The spinel structure means that interfaces with spinel electrodes, such as LiyMn2O4 and Li4 +3 zTi5O12 , may be lattice matched, with potentially low interfacial resistances. Small lattice parameter differences across a lattice-matched interface are unavoidable, causing residual epitaxial strain. This strain potentially modifies lithium diffusion near the electrolyte-electrode interface, contributing to interfacial resistance. Here, we report a density functional theory study of strain effects on lithium diffusion pathways for (Li,Al)-codoped magnesium spinel, for xLi=0.25 and xLi=0.5 . We have calculated diffusion profiles for the unstrained materials, and for isotropic and biaxial tensile strains of up to 6 % , corresponding to {100 } epitaxial interfaces with LiyMn2O4 and Li4 +3 zTi5O12 . We find that isotropic tensile strain reduces lithium diffusion barriers by as much as 0.32 eV , with typical barriers reduced by ˜0.1 eV. This effect is associated with increased volumes of transitional octahedral sites, and broadly follows qualitative changes in local electrostatic potentials. For biaxial (epitaxial) strain, which more closely approximates strain at a lattice-matched electrolyte-electrode interface, changes in octahedral site volumes and in lithium diffusion barriers are much smaller than under isotropic strain. Typical barriers are reduced by only ˜0.05 eV. Individual effects, however, depend on the pathway considered and the relative strain orientation. These results predict that isotropic strain strongly affects ionic conductivities in (Li,Al)-codoped magnesium spinel electrolytes, and that tensile strain is a potential route to enhanced lithium transport. For a lattice-matched interface with candidate spinel-structured electrodes, however, epitaxial strain has a small, but complex, effect on lithium diffusion barriers.
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Hirotani, Yoshihiko; Ikeda, Kenji; Kato, Ryuji; Myotoku, Michiaki; Umeda, Takashi; Ijiri, Yoshio; Tanaka, Kazuhiko
2008-09-01
Indirect evidence suggests that lactoferrin (Lf), a major iron-binding protein in human milk, induces enterocyte growth and proliferation, depending on its concentration and affects the function and permeability of the intestinal mucosa. The bacterial endotoxin (lipopolysaccharide, LPS) is known to cause mucosal hyperpermeability in vivo. However, protective effects of Lf against LPS-mediated intestinal mucosal damage and barrier function in epithelial cells are not yet fully clarified. The aim of this study was to investigate whether Lf can reduce the cellular injury and alter epithelial hyperpermeability caused by LPS in human intestinal Caco-2 cells. When cell viability was measured by a WST-1 assay (tetrazolium salt-based assay), the protective effects against LPS-induced damage to Caco-2 cells were observed at doses of 800 and 1000 microg/ml Lf. The barrier function of Caco-2 monolayer tight junctions was assessed by measuring transepithelial electrical resistance (TEER) and permeability of FITC-labeled dextran 4000 (FD-4). The treatment of Caco-2 cells with Lf at doses of 400 and 1000 microg/ml significantly increased TEER as compared to treatment with LPS alone for 2 h (p<0.05). Further, at doses of 400 and 1000 microg/ml, Lf inhibited the enhancement of LPS-mediated permeability in Caco-2 cell monolayer. The results of this study suggest that Lf may have protective effects against LPS-mediated intestinal mucosal damage and impairment of barrier function in intestinal epithelial cells.
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The efficacy of activated protein C in murine endotoxemia is dependent on integrin CD11b
Cao, Chunzhang; Gao, Yamei; Li, Yang; Antalis, Toni M.; Castellino, Francis J.; Zhang, Li
2010-01-01
Activated protein C (APC), the only FDA-approved biotherapeutic drug for sepsis, possesses anticoagulant, antiinflammatory, and barrier-protective activities. However, the mechanisms underlying its antiinflammatory functions are not well defined. Here, we report that the antiinflammatory activity of APC on macrophages is dependent on integrin CD11b/CD18, but not on endothelial protein C receptor (EPCR). We showed that CD11b/CD18 bound APC within specialized membrane microdomains/lipid rafts and facilitated APC cleavage and activation of protease-activated receptor–1 (PAR1), leading to enhanced production of sphingosine-1-phosphate (S1P) and suppression of the proinflammatory response of activated macrophages. Deletion of the γ-carboxyglutamic acid domain of APC, a region critical for its anticoagulant activity and EPCR-dependent barrier protection, had no effect on its antiinflammatory function. Genetic inactivation of CD11b, PAR1, or sphingosine kinase–1, but not EPCR, abolished the ability of APC to suppress the macrophage inflammatory response in vitro. Using an LPS-induced mouse model of lethal endotoxemia, we showed that APC administration reduced the mortality of wild-type mice, but not CD11b-deficient mice. These data establish what we believe to be a novel mechanism underlying the antiinflammatory activity of APC in the setting of endotoxemia and provide clear evidence that the antiinflammatory function of APC is distinct from its barrier-protective function and anticoagulant activities. PMID:20458145
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Chiral tunneling in gated inversion symmetric Weyl semimetal.
Bai, Chunxu; Yang, Yanling; Chang, Kai
2016-02-18
Based on the chirality-resolved transfer-matrix method, we evaluate the chiral transport tunneling through Weyl semimetal multi-barrier structures created by periodic gates. It is shown that, in sharp contrast to the cases of three dimensional normal semimetals, the tunneling coefficient as a function of incident angle shows a strong anisotropic behavior. Importantly, the tunneling coefficients display an interesting periodic oscillation as a function of the crystallographic angle of the structures. With the increasement of the barriers, the tunneling current shows a Fabry-Perot type interferences. For superlattice structures, the fancy miniband effect has been revealed. Our results show that the angular dependence of the first bandgap can be reduced into a Lorentz formula. The disorder suppresses the oscillation of the tunneling conductance, but would not affect its average amplitude. This is in sharp contrast to that in multi-barrier conventional semiconductor structures. Moreover, numerical results for the dependence of the angularly averaged conductance on the incident energy and the structure parameters are presented and contrasted with those in two dimensional relativistic materials. Our work suggests that the gated Weyl semimetal opens a possible new route to access to new type nanoelectronic device.
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Satoh, T; Izumi, H; Iwabuchi, N; Odamaki, T; Namba, K; Abe, F; Xiao, J Z
2016-02-01
Necrotising enterocolitis (NEC) is associated with inflammatory responses and barrier dysfunction in the gut. In this study, we investigated the effect of Bifidobacterium breve M-16V on factors related to NEC development using an experimental rat model. Caesarean-sectioned rats were given formula milk with or without B. breve M-16V by oral gavage thrice daily, and experimental NEC was induced by exposing the rats to hypoxic conditions. Naturally delivered rats that were reared by their mother were used as healthy controls. The pathological score of NEC and the expression of molecules related to inflammatory responses and the barrier function were assessed in the ileum. B. breve M-16V reduced the pathological scores of NEC and resulted in some improvement in survivability. B. breve M-16V suppressed the increased expression of molecules related to inflammation and barrier function that resulted from NEC induction. B. breve M-16V normalised Toll-like receptor (TRL)4 expression and enhanced TLR2 expression. Our data suggest that B. breve M-16V prevents NEC development by modulating TLR expressions and suppressing inflammatory responses in a rat model.
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Chiral tunneling in gated inversion symmetric Weyl semimetal
Bai, Chunxu; Yang, Yanling; Chang, Kai
2016-01-01
Based on the chirality-resolved transfer-matrix method, we evaluate the chiral transport tunneling through Weyl semimetal multi-barrier structures created by periodic gates. It is shown that, in sharp contrast to the cases of three dimensional normal semimetals, the tunneling coefficient as a function of incident angle shows a strong anisotropic behavior. Importantly, the tunneling coefficients display an interesting periodic oscillation as a function of the crystallographic angle of the structures. With the increasement of the barriers, the tunneling current shows a Fabry-Perot type interferences. For superlattice structures, the fancy miniband effect has been revealed. Our results show that the angular dependence of the first bandgap can be reduced into a Lorentz formula. The disorder suppresses the oscillation of the tunneling conductance, but would not affect its average amplitude. This is in sharp contrast to that in multi-barrier conventional semiconductor structures. Moreover, numerical results for the dependence of the angularly averaged conductance on the incident energy and the structure parameters are presented and contrasted with those in two dimensional relativistic materials. Our work suggests that the gated Weyl semimetal opens a possible new route to access to new type nanoelectronic device. PMID:26888491
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Gao, Jin-Hang; Wen, Shi-Lei; Tong, Huan; Wang, Chun-Hui; Yang, Wen-Juan; Tang, Shi-Hang; Yan, Zhao-Ping; Tai, Yang; Ye, Cheng; Liu, Rui; Huang, Zhi-Yin; Tang, Ying-Mei; Yang, Jin-Hui; Tang, Cheng-Wei
2016-06-01
Inflammatory transport through the gut-liver axis may facilitate liver cirrhosis. Cyclooxygenase-2 (COX-2) has been considered as one of the important molecules that regulates intestinal epithelial barrier function. This study was aimed to test the hypothesis that inhibition of COX-2 by celecoxib might alleviate liver cirrhosis via reduction of intestinal inflammatory transport in thiacetamide (TAA) rat model. COX-2/prostaglandin E2 (PGE2)/EP-2/p-ERK integrated signal pathways regulated the expressions of intestinal zonula occludens-1 (ZO-1) and E-cadherin, which maintain the function of intestinal epithelial barrier. Celecoxib not only decreased the intestinal permeability to a 4-kDa FITC-dextran but also significantly increased expressions of ZO-1 and E-cadherin. When celecoxib greatly decreased intestinal levels of LPS, TNF-α, and IL-6, it significantly enhanced T cell subsets reduced by TAA. As a result, liver fibrosis induced by TAA was significantly alleviated in the celecoxib group. These data indicated that celecoxib improved the integrity of intestinal epithelial barrier, blocked inflammatory transport through the dysfunctional gut-liver axis, and ameliorated the progress of liver cirrhosis. Copyright © 2016 the American Physiological Society.
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Gelatin tannate and tyndallized probiotics: a novel approach for treatment of diarrhea.
Lopetuso, L; Graziani, C; Guarino, A; Lamborghini, A; Masi, S; Stanghellini, V
2017-02-01
Intestinal permeability impairment is implicated in many gastrointestinal (GI) diseases. Chronic diarrhea, defined as the presence of diarrhea for more than 3 weeks in adults and 2 weeks in children, requires a different diagnostic and therapeutic work-up than acute diarrhea. Gelatin tannate, by reducing the clinical activity of acute colitis and the proinflammatory effects of lipopolysaccharide (LPS), is emerging as a mucosal barrier protector. New therapeutic strategies focusing on the physiological function of the intestinal barrier, may offer an innovative approach for the clinical improvement of highly debilitating chronic GI diseases. We review the available data on the role of gelatin tannate and tyndallized probiotics in the treatment of diarrhea. Gelatin tannate and tyndallized probiotics can be used to re-establish the physiological functions of the gut barrier, as well as for preventing dysbiosis. There is evidence that due to their particular properties, gelatin tannate and tyndallized probiotics are highly effective in the treatment of acute gastroenteritis and may be especially indicated in the management of moderate and prolonged diarrhea. Gelatin tannate and tyndallized probiotics may be effective in the management of chronic diarrhea. Further clinical trials are necessary to further explore their effects in clinical practice.
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Argüeso, Pablo; Guzman-Aranguez, Ana; Mantelli, Flavio; Cao, Zhiyi; Ricciuto, Jessica; Panjwani, Noorjahan
2009-01-01
Maintenance of an intact mucosal barrier is critical to preventing damage to and infection of wet-surfaced epithelia. The mechanism of defense has been the subject of much investigation, and there is evidence now implicating O-glycosylated mucins on the epithelial cell surface. Here we investigate a new role for the carbohydrate-binding protein galectin-3 in stabilizing mucosal barriers through its interaction with mucins on the apical glycocalyx. Using the surface of the eye as a model system, we found that galectin-3 colocalized with two distinct membrane-associated mucins, MUC1 and MUC16, on the apical surface of epithelial cells and that both mucins bound to galectin-3 affinity columns in a galactose-dependent manner. Abrogation of the mucin-galectin interaction in four different mucosal epithelial cell types using competitive carbohydrate inhibitors of galectin binding, β-lactose and modified citrus pectin, resulted in decreased levels of galectin-3 on the cell surface with concomitant loss of barrier function, as indicated by increased permeability to rose bengal diagnostic dye. Similarly, down-regulation of mucin O-glycosylation using a stable tetracycline-inducible RNA interfering system to knockdown c1galt1 (T-synthase), a critical galactosyltransferase required for the synthesis of core 1 O-glycans, resulted in decreased cell surface O-glycosylation, reduced cell surface galectin-3, and increased epithelial permeability. Taken together, these results suggest that galectin-3 plays a key role in maintaining mucosal barrier function through carbohydrate-dependent interactions with cell surface mucins. PMID:19556244
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NASA Technical Reports Server (NTRS)
Dellacorte, Christhopher; Steinetz, Bruce M.; Brindley, Pamela K.
1990-01-01
Tribological properties of Ti3Al-Nb intermetallic disks sliding against alumina-boria-silicate fabric were ascertained in air at temperatures from 25 to 700 C. These materials are candidates for sliding seal applications for the National AeroSpace Plane. The tests were done using a pin on disk tribometer. Sliding was unidirectional at 0.27 m/sec under a nominal contact stress of 340 kPa. Gold sputter or ion plating deposited films were used to reduce friction and wear. Rhodium and palladium films were used beneath the gold lubricating films to prevent diffusion of the substrate into the gold at high temperature. The friction and wear of the unlubricated specimens was unacceptable. Friction coefficients were generally greater than 1.0. The ion plated gold films, when used with a rhodium diffusion barrier reduced friction by almost a factor of 2. Wear was also substantially reduced. The sputter deposited films were not adherent unless the substrate was sputter cleaned immediately prior to film deposition. Palladium did not function as a diffusion barrier.
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NASA Technical Reports Server (NTRS)
Dellacorte, Christopher; Steinetz, Bruce M.; Brindley, Pamela K.
1989-01-01
Tribological properties of Ti3Al-Nb intermetallic disks sliding against alumina-boria-silicate fabric were ascertained in air at temperatures from 25 to 700 C. These materials are candidates for sliding seal applications for the National AeroSpace Plane. The tests were done using a pin on disk tribometer. Sliding was unidirectional at 0.27 m/sec under a nominal contact stress of 340 kPa. Gold sputter or ion plating deposited films were used to reduce friction and wear. Rhodium and palladium films were used beneath the gold lubricating films to prevent diffusion of the substrate into the gold at high temperature. The friction and wear of the unlubricated specimens was unacceptable. Friction coefficients were generally greater than 1.0. The ion plated gold films, when used with a rhodium diffusion barrier reduced friction by almost a factor of 2. Wear was also substantially reduced. The sputter deposited films were not adherent unless the substrate was sputter cleaned immediately prior to film deposition. Palladium did not function as a diffusion barrier.
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Homoclinic orbits and critical points of barrier functions
NASA Astrophysics Data System (ADS)
Cannarsa, Piermarco; Cheng, Wei
2015-06-01
We interpret the close link between the critical points of Mather's barrier functions and minimal homoclinic orbits with respect to the Aubry sets on {{T}}n . We also prove a critical point theorem for barrier functions and the existence of such homoclinic orbits on {{T}}2 as an application.
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Chen, Tingting; Kim, Choon Young; Kaur, Amandeep; Lamothe, Lisa; Shaikh, Maliha; Keshavarzian, Ali; Hamaker, Bruce R
2017-03-22
Impaired gut barrier function plays an important role in the development of many diseases such as obesity, inflammatory bowel disease, and in HIV infection. Dietary fibres have been shown to improve intestinal barrier function through their fermentation products, short chain fatty acids (SCFAs), and the effects of individual SCFAs have been studied. Here, different SCFA mixtures representing possible compositions from fibre fermentation products were studied for protective and reparative effects on intestinal barrier function. The effect of fermentation products from four dietary fibres, i.e. resistant starch, fructooligosaccharides, and sorghum and corn arabinoxylan (varying in their branched structure) on barrier function was positively correlated with their SCFA concentration. Pure SCFA mixtures of various concentrations and compositions were tested using a Caco-2 cell model. SCFAs at a moderate concentration (40-80 mM) improved barrier function without causing damage to the monolayer. In a 40 mM SCFA mixture, the butyrate proportion at 20% and 50% showed both a protective and a reparative effect on the monolayer to disrupting agents (LPS/TNF-α) applied simultaneously or prior to the SCFA mixtures. Relating this result to dietary fibre selection, slow fermenting fibres that deliver appropriate concentrations of SCFAs to the epithelium with a high proportion of butyrate may improve barrier function.
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Could tight junctions regulate the barrier function of the aged skin?
Svoboda, Marek; Bílková, Zuzana; Muthný, Tomáš
2016-03-01
The skin is known to be the largest organ in human organism creating interface with outer environment. The skin provides protective barrier against pathogens, physical and chemical insults, and against uncontrolled loss of water. The barrier function was primarily attributed to the stratum corneum (SC) but recent studies confirmed that epidermal tight junctions (TJs) also play important role in maintaining barrier properties of the skin. Independent observations indicate that barrier function and its recovery is impaired in aged skin. However, trans-epidermal water loss (TEWL) values remains rather unchanged in elderly population. UV radiation as major factor of photoageing impairs TJ proteins, but TJs have great self-regenerative potential. Since it may be possible that TJs can compensate TEWL in elderly due to its regenerative and compensatory capabilities, important question remains to be answered: how are TJs regulated during skin ageing? This review provides an insight into TJs functioning as epidermal barrier and summarizes current knowledge about the impact of ageing on the barrier function of the skin and epidermal TJs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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Reducing Barriers To The Use of High-Efficiency Lighting Systems
DOE Office of Scientific and Technical Information (OSTI.GOV)
Peter Morante
2005-12-31
With funding from the U.S. Department of Energy (DOE), the Lighting Research Center (LRC) at Rensselaer Polytechnic Institute completed the four-year research project, Reducing Barriers to the Use of High-Efficiency Lighting Systems. The initial objectives were: (1) identifying barriers to widespread penetration of lighting controls in commercial/industrial (C/I) applications that employ fluorescent lamp technologies, and (2) making recommendations to overcome these barriers. The addition of a fourth year expanded the original project objectives to include an examination of the impact on fluorescent lamps from dimming utilizing different lamp electrode heating and dimming ratios. The scope of the project was narrowedmore » to identify barriers to the penetration of lighting controls into commercial-industrial (C/I) applications that employ fluorescent lamp technologies, and to recommend means for overcoming these barriers. Working with lighting manufacturers, specifiers, and installers, the project identified technological and marketing barriers to the widespread use of lighting controls, specifically automatic-off controls, occupancy sensors, photosensors, dimming systems, communication protocols and load-shedding ballasts. The primary barriers identified include cost effectiveness of lighting controls to the building owner, lack of standard communication protocols to allow different part of the control system to communicate effectively, and installation and commissioning issues. Overcoming the identified barriers requires lighting control products on the market to achieve three main goals: (1) Achieve sufficient functionality to meet the key requirements of their main market. (2) Allow significant cost reduction compared to current market standard systems. Cost should consider: hardware capital cost including wiring, design time required by the specifier and the control system manufacturer, installation time required by the electrician, and commissioning time and remedial time required by the electrician and end user. (3) Minimize ongoing perceived overhead costs and inconvenience to the end user, or in other words, systems should be simple to understand and use. In addition, we believe that no lighting controls solution is effective or acceptable unless it contributes to, or does not compromise, the following goals: (1) Productivity--Planning, installation, commissioning, maintenance, and use of controls should not decrease business productivity; (2) Energy savings--Lighting controls should save significant amounts of energy and money in relation to the expense involved in using them (acceptable payback period); and/or (3) Reduced power demand--Society as a whole should benefit from the lowered demand for expensive power and for more natural resources. Discussions of technology barriers and developments are insufficient by themselves to achieve higher penetration of lighting controls in the market place. Technology transfer efforts must play a key role in gaining market acceptance. The LRC developed a technology transfer model to better understand what actions are required and by whom to move any technology toward full market acceptance.« less
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Goodrich, Katheryn M; Fundaro, Gabrielle; Griffin, Laura E; Grant, Ar'quette; Hulver, Matthew W; Ponder, Monica A; Neilson, Andrew P
2012-10-01
Animal studies have demonstrated the potential of grape seed extract (GSE) to prevent metabolic syndrome, obesity, and type 2 diabetes. Recently, metabolic endotoxemia induced by bacterial endotoxins produced in the colon has emerged as a possible factor in the etiology of metabolic syndrome. Improving colonic barrier function may control endotoxemia by reducing endotoxin uptake. However, the impact of GSE on colonic barrier integrity and endotoxin uptake has not been evaluated. We performed a secondary analysis of samples collected from a chronic GSE feeding study with pharmacokinetic end points to examine potential modulation of biomarkers of colonic integrity and endotoxin uptake. We hypothesized that a secondary analysis would indicate that chronic GSE administration increases colonic expression of intestinal tight junction proteins and reduces circulating endotoxin levels, even in the absence of an obesity-promoting stimulus. Wistar Furth rats were administered drinking water containing 0.1% GSE for 21 days. Grape seed extract significantly increased the expression of gut junction protein occludin in the proximal colon and reduced fecal levels of the neutrophil protein calprotectin, compared with control. Grape seed extract did not significantly reduce serum or fecal endotoxin levels compared with control, although the variability in serum levels was widely increased by GSE. These data suggest that the improvement of gut barrier integrity and potential modulation of endotoxemia warrant investigation as a possible mechanism by which GSE prevents metabolic syndrome and associated diseases. Further investigation of this mechanism in high-fat feeding metabolic syndrome and obesity models is therefore justified. Copyright © 2012 Elsevier Inc. All rights reserved.
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Parikh, Ishita; Guo, Janet; Chuang, Kai-Hsiang; Zhong, Yu; Rempe, Ralf G; Hoffman, Jared D; Armstrong, Rachel; Bauer, Björn; Hartz, Anika M S; Lin, Ai-Ling
2016-11-08
Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of rapamycin expression, elevated endothelial nitric oxide synthase signaling, and increased ketone bodies utilization. With age, CR decelerated the rate of decline in CBF. The preserved CBF in hippocampus and frontal cortex were highly correlated with preserved memory and learning, and reduced anxiety, of the aging mice treated with CR (18-20 months of age). Our results suggest that dietary intervention started in the early stage (e.g., young adults) may benefit cognitive and mental reserve in aging. Understanding nutritional effects on neurovascular functions may have profound implications in human brain aging and age-related neurodegenerative disorders.
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Barriers and strategies for taking medicines in adult patients with renal transplantation.
Cedillo-Galindo, H; Gracida, C
2011-11-01
Adherence to the immunosuppressant medications is important for the proper function a renal graft, but there are factors that make this difficult. This study describes strategies and barriers to adequate intake of these medicines based upon 177 surveys in renal transplant patients. Medication adherence was reported to be high (84%), but there were barriers to taking medications (64.95%): the most common were that the pharmacy did not work medicines (28.81%), changes in medication or dose (24.29%), failure to remember (9.6%), and lack of time (6.78%). The most common strategies for taking medications were: the use of cell phone alarms (15.25%) or alarm clocks (9.04%), schedules (5.65%), drug-related meals (5.08%), drug use book (2.26%), and visibility on the table (2.26%). Proper understanding of the barriers to medication adherence and strategies used by recipients may help physicians more adequately educate patients, thereby reducing the risk of rejection related to nonadherence and suggest, specific interventions for improvement. Copyright © 2011 Elsevier Inc. All rights reserved.
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An Electromagnetic/Capacitive Composite Sensor for Testing of Thermal Barrier Coatings
Ren, Yuan; Pan, Mengchun; Chen, Dixiang; Tian, Wugang
2018-01-01
Thermal barrier coatings (TBCs) can significantly reduce the operating temperature of the aeroengine turbine blade substrate, and their testing technology is very urgently demanded. Due to their complex multi-layer structure, it is hard to evaluate TBCs with a single function sensor. In this paper, an electromagnetic/capacitive composite sensor is proposed for the testing of thermal barrier coatings. The dielectric material is tested with planar capacitor, and the metallic material is tested with electromagnetic coils. Then, the comprehensive test and evaluation of thermal barrier coating system can be realized. The sensor is optimized by means of theoretical and simulation analysis, and the interaction between the planar capacitor and the electromagnetic coil is studied. The experimental system is built based on an impedance analyser and multiplex unit to evaluate the performance of the composite sensor. The transimpedances and capacitances are measured under different coating parameters, such as thickness and permittivity of top coating as well as bond layer conductivity. The experimental results agree with the simulation analysis, and the feasibility of the sensor is proved. PMID:29783746
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Thiolated silicone oils as adhesive skin protectants for improved barrier function.
Partenhauser, A; Zupančič, O; Rohrer, J; Bonengel, S; Bernkop-Schnürch, A
2016-06-01
The purpose of this study was the evaluation of thiolated silicone oil as novel skin protectant exhibiting prolonged residence time, enhanced barrier function and reinforced occlusivity. Two silicone conjugates were synthesized with mercaptopropionic acid (MPA) and thioglycolic acid (TGA) as thiol ligands. Adhesion, protection against artificial urine and water vapour permeability with both a Payne cup set-up and transepidermal water loss (TEWL) measurements on porcine skin were assessed. Silicone thiomers showed pronounced substantivity on skin with 22.1 ± 6.3% and 39.2 ± 6.7% remaining silicone after 8 h for silicone-TGA and silicone-MPA, respectively, whereas unmodified silicone oil and dimethicone were no longer detectable. In particular, silicone-MPA provided a protective shield against artificial urine penetration with less than 25% leakage within 6 h. An up to 2.5-fold improved water vapour impermeability for silicone-MPA in comparison with unmodified control was discovered with the Payne cup model. In addition, for silicone-MPA a reduced TEWL by two-thirds corresponding to non-thiolated control was determined for up to 8 h. Thiolation of silicone oil leads to enhanced skin adhesiveness and barrier function, which is a major advantage compared to commonly used silicones and might thus be a promising treatment modality for various topical applications. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.
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Pipkin, Mary; Eggers, Paul W; Larive, Brett; Rocco, Michael V; Stokes, John B; Suri, Rita S; Lockridge, Robert S
2010-09-01
We assessed perceived barriers and incentives to home hemodialysis and evaluated potential correlates with the duration of home hemodialysis training. Surveys were sent to the principal investigator and study coordinator for each clinical center in the Frequent Hemodialysis Network Nocturnal Trial. Baseline data were obtained on medical comorbidities, cognitive and physical functioning, sessions required for home hemodialysis training, and costs of home renovations. The most commonly perceived barriers included lack of patient motivation, unwillingness to change from in-center modality, and fear of self-cannulation. The most common incentives were greater scheduling flexibility and reduced travel time. The median costs for home renovations varied between $1191 and $4018. The mean number of home hemodialysis training sessions was 27.7 +/- 10.4 (11-59 days). Average training time was less for patients with experience in either self-care or both self-care and cannulation. The number of training sessions was unrelated to the score on the Modified Mini Mental Status or Trailmaking B tests or patient's education level. Training time also did not correlate with the SF-36 Physical Function subscale but did with the modified Charlson comorbidity score and older patient age. Lack of patient or family motivation and fear of the dialysis process are surmountable barriers for accepting home hemodialysis as a modality for renal replacement therapy. Formal education and scores on cognitive function tests are not predictors of training time.
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Homoepitaxial graphene tunnel barriers for spin transport
NASA Astrophysics Data System (ADS)
Friedman, Adam
Tunnel barriers are key elements for both charge-and spin-based electronics, offering devices with reduced power consumption and new paradigms for information processing. Such devices require mating dissimilar materials, raising issues of heteroepitaxy, interface stability, and electronic states that severely complicate fabrication and compromise performance. Graphene is the perfect tunnel barrier. It is an insulator out-of-plane, possesses a defect-free, linear habit, and is impervious to interdiffusion. Nonetheless, true tunneling between two stacked graphene layers is not possible in environmental conditions (magnetic field, temperature, etc.) usable for electronics applications. However, two stacked graphene layers can be decoupled using chemical functionalization. We demonstrate successful tunneling, charge, and spin transport with a fluorinated graphene tunnel barrier on a graphene channel. We show that while spin transport stops short of room temperature, spin polarization efficiency values are the highest of any graphene spin devices. We also demonstrate that hydrogenation of graphene can also be used to create a tunnel barrier. We begin with a four-layer stack of graphene and hydrogenate the top few layers to decouple them from the graphene transport channel beneath. We demonstrate successful tunneling by measuring non-linear IV curves and a weakly temperature dependent zero-bias resistance. We demonstrate lateral transport of spin currents in non-local spin-valve structures and determine spin lifetimes with the non-local Hanle effect to be commensurate with previous studies. The measured spin polarization efficiencies for hydrogenated graphene are higher than most oxide tunnel barriers on graphene, but not as high as with fluorinated graphene tunnel barriers. However, here we show that spin transport persists up to room temperature. Our results for the hydrogenated graphene tunnel barriers are compared with fluorinated tunnel barriers and we discuss the possibility that magnetic moments in the graphene tunnel barriers affect the spin transport of our devices.
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Li, Ming Xin; Liu, Jun Feng; Lu, Jian Da; Zhu, Ying; Kuang, Ding Wei; Xiang, Jian Bing; Sun, Peng; Wang, Wei; Xue, Jun; Gu, Yong; Hao, Chuan Ming
2016-12-01
The object of this study is to explore whether the plasmadiafiltration (PDF) is more effective in improving the intestinal mucosal barrier function by removing more key large molecular inflammatory mediators and then prolonging the survival time. Totally, 24 porcine sepsis models induced by cecal ligation and puncture (CLP) operation were randomly divided into three groups: PDF group, high-volume hemofiltration (HVHF) group, and control group, and received 8 h treatment, respectively. The expression of ZO-1 and occludin in intestinal mucosal epithelial cells were detected by immunohistochemistry, and apoptotic protein caspase-3-positive lymphocytes were signed in mesenteric lymph nodes by TUNEL staining. The hemodynamic parameters were measured by invasive cavity detection. The tumor necrosis factor alpha (TNFα) and high-mobility group protein 1 (HMGB1) were tested by ELISA method. And then, the survival curves with all-cause death were compared with three groups. PDF led to a superior reversal of sepsis-related hemodynamic impairment and serum biochemistry abnormalities and resulted in longer survival time compared with HVHF and control (p < 0.01). Definitive protection from excessive TNF-α and HMGB1 response were only achieved by PDF. A more regular distribution pattern of ZO-1 and occludin along the epithelium was found in PDF animals (p < 0.01). The presence of apoptotic lymphocytes was significantly reduced in the PDF animals (p < 0.01). PDF can effectively eliminate more pivotal inflammatory mediators of TNFα and HMGB1 and reduce the inflammation damage of the intestinal mucosal barrier and apoptosis of lymphocyte then improve the circulation function and prolong the survival time.
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Barrier island community change: What controls it?
NASA Astrophysics Data System (ADS)
Dows, B.; Young, D.; Zinnert, J.
2014-12-01
Conversion from grassland to woody dominated communities has been observed globally. In recent decades, this pattern has been observed in coastal communities along the mid-Atlantic U.S. In coastal environments, a suite of biotic and abiotic factors interact as filters to determine plant community structure and distribution. Microclimatic conditions: soil and air temperature, soil moisture and salinity, and light attenuation under grass cover were measured across a grassland-woody encroachment gradient on a Virginia barrier island; to identify the primary factors that mediate this change. Woody establishment was associated with moderately dense (2200 shoots/m2) grass cover, but reduced at high (> 6200 shoots/ m2) and low (< 1250 shoots/ m2) densities. Moderately dense grass cover reduced light attenuation (82.50 % reduction) to sufficiently reduce soil temperature thereby limiting soil moisture evaporation. However, high grass density reduced light attenuation (98.7 % reduction) enough to inhibit establishment of woody species; whereas low grass density attenuated much less light (48.7 % reduction) which allowed for greater soil moisture evaporation. Soil salinity was dynamic as rainfall, tidal inundation, and sea spray produce spatiotemporal variation throughout the barrier island landscape. The importance of light and temperature were compounded as they also indirectly affect soil salinity via their affects on soil moisture. Determining how these biotic and abiotic factors relate to sea level rise and climate change will improve understanding coastal community response as global changes proceed. Understanding how community shifts affect ecosystem function and their potential to affect adjacent systems will also improve predictive ability of coastal ecosystem responses.
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Montgomery, William; Liu, Li; Stensland, Michael D; Xue, Hai Bo; Treuer, Tamas; Ascher-Svanum, Haya
2013-01-01
Background This article describes the personal, societal, and economic burden attributable to schizophrenia in the People’s Republic of China and highlights the potential for effective outpatient treatment to reduce this burden given recent changes in the Chinese health care system. The importance of effective antipsychotic therapy in reducing the burden of schizophrenia is also examined. Methods Published research on the burden, disability, management, and economic costs of schizophrenia in the People’s Republic of China was examined in the context of the larger body of global research. Research written in English or Chinese and published before June 2012 was identified using PubMed, CNKI, and Wanfang Med database searches. The contribution of effective antipsychotic therapy in reducing the risk for relapse and hospitalization and improving patients’ functioning is described. Results Schizophrenia imposes a substantial burden on Chinese society, with indirect costs accounting for the majority of the total cost. Functional impairment is high, leading to lost wages and work impairment. In the People’s Republic of China, schizophrenia is the most common diagnosis among hospitalized psychiatric patients. Ongoing changes in the Chinese health care system may reduce some barriers to effective relapse prevention in schizophrenia and potentially reduce hospitalizations. The use of antipsychotics for acute episodes and maintenance treatment has been shown to decrease symptom severity and reduce the risk for relapse and hospitalization. However, discontinuing antipsychotic medication appears common and is a strong predictor of relapse. Cost-effectiveness research in the People’s Republic of China is needed to examine the potential gains from improved outpatient antipsychotic treatment. Conclusion Schizophrenia is a very costly mental illness in terms of personal, economic, and societal burden, both in the People’s Republic of China and globally. When treated effectively, patients tend to persist longer with antipsychotic treatment, have fewer costly relapses, and have improved functioning. Further research examining the long-term effects of reducing barriers to effective treatments on the societal burden of schizophrenia in the People’s Republic of China is needed. PMID:23983478
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Usability Testing of the BRANCH Smartphone App Designed to Reduce Harmful Drinking in Young Adults.
Milward, Joanna; Deluca, Paolo; Drummond, Colin; Watson, Rod; Dunne, Jacklyn; Kimergård, Andreas
2017-08-08
Electronic screening and brief intervention (eSBI) apps demonstrate potential to reduce harmful drinking. However, low user engagement rates with eSBI reduce overall effectiveness of interventions. As "Digital Natives," young adults have high expectations of app quality. Ensuring that the design, content, and functionality of an eSBI app are acceptable to young adults is an integral stage to the development process. The objective of this study was to identify usability barriers and enablers for an app, BRANCH, targeting harmful drinking in young adults. The BRANCH app contains a drinking diary, alcohol reduction goal setting functions, normative drinking feedback, and information on risks and advice for cutting down. The app includes a social feature personalized to motivate cutting down and to promote engagement with a point-based system for usage. Three focus groups were conducted with 20 users who had tested the app for 1 week. A detailed thematic analysis was undertaken. The first theme, "Functionality" referred to how users wanted an easy-to-use interface, with minimum required user-input. Poor functionality was considered a major usability barrier. The second theme, "Design" described how an aesthetic with minimum text, clearly distinguishable tabs and buttons and appealing infographics was integral to the level of usability. The final theme, "Content" described how participants wanted all aspects of the app to be automatically personalized to them, as well as providing them with opportunities to personalize the app themselves, with increased options for social connectivity. There are high demands for apps such as BRANCH that target skilled technology users including young adults. Key areas to optimize eSBI app development that emerged from testing BRANCH with representative users include high-quality functionality, appealing aesthetics, and improved personalization. ©Joanna Milward, Paolo Deluca, Colin Drummond, Rod Watson, Jacklyn Dunne, Andreas Kimergård. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 08.08.2017.
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Chen, Yueping; Zhang, Hao; Cheng, Yefei; Li, Yue; Wen, Chao; Zhou, Yanmin
2018-06-01
This study was conducted to investigate the protective effects of l-threonine (l-Thr) supplementation on growth performance, inflammatory responses and intestinal barrier function of young broilers challenged with lipopolysaccharide (LPS). A total of 144 1-d-old male chicks were allocated to one of three treatments: non-challenged broilers fed a basal diet (control group), LPS-challenged broilers fed a basal diet without l-Thr supplementation and LPS-challenged broilers fed a basal diet supplemented with 3·0 g/kg l-Thr. LPS challenge was performed intraperitoneally at 17, 19 and 21 d of age, whereas the control group received physiological saline injection. Compared with the control group, LPS challenge impaired growth performance of broilers, and l-Thr administration reversed LPS-induced increase in feed/gain ratio. LPS challenge elevated blood cell counts related to inflammation, and pro-inflammatory cytokine concentrations in serum (IL-1β and TNF-α), spleen (IL-1β and TNF-α) and intestinal mucosa (jejunal interferon-γ (IFN-γ) and ileal IL-1β). The concentrations of intestinal cytokines in LPS-challenged broilers were reduced by l-Thr supplementation. LPS administration increased circulating d-lactic acid concentration, whereas it reduced villus height, the ratio between villus height and crypt depth and goblet density in both jejunum and ileum. LPS-induced decreases in jejunal villus height, intestinal villus height:crypt depth ratio and ileal goblet cell density were reversed with l-Thr supplementation. Similarly, LPS-induced alterations in the intestinal mRNA abundances of genes related to intestinal inflammation and barrier function (jejunal toll-like receptor 4, IFN- γ and claudin-3, and ileal IL-1 β and zonula occludens-1) were normalised with l-Thr administration. It can be concluded that l-Thr supplementation could attenuate LPS-induced inflammatory responses and intestinal barrier damage of young broilers.
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Symmetry analysis of a model for the exercise of a barrier option
NASA Astrophysics Data System (ADS)
O'Hara, J. G.; Sophocleous, C.; Leach, P. G. L.
2013-09-01
A barrier option takes into account the possibility of an unacceptable change in the price of the underlying stock. Such a change could carry considerable financial loss. We examine one model based upon the Black-Scholes-Merton Equation and determine the functional forms of the barrier function and rebate function which are consistent with a solution of the underlying evolution partial differential equation using the Lie Theory of Extended Groups. The solution is consistent with the possibility of no rebate and the barrier function is very similar to one adopted on an heuristic basis.
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Sacral nerve stimulation enhances epithelial barrier of the rectum: results from a porcine model.
Meurette, G; Blanchard, C; Duchalais-Dassonneville, E; Coquenlorge, S; Aubert, P; Wong, M; Lehur, P-A; Neunlist, M
2012-03-01
The mechanism of action of sacral nerve stimulation (SNS) remains largely elusive. The aims of this study were to develop a clinically relevant animal model for percutaneous SNS and to describe its effect on the epithelial barrier of the rectum. Under general anesthesia and after percutaneous electrode placement for S3 nerve root stimulation, six pigs underwent unilateral stimulation and six bilateral stimulation. Animals were stimulated for 3 h using an external pulse generator (1-2.5 V; 14 Hz; 210 μs). Six animals underwent electrode implantation without stimulation and served as controls. Full-thickness rectal biopsies were performed prior to and after stimulation. Paracellular permeability was evaluated by measuring sulfonic acid flux across the rectal mucosa in Ussing chambers. Histological assessment of mucosal thickness, epithelial desquamation, and mucus expression were performed. Percutaneous stimulation resulted in successful anal contractions whose amplitude and uniformity was enhanced following bilateral compared with unilateral stimulation. In controls, paracellular permeability significantly increased during the stimulation period whereas it remained unchanged following unilateral stimulation. In contrast, permeability was significantly reduced by bilateral stimulation. This effect was associated with a concomitant reduction in mucosal thickness and a trend toward increased amount of mucus on surface epithelium compared with controls. The development of a porcine model of percutaneous SNS revealed the ability of neuromodulation to reinforce rectal epithelial barrier. Furthermore, our results suggest that SNS could be used for treatment of gastrointestinal pathologies with reduced rectal mucosal barrier functions. © 2012 Blackwell Publishing Ltd.
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Schottky barrier amorphous silicon solar cell with thin doped region adjacent metal Schottky barrier
Carlson, David E.; Wronski, Christopher R.
1979-01-01
A Schottky barrier amorphous silicon solar cell incorporating a thin highly doped p-type region of hydrogenated amorphous silicon disposed between a Schottky barrier high work function metal and the intrinsic region of hydrogenated amorphous silicon wherein said high work function metal and said thin highly doped p-type region forms a surface barrier junction with the intrinsic amorphous silicon layer. The thickness and concentration of p-type dopants in said p-type region are selected so that said p-type region is fully ionized by the Schottky barrier high work function metal. The thin highly doped p-type region has been found to increase the open circuit voltage and current of the photovoltaic device.
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Flexible barrier film, method of forming same, and organic electronic device including same
Blizzard, John; Tonge, James Steven; Weidner, William Kenneth
2013-03-26
A flexible barrier film has a thickness of from greater than zero to less than 5,000 nanometers and a water vapor transmission rate of no more than 1.times.10.sup.-2 g/m.sup.2/day at 22.degree. C. and 47% relative humidity. The flexible barrier film is formed from a composition, which comprises a multi-functional acrylate. The composition further comprises the reaction product of an alkoxy-functional organometallic compound and an alkoxy-functional organosilicon compound. A method of forming the flexible barrier film includes the steps of disposing the composition on a substrate and curing the composition to form the flexible barrier film. The flexible barrier film may be utilized in organic electronic devices.
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Amone-P'Olak, Kennedy; Jones, Peter; Meiser-Stedman, Richard; Abbott, Rosemary; Ayella-Ataro, Paul Stephen; Amone, Jackson; Ovuga, Emilio
2014-12-01
Exposure to war is associated with considerable risks for long-term mental health problems (MHP) and poor functioning. Yet little is known about functioning and mental health service (MHS) use among former child soldiers (FCS). We assessed whether different categories of war experiences predict functioning and perceived need for, sources of and barriers to MHS among FCS. Data were drawn from an on-going War-affected Youths (WAYS) cohort study of FCS in Uganda. Participants completed questionnaires about war experiences, functioning and perceived need for, sources of and barriers to MHS. Regression analyses and parametric tests were used to assess between-group differences. Deaths, material losses, threat to loved ones and sexual abuse significantly predicted poor functioning. FCS who received MHS function better than those who did not. Females reported more emotional and behavioural problems and needed MHS more than males. FCS who function poorly indicated more barriers to MHS than those who function well. Stigma, fear of family break-up and lack of health workers were identified as barriers to MHS. Various war experiences affect functioning differently. A significant need for MHS exists amidst barriers to MHS. Nevertheless, FCS are interested in receiving MHS and believe it would benefit them. © The Author 2014. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Nanoparticle/Polymer Nanocomposite Bond Coat or Coating
NASA Technical Reports Server (NTRS)
Miller, Sandi G.
2011-01-01
This innovation addresses the problem of coatings (meant to reduce gas permeation) applied to polymer matrix composites spalling off in service due to incompatibility with the polymer matrix. A bond coat/coating has been created that uses chemically functionalized nanoparticles (either clay or graphene) to create a barrier film that bonds well to the matrix resin, and provides an outstanding barrier to gas permeation. There is interest in applying clay nanoparticles as a coating/bond coat to a polymer matrix composite. Often, nanoclays are chemically functionalized with an organic compound intended to facilitate dispersion of the clay in a matrix. That organic modifier generally degrades at the processing temperature of many high-temperature polymers, rendering the clay useless as a nano-additive to high-temperature polymers. However, this innovation includes the use of organic compounds compatible with hightemperature polymer matrix, and is suitable for nanoclay functionalization, the preparation of that clay into a coating/bondcoat for high-temperature polymers, the use of the clay as a coating for composites that do not have a hightemperature requirement, and a comparable approach to the preparation of graphene coatings/bond coats for polymer matrix composites.
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Three-Dimensional Blood-Brain Barrier Model for in vitro Studies of Neurovascular Pathology
NASA Astrophysics Data System (ADS)
Cho, Hansang; Seo, Ji Hae; Wong, Keith H. K.; Terasaki, Yasukazu; Park, Joseph; Bong, Kiwan; Arai, Ken; Lo, Eng H.; Irimia, Daniel
2015-10-01
Blood-brain barrier (BBB) pathology leads to neurovascular disorders and is an important target for therapies. However, the study of BBB pathology is difficult in the absence of models that are simple and relevant. In vivo animal models are highly relevant, however they are hampered by complex, multi-cellular interactions that are difficult to decouple. In vitro models of BBB are simpler, however they have limited functionality and relevance to disease processes. To address these limitations, we developed a 3-dimensional (3D) model of BBB on a microfluidic platform. We verified the tightness of the BBB by showing its ability to reduce the leakage of dyes and to block the transmigration of immune cells towards chemoattractants. Moreover, we verified the localization at endothelial cell boundaries of ZO-1 and VE-Cadherin, two components of tight and adherens junctions. To validate the functionality of the BBB model, we probed its disruption by neuro-inflammation mediators and ischemic conditions and measured the protective function of antioxidant and ROCK-inhibitor treatments. Overall, our 3D BBB model provides a robust platform, adequate for detailed functional studies of BBB and for the screening of BBB-targeting drugs in neurological diseases.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Varghese, Jithin J.; Mushrif, Samir H., E-mail: shmushrif@ntu.edu.sg
Small metal clusters exhibit unique size and morphology dependent catalytic activity. The search for alternate minimum energy pathways and catalysts to transform methane to more useful chemicals and carbon nanomaterials led us to investigate collision induced dissociation of methane on small Cu clusters. We report here for the first time, the free energy barriers for the collision induced activation, dissociation, and coupling of methane on small Cu clusters (Cu{sub n} where n = 2–12) using ab initio molecular dynamics and metadynamics simulations. The collision induced activation of the stretching and bending vibrations of methane significantly reduces the free energy barriermore » for its dissociation. Increase in the cluster size reduces the barrier for dissociation of methane due to the corresponding increase in delocalisation of electron density within the cluster, as demonstrated using the electron localisation function topology analysis. This enables higher probability of favourable alignment of the C–H stretching vibration of methane towards regions of high electron density within the cluster and makes higher number of sites available for the chemisorption of CH{sub 3} and H upon dissociation. These characteristics contribute in lowering the barrier for dissociation of methane. Distortion and reorganisation of cluster geometry due to high temperature collision dynamics disturb electron delocalisation within them and increase the barrier for dissociation. Coupling reactions of CH{sub x} (x = 1–3) species and recombination of H with CH{sub x} have free energy barriers significantly lower than complete dehydrogenation of methane to carbon. Thus, competition favours the former reactions at high hydrogen saturation on the clusters.« less
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Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice
Zhou, Yu-Kun; Qin, Huan-Long; Zhang, Ming; Shen, Tong-Yi; Chen, Hong-Qi; Ma, Yan-Lei; Chu, Zhao-Xin; Zhang, Peng; Liu, Zhi-Hua
2012-01-01
AIM: To investigate the mechanisms of Lactobacillus plantarum (L. plantarum) action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats. METHODS: Forty rats were randomly divided into groups of sham-operation, bile duct ligation (BDL), BDL + L. plantarum, BDL + internal biliary drainage (IBD), and BDL + IBD + L. plantarum. Ten days after L. plantarum administration, blood and ileal samples were collected from the rats for morphological examination, and intestinal barrier function, liver function, intestinal oxidative stress and protein kinase C (PKC) activity measurement. The distribution and expression of the PKC and tight junction (TJ) proteins, such as occludin, zonula occludens-1, claudin-1, claudin-4, junction adhesion molecule-A and F-actin, were examined by confocal laser scanning microscopy, immunohistochemistry, Western blotting, real-time fluorescent quantitative polymerase chain reaction assay. RESULTS: L. plantarum administration substantially restored gut barrier, decreased enterocyte apoptosis, improved intestinal oxidative stress, promoted the activity and expression of protein kinase (BDL vs BDL + L. plantarum, 0.295 ± 0.007 vs 0.349 ± 0.003, P < 0.05; BDL + IBD vs BDL + IBD + L. plantarum, 0.407 ± 0.046 vs 0.465 ± 0.135, P < 0.05), and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice (BDL vs BDL + L. plantarum, 0.266 ± 0.118 vs 0.326 ± 0.009, P < 0.05). The protective effect of L. plantarum was more prominent after internal biliary drainage ( BDL + IBD vs BDL + IBD + L. plantarum, 0.415 ± 0.105 vs 0.494 ± 0.145, P < 0.05). CONCLUSION: L. plantarum can decrease intestinal epithelial cell apoptosis, reduce oxidative stress, and prevent TJ disruption in biliary obstruction by activating the PKC pathway. PMID:22912548
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McClusky, Leon M
2006-09-01
Naturally occurring heavy metals and synthetic compounds are potentially harmful for testicular function but evidence linking heavy metal exposure to reduced semen parameters is inconclusive. Elucidation of the exact stage at which the toxicant interferes with spermatogenesis is difficult because the various germ cell stages may have different sensitivities to any given toxicant, germ cell development is influenced by supporting testicular somatic cells and the presence of inter-Sertoli cell tight junctions create a blood-testis barrier, sequestering meiotic and postmeiotic germ cells in a special microenvironment. Sharks such as Squalus acanthias provide a suitable model for studying aspects of vertebrate spermatogenosis because of their unique features: spermatogenesis takes place within spermatocysts and relies mainly on Sertoli cells for somatic cell support; spermatocysts are linearly arranged in a maturational order across the diameter of the elongated testis; spermatocysts containing germ cells at different stages of development are topographically separated, resulting in visible zonation in testicular cross sections. We have used the vital dye acridine orange and a novel fluorescence staining technique to study this model to determine (1) the efficacy of these methods in assays of apoptosis and blood-testis barrier function, (2) the sensitivity of the various spermatogonial generations in Squalus to cadmium (as an illustrative spermatotoxicant) and (3) the way that cadmium might affect more mature spermatogenic stages and other physiological processes in the testis. Our results show that cadmium targets early spermatogenic stages, where it specifically activates a cell death program in susceptible (mature) spermatogonial clones, and negatively affects blood-testis barrier function. Since other parameters are relatively unaffected by cadmium, the effects of this toxicant on apoptosis are presumably process-specific and not attributable to general toxicity.
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Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice.
Zhou, Yu-Kun; Qin, Huan-Long; Zhang, Ming; Shen, Tong-Yi; Chen, Hong-Qi; Ma, Yan-Lei; Chu, Zhao-Xin; Zhang, Peng; Liu, Zhi-Hua
2012-08-14
To investigate the mechanisms of Lactobacillus plantarum (L. plantarum) action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats. Forty rats were randomly divided into groups of sham-operation, bile duct ligation (BDL), BDL + L. plantarum, BDL + internal biliary drainage (IBD), and BDL + IBD + L. plantarum. Ten days after L. plantarum administration, blood and ileal samples were collected from the rats for morphological examination, and intestinal barrier function, liver function, intestinal oxidative stress and protein kinase C (PKC) activity measurement. The distribution and expression of the PKC and tight junction (TJ) proteins, such as occludin, zonula occludens-1, claudin-1, claudin-4, junction adhesion molecule-A and F-actin, were examined by confocal laser scanning microscopy, immunohistochemistry, Western blotting, real-time fluorescent quantitative polymerase chain reaction assay. L. plantarum administration substantially restored gut barrier, decreased enterocyte apoptosis, improved intestinal oxidative stress, promoted the activity and expression of protein kinase (BDL vs BDL + L. plantarum, 0.295 ± 0.007 vs 0.349 ± 0.003, P < 0.05; BDL + IBD vs BDL + IBD + L. plantarum, 0.407 ± 0.046 vs 0.465 ± 0.135, P < 0.05), and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice (BDL vs BDL + L. plantarum, 0.266 ± 0.118 vs 0.326 ± 0.009, P < 0.05). The protective effect of L. plantarum was more prominent after internal biliary drainage ( BDL + IBD vs BDL + IBD + L. plantarum, 0.415 ± 0.105 vs 0.494 ± 0.145, P < 0.05). L. plantarum can decrease intestinal epithelial cell apoptosis, reduce oxidative stress, and prevent TJ disruption in biliary obstruction by activating the PKC pathway.
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In Vitro Effects of Preserved and Unpreserved Anti-Allergic Drugs on Human Corneal Epithelial Cells
Calvo, Patricia; Ropero, Inés; Pintor, Jesús
2014-01-01
Abstract Purpose: Treatment with topical eye drops for long-standing ocular diseases like allergy can induce detrimental side effects. The purpose of this study was to investigate in vitro cytotoxicity of commercially preserved and unpreserved anti-allergic eye drops on the viability and barrier function of monolayer and stratified human corneal-limbal epithelial cells. Methods: Cells were treated with unpreserved ketotifen solution, benzalkonium chloride (BAC)-containing anti-allergic drugs (ketotifen, olopatadine, levocabastine) as well as BAC alone. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to determine cell viability. Effects of compounds on barrier function were analyzed measuring transepithelial electrical resistance (TEER) to determine paracellular permeability and rose bengal assays to evaluate transcellular barrier formation. Results: The BAC-preserved anti-allergic formulations and BAC alone significantly reduced cell viability, monolayer cultures being more sensitive to damage by these solutions. Unpreserved ketotifen induced the least diminution in cell viability. The extent of decrease of cell viability was clearly dependent of BAC presence, but it was also affected by the different types of drugs when the concentration of BAC was low and the short time of exposure. Treatment with BAC-containing anti-allergic drugs and BAC alone resulted in increased paracellular permeability and loss of transcellular barrier function as indicated by TEER measurement and rose bengal assays. Conclusions: The presence of the preservative BAC in anti-allergic eye drop formulations contributes importantly to the cytotoxic effects induced by these compounds. Stratified cell cultures seem to be a more relevant model for toxicity evaluation induced on the ocular surface epithelia than monolayer cultures. PMID:25100331
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Effects of polysaccharide from mycelia of Ganoderma lucidum on intestinal barrier functions of rats.
Jin, Mingliang; Zhu, Yimin; Shao, Dongyan; Zhao, Ke; Xu, Chunlan; Li, Qi; Yang, Hui; Huang, Qingsheng; Shi, Junling
2017-01-01
The intestinal mucosal barriers play essential roles not only in the digestion and absorption of nutrients, but also the innate defense against most intestinal pathogens. In the present study, polysaccharide from the mycelia of Ganoderma lucidum was given via oral administration to rats (100mg/kg body weight, 21days) to investigate its effects on intestinal barrier functions, including the mechanical barrier, immunological barrier and biological barrier function. It was found that the polysaccharide administration could significantly up-regulate the expression of occludin, nuclear factor-κB p65 (NF-κB p65) and secretory immunoglobulin A (SIgA) in ileum, markedly improve the levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), and IL-4, and decrease the level of diamine oxidase (DAO) in serum. Meanwhile, rats from the polysaccharide group showed significant higher microbiota richness in cecum as reflected by the Chao 1 index compared with the control group. Moreover, the polysaccharide decreased the Firmicutes-to-Bacteroidetes ratio. Our results indicated that the polysaccharide from the mycelia of G. lucidum might be used as functional agent to regulate the intestinal barrier functions. Copyright © 2016 Elsevier B.V. All rights reserved.
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Simson, Päivo; Jepihhina, Natalja; Laasmaa, Martin; Peterson, Pearu; Birkedal, Rikke; Vendelin, Marko
2016-08-01
Adequate intracellular energy transfer is crucial for proper cardiac function. In energy starved failing hearts, partial restoration of energy transfer can rescue mechanical performance. There are two types of diffusion obstacles that interfere with energy transfer from mitochondria to ATPases: mitochondrial outer membrane (MOM) with voltage-dependent anion channel (VDAC) permeable to small hydrophilic molecules and cytoplasmatic diffusion barriers grouping ATP-producers and -consumers. So far, there is no method developed to clearly distinguish the contributions of cytoplasmatic barriers and MOM to the overall diffusion restriction. Furthermore, the number of open VDACs in vivo remains unknown. The aim of this work was to establish the partitioning of intracellular diffusion obstacles in cardiomyocytes. We studied the response of mitochondrial oxidative phosphorylation of permeabilized rat cardiomyocytes to changes in extracellular ADP by recording 3D image stacks of NADH autofluorescence. Using cell-specific mathematical models, we determined the permeability of MOM and cytoplasmatic barriers. We found that only ~2% of VDACs are accessible to cytosolic ADP and cytoplasmatic diffusion barriers reduce the apparent diffusion coefficient by 6-10×. In cardiomyocytes, diffusion barriers in the cytoplasm and by the MOM restrict ADP/ATP diffusion to similar extents suggesting a major role of both barriers in energy transfer and other intracellular processes. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Placing barrier-island transgression in a blue-carbon context
NASA Astrophysics Data System (ADS)
Theuerkauf, Ethan J.; Rodriguez, Antonio B.
2017-07-01
Backbarrier saltmarshes are considered carbon sinks; however, barrier island transgression and the associated processes of erosion and overwash are typically not included in coastal carbon budgets. Here, we present a carbon-budget model for transgressive barrier islands that includes a dynamic carbon-storage term, driven by backbarrier-marsh width, and a carbon-export term, driven by ocean and backbarrier shoreline erosion. To examine the impacts of storms, human disturbances and the backbarrier setting of a transgressive barrier island on carbon budgets and reservoirs, the model was applied to sites at Core Banks and Onslow Beach, NC, USA. Results show that shoreline erosion and burial of backbarrier marsh from washover deposition and dredge-spoil disposal temporarily transitioned each site into a net exporter (source) of carbon. The magnitude of the carbon reservoir was linked to the backbarrier setting of an island. Carbon reservoirs of study sites separated from the mainland by only backbarrier marsh (no lagoon) decreased for over a decade because carbon storage could not keep pace with erosion. With progressive narrowing of the backbarrier marsh, these barriers will begin to function more persistently as carbon sources until the reservoir is depleted at the point where the barrier welds with the mainland. Undeveloped barrier islands with wide lagoons are carbon sources briefly during erosive periods; however, at century time scales are net carbon importers (sinks) because new marsh habitat can form during barrier rollover. Human development on backbarrier saltmarsh serves to reduce the carbon storage capacity and can hasten the transition of an island from a sink to a source.
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NASA Astrophysics Data System (ADS)
Sun, Qiang; Selloni, Annabella; Myers, T. H.; Doolittle, W. Alan
2006-11-01
Density functional theory calculations of oxygen adsorption and incorporation at the polar GaN(0001) and GaN(0001¯) surfaces have been carried out to explain the experimentally observed reduced oxygen concentration in GaN samples grown by molecular beam epitaxy in the presence of high energy (˜10keV) electron beam irradiation [Myers , J. Vac. Sci. Technol. B 18, 2295 (2000)]. Using a model in which the effect of the irradiation is to excite electrons from the valence to the conduction band, we find that both the energy cost of incorporating oxygen impurities in deeper layers and the oxygen adatom diffusion barriers are significantly reduced in the presence of the excitation. The latter effect leads to a higher probability for two O adatoms to recombine and desorb, and thus to a reduced oxygen concentration in the irradiated samples, consistent with experimental observations.
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Abnormal Barrier Function in Gastrointestinal Disorders.
Farré, Ricard; Vicario, María
2017-01-01
There is increasing concern in identifying the mechanisms underlying the intimate control of the intestinal barrier, as deregulation of its function is strongly associated with digestive (organic and functional) and a number of non-digestive (schizophrenia, diabetes, sepsis, among others) disorders. The intestinal barrier is a complex and effective defensive functional system that operates to limit luminal antigen access to the internal milieu while maintaining nutrient and electrolyte absorption. Intestinal permeability to substances is mainly determined by the physicochemical properties of the barrier, with the epithelium, mucosal immunity, and neural activity playing a major role. In functional gastrointestinal disorders (FGIDs), the absence of structural or biochemical abnormalities that explain chronic symptoms is probably close to its end, as recent research is providing evidence of structural gut alterations, at least in certain subsets, mainly in functional dyspepsia (FD) and irritable bowel syndrome (IBS). These alterations are associated with increased permeability, which seems to reflect mucosal inflammation and neural activation. The participation of each anatomical and functional component of barrier function in homeostasis and intestinal dysfunction is described, with a special focus on FGIDs.
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Khode, Rajiv Tarachand; Shenoi, Pratima Ramakrishna; Kubde, Rajesh R; Makade, Chetana S; Wadekar, Kanchan D; Khode, Priyanka Tarachand
2017-01-01
This study evaluated effect of infection control barriers on light intensity (LI) of light-curing unit (LCU) and microhardness of composite. Four different disposable barriers ( n = 30) were tested against the control. LI for each barrier was measured with Lux meter. One hundred and fifty Teflon molds were equally divided into five groups of thirty each. Composite was filled in bulk in these molds and cured without and with barrier. Microhardness was evaluated on top and bottom surface of composite specimen with microhardness testing machine and hardness ratio (HR) was derived. One-way analysis of variance, Tukey's honestly significant difference test, and paired t -test using SPSS version 18 software. All barriers had significantly reduced the baseline LI of LCU ( P < 0.0001), but only Cure Elastic Steri-Shield and latex cut glove pieces (LCGP) significantly reduced the microhardness of the composite ( P < 0.05). However, HR determined inadequate curing only with LCGP. Although entire tested barrier significantly reduced the LI; none, except LCGP markedly affected the degree of cure of the composite.
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Inhibition of Na+/H+ exchanger 1 by cariporide reduces burn-induced intestinal barrier breakdown.
Yang, Xuekang; Chen, Ji; Bai, Hua; Tao, Ke; Zhou, Qin; Hou, Hongyi; Hu, Dahai
2013-12-01
Severe burns initiate an inflammatory cascade within the gut, which leads to intestinal mucosal injury. Although Na(+)/H(+) exchanger 1 (NHE1) is recognised as a pivotal player in several inflammatory processes, its role in burn-induced intestinal injury is relatively unknown. We hypothesised that NHE1 might be involved in the increased intestinal permeability and barrier breakdown after severe burns. Thus, we here investigate whether the inhibition of NHE1 has a protective effect on burn-induced intestinal injury. Mice were subjected to a 30% total body surface area (TBSA) full-thickness steam burn. Cariporide was used to assess the function of NHE1 in mice with burn-induced intestinal injury by fluorescence spectrophotometry, Western blotting and enzyme linked immunosorbent assay (ELISA). We found that severe burn increased intestinal permeability, associated with the up-regulation of NHE1 and raised inflammatory cytokine levels. Mice treated with the NHE1 inhibitor cariporide had significantly attenuated burn-induced intestinal permeability and a reduced inflammatory response. NHE1 inhibition also reduced nuclear factor-κB (NF-κB) activation and attenuated p38 mitogen-activated protein kinase (MAPK) phosphorylation. Our study suggests that NHE1 plays an important role in burn-induced intestinal permeability through the regulation of the inflammatory response. Inhibition of NHE1 may be adopted as a potential therapeutic strategy for attenuating intestinal barrier breakdown. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.
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[Advance in studies on food allergy mechanism based on gut barrier].
Wang, Juan-hong; Li, Huan-zhou; Li, Meng; Pan, Su-hua
2015-04-01
Food allergies, as a type of adverse immune-mediated reactions to ingested food proteins, have become a serious public health issue that harms children and adults health, with increasing incidence year by year. However, without effective therapy for food allergies, doctors-have mostly advised to avoid allergens and provided symptomatic treatment. According to the findings of many studies, allergic diseases are correlated with intestinal barrier function injury, as evidenced by the significant increase in the intestinal permeability among patients with food allergies. In this paper, recent studies on correlations between food allergies and intestinal barrier functions, intestinal barrier function injury mechanisms of allergic foods and food allergy intervention strategies based on intestinal barrier functions were summarized to provide reference for laboratory researches and clinical treatment of food allergic diseases.
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Farchi, Moshe; Gidron, Yori
2010-05-01
Anxiety and hopelessness are common reactions of citizens exposed to continuous war threats. Common interventions focus on support, calming, and emotional ventilation, with few attempts to reduce people's cognitive barriers concerning active coping, which could increase their resilience. This study tested the effects of psychological inoculation (PI), which specifically aims to challenge such barriers, on the mental resilience of Israeli citizens living in Sderot. Participants were randomly assigned to either 2 PI sessions or 2 ventilation sessions, provided over the phone. Anxiety, helplessness, pessimism, and functioning were briefly assessed at baseline and 1 week after interventions. No time, group, or group x time interactions were observed. However, a time x group x sex interaction emerged for helplessness: Men benefited from the PI whereas women benefited from ventilation, in reducing helplessness. Under chronic war stress, it seems difficult to improve people's resilience, although PI may be partly beneficial for men. Further research is needed to test the effects of PI on mental resilience.
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Reducing the nucleation barrier in magnetocaloric Heusler alloys by nanoindentation
NASA Astrophysics Data System (ADS)
Niemann, R.; Hahn, S.; Diestel, A.; Backen, A.; Schultz, L.; Nielsch, K.; Wagner, M. F.-X.; Fähler, S.
2016-06-01
Magnetocaloric materials are promising as solid state refrigerants for more efficient and environmentally friendly cooling devices. The highest effects have been observed in materials that exhibit a first-order phase transition. These transformations proceed by nucleation and growth which lead to a hysteresis. Such irreversible processes are undesired since they heat up the material and reduce the efficiency of any cooling application. In this article, we demonstrate an approach to decrease the hysteresis by locally changing the nucleation barrier. We created artificial nucleation sites and analyzed the nucleation and growth processes in their proximity. We use Ni-Mn-Ga, a shape memory alloy that exhibits a martensitic transformation. Epitaxial films serve as a model system, but their high surface-to-volume ratio also allows for a fast heat transfer which is beneficial for a magnetocaloric regenerator geometry. Nanoindentation is used to create a well-defined defect. We quantify the austenite phase fraction in its proximity as a function of temperature which allows us to determine the influence of the defect on the transformation.
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Similarity tests of turbine vanes, effects of ceramic thermal barrier coatings
NASA Technical Reports Server (NTRS)
Gladden, H. J.
1980-01-01
The role of material thermal conductivity was analyzed for its effect on the thermal performance of air-cooled gas turbine components coated with a ceramic thermal barrier material when tested at reduced temperatures and pressures. It is shown that the thermal performance can be evaluated reliably at reduced gas and coolant conditions; however, thermal conductivity corrections are required for the data at reduced conditions. Corrections for a ceramic thermal barrier coated vane are significantly different than for an uncoated vane. Comparison of uncorrected test data, therefore, would show erroneously that the thermal barrier coating was ineffective. When thermal conductivity corrections are applied to the test data these data are then shown to be representative of engine data and also show that the thermal barrier coating increases the vane cooling effectiveness by 12.5 percent.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Hyungchul; Singh, Ankit Kumar; Wang, Cheng-Yin
In the development of ultrabarrier films for packaging electronics, the effective water vapor transmission rate is a combination of permeation through pinhole defects and the intrinsic permeation through the actual barrier film. While it is possible to measure the effective permeation rate through barriers, it is important to develop a better understanding of the contribution from defects to the overall effective barrier performance. Here, we demonstrate a method to investigate independently defect-assisted permeation and intrinsic permeation rates by observing the degradation of a calcium layer encapsulated with a hybrid barrier film, that is, prepared using atomic layer deposition (ALD) andmore » plasma enhanced deposition (PECVD). The results are rationalized using an analytical diffusion model to calculate the permeation rate as a function of spatial position within the barrier. It was observed that a barrier film consisting of a PECVD SiN{sub x} layer combined with an ALD Al{sub 2}O{sub 3}/HfO{sub x} nanolaminate resulted in a defect-assisted water vapor transmission rate (WVTR) of 4.84 × 10{sup −5} g/m{sup 2} day and intrinsic WVTR of 1.41 × 10{sup −4} g/m{sup 2} day at 50 °C/85% RH. Due to the low defect density of the tested barrier film, the defect-assisted WVTR was found to be three times lower than the intrinsic WVTR, and an effective (or total) WVTR value was 1.89 × 10{sup −4} g/m{sup 2} day. Thus, improvements of the barrier performance should focus on reducing the number of defects while also improving the intrinsic barrier performance of the hybrid layer.« less
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Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M.; Mariani, John N.; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S.
2015-01-01
In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood–brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood–brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood–brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood–brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood–brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood–brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP as an astrocyte-derived permeability factor, and suggest TYMP and VEGFA together promote blood–brain barrier breakdown. PMID:25805644
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An oncological view on the blood-testis barrier.
Bart, Joost; Groen, Harry J M; van der Graaf, Winette T A; Hollema, Harry; Hendrikse, N Harry; Vaalburg, Willem; Sleijfer, Dirk T; de Vries, Elisabeth G E
2002-06-01
The function of the blood-testis barrier is to protect germ cells from harmful influences; thus, it also impedes the delivery of chemotherapeutic drugs to the testis. The barrier has three components: first, a physicochemical barrier consisting of continuous capillaries, Sertoli cells in the tubular wall, connected together with narrow tight junctions, and a myoid-cell layer around the seminiferous tubule. Second, an efflux-pump barrier that contains P-glycoprotein in the luminal capillary endothelium and on the myoid-cell layer; and multidrug-resistance associated protein 1 located basolaterally on Sertoli cells. Third, an immunological barrier, consisting of Fas ligand on Sertoli cells. Inhibition of P-glycoprotein function offers the opportunity to increase the delivery of cytotoxic drugs to the testis. In the future, visualisation of function in the blood-testis barrier may also be helpful to identify groups of patients in whom testis conservation is safe or to select drugs that are less harmful to fertility.
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Clinical severity correlates with impaired barrier in filaggrin-related eczema.
Nemoto-Hasebe, Ikue; Akiyama, Masashi; Nomura, Toshifumi; Sandilands, Aileen; McLean, W H Irwin; Shimizu, Hiroshi
2009-03-01
Mutations in the gene-encoding filaggrin (FLG), a key molecule involved in skin barrier function, have been shown to be a major predisposing factor for atopic dermatitis (AD; eczema). To elucidate the pathomechanisms underlying filaggrin-related AD, we investigated stratum corneum (SC) hydration and transepidermal water loss (TEWL) as parameters of barrier function in AD patients harboring FLG mutations compared to AD patients without any FLG mutation. In filaggrin-related AD, SC hydration was both significantly reduced (P<0.01-0.05) and thicker (P<0.01-0.05) than that in healthy controls. TEWL was demonstrably increased in non-filaggrin AD compared to healthy controls (P<0.01-0.05). The objective score of atopic dermatitis (OSCORAD), a disease clinical severity index, significantly correlated with TEWL (r=0.81, P<0.005), SC hydration (r=-0.65, P<0.05), and SC thickness (r=0.59, P<0.05) in filaggrin-related AD. On the contrary, there was no correlation between these parameters and the OSCORAD in non-filaggrin AD. Furthermore, a significant correlation was obtained between the OSCORAD and specific IgE for house dust (r=0.66, P<0.05), mite allergen (r=0.53, P<0.05), and cat dander (r=0.64, P<0.05) in filaggrin-related AD, but not in non-filaggrin AD. All these data suggest that experimentally demonstrable skin barrier defects due to FLG mutations may play a crucial role in the pathogenesis of AD.
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The effect of topical treatments for CRS on the sinonasal epithelial barrier.
Ramezanpour, M; Rayan, A; Smith, J L P; Vreugde, S
2017-06-01
Several topical treatments are used in the management of Chronic Rhinosinusitis (CRS), some of which the safety and efficacy has yet to be determined. The purpose of this study was to investigate the effect of commonly used topical treatments on the sinonasal epithelial barrier. Normal saline (0.9% Sodium Chloride), hypertonic saline (3% Sodium Chloride), FESS Sinu-Cleanse Hypertonic, FLO Sinus Care and Budesonide 1 mg/ 2 ml were applied to the apical side of air-liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs) from CRS patients (n=3) and non-CRS controls (n=3) for 24 hours. Epithelial barrier structure and function was assessed using trans-epithelial electrical resistance (TEER), measuring the passage of Fluorescein Isothiocyanate labelled Dextrans (FITC-Dextrans) and assessing the expression of the tight junction protein Zona Occludens-1 (ZO-1) using immunofluorescence. Toxicity was assessed using a Lactate Dehydrogenase (LDH) assay. Data was analysed using ANOVA, followed by Tukey HSD post hoc test. Hypertonic solution and budesonide significantly increased TEER values in CRS derived HNECs. In contrast, FESS Sinu-Cleanse Hypertonic significantly reduced TEER 5 minutes after application of the solution followed by an increase in paracellular permeability of FITC-Dextrans (30 minutes) and increased LDH levels 6 hours after application of the solution. Our findings confirm that isotonic and hypertonic saline solutions do not compromise epithelial barrier function in vitro but underscore the importance of examining safety and efficacy of over-the-counter wash solutions.
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Plichta, Jennifer K.; Holmes, Casey J.; Gamelli, Richard L.; Radek, Katherine A.
2016-01-01
Burn injury increases the risk of morbidity and mortality by promoting severe hemodynamic shock and risk for local or systemic infection. Graft failure due to poor wound healing or infection remains a significant problem for burn subjects. The mechanisms by which local burn injury compromises the epithelial antimicrobial barrier function in the burn margin, containing the elements necessary for healing of the burn site, and in distal unburned skin, which serves as potential donor tissue, are largely unknown. The objective of this study was to establish defects in epidermal barrier function in human donor skin and burn margin, in order to identify potential mechanisms that may lead to graft failure and/or impaired burn wound healing. In the present study, we established that epidermal lipids and respective lipid synthesis enzymes were significantly reduced in both donor skin and burn margin. We further identified diverse changes in the gene expression and protein production of several candidate skin antimicrobial peptides (AMPs) in both donor skin and burn margin. These results also parallel changes in cutaneous AMP activity against common burn wound pathogens, aberrant production of epidermal proteases known to regulate barrier permeability and AMP activity, and greater production of pro-inflammatory cytokines known to be induced by AMPs. These findings suggest that impaired epidermal lipid and AMP regulation could contribute to graft failure and infectious complications in subjects with burn or other traumatic injury. PMID:27183442
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Zamorano, Patricia; Marín, Natalie; Córdova, Francisco; Aguilar, Alejandra; Meininger, Cynthia; Boric, Mauricio P; Golenhofen, Nikola; Contreras, Jorge E; Sarmiento, José; Durán, Walter N; Sánchez, Fabiola A
2017-07-01
We tested the hypothesis that platelet-activating factor (PAF) induces S -nitrosylation of vasodilator-stimulated phosphoprotein (VASP) as a mechanism to reduce microvascular endothelial barrier integrity and stimulate hyperpermeability. PAF elevated S -nitrosylation of VASP above baseline levels in different endothelial cells and caused hyperpermeability. To ascertain the importance of endothelial nitric oxide synthase (eNOS) subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX). PAF induced S -nitrosylation of VASP in cells with cytosolic eNOS but not in cells wherein eNOS is anchored to the cell membrane. Reconstitution of VASP knockout myocardial endothelial cells with cysteine mutants of VASP demonstrated that S -nitrosylation of cysteine 64 is associated with PAF-induced hyperpermeability. We propose that regulation of VASP contributes to endothelial cell barrier integrity and to the onset of hyperpermeability. S -nitrosylation of VASP inhibits its function in barrier integrity and leads to endothelial monolayer hyperpermeability in response to PAF, a representative proinflammatory agonist. NEW & NOTEWORTHY Here, we demonstrate that S -nitrosylation of vasodilator-stimulated phosphoprotein (VASP) on C64 is a mechanism for the onset of platelet-activating factor-induced hyperpermeability. Our results reveal a dual role of VASP in endothelial permeability. In addition to its well-documented function in barrier integrity, we show that S -nitrosylation of VASP contributes to the onset of endothelial permeability. Copyright © 2017 the American Physiological Society.
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Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F
2015-01-01
Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (Isc). Subsequent Isc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. Isc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation. PMID:26038704
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Kang, Sang Bum; Marchelletta, Ronald R; Penrose, Harrison; Docherty, Michael J; McCole, Declan F
2015-03-01
Linaclotide, a synthetic guanylyl cyclase C (GC-C) agonist, and the prostone analog, Lubiprostone, are approved to manage chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in ischemia. GC-C signaling regulates local fluid balance and other components of intestinal mucosal homeostasis including epithelial barrier function. The aim of this study was to compare if select dosing regimens differentially affect linaclotide and lubiprostone modulation of ion transport and barrier properties of normal human colonic mucosa. Normal sigmoid colon biopsies from healthy subjects were mounted in Ussing chambers. Tissues were treated with linaclotide, lubiprostone, or vehicle to determine effects on short-circuit current (I sc). Subsequent I sc responses to the cAMP agonist, forskolin, and the calcium agonist, carbachol, were also measured to assess if either drug caused desensitization. Barrier properties were assessed by measuring transepithelial electrical resistance. I sc responses to linaclotide and lubiprostone were significantly higher than vehicle control when administered bilaterally or to the mucosal side only. Single versus cumulative concentrations of linaclotide showed differences in efficacy while cumulative but not single dosing caused desensitization to forskolin. Lubiprostone reduced forskolin responses under all conditions. Linaclotide and lubiprostone exerted a positive effect on TER that was dependent on the dosing regimen. Linaclotide and lubiprostone increase ion transport responses across normal human colon but linaclotide displays increased sensitivity to the dosing regimen used. These findings may have implications for dosing protocols of these agents in patients with constipation.
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Pfeiffer, Friederike; Schäfer, Julia; Lyck, Ruth; Makrides, Victoria; Brunner, Sarah; Schaeren-Wiemers, Nicole; Deutsch, Urban; Engelhardt, Britta
2011-11-01
In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), loss of the blood-brain barrier (BBB) tight junction (TJ) protein claudin-3 correlates with immune cell infiltration into the CNS and BBB leakiness. Here we show that sealing BBB TJs by ectopic tetracycline-regulated expression of the TJ protein claudin-1 in Tie-2 tTA//TRE-claudin-1 double transgenic C57BL/6 mice had no influence on immune cell trafficking across the BBB during EAE and furthermore did not influence the onset and severity of the first clinical disease episode. However, expression of claudin-1 did significantly reduce BBB leakiness for both blood borne tracers and endogenous plasma proteins specifically around vessels expressing claudin-1. In addition, mice expressing claudin-1 exhibited a reduced disease burden during the chronic phase of EAE as compared to control littermates. Our study identifies BBB TJs as the critical structure regulating BBB permeability but not immune cell trafficking into CNS during EAE, and indicates BBB dysfunction is a potential key event contributing to disease burden in the chronic phase of EAE. Our observations suggest that stabilizing BBB barrier function by therapeutic targeting of TJs may be beneficial in treating MS, especially when anti-inflammatory treatments have failed.
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van Vliet, Erwin A; Otte, Willem M; Wadman, Wytse J; Aronica, Eleonora; Kooij, Gijs; de Vries, Helga E; Dijkhuizen, Rick M; Gorter, Jan A
2016-01-01
Blood-brain barrier (BBB) leakage may play a pro-epileptogenic role after status epilepticus. In the accompanying contrast-enhanced magnetic resonance imaging (CE-MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activity during the chronic epileptic phase. Given rapamycin's role in growth and immune response, the potential therapeutic effects of rapamycin after status epilepticus with emphasis on brain inflammation and brain vasculature were investigated. Seven weeks after kainic acid-induced status epilepticus, rats were perfusion fixed and (immuno)histochemistry was performed using several glial and vascular markers. In addition, an in vitro model for the human BBB was used to determine the effects of rapamycin on transendothelial electrical resistance as a measure for BBB integrity. (Immuno)histochemistry showed that local blood vessel density, activated microglia, and astrogliosis were reduced in rapamycin-treated rats compared to vehicle-treated rats. In vitro studies showed that rapamycin could attenuate TNFα-induced endothelial barrier breakdown. These data suggest that rapamycin improves BBB function during the chronic epileptic phase by a reduction of local brain inflammation and blood vessel density that can contribute to a milder form of epilepsy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
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Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders.
Fiorentino, Maria; Sapone, Anna; Senger, Stefania; Camhi, Stephanie S; Kadzielski, Sarah M; Buie, Timothy M; Kelly, Deanna L; Cascella, Nicola; Fasano, Alessio
2016-01-01
Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to these disorders. Our goal was to investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD. Postmortem cerebral cortex and cerebellum tissues from ASD, schizophrenia (SCZ), and healthy subjects (HC) and duodenal biopsies from ASD and HC were analyzed for gene and protein expression profiles. Tight junctions and other key molecules associated with the neurovascular unit integrity and function and neuroinflammation were investigated. Claudin ( CLDN )-5 and -12 were increased in the ASD cortex and cerebellum. CLDN-3 , tricellulin , and MMP-9 were higher in the ASD cortex. IL-8 , tPA , and IBA-1 were downregulated in SCZ cortex; IL-1b was increased in the SCZ cerebellum. Differences between SCZ and ASD were observed for most of the genes analyzed in both brain areas. CLDN-5 protein was increased in ASD cortex and cerebellum, while CLDN-12 appeared reduced in both ASD and SCZ cortexes. In the intestine, 75% of the ASD samples analyzed had reduced expression of barrier-forming TJ components ( CLDN-1 , OCLN , TRIC ), whereas 66% had increased pore-forming CLDNs ( CLDN-2 , -10 , -15 ) compared to controls. In the ASD brain, there is an altered expression of genes associated with BBB integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. While these findings seem to be specific for ASD, the possibility of more distinct SCZ subgroups should be explored with additional studies.
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First-principles study for the enhanced sulfur tolerance of Ni(1 1 1) surface alloyed with Pb
NASA Astrophysics Data System (ADS)
Zhang, Yanxing; Yang, Zongxian
2018-04-01
The adsorption of H2S, HS, S, H and the dissociation of H2S on the Ni2Pb/Ni (1 1 1) are systematically studied using the first-principles method based on density functional theory. It is found that H2S dissociation barriers are greatly increased by alloying with Pb atoms in the Ni(1 1 1) surface, while the barrier for H2S formation is greatly reduced. In addition, the adsorption of sulfur atom is weakened a lot. The results indicate that alloying with Pb may be a good way to increase the sulfur tolerance of Ni based anode catalysts of solid oxide fuel cells.
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NASA Astrophysics Data System (ADS)
Zeitlin, Bruce A.; Pyon, Taeyoung; Gregory, Eric; Scanlan, R. M.
2002-05-01
A number of configurations of a mono element internal tin conductor (MEIT) were fabricated designed to explore the effect of local ratio, niobium content, and tin content on the overall current density. Critical current densities on four configurations were measured, two to 17T. Current density as a function of filament size was also measured with filaments sizes ranging from 1.8 to 7.1 microns. A Nb60wt%Ta barrier was also explored as a means to reduce the high cost of the Tantalum barrier. The effectiveness of radial copper channels in high Nb conductors is also evaluated. Results are used to suggest designs for more optimized conductors.
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The re-emergence of natural products for drug discovery in the genomics era.
Harvey, Alan L; Edrada-Ebel, RuAngelie; Quinn, Ronald J
2015-02-01
Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced these barriers. We also assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products, and highlight recent examples of natural products in antimicrobial drug discovery and as inhibitors of protein-protein interactions. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery.
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Hill, Jennifer N; Balbale, Salva; Lones, Keshonna; LaVela, Sherri L
2017-01-01
Assessments of function in persons with spinal cord injury (SCI) often utilize pre-defined constructs and measures without consideration of patient context, including how patients define function and what matters to them. We utilized photovoice to understand how individuals define function, facilitators and barriers to function, and adaptations to support functioning. Veterans with SCI were provided with cameras and guidelines to take photographs of things that: (1) help with functioning, (2) are barriers to function, and (3) represent adaptations used to support functioning. Interviews to discuss photographs followed and were audio-recorded, transcribed, and analyzed using grounded-thematic coding. Nvivo 8 was used to store and organize data. Participants (n = 9) were male (89%), Caucasian (67%), had paraplegia (75%), averaged 64 years of age, and were injured, on average, for 22 years. Function was described in several ways: the concept of 'normalcy,' aspects of daily living, and ability to be independent. Facilitators included: helpful tools, physical therapy/therapists, transportation, and caregivers. Barriers included: wheelchair-related issues and interior/exterior barriers both in the community and in the hospital. Examples of adaptations included: traditional examples like ramps, and also creative examples like the use of rubber bands on a can to help with grip. Patient-perspectives elicited in-depth information that expanded the common definition of function by highlighting the concept of "normality," facilitators and barriers to function, and adaptations to optimize function. These insights emphasize function within a patient-context, emphasizing a holistic definition of function that can be used to develop personalized, patient-driven care plans. Published by Elsevier Inc.
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Fang, Shenglin; Zhuo, Zhao; Yu, Xiaonan; Wang, Haichao; Feng, Jie
2018-05-01
The aim of this study was to determine the toxicological effects of excess iron in a liquid iron preparation (especially on intestinal barrier function) and the possible etiology of side effects or diseases caused by the excess iron. In study 1, forty male Sprague-Dawley rats (4-5 wk old) were subjected to oral gavage with 1 ml vehicle (0.01 mol/L HCl) or 1 ml liquid iron preparation containing 8 mg, 16 mg or 24 mg of iron for 30 d. Iron status, oxidative stress, histology (H&E staining), ultrastructure (electron microscopy) and apoptosis (TUNEL assay) in the intestines and liver were assessed. The cecal microbiota was evaluated by 16S rRNA sequencing. In study 2, twenty rats with the same profile as above were subjected to oral gavage with 1 ml vehicle or 24 mg Fe for 30 d. The intestinal barrier function was determined by in vivo studies and an Ussing chamber assay; tight junction proteins and serum pro-inflammatory cytokines were observed by enzyme-linked immunosorbent assay. In study 1, the intestinal mucosa and liver showed apparent oxidative stress. In addition, iron concentration-dependent ultrastructural alterations to duodenal enterocytes and hepatocytes and histological damage to the colonic mucosa were detected. Notably, apoptosis was increased in duodenal enterocytes and hepatocytes. Impaired intestinal barrier function and lower expression of intestinal tight junction proteins were observed, and the phenotype was more severe in the colon than in the duodenum. A trend toward higher expression of serum pro-inflammatory cytokines might indicate systemic inflammation. Furthermore, the caecal microbiota showed a significant change, with increased Defluviitaleaceae, Ruminococcaceae, and Coprococcus and reduced Lachnospiraceae and Allobaculum, which could mediate the detrimental effects of excess iron on gut health. We concluded that excessive iron exposure from liquid iron preparation induces oxidative stress and histopathological alterations in the intestine and liver. Impaired intestinal barrier function could increase iron transportation, and inflammation along with oxidative stress-enhanced liver iron deposition may cause further liver injury in a vicious circle. These effects were accompanied by lower intestinal segment damage and altered gut microbial composition of rats toward a profile with an increased risk of gut disease. Copyright © 2018 Elsevier GmbH. All rights reserved.
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Yonezawa, Kaori; Haruna, Megumi; Matsuzaki, Masayo; Shiraishi, Mie; Kojima, Reiji
2018-01-01
An effective newborn skincare protocol has not been established. We aimed to evaluate the effects of moisturizing skincare, including using lotion and reducing routine bathing. Our hypothesis was that moisturizing skincare would improve skin barrier function. This randomized controlled trial included 227 healthy Asian newborns between 1 week and 3 months old. We compared moisturizing skincare (bathing every 2 days and using lotion daily; intervention, n = 113) to daily bathing without lotion (control, n = 114). We assessed the skin barrier function (transepidermal water loss [TEWL], stratum corneum hydration [SCH], skin pH and sebum secretion) as a primary outcome at 3 months old. We also assessed the incidence of skin problems according to parents' diary reports. Compared with the control, the intervention group had a lower face TEWL (mean ± standard deviation, 14.69 ± 7.38 vs 17.08 ± 8.26 g/m 2 per h, P = 0.033), higher face SCH (60.38 ± 13.66 vs 53.52 ± 14.55, P = 0.001) and higher body SCH (58.89 ± 12.96 vs 53.02 ± 10.08, P < 0.001). Compared with the control, newborns in the intervention group had significantly lower rates of diaper dermatitis between birth and 1 month old (6.3% vs 15.9%, P = 0.022), and tended to have lower rates of body skin problems between 1 and 3 months (42.1% vs 55.2%, P = 0.064). Moisturizing skincare was effective for improving skin barrier function and preventing newborns' diaper dermatitis. The results of our study may help parents make informed decisions about newborn skincare. © 2017 Japanese Dermatological Association.
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Tight Junction Defects in Atopic Dermatitis
De Benedetto, Anna; Rafaels, Nicholas M.; McGirt, Laura Y.; Ivanov, Andrei I.; Georas, Steve N.; Cheadle, Chris; Berger, Alan E.; Zhang, Kunzhong; Vidyasagar, Sadasivan; Yoshida, Takeshi; Boguniewicz, Mark; Hata, Tissa; Schneider, Lynda C.; Hanifin, Jon M.; Gallo, Richard L.; Novak, Natalija; Weidinger, Stephan; Beaty, Terri H.; Leung, Donald Y.; Barnes, Kathleen C.; Beck, Lisa A.
2010-01-01
Background Atopic dermatitis (AD) is characterized by dry skin and a hyperreactive immune response to allergens, two cardinal features that are caused in part by epidermal barrier defects. Tight junctions (TJ) reside immediately below the stratum corneum and regulate the selective permeability of the paracellular pathway. Objective We evaluated the expression/function of the TJ protein, claudin-1 in epithelium from AD and nonatopic (NA) subjects and screened two American populations for SNPs in CLDN1. Methods Expression profiles of nonlesional epithelium from extrinsic AD, NA and psoriasis subjects were generated using Illumina’s BeadChips. Dysregulated intercellular proteins were validated by tissue staining and qPCR. Bioelectric properties of epithelium were measured in Ussing chambers. Functional relevance of claudin-1 was assessed using a knockdown approach in primary human keratinocytes (PHK). Twenty seven haplotype-tagging SNPs in CLDN1 were screened in two independent AD populations. Results We observed strikingly reduced expression of the TJ proteins claudin-1 and -23 only in AD, which were validated at the mRNA and protein levels. Claudin-1 expression inversely correlated with Th2 biomarkers. We observed a remarkable impairment of the bioelectric barrier function in AD epidermis. In vitro, we confirmed that silencing claudin-1 expression in human keratinocytes diminishes TJ function while enhancing keratinocyte proliferation. Finally, CLDN1 haplotype-tagging single nucleotide polymorphisms revealed associations with AD in two North American populations. Conclusion Taken together, these data suggest that an impaired epidermal TJ is a novel feature of skin barrier dysfunction and immune dysregulation observed in AD, and that CLDN1 may be a new susceptibility gene in this disease. PMID:21163515
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Sexual functioning in military personnel: preliminary estimates and predictors.
Wilcox, Sherrie L; Redmond, Sarah; Hassan, Anthony M
2014-10-01
Although the military is a young and vigorous force, service members and veterans may experience sexual functioning problems (SFPs) as a result of military service. Sexual functioning can be impaired by physical, psychological, and social factors and can impact quality of life (QOL) and happiness. This study aims to estimate rates and correlates of SFPs in male military personnel across demographic and psychosocial characteristics, to examine the QOL concomitants, and to evaluate barriers for treatment seeking. This exploratory cross-sectional study was conducted using data from a larger nationwide study conducted between October 2013 and November 2013. This sample consists of 367 male active duty service members and recent veterans (military personnel) age 40 or younger. Erectile dysfunction (ED) was determined using the five-item International Index of Erectile Function, sexual dysfunction (SD) was determined using the Arizona Sexual Experiences Scale, Male, and QOL was determined using the World Health Organization Quality of Life, Brief. SFPs were associated with various demographic, physical, and psychosocial risk factors. The rates of SD and ED were 8.45% and 33.24%, respectively, for male military personnel aged 21-40. Those who were 36-40, nonmarried, nonwhite, and of lower educational attainment reported the highest rates of SFPs. Male military personnel with poor physical and psychosocial health presented the greatest risk for ED and SD. SFPs were associated with reduced QOL and lower happiness, and barriers for treatment were generally related to social barriers. SFPs in young male military personnel are an important public health concern that can severely impact QOL and happiness. © 2014 International Society for Sexual Medicine.
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Holdsworth, Clare; Haines, Kimberley J; Francis, Jill J; Marshall, Andrea; O'Connor, Denise; Skinner, Elizabeth H
2015-12-01
Early mobilization in intensive care unit (ICU) is safe, feasible, and beneficial. However, mobilization frequently does not occur in practice. The study objective was to elicit attitudinal, normative, and control beliefs (barriers and enablers) toward the mobilization of ventilated patients, to inform development of targeted implementation interventions. A 9-item elicitation questionnaire was administered electronically to a convenience sample of multidisciplinary staff in a tertiary ICU. A snowball recruitment approach was used to target a sample size of 20 to 25. Two investigators performed word count and thematic analyses independently. Themes were cross-checked by a third investigator. Twenty-two questionnaires were completed. Respondents wrote the most text about disadvantages. Positive attitudinal beliefs included better respiratory function, reduced functional decline, and reduced muscle wasting/weakness. The main negative attitudinal beliefs were that mobilization is perceived as time consuming and poses a risk of line dislodgement/disconnection. Positive control beliefs (enablers) included increased staff availability, positive staff attitudes, engagement, and teamwork. Negative control beliefs (barriers) included unstable patient physiology and negative workplace culture. Intensive care unit staff expressed positive and negative attitudinal, normative, and control beliefs across the spectrum, and disadvantages were most frequently reported. Identified beliefs can be used to inform development of future interventions. Copyright © 2015 Elsevier Inc. All rights reserved.
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Kong, Jianping; Crissey, Mary Ann; Funakoshi, Shinsuke; Kreindler, James L.; Lynch, John P.
2011-01-01
Barrett's esophagus (BE) is an intestinal metaplasia that occurs in the setting of chronic acid and bile reflux and is associated with a risk for adenocarcinoma. Expression of intestine-specific transcription factors in the esophagus likely contributes to metaplasia development. Our objective was to explore the effects of an intestine-specific transcription factor when expressed in the mouse esophageal epithelium. Transgenic mice were derived in which the transcription factor Cdx2 is expressed in squamous epithelium using the murine Keratin-14 gene promoter. Effects of the transgene upon cell proliferation and differentiation, gene expression, and barrier integrity were explored. K14-Cdx2 mice express the Cdx2 transgene in esophageal squamous tissues. Cdx2 expression was associated with reduced basal epithelial cell proliferation and altered cell morphology. Ultrastructurally two changes were noted. Cdx2 expression was associated with dilated space between the basal cells and diminished cell-cell adhesion caused by reduced Desmocollin-3 mRNA and protein expression. This compromised epithelial barrier function, as the measured trans-epithelial electrical resistance (TEER) of the K14-Cdx2 epithelium was significantly reduced compared to controls (1189 Ohm*cm2 ±343.5 to 508 Ohm*cm2±92.48, p = 0.0532). Secondly, basal cells with features of a transitional cell type, intermediate between keratinocytes and columnar Barrett's epithelial cells, were observed. These cells had reduced keratin bundles and increased endoplasmic reticulum levels, suggesting the adoption of secretory-cell features. Moreover, at the ultrastructural level they resembled “Distinctive” cells associated with multilayered epithelium. Treatment of the K14-Cdx2 mice with 5′-Azacytidine elicited expression of BE-associated genes including Cdx1, Krt18, and Slc26a3/Dra, suggesting the phenotype could be advanced under certain conditions. We conclude that ectopic Cdx2 expression in keratinocytes alters cell proliferation, barrier function, and differentiation. These altered cells represent a transitional cell type between normal squamous and columnar BE cells. The K14-Cdx2 mice represent a useful model to study progression from squamous epithelium to BE. PMID:21494671
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Kong, Jianping; Crissey, Mary Ann; Funakoshi, Shinsuke; Kreindler, James L; Lynch, John P
2011-04-06
Barrett's esophagus (BE) is an intestinal metaplasia that occurs in the setting of chronic acid and bile reflux and is associated with a risk for adenocarcinoma. Expression of intestine-specific transcription factors in the esophagus likely contributes to metaplasia development. Our objective was to explore the effects of an intestine-specific transcription factor when expressed in the mouse esophageal epithelium. Transgenic mice were derived in which the transcription factor Cdx2 is expressed in squamous epithelium using the murine Keratin-14 gene promoter. Effects of the transgene upon cell proliferation and differentiation, gene expression, and barrier integrity were explored. K14-Cdx2 mice express the Cdx2 transgene in esophageal squamous tissues. Cdx2 expression was associated with reduced basal epithelial cell proliferation and altered cell morphology. Ultrastructurally two changes were noted. Cdx2 expression was associated with dilated space between the basal cells and diminished cell-cell adhesion caused by reduced Desmocollin-3 mRNA and protein expression. This compromised epithelial barrier function, as the measured trans-epithelial electrical resistance (TEER) of the K14-Cdx2 epithelium was significantly reduced compared to controls (1189 Ohm*cm(2) ±343.5 to 508 Ohm*cm(2)±92.48, p = 0.0532). Secondly, basal cells with features of a transitional cell type, intermediate between keratinocytes and columnar Barrett's epithelial cells, were observed. These cells had reduced keratin bundles and increased endoplasmic reticulum levels, suggesting the adoption of secretory-cell features. Moreover, at the ultrastructural level they resembled "Distinctive" cells associated with multilayered epithelium. Treatment of the K14-Cdx2 mice with 5'-Azacytidine elicited expression of BE-associated genes including Cdx1, Krt18, and Slc26a3/Dra, suggesting the phenotype could be advanced under certain conditions. We conclude that ectopic Cdx2 expression in keratinocytes alters cell proliferation, barrier function, and differentiation. These altered cells represent a transitional cell type between normal squamous and columnar BE cells. The K14-Cdx2 mice represent a useful model to study progression from squamous epithelium to BE.
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USDA-ARS?s Scientific Manuscript database
Barrier treatments can be effective in reducing host seeking mosquito vectors and provide an additional layer of passive defense, reducing disease risk. Devices designed to release spatial repellents or direct application of spatial repellents to artificial surfaces can serve as efficient barriers r...
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[Functions of participatory ergonomics programs in reducing work-related musculoskeletal disorders].
Guo, M J; Liu, J J; Yao, H Y
2016-08-10
Work-related musculoskeletal disorders (MSDs) are most commonly seen in all the occupational non-fatal injuries and illnesses for workers, especially those who are involved in labor-intensive industries. Participatory ergonomics is frequently used to prevent musculoskeletal disorders. This paper gives an overview of a historical perspective on the use of participatory ergonomics approach in reducing the health effects of labor-intensive industries. Progress, barriers and facilitators on the organization, implementation and evaluation of participatory ergonomics programs are studied. Participatory ergonomics seems a successful method to develop, prioritize measures to prevent MSDs. Participatory ergonomics can help industries reduce musculoskeletal injuries and disorders, improve workplace condition and promote health conditions of the workers.
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Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier.
Couch, Jessica A; Yu, Y Joy; Zhang, Yin; Tarrant, Jacqueline M; Fuji, Reina N; Meilandt, William J; Solanoy, Hilda; Tong, Raymond K; Hoyte, Kwame; Luk, Wilman; Lu, Yanmei; Gadkar, Kapil; Prabhu, Saileta; Ordonia, Benjamin A; Nguyen, Quyen; Lin, Yuwen; Lin, Zhonghua; Balazs, Mercedesz; Scearce-Levie, Kimberly; Ernst, James A; Dennis, Mark S; Watts, Ryan J
2013-05-01
Bispecific antibodies using the transferrin receptor (TfR) have shown promise for boosting antibody uptake in brain. Nevertheless, there are limited data on the therapeutic properties including safety liabilities that will enable successful development of TfR-based therapeutics. We evaluate TfR/BACE1 bispecific antibody variants in mouse and show that reducing TfR binding affinity improves not only brain uptake but also peripheral exposure and the safety profile of these antibodies. We identify and seek to address liabilities of targeting TfR with antibodies, namely, acute clinical signs and decreased circulating reticulocytes observed after dosing. By eliminating Fc effector function, we ameliorated the acute clinical signs and partially rescued a reduction in reticulocytes. Furthermore, we show that complement mediates a residual decrease in reticulocytes observed after Fc effector function is eliminated. These data raise important safety concerns and potential mitigation strategies for the development of TfR-based therapies that are designed to cross the blood-brain barrier.
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The menstrual cycle and the skin.
Raghunath, R S; Venables, Z C; Millington, G W M
2015-03-01
Perimenstrual exacerbations of dermatoses are commonly recognized, yet our knowledge of the underlying pathophysiological mechanisms remains imperfect. Research into the effects of oestrogen on the skin has provided evidence to suggest that oestrogen is associated with increases in skin thickness and dermal water content, improved barrier function, and enhanced wound healing. Research into the effects of progesterone suggests that the presence of various dermatoses correlates with peak levels of progesterone. Dermatoses that are exacerbated perimenstrually include acne, psoriasis, atopic eczema and irritant dermatitis, and possibly also erythema multiforme. Exacerbations occur at the peak levels of progesterone in the menstrual cycle. Underlying mechanisms include reduced immune and barrier functions as a result of cyclical fluctuations in oestrogen and/or progesterone. Autoimmune progesterone and oestrogen dermatitis are the best-characterized examples of perimenstrual cutaneous reactions to hormones produced during the menstrual cycle. In this review, we describe the current understanding of the menstrual cycle, and its effect on the skin and cutaneous disorders. © 2015 British Association of Dermatologists.
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The skin of fish as a transport epithelium: a review.
Glover, Chris N; Bucking, Carol; Wood, Chris M
2013-10-01
The primary function of fish skin is to act as a barrier. It provides protection against physical damage and assists with the maintenance of homoeostasis by minimising exchange between the animal and the environment. However in some fish, the skin may play a more active physiological role. This is particularly true in species that inhabit specialised environmental niches (e.g. amphibious and air-breathing fish such as the lungfish), those with physiological characteristics that may subvert the need for the integument as a barrier (e.g. the osmoconforming hagfish), and/or fish with anatomical modifications of the epidermis (e.g. reduced epithelial thickness). Using examples from different fish groups (e.g. hagfishes, elasmobranchs and teleosts), the importance of fish skin as a transport epithelium for gases, ions, nitrogenous waste products, and nutrients was reviewed. The role of the skin in larval fish was also examined, with early life stages often utilising the skin as a surrogate gill, prior to the development of a functional branchial epithelium.
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Diffusion of hydrogen into and through γ-iron by density functional theory
NASA Astrophysics Data System (ADS)
Chohan, Urslaan K.; Koehler, Sven P. K.; Jimenez-Melero, Enrique
2018-06-01
This study is concerned with the early stages of hydrogen embrittlement on an atomistic scale. We employed density functional theory to investigate hydrogen diffusion through the (100), (110) and (111) surfaces of γ-Fe. The preferred adsorption sites and respective energies for hydrogen adsorption were established for each plane, as well as a minimum energy pathway for diffusion. The H atoms adsorb on the (100), (110) and (111) surfaces with energies of ∼4.06 eV, ∼3.92 eV and ∼4.05 eV, respectively. The barriers for bulk-like diffusion for the (100), (110) and (111) surfaces are ∼0.6 eV, ∼0.5 eV and ∼0.7 eV, respectively. We compared these calculated barriers with previously obtained experimental data in an Arrhenius plot, which indicates good agreement between experimentally measured and theoretically predicted activation energies. Texturing austenitic steels such that the (111) surfaces of grains are preferentially exposed at the cleavage planes may be a possibility to reduce hydrogen embrittlement.
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Wang, Junling; Ma, Chao; Mu, Xiaowei; Cai, Wei; Liu, Longxiang; Zhou, Xia; Hu, Weizhao; Hu, Yuan
2018-06-15
Organic modification of MoSe 2 sheets is firstly achieved by Atherton-Todd reaction, aiming at the acquisition of multifunctional MoSe 2 hybrid. Simultaneous enhancements in fire safety and mechanical property of thermalplastic polyurethane (TPU) are obtained with the presence of this hybrid. Strong interfacial interactions between the functionalized MoSe 2 sheets and TPU can be obtained, making more efficient load transfer from the weak polymer chains to the robust sheets. Besides, more coherent barrier network may be formed in polymer matrix, restraining the diffusion of decomposed fragments and reducing the supply for combustion fuel. Consequently, the decreases in heat release are observed for polymer composites. Notably, the releases of toxic gases, such as HCN and CO, are also suppressed by this barrier network, resulting in the reductions in fire toxicity. This work may open a new door for the functionalization of MoSe 2 sheets and evoke significant developments in its promising applications. Copyright © 2018. Published by Elsevier B.V.
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Schottky-type grain boundaries in CCTO ceramics
NASA Astrophysics Data System (ADS)
Felix, A. A.; Orlandi, M. O.; Varela, J. A.
2011-10-01
In this work we studied electrical barriers existing at CaCu 3Ti 4O 12 (CCTO) ceramics using dc electrical measurements. CCTO pellets were produced by solid state reaction method and X-ray diffractograms showed which single phase polycrystalline samples were obtained. The samples were electrically characterized by dc and ac measurements as a function of temperature, and semiconductor theory was applied to analyze the barrier at grain boundaries. The ac results showed the sample's permittivity is almost constant ( 104) as function of temperature at low frequencies and it changes from 100 to 104 as the temperature increases at high frequencies. Using dc measurements as a function of temperature, the behavior of barriers was studied in detail. Comparison between Schottky and Poole-Frenkel models was performed, and results prove that CCTO barriers are more influenced by temperature than by electric field (Schottky barriers). Besides, the behavior of barrier width as function of temperature was also studied and experimental results confirm the theoretical assumptions.
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Barriers to activity and participation for stroke survivors in rural China.
Zhang, Lifang; Yan, Tiebin; You, Liming; Li, Kun
2015-07-01
To investigate environmental barriers reported by stroke survivors in the rural areas of China and to determine the impact of environmental barriers on activity and participation relative to demographic characteristics and body functioning. Cross-sectional survey. Structured interviews in the participants' homes. Community-dwelling stroke survivors in the rural areas of China (N=639). Not applicable. Activity and participation (Chinese version of the World Health Organization Disability Assessment Schedule 2.0), environmental barriers (Craig Hospital Inventory of Environmental Factors), neurological function (Canadian Neurological Scale), cognitive function (Abbreviated Mental Test), and depression (6-item Hamilton Rating Scale for Depression). Physical/structural barriers are the major impediment to activity and participation for these participants (odds ratio, 1.86 and 1.99 for activity and participation, respectively; P<.01). Services/assistance barriers primarily impede participation rather than activity (odds ratio, 1.58 in participation; P<.05). Physical/structural and services/assistance barriers were considered the dominant barriers to activity and participation for stroke survivors in the rural areas of China. Attitudinal/support and policy barriers did not emerge as serious concerns. To generate an enabling environment, physical/structural and services/assistance barriers are the environmental barriers to be decreased and eliminated first. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
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Probiotics promote endocytic allergen degradation in gut epithelial cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Song, Chun-Hua; Liu, Zhi-Qiang; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON
Highlights: Black-Right-Pointing-Pointer Knockdown of A20 compromised the epithelial barrier function. Black-Right-Pointing-Pointer The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Black-Right-Pointing-Pointer Antigens transported across A20-deficient HT-29 monolayers conserved antigenicity. Black-Right-Pointing-Pointer Probiotic proteins increased the expression of A20 in HT-29 cells. -- Abstract: Background and aims: Epithelial barrier dysfunction plays a critical role in the pathogenesis of allergic diseases; the mechanism is to be further understood. The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells. This study aims to elucidate the role of A20 in the maintenance of gut epithelial barriermore » function. Methods: Gut epithelial cell line, HT-29 cell, was cultured into monolayers to evaluate the barrier function in transwells. RNA interference was employed to knock down the A20 gene in HT-29 cells to test the role of A20 in the maintenance of epithelial barrier function. Probiotic derived proteins were extracted from the culture supernatants using to enhance the expression of A20 in HT-29 cells. Results: The results showed that the knockdown of A20 compromised the epithelial barrier function in HT-29 monolayers, mainly increased the intracellular permeability. The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Allergens collected from the transwell basal chambers of A20-deficient HT-29 monolayers still conserved functional antigenicity. Treating with probiotic derived proteins increased the expression of A20 in HT-29 cells and promote the barrier function. Conclusion: A20 plays an important role in the maintenance of epithelial barrier function as shown by HT-29 monolayer. Probiotic derived protein increases the expression of A20 and promote the HT-29 monolayer barrier function.« less
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Functional analysis of the sea urchin-derived arylsulfatase (Ars)-element in mammalian cells.
Watanabe, Satoshi; Watanabe, Sachiko; Sakamoto, Naoaki; Sato, Masahiro; Akasaka, Koji
2006-09-01
An insulator is a DNA sequence that has both enhancer-blocking activity, through its ability to modify the influence of neighboring cis-acting elements, and a barrier function that protects a transgene from being silenced by surrounding chromatin. Previously, we isolated and characterized a 582-bp-long element from the sea urchin arylsulfatase gene (Ars). This Ars-element was effective in sea urchin and Drosophila embryos and in plant cells. To investigate Ars-element activity in mammalian cells, we placed the element between the cytomegalovirus enhancer and a luciferase (luc) expression cassette. In contrast to controls lacking the Ars-element, NIH3T3 and 293T cells transfected with the element-containing construct displayed reduced luciferase activities. The Ars-element therefore acts as an enhancer-blocking element in mammalian cells. We assessed the barrier activity of the Ars-element using vectors in which a luc expression cassette was placed between two elements. Transfection experiments demonstrated that luc activity in these vectors was approximately ten-fold higher than in vectors lacking elements. Luc activities were well maintained even after 12 weeks in culture. Our observations demonstrate that the Ars-element has also a barrier activity. These results indicated that the Ars-element act as an insulator in mammalian cells.
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NASA Astrophysics Data System (ADS)
Emmons, D. J.; Weeks, D. E.; Eshel, B.; Perram, G. P.
2018-01-01
Simulations of an α-mode radio frequency dielectric barrier discharge are performed for varying mixtures of argon and helium at pressures ranging from 200 to 500 Torr using both zero and one-dimensional models. Metastable densities are analyzed as a function of argon-helium mixture and pressure to determine the optimal conditions, maximizing metastable density for use in an optically pumped rare gas laser. Argon fractions corresponding to the peak metastable densities are found to be pressure dependent, shifting from approximately 15% Ar in He at 200 Torr to 10% at 500 Torr. A decrease in metastable density is observed as pressure is increased due to a diminution in the reduced electric field and a quadratic increase in metastable loss rates through A r2* formation. A zero-dimensional effective direct current model of the dielectric barrier discharge is implemented, showing agreement with the trends predicted by the one-dimensional fluid model in the bulk plasma.
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Runge-Lenz wave packet in multichannel Stark photoionization
DOE Office of Scientific and Technical Information (OSTI.GOV)
Texier, F.
2005-01-01
In a previous slow photoionization experiment, modulations of ionization rings were manifested for Xe in a constant electric field. The present quantum calculation reveals that the modulation is an effect of the multichannel core scattering and of tunneling waves through the Coulomb-Stark potential barrier: the barrier reduces the number of oscillations that is observed relatively to the number of oscillations of the short range wave functions, and the nonhydrogenic core phase shifts modify the position of the ionization rings. We find a hidden difference, in the ionization process, for two close values of the energy depending on the resonance withmore » the barrier. The ionization intensity is interpreted as a Runge-Lenz wave packet; thus, we can relate the quantum modulation to the classical Coulomb-Stark trajectories. The Runge-Lenz wave packet differs from a usual temporal wave packet because its components are eigenstates of the Runge-Lenz vector z projection and its evolution is not temporal but spatial.« less
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Functions of an engineered barrier system for a nuclear waste repository in basalt
NASA Astrophysics Data System (ADS)
Coons, W. E.; Moore, E. L.; Smith, M. J.; Kaser, J. D.
1980-01-01
The functions of components selected for an engineered barrier system for a nuclear waste repository in basalt are defined providing a focal point for barrier material research and development by delineating the purpose and operative lifetime of each component of the engineered system. A five component system (comprised of waste form, canister, buffer, overpack, and tailored backfill) is discussed. Redundancy is provided by subsystems of physical and chemical barriers which act in concert with the geology to provide a formidable barrier to transport of hazardous materials to the biosphere. The barrier system is clarified by examples pertinent to storage in basalt, and a technical approach to barrier design and material selection is proposed.
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NASA Astrophysics Data System (ADS)
Salavati-fard, Taha; Caratzoulas, Stavros; Doren, Douglas J.
2017-03-01
Dehydration of the cycloadduct produced from the Diels-Alder reaction between 2,5-dimethylfuran and maleic anhydride to 3,6-dimethylphthalic anhydride exemplifies an important step in producing platform chemicals from biomass. The mechanisms of dehydration and catalytic effects of Lewis and Brønsted acids are investigated with density functional theory. The uncatalyzed reaction has a very high activation barrier (68.7 kcal/mol) in the gas phase and it is not significantly affected by solvation. With a Lewis acid catalyst, modeled as an alkali ion, the activation barriers are reduced, but intermediates are also stabilized. The net effect in vacuum is that the energetic span, or apparent activation energy of the catalytic cycle, is 77.9 kcal/mol, even higher than the barrier in the uncatalyzed case. In solution, however, the energetic span is reduced by as much as 20 kcal/mol, due to differences in the solvation energy of the transition states and intermediates. In the case of a Brønsted acid catalyst, modeled as a proton, the gas phase transition state energies are reduced even more than in the Lewis acid case, and there is no strong stabilization of the intermediates. The energetic span in vacuum is only 13.8 kcal/mol and is reduced even further in solution. Brønsted acid catalysis appears to be the preferred mechanism for dehydration of this cycloadduct. Since the Diels-Alder reaction that produced the molecule has previously been shown to be catalyzed by Brønsted acids, this suggests that a single catalyst could be used to accelerate both steps.
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Language barriers and patient safety risks in hospital care. A mixed methods study.
van Rosse, Floor; de Bruijne, Martine; Suurmond, Jeanine; Essink-Bot, Marie-Louise; Wagner, Cordula
2016-02-01
A language barrier has been shown to be a threat for quality of hospital care. International studies highlighted a lack of adequate noticing, reporting, and bridging of a language barrier. However, studies on the link between language proficiency and patient safety are scarce, especially in Europe. The present study investigates patient safety risks due to language barriers during hospitalization, and the way language barriers are detected, reported, and bridged in Dutch hospital care. We combined quantitative and qualitative methods in a sample of 576 ethnic minority patients who were hospitalized on 30 wards within four urban hospitals. The nursing and medical records of 17 hospital admissions of patients with language barriers were qualitatively analyzed, and complemented by 12 in-depth interviews with care providers and patients and/or their relatives to identify patient safety risks during hospitalization. The medical records of all 576 patients were screened for language barrier reports. The results were compared to patients' self-reported Dutch language proficiency. The policies of wards regarding bridging language barriers were compared with the reported use of interpreters in the medical records. Situations in hospital care where a language barrier threatened patient safety included daily nursing tasks (i.e. medication administration, pain management, fluid balance management) and patient-physician interaction concerning diagnosis, risk communication and acute situations. In 30% of the patients that reported a low Dutch proficiency, no language barrier was documented in the patient record. Relatives of patients often functioned as interpreter for them and professional interpreters were hardly used. The present study showed a wide variety of risky situations in hospital care for patients with language barriers. These risks can be reduced by adequately bridging the language barrier, which, in the first place, demands adequate detecting and reporting of a language barrier. This is currently not sufficiently done in most Dutch hospitals. Moreover, new solutions to bridge language barriers are needed for situations such as routine safety checks performed by nurses, in which a professional or even informal interpreter is not feasible. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Loma, P; Guzman-Aranguez, A; Pérez de Lara, M J; Pintor, J
2015-02-01
Here, we have studied the effects of the dinucleotide P(1), P(4)-Di (adenosine-5') tetraphosphate (Ap4 A) on corneal barrier function conferred by the tight junction (TJ) proteins and its possible involvement in ocular drug delivery and therapeutic efficiency. Experiments in vitro were performed using human corneal epithelial cells (HCLEs) treated with Ap4 A (100 μM) for 5 min. Western blot analysis and transepithelial electrical resistance (TEER) were performed to study the TJ protein levels and barrier function respectively. Intracellular pathways involved were determined using an ERK inhibitor and P2Y(2) receptor siRNAs. In in vivo assays with New Zealand rabbits, TJ integrity was examined by zonula occludens-1 (ZO-1) staining. The hypotensive compound 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) was used to assess improved delivery, measuring its levels by HPLC and measuring intraocular pressure using 5-MCA-NAT, P2Y receptor antagonists and P2Y2 siRNAs. Two hours after Ap4 A pretreatment, TJ protein levels in HCLE cells were reduced around 40% compared with control. TEER values were significantly reduced at 2 and 4 h (68 and 52% respectively). TJ reduction and ERK activation were blocked by the ERK inhibitor U012 and P2Y(2) siRNAs. In vivo, topical application of Ap4 A disrupted ZO-1 membrane distribution. 5-MCA-NAT levels in the aqueous humour were higher when Ap4 A was previously instilled and its hypotensive effect was also increased. This action was reversed by P2Y receptor antagonists and P2Y(2) siRNA. Ap4 A increased corneal epithelial barrier permeability. Its application could improve ocular drug delivery and consequently therapeutic efficiency. © 2014 The British Pharmacological Society.
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Lee, Jounghee; Park, Sohyun
2016-04-01
The sodium content of meals provided at worksite cafeterias is greater than the sodium content of restaurant meals and home meals. The objective of this study was to assess the relationships between sodium-reduction practices, barriers, and perceptions among food service personnel. We implemented a cross-sectional study by collecting data on perceptions, practices, barriers, and needs regarding sodium-reduced meals at 17 worksite cafeterias in South Korea. We implemented Chi-square tests and analysis of variance for statistical analysis. For post hoc testing, we used Bonferroni tests; when variances were unequal, we used Dunnett T3 tests. This study involved 104 individuals employed at the worksite cafeterias, comprised of 35 men and 69 women. Most of the participants had relatively high levels of perception regarding the importance of sodium reduction (very important, 51.0%; moderately important, 27.9%). Sodium reduction practices were higher, but perceived barriers appeared to be lower in participants with high-level perception of sodium-reduced meal provision. The results of the needs assessment revealed that the participants wanted to have more active education programs targeting the general population. The biggest barriers to providing sodium-reduced meals were use of processed foods and limited methods of sodium-reduced cooking in worksite cafeterias. To make the provision of sodium-reduced meals at worksite cafeterias more successful and sustainable, we suggest implementing more active education programs targeting the general population, developing sodium-reduced cooking methods, and developing sodium-reduced processed foods.
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Parikh, Ishita; Guo, Janet; Chuang, Kai-Hsiang; Zhong, Yu; Rempe, Ralf G.; Hoffman, Jared D.; Armstrong, Rachel; Bauer, Björn; Hartz, Anika M.S.; Lin, Ai-Ling
2016-01-01
Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of rapamycin expression, elevated endothelial nitric oxide synthase signaling, and increased ketone bodies utilization. With age, CR decelerated the rate of decline in CBF. The preserved CBF in hippocampus and frontal cortex were highly correlated with preserved memory and learning, and reduced anxiety, of the aging mice treated with CR (18-20 months of age). Our results suggest that dietary intervention started in the early stage (e.g., young adults) may benefit cognitive and mental reserve in aging. Understanding nutritional effects on neurovascular functions may have profound implications in human brain aging and age-related neurodegenerative disorders. PMID:27829242
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Rafferty, Jake L; Siepmann, J Ilja; Schure, Mark R
2008-08-15
Stationary phases with embedded polar groups possess several advantages over conventional alkylsilane phases, such as reduced peak tailing, enhanced selectivity for specific functional groups, and the ability to use a highly aqueous mobile phase. To gain a deeper understanding of the retentive properties of these reversed-phase packings, molecular simulations were carried out for three different stationary phases in contact with mobile phases of various water/methanol ratios. Two polar-embedded phases were modeled, namely, amide and ether containing, and compared to a conventional octadecylsilane phase. The simulations show that, due to specific hydrogen bond interactions, the polar-embedded phases take up significantly more solvent and are more ordered than their alkyl counterparts. Alkane and alcohol probe solutes indicate that the polar-embedded phases are less retentive than alkyl phases for nonpolar species, whereas polar species are more retained by them due to hydrogen bonding with the embedded groups and the increased amount of solvent within the stationary phase. This leads to a significant reduction of the free-energy barrier for the transfer of polar species from the mobile phase to residual silanols, and this reduced barrier provides a possible explanation for reduced peak tailing.
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Ischemic preconditioning enhances integrity of coronary endothelial tight junctions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Zhao; Jin, Zhu-Qiu, E-mail: zhu-qiu.jin@sdstate.edu
2012-08-31
Highlights: Black-Right-Pointing-Pointer Cardiac tight junctions are present between coronary endothelial cells. Black-Right-Pointing-Pointer Ischemic preconditioning preserves the structural and functional integrity of tight junctions. Black-Right-Pointing-Pointer Myocardial edema is prevented in hearts subjected to ischemic preconditioning. Black-Right-Pointing-Pointer Ischemic preconditioning enhances translocation of ZO-2 from cytosol to cytoskeleton. -- Abstract: Ischemic preconditioning (IPC) is one of the most effective procedures known to protect hearts against ischemia/reperfusion (IR) injury. Tight junction (TJ) barriers occur between coronary endothelial cells. TJs provide barrier function to maintain the homeostasis of the inner environment of tissues. However, the effect of IPC on the structure and function of cardiacmore » TJs remains unknown. We tested the hypothesis that myocardial IR injury ruptures the structure of TJs and impairs endothelial permeability whereas IPC preserves the structural and functional integrity of TJs in the blood-heart barrier. Langendorff hearts from C57BL/6J mice were prepared and perfused with Krebs-Henseleit buffer. Cardiac function, creatine kinase release, and myocardial edema were measured. Cardiac TJ function was evaluated by measuring Evans blue-conjugated albumin (EBA) content in the extravascular compartment of hearts. Expression and translocation of zonula occludens (ZO)-2 in IR and IPC hearts were detected with Western blot. A subset of hearts was processed for the observation of ultra-structure of cardiac TJs with transmission electron microscopy. There were clear TJs between coronary endothelial cells of mouse hearts. IR caused the collapse of TJs whereas IPC sustained the structure of TJs. IR increased extravascular EBA content in the heart and myocardial edema but decreased the expression of ZO-2 in the cytoskeleton. IPC maintained the structure of TJs. Cardiac EBA content and edema were reduced in IPC hearts. IPC enhanced the translocation of ZO-2 from cytosol to cytoskeleton. In conclusion, TJs occur in normal mouse heart. IPC preserves the integrity of TJ structure and function that are vulnerable to IR injury.« less
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Khode, Rajiv Tarachand; Shenoi, Pratima Ramakrishna; Kubde, Rajesh R.; Makade, Chetana S.; Wadekar, Kanchan D.; Khode, Priyanka Tarachand
2017-01-01
Aims: This study evaluated effect of infection control barriers on light intensity (LI) of light-curing unit (LCU) and microhardness of composite. Materials and Methods: Four different disposable barriers (n = 30) were tested against the control. LI for each barrier was measured with Lux meter. One hundred and fifty Teflon molds were equally divided into five groups of thirty each. Composite was filled in bulk in these molds and cured without and with barrier. Microhardness was evaluated on top and bottom surface of composite specimen with microhardness testing machine and hardness ratio (HR) was derived. Statistical Analysis Used: One-way analysis of variance, Tukey's honestly significant difference test, and paired t-test using SPSS version 18 software. Results: All barriers had significantly reduced the baseline LI of LCU (P < 0.0001), but only Cure Elastic Steri-Shield and latex cut glove pieces (LCGP) significantly reduced the microhardness of the composite (P < 0.05). However, HR determined inadequate curing only with LCGP. Conclusions: Although entire tested barrier significantly reduced the LI; none, except LCGP markedly affected the degree of cure of the composite. PMID:29279622
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Silicon oxide permeation barrier coating of PET bottles and foils
NASA Astrophysics Data System (ADS)
Steves, Simon; Deilmann, Michael; Awakowicz, Peter
2009-10-01
Modern packaging materials such as polyethylene terephthalate (PET) have displaced established materials in many areas of food and beverage packaging. Plastic packing materials offer are various advantages concerning production and handling. PET bottles for instance are non-breakable and lightweight compared to glass and metal containers. However, PET offers poor barrier properties against gas permeation. Therefore, the shelf live of packaged food is reduced. Permeation of gases can be reduced by depositing transparent plasma polymerized silicon oxide (SiOx) barrier coatings. A microwave (2.45 GHz) driven low pressure plasma reactor is developed based on a modified Plasmaline antenna to treat PET foils or bottles. To increase the barrier properties of the coatings furthermore a RF substrate bias (13.56 MHz) is applied. The composition of the coatings is analyzed by means of Fourier transform infrared (FTIR) spectroscopy regarding carbon and hydrogen content. Influence of gas phase composition and substrate bias on chemical composition of the coatings is discussed. A strong relation between barrier properties and film composition is found: good oxygen barriers are observed as carbon content is reduced and films become quartz-like. Regarding oxygen permeation a barrier improvement factor (BIF) of 70 is achieved.
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Usability Testing of the BRANCH Smartphone App Designed to Reduce Harmful Drinking in Young Adults
Deluca, Paolo; Drummond, Colin; Watson, Rod; Dunne, Jacklyn; Kimergård, Andreas
2017-01-01
Background Electronic screening and brief intervention (eSBI) apps demonstrate potential to reduce harmful drinking. However, low user engagement rates with eSBI reduce overall effectiveness of interventions. As “Digital Natives,” young adults have high expectations of app quality. Ensuring that the design, content, and functionality of an eSBI app are acceptable to young adults is an integral stage to the development process. Objective The objective of this study was to identify usability barriers and enablers for an app, BRANCH, targeting harmful drinking in young adults. Methods The BRANCH app contains a drinking diary, alcohol reduction goal setting functions, normative drinking feedback, and information on risks and advice for cutting down. The app includes a social feature personalized to motivate cutting down and to promote engagement with a point-based system for usage. Three focus groups were conducted with 20 users who had tested the app for 1 week. A detailed thematic analysis was undertaken. Results The first theme, “Functionality” referred to how users wanted an easy-to-use interface, with minimum required user-input. Poor functionality was considered a major usability barrier. The second theme, “Design” described how an aesthetic with minimum text, clearly distinguishable tabs and buttons and appealing infographics was integral to the level of usability. The final theme, “Content” described how participants wanted all aspects of the app to be automatically personalized to them, as well as providing them with opportunities to personalize the app themselves, with increased options for social connectivity. Conclusions There are high demands for apps such as BRANCH that target skilled technology users including young adults. Key areas to optimize eSBI app development that emerged from testing BRANCH with representative users include high-quality functionality, appealing aesthetics, and improved personalization. PMID:28790022
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Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro.
Chaitanya, Ganta V; Cromer, Walter E; Wells, Shannon R; Jennings, Merilyn H; Couraud, P Olivier; Romero, Ignacio A; Weksler, Babette; Erdreich-Epstein, Anat; Mathis, J Michael; Minagar, Alireza; Alexander, J Steven
2011-11-23
The glio-vascular unit (G-unit) plays a prominent role in maintaining homeostasis of the blood-brain barrier (BBB) and disturbances in cells forming this unit may seriously dysregulate BBB. The direct and indirect effects of cytokines on cellular components of the BBB are not yet unclear. The present study compares the effects of cytokines and cytokine-treated astrocytes on brain endothelial barrier. 3-dimensional transwell co-cultures of brain endothelium and related-barrier forming cells with astrocytes were used to investigate gliovascular barrier responses to cytokines during pathological stresses. Gliovascular barrier was measured using trans-endothelial electrical resistance (TEER), a sensitive index of in vitro barrier integrity. We found that neither TNF-α, IL-1β or IFN-γ directly reduced barrier in human or mouse brain endothelial cells or ECV-304 barrier (independent of cell viability/metabolism), but found that astrocyte exposure to cytokines in co-culture significantly reduced endothelial (and ECV-304) barrier. These results indicate that the barrier established by human and mouse brain endothelial cells (and other cells) may respond positively to cytokines alone, but that during pathological conditions, cytokines dysregulate the barrier forming cells indirectly through astrocyte activation involving reorganization of junctions, matrix, focal adhesion or release of barrier modulating factors (e.g. oxidants, MMPs). © 2011 Chaitanya et al; licensee BioMed Central Ltd.
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Kekenes-Huskey, Peter M.; Eun, Changsun; McCammon, J. A.
2015-01-01
Biochemical reaction networks consisting of coupled enzymes connect substrate signaling events with biological function. Substrates involved in these reactions can be strongly influenced by diffusion “barriers” arising from impenetrable cellular structures and macromolecules, as well as interactions with biomolecules, especially within crowded environments. For diffusion-influenced reactions, the spatial organization of diffusion barriers arising from intracellular structures, non-specific crowders, and specific-binders (buffers) strongly controls the temporal and spatial reaction kinetics. In this study, we use two prototypical biochemical reactions, a Goodwin oscillator, and a reaction with a periodic source/sink term to examine how a diffusion barrier that partitions substrates controls reaction behavior. Namely, we examine how conditions representative of a densely packed cytosol, including reduced accessible volume fraction, non-specific interactions, and buffers, impede diffusion over nanometer length-scales. We find that diffusion barriers can modulate the frequencies and amplitudes of coupled diffusion-influenced reaction networks, as well as give rise to “compartments” of decoupled reactant populations. These effects appear to be intensified in the presence of buffers localized to the diffusion barrier. These findings have strong implications for the role of the cellular environment in tuning the dynamics of signaling pathways. PMID:26342355
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Use of electrical barriers to deter movement of round goby
Savino, Jacqueline F.; Jude, David J.; Kostich, Melissa J.; Coutant, Charles C.
2001-01-01
An electrical barrier was chosen as a possible means to deter movement of round goby Neogobius melanostomus. Feasibility studies in a 2.1-m donut-shaped tank determined the electrical parameters necessary to inhibit round goby from crossing the 1-m stretch of the benthic, electrical barrier. Increasing electrical pulse duration and voltage increased effectiveness of the barrier in deterring round goby movement through the barrier. Differences in activity of round goby during daytime and nocturnal tests did not change the effectiveness of the barrier. In field verification studies, an electrical barrier was placed between two blocking nets in the Shiawassee River, Michigan. The barrier consisted of a 6-m wide canvas on which were laid four cables carrying the electrical current. Seven experiments were conducted, wherein 25 latex paint-marked round goby were introduced upstream of the electrical barrier and recovered 24 h later upstream, on, and downstream of the barrier. During control studies, round goby moved across the barrier within 20 min from release upstream. With the barrier on and using the prescribed electrical settings shown to inhibit passage in the laboratory, the only marked round goby found below the barrier were dead. At reduced pulse durations, a few round goby (mean one/test) were found alive, but debilitated, below the barrier. The electrical barrier could be incorporated as part of a program in reducing movement of adult round goby through artificial connections between watersheds.
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Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen
2013-01-01
Background Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). Methods The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Principal Findings Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Conclusion Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the “gut-liver axis”. PMID:24098410
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Ren, Zhigang; Cui, Guangying; Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen
2013-01-01
Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The "gut-liver axis" closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the "gut-liver axis".
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Multidimensionally constrained relativistic mean-field study of triple-humped barriers in actinides
NASA Astrophysics Data System (ADS)
Zhao, Jie; Lu, Bing-Nan; Vretenar, Dario; Zhao, En-Guang; Zhou, Shan-Gui
2015-01-01
Background: Potential energy surfaces (PES's) of actinide nuclei are characterized by a two-humped barrier structure. At large deformations beyond the second barrier, the occurrence of a third barrier was predicted by macroscopic-microscopic model calculations in the 1970s, but contradictory results were later reported by a number of studies that used different methods. Purpose: Triple-humped barriers in actinide nuclei are investigated in the framework of covariant density functional theory (CDFT). Methods: Calculations are performed using the multidimensionally constrained relativistic mean field (MDC-RMF) model, with the nonlinear point-coupling functional PC-PK1 and the density-dependent meson exchange functional DD-ME2 in the particle-hole channel. Pairing correlations are treated in the BCS approximation with a separable pairing force of finite range. Results: Two-dimensional PES's of 226,228,230,232Th and 232,235,236,238U are mapped and the third minima on these surfaces are located. Then one-dimensional potential energy curves along the fission path are analyzed in detail and the energies of the second barrier, the third minimum, and the third barrier are determined. The functional DD-ME2 predicts the occurrence of a third barrier in all Th nuclei and 238U . The third minima in 230 ,232Th are very shallow, whereas those in 226 ,228Th and 238U are quite prominent. With the functional PC-PK1 a third barrier is found only in 226 ,228 ,230Th . Single-nucleon levels around the Fermi surface are analyzed in 226Th, and it is found that the formation of the third minimum is mainly due to the Z =90 proton energy gap at β20≈1.5 and β30≈0.7 . Conclusions: The possible occurrence of a third barrier on the PES's of actinide nuclei depends on the effective interaction used in multidimensional CDFT calculations. More pronounced minima are predicted by the DD-ME2 functional, as compared to the functional PC-PK1. The depth of the third well in Th isotopes decreases with increasing neutron number. The origin of the third minimum is due to the proton Z =90 shell gap at relevant deformations.
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The Drosophila blood-brain barrier: development and function of a glial endothelium.
Limmer, Stefanie; Weiler, Astrid; Volkenhoff, Anne; Babatz, Felix; Klämbt, Christian
2014-01-01
The efficacy of neuronal function requires a well-balanced extracellular ion homeostasis and a steady supply with nutrients and metabolites. Therefore, all organisms equipped with a complex nervous system developed a so-called blood-brain barrier, protecting it from an uncontrolled entry of solutes, metabolites or pathogens. In higher vertebrates, this diffusion barrier is established by polarized endothelial cells that form extensive tight junctions, whereas in lower vertebrates and invertebrates the blood-brain barrier is exclusively formed by glial cells. Here, we review the development and function of the glial blood-brain barrier of Drosophila melanogaster. In the Drosophila nervous system, at least seven morphologically distinct glial cell classes can be distinguished. Two of these glial classes form the blood-brain barrier. Perineurial glial cells participate in nutrient uptake and establish a first diffusion barrier. The subperineurial glial (SPG) cells form septate junctions, which block paracellular diffusion and thus seal the nervous system from the hemolymph. We summarize the molecular basis of septate junction formation and address the different transport systems expressed by the blood-brain barrier forming glial cells.
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Containment of subsurface contaminants
Corey, John C.
1994-01-01
A barrier for reducing the spread of a plume of subsurface contaminants. The apparatus includes a well system for injecting a fluid, such as air, just outside and below the periphery of the plume. The fluid is injected at a pressure sufficient to lower the hydraulic conductivity of the soil from the point of injection to the surface thus establishing a curtain-like barrier to groundwater movement. The barrier is established upgradient of the plume to divert groundwater away, or preferably completely around the plume to reduce the flow of groundwater into or out of the plume. The barrier enables the remediation of the confined contamination and then, when the injection of the fluid is halted, the barrier quickly dissipates.
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Bina, Rena; Barak, Adi; Posmontier, Barbara; Glasser, Saralee; Cinamon, Tali
2018-01-01
Research on evidence-based practice (EBP) implementation in social work often neglects to include evaluation of application barriers. This qualitative study examined social workers' perspectives of provider- and organisational-related barriers to implementing a brief eight-session interpersonal therapy (IPT) intervention, a time-limited EBP that addresses reducing depressive symptoms and improving interpersonal functioning. Implementation took place in a primary care setting in Israel and was aimed at treating women who have postpartum depression (PPD) symptoms. Using purposeful sampling, 25 primary care licensed social workers were interviewed between IPT training and implementation regarding their perceived barriers to implementing IPT in practice. Data analysis was facilitated using a phenomenological approach, which entails identifying the shared themes and shared experiences of research participants regarding barriers to implementing IPT. Three themes emerged from the analysis of interviews: Perceived lack of flexibility of IPT intervention in comparison with more familiar methods social workers previously applied, specifically regarding the number of sessions and therapeutic topics included in the IPT protocol; insecurity and hesitance to gain experience with a new method of intervention; and organisational barriers, including difficulties with referrals, the perception of HMOs as health facilities not suitable for therapy, and time constraints. Addressing perceived barriers of social workers toward implementing EBPs, such as IPT for postpartum depression, during the training phase is crucial for enabling appropriate implementation. Future training should include examining practitioners' attitudes toward implementation of EBPs, as part of standardised training protocols. © 2017 John Wiley & Sons Ltd.
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Wang, Feng-yun; Su, Min; Zheng, Yong-qiu; Wang, Xiao-ge; Kang, Nan; Chen, Ting; Zhu, En-lin; Bian, Zhao-xiang; Tang, Xu-dong
2015-01-01
Aim: The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model. Methods: A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g·kg−1·d−1, ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4+ and CD8+ cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. Results: PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4+/CD8+ cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4+/CD8+ cell ratio and expression of IL-1β and IL-4. Conclusion: Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects. PMID:25960135
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Wang, Feng-yun; Su, Min; Zheng, Yong-qiu; Wang, Xiao-ge; Kang, Nan; Chen, Ting; Zhu, En-lin; Bian, Zhao-xiang; Tang, Xu-dong
2015-06-01
The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model. A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g · kg(-1) · d(-1), ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4(+) and CD8(+) cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4(+)/CD8(+) cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4(+)/CD8(+) cell ratio and expression of IL-1β and IL-4. Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.
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Naeem, Aishath S; Tommasi, Cristina; Cole, Christian; Brown, Stuart J; Zhu, Yanan; Way, Benjamin; Willis Owen, Saffron A G; Moffatt, Miriam; Cookson, William O; Harper, John I; Di, Wei-Li; Brown, Sara J; Reinheckel, Thomas; O'Shaughnessy, Ryan F L
2017-04-01
Filaggrin, which is encoded by the filaggrin gene (FLG), is an important component of the skin's barrier to the external environment, and genetic defects in FLG strongly associate with atopic dermatitis (AD). However, not all patients with AD have FLG mutations. We hypothesized that these patients might possess other defects in filaggrin expression and processing contributing to barrier disruption and AD, and therefore we present novel therapeutic targets for this disease. We describe the relationship between the mechanistic target of rapamycin complex 1/2 protein subunit regulatory associated protein of the MTOR complex 1 (RAPTOR), the serine/threonine kinase V-Akt murine thymoma viral oncogene homolog 1 (AKT1), and the protease cathepsin H (CTSH), for which we establish a role in filaggrin expression and processing. Increased RAPTOR levels correlated with decreased filaggrin expression in patients with AD. In keratinocyte cell cultures RAPTOR upregulation or AKT1 short hairpin RNA knockdown reduced expression of the protease CTSH. Skin of CTSH-deficient mice and CTSH short hairpin RNA knockdown keratinocytes showed reduced filaggrin processing, and the mouse had both impaired skin barrier function and a mild proinflammatory phenotype. Our findings highlight a novel and potentially treatable signaling axis controlling filaggrin expression and processing that is defective in patients with AD. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
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Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats
Bradaric, Brinda D.; Dodiya, Hemraj B.; Ohene-Nyako, Michael; Forsyth, Christopher B.; Keshavarzian, Ali; Shaikh, Maliha; Napier, T. Celeste
2018-01-01
The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1), two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults. PMID:29293553
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Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats.
Persons, Amanda L; Bradaric, Brinda D; Dodiya, Hemraj B; Ohene-Nyako, Michael; Forsyth, Christopher B; Keshavarzian, Ali; Shaikh, Maliha; Napier, T Celeste
2018-01-01
The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1), two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults.
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Reducing barriers to breast cancer care through Avon patient navigation programs.
Stanley, Sandte; Arriola, Kimberly Jacob; Smith, Shakiyla; Hurlbert, Marc; Ricci, Carolyn; Escoffery, Cam
2013-01-01
Avon Foundation for Women grantees provide breast cancer services through patient navigation (PN) in an effort to alleviate barriers to care among underserved women. To gain a better understanding of how PN programs function, this study explores variations in the use of navigators, types of services offered, description of clients they serve, tracking of treatment completion, and evaluation mechanisms. Fifty-six Avon PN programs funded since 2008 throughout the United States were contacted. An online survey was distributed to the grantees of which 44 (81%) complete responses were collected and analyzed. Clients were racially and ethnically diverse, mostly in the 40- to 64-year old age range (64%) and 91.6% with an average income of less than $30 000. Women were either uninsured (50.7%) or receiving Medicaid (32.4%). PN programs were both community and hospital-based (22.5%); many hospitals (35.2%) were described as safety nets (eg, provide a significant level of care to low-income, uninsured, vulnerable populations). On-site services included breast screening (eg, mammography and breast ultrasound) and treatment (eg, breast surgery and radiation therapy). Some barriers to care identified by the programs included transportation, access to appointments, language, and financial issues (eg, cost of screening and treatment specifically for those uninsured). More than 39% of programs provided care across the cancer continuum. Many Avon PN programs incorporated navigation services that span the cancer care continuum. They addressed disparities by offering navigation and on-site medical services to reduce multiple systems barriers and social issues related to breast care.
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Tonic regulation of vascular permeability
Curry, Fitz-Roy E.; Adamson, Roger H.
2014-01-01
Our major theme is that the layered structure of the endothelial barrier requires continuous activation of signaling pathways regulated by S1P and intracellular cAMP. These pathways modulate the adherens junction, continuity of tight junction strands, and the balance of synthesis and degradation of glycocalyx components. We evaluate recent evidence that baseline permeability is maintained by constant activity of mechanisms involving the small GTPases Rap1 and Rac1. In the basal state, the barrier is compromised when activities of the small GTPases are reduced by low S1P supply or delivery. With inflammatory stimulus, increased permeability can be understood in part as the action of signaling to reduce Rap1 and Rac1 activation. With the hypothesis that microvessel permeability and selectivity under both normal and inflammatory conditions are regulated by mechanisms that are continuously active it follows that when S1P or intracellular cAMP are elevated at the time of inflammatory stimulus, they can buffer changes induced by inflammatory agents and maintain normal barrier stability. When endothelium is exposed to inflammatory conditions and subsequently exposed to elevated S1P or intracellular cAMP, the same processes restore the functional barrier by first reestablishing the adherens junction, then modulating tight junctions and glycocalyx. In more extreme inflammatory conditions, loss of the inhibitory actions of Rac1 dependent mechanisms may promote expression of more inflammatory endothelial phenotypes by contributing to the up-regulation of RhoA dependent contractile mechanisms and the sustained loss of surface glycocalyx allowing access of inflammatory cells to the endothelium. PMID:23374222
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Ijssennagger, Noortje; Belzer, Clara; Hooiveld, Guido J; Dekker, Jan; van Mil, Saskia W C; Müller, Michael; Kleerebezem, Michiel; van der Meer, Roelof
2015-08-11
Colorectal cancer risk is associated with diets high in red meat. Heme, the pigment of red meat, induces cytotoxicity of colonic contents and elicits epithelial damage and compensatory hyperproliferation, leading to hyperplasia. Here we explore the possible causal role of the gut microbiota in heme-induced hyperproliferation. To this end, mice were fed a purified control or heme diet (0.5 μmol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme-induced hyperproliferation was shown to depend on the presence of the gut microbiota, because hyperproliferation was completely eliminated by antibiotics, although heme-induced luminal cytotoxicity was sustained in these mice. Colon mucosa transcriptomics revealed that antibiotics block heme-induced differential expression of oncogenes, tumor suppressors, and cell turnover genes, implying that antibiotic treatment prevented the heme-dependent cytotoxic micelles to reach the epithelium. Our results indicate that this occurs because antibiotics reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin-degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds and can drive mucin denaturation and microbial access to the mucus layer. This reduction results in formation of trisulfides that can be detected in vitro and in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis and thus as a proxy for mucus barrier reduction. In feces, antibiotics drastically decreased trisulfides but increased mucin polymers that can be lysed by sulfide. We conclude that the gut microbiota is required for heme-induced epithelial hyperproliferation and hyperplasia because of the capacity to reduce mucus barrier function.
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Choi, Isabella; Sharpe, Louise; Li, Stephen; Hunt, Caroline
2015-01-01
Internet treatments have the potential to improve access, especially for cultural groups who face considerable treatment barriers. This study explored the perceived barriers and likelihood of using Internet and face-to-face treatments for depression among Chinese and Caucasian Australian participants. Three-hundred ninety-five (289 Chinese, 106 Caucasian) primary care patients completed a questionnaire about depression history, previous help-seeking, perceived barriers to Internet and face-to-face treatment, and likelihood of using either treatment for depressive symptoms. Internet treatment reduced perceived barriers (including stigma, lack of motivation, concerns of bringing up upsetting feelings, time constraints, transport difficulties, and cost) for both groups to a similar degree, except for time constraints. There were heightened concerns about the helpfulness, suitability, and confidentiality of Internet treatments. Chinese participants and individuals with a probable depression history reported increased perceived barriers across treatments. Both Chinese and Caucasian groups preferred face-to-face treatment across depression severity. However, when age was controlled, there were no significant concerns about Internet treatment, and face-to-face treatment was only preferred for severe depression. Only 12 % of the entire sample refused to try Internet treatment for depression. Endorsement of perceived Internet treatment barriers (including concerns of bringing up upsetting feelings, that treatment would be unhelpful or unsuitable, lack of motivation, cost, cultural sensitivity, and confidentiality) reduced the likelihood to try Internet treatments. Internet treatment reduced perceived treatment barriers across groups, with encouraging support for Internet treatment as an acceptable form of receiving help. Negative concerns about Internet treatment need to be addressed to encourage use.
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Future Optical Communications Systems
2008-06-01
rich handsets are driving growth in the wireless backhaul market. Both the iPhone and Blackberry are growing in popularity. Figure 49 forecasts the...electronic emission and tunneling , and hetero-barrier leakage. In barrier thermo-electronic emission, the conduction band of the quantum well laser is...barrier can reduce the mod- ulation bandwidth of the laser and reduce high-temperature performance due to tunneling out of the p-n junction or due
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Lee, Ji-Hae; Choi, Chang Soon; Bae, Il-Hong; Choi, Jin Kyu; Park, Young-Ho; Park, Miyoung
2018-04-30
Although it is established that epidermal barrier disturbance and immune dysfunction resulting in IgE sensitization are critical factors in the development of cutaneous inflammation, the pathogenesis and targeted therapy of atopic dermatitis (AD)-specific pathways have still been unknown. Taking into account the fact that Th2 cytokines in AD have both unique and overlapping functions including increased epidermal thickening, inflammation, and decreased expressing of the barrier proteins keratinocyte differentiation, we sought to clarify our hypothesis that TRPV1 antagonist plays a critical role in skin barrier function and can be a therapeutic target for AD. AD-like dermatitis was induced in hairless mice by repeated oxazolone (Ox) challenges to hairless mice. The functional studies concerning skin barrier function, anti-inflammatory action, and molecular mechanism by TRPV1 antagonism were conducted by histopathological assays, ELISA, qPCR, western blotting, and skin blood flow measurement. Topically administered TRPV1 antagonist, PAC-14028 (Asivatrep: C 21 H 22 F 5 N 3 O 3 S), improved AD-like dermatitis and skin barrier functions, and restored the expression of epidermal differentiation markers. In addition, the PAC-14028 cream significantly inhibited cutaneous inflammation by decreasing the expression of serum IgE, and the epidermal expression of IL-4, and IL-13 in Ox-AD mice. These results may provide a novel insight into the molecular mechanism of PAC-14028 cream involved in anti-inflammatory effects and skin barrier functions by suppressing the multiple signaling pathways including IL-4/-13-mediated activation of JAK/STAT, TRPV1, and neuropeptides. PAC-14028 cream can be a potential therapeutic tool for the treatment of chronic inflammation and disrupted barrier function in patients with AD. Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
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Xin, Mei-Ling; Yang, Jia-Wen; Li, Yu
2017-07-11
The reaction pathways of PCB-77 in the atmosphere with ·OH, O 2 , NO x , and 1 O 2 were inferred based on density functional theory calculations with the 6-31G* basis set. The structures the reactants, transition states, intermediates, and products were optimized. The energy barriers and reaction heats were obtained to determine the energetically favorable reaction pathways. To study the solvation effect, the energy barriers and reaction rates for PCB-77 with different polar and nonpolar solvents (cyclohexane, benzene, carbon tetrachloride, chloroform, acetone, dichloromethane, ethanol, methanol, acetonitrile, dimethylsulfoxide, and water) were calculated. The results showed that ·OH preferentially added to the C5 atom of PCB-77, which has no Cl atom substituent, to generate the intermediate IM5. This intermediate subsequently reacted with O 2 via pathway A to generate IM5a, with an energy barrier of 7.27 kcal/mol and total reaction rate of 8.45 × 10 -8 cm 3 /molecule s. Pathway B involved direct dehydrogenation of IM5 to produce the OH-PCBs intermediate IM5b, with an energy barrier of 28.49 kcal/mol and total reaction rate of 1.15 × 10 -5 cm 3 /molecule s. The most likely degradation pathway of PCB-77 in the atmosphere is pathway A to produce IM5a. The solvation effect results showed that cyclohexane, carbon tetrachloride, and benzene could reduce the reaction energy barrier of pathway A. Among these solvents, the solvation effect of benzene was the largest, and could reduce the total reaction energy barrier by 25%. Cyclohexane, carbon tetrachloride, benzene, dichloromethane, acetone, and ethanol could increase the total reaction rate of pathway A. The increase in the reaction rate of pathway A with benzene was 8%. The effect of solvents on oxidative degradation of PCB-77 in the atmosphere is important. Graphical abstract The reaction pathways of PCB-77 in the atmosphere with •OH, O2, NOx, and 1O2 were inferred based on density functional theory calculations with the 6-31G* basis set. Different polar and nonpolar solvents: cyclohexane, benzene, carbon tetrachloride, chloroform, acetone, dichloromethane, ethanol, methanol, acetonitrile, dimethylsulfoxide, and water were selected to study the solvation effect on the favorable reaction pathways. The investigated results showed what kind of pathway was most likely to occur and the solvent effect on the reaction pathway.
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Liu, Fan; Cottrell, Jeremy J; Furness, John B; Rivera, Leni R; Kelly, Fletcher W; Wijesiriwardana, Udani; Pustovit, Ruslan V; Fothergill, Linda J; Bravo, David M; Celi, Pietro; Leury, Brian J; Gabler, Nicholas K; Dunshea, Frank R
2016-07-01
What is the central question of this study? Oxidative stress may play a role in compromising intestinal epithelial barrier integrity in pigs subjected to heat stress, but it is unknown whether an increase of dietary antioxidants (selenium and vitamin E) could alleviate gut leakiness in heat-stressed pigs. What is the main finding and its importance? Levels of dietary selenium (1.0 p.p.m.) and vitamin E (200 IU kg(-1) ) greater than those usually recommended for pigs reduced intestinal leakiness caused by heat stress. This finding suggests that oxidative stress plays a role in compromising intestinal epithelial barrier integrity in heat-stressed pigs and also provides a nutritional strategy for mitigating these effects. Heat stress compromises the intestinal epithelial barrier integrity of mammals through mechanisms that may include oxidative stress. Our objective was to test whether dietary supplementation with antioxidants, selenium (Se) and vitamin E (VE), protects intestinal epithelial barrier integrity in heat-stressed pigs. Female growing pigs (n = 48) were randomly assigned to four diets containing from 0.2 p.p.m. Se and 17 IU kg(-1) VE (control, National Research Council recommended) to 1.0 p.p.m. Se and 200 IU kg(-1) VE for 14 days. Six pigs from each dietary treatment were then exposed to either thermoneutral (20°C) or heat-stress conditions (35°C 09.00-17.00 h and 28°C overnight) for 2 days. Transepithelial electrical resistance and fluorescein isothiocyanate-dextran (4 kDa; FD4) permeability were measured in isolated jejunum and ileum using Ussing chambers. Rectal temperature, respiratory rate and intestinal HSP70 mRNA abundance increased (all P < 0.001), and respiratory alkalosis occurred, suggesting that pigs were heat stressed. Heat stress also increased FD4 permeability and decreased transepithelial electrical resistance (both P < 0.01). These changes were associated with changes indicative of oxidative stress, a decreased glutathione peroxidase (GPX) activity and an increased glutathione disulfide (GSSG)-to-glutathione (GSH) ratio (both P < 0.05). With increasing dosage of Se and VE, GPX-2 mRNA (P = 0.003) and GPX activity (P = 0.049) increased linearly, the GSSG:GSH ratio decreased linearly (P = 0.037), and the impacts of heat stress on intestinal barrier function were reduced (P < 0.05 for both transepithelial electrical resistance and FD4 permeability). In conclusion, in pigs an increase of dietary Se and VE mitigated the impacts of heat stress on intestinal barrier integrity, associated with a reduction in oxidative stress. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.
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Mapping the membrane-aqueous border for the voltage-sensing domain of a potassium channel.
Neale, Edward J; Rong, Honglin; Cockcroft, Christopher J; Sivaprasadarao, Asipu
2007-12-28
Voltage-sensing domains (VSDs) play diverse roles in biology. As integral components, they can detect changes in the membrane potential of a cell and couple these changes to activity of ion channels and enzymes. As independent proteins, homologues of the VSD can function as voltage-dependent proton channels. To sense voltage changes, the positively charged fourth transmembrane segment, S4, must move across the energetically unfavorable hydrophobic core of the bilayer, which presents a barrier to movement of both charged species and protons. To reduce the barrier to S4 movement, it has been suggested that aqueous crevices may penetrate the protein, reducing the extent of total movement. To investigate this hypothesis in a system containing fully functional channels in a native environment with an intact membrane potential, we have determined the contour of the membrane-aqueous border of the VSD of KvAP in Escherichia coli by examining the chemical accessibility of introduced cysteines. The results revealed the contour of the membrane-aqueous border of the VSD in its activated conformation. The water-inaccessible regions of S1 and S2 correspond to the standard width of the membrane bilayer (~28 A), but those of S3 and S4 are considerably shorter (> or = 40%), consistent with aqueous crevices pervading both the extracellular and intracellular ends. One face of S3b and the entire S3a were water-accessible, reducing the water-inaccessible region of S3 to just 10 residues, significantly shorter than for S4. The results suggest a key role for S3 in reducing the distance S4 needs to move to elicit gating.
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Reducing Barriers to Care in the Office-Based Health Care Setting for Children With Autism.
Bultas, Margaret W; McMillin, Stephen Edward; Zand, Debra H
2016-01-01
The purpose of this survey-design research study was to evaluate the usefulness of a researcher-developed tool designed to improve office-based health care services and to assess the barriers and resources affecting office-based health care services for children with autism spectrum disorder. Fifty-four health care providers (HCPs) and 59 parents participated in the study. HCPs reported child behaviors, communication, and fears as barriers to providing care, whereas parents reported child behavior, sensory issues, and feelings of a disconnect with the HCP as barriers. HCPs identified the parent as a key resource. Parent-identified resources included provider adaptations to the patient, including slowing down the delivery of care and environmental adaptations to the office. In addition, both HCPs and parents indicated that the researcher-developed tool would be useful in reducing barriers during the HCE. Reducing barriers and improving health care interactions during delivery of care for children with autism spectrum disorder has the potential to improve health outcomes. Copyright © 2016 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.
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Effects of Fe particle irradiation on human endothelial barrier structure and function
NASA Astrophysics Data System (ADS)
Sharma, Preety; Guida, Peter; Grabham, Peter
2014-07-01
Space travel involves exposure to biologically effective heavy ion radiation and there is consequently a concern for possible degenerative disorders in humans. A significant target for radiation effects is the microvascular system, which is crucial to healthy functioning of the tissues. Its pathology is linked to disrupted endothelial barrier function and is not only a primary event in a range of degenerative diseases but also an important influencing factor in many others. Thus, an assessment of the effects of heavy ion radiation on endothelial barrier function would be useful for estimating the risks of space travel. This study was aimed at understanding the effects of high LET Fe particles (1 GeV/n) and is the first investigation of the effects of charged particles on the function of the human endothelial barrier. We used a set of established and novel endpoints to assess barrier function after exposure. These include, trans-endothelial electrical resistance (TEER), morphological effects, localization of adhesion and cell junction proteins (in 2D monolayers and in 3D tissue models), and permeability of molecules through the endothelial barrier. A dose of 0.50 Gy was sufficient to cause a progressive reduction in TEER measurements that were significant 48 hours after exposure. Concurrently, there were morphological changes and a 14% loss of cells from monolayers. Gaps also appeared in the normally continuous cell-border localization of the tight junction protein - ZO-1 but not the Platelet endothelial cell adhesion molecule (PECAM-1) in both monolayers and in 3D vessel models. Disruption of barrier function was confirmed by increased permeability to 3 kDa and 10 kDa dextran molecules. A dose of 0.25 Gy caused no detectible change in cell number, morphology, or TEER, but did cause barrier disruption since there were gaps in the cell border localization of ZO-1 and an increased permeability to 3 kDa dextran. These results indicate that Fe particles potently have impact on human endothelial barrier function and represent a risk for degenerative diseases in the space environment.
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Barriers to ART adherence & follow ups among patients attending ART centres in Maharashtra, India.
Joglekar, N; Paranjape, R; Jain, R; Rahane, G; Potdar, R; Reddy, K S; Sahay, S
2011-12-01
Adherence to ART is a patient specific issue influenced by a variety of situations that a patient may encounter, especially in resource-limited settings. A study was conducted to understand factors and influencers of adherence to ART and their follow ups among patients attending ART centres in Maharashtra, India. Between January and March 2009, barriers to ART adherence among 32 patients at three selected ART centres functioning under national ART roll-out programme in Maharashtra, India, were studied using qualitative methods. Consenting patients were interviewed to assess barriers to ART adherence. Constant comparison method was used to identify grounded codes. Patients reported multiple barriers to ART adherence and follow up as (i) Financial barriers where the contributing factors were unemployment, economic dependency, and debt, (ii) social norm of attending family rituals, and fulfilling social obligations emerged as socio-cultural barriers, (iii) patients' belief, attitude and behaviour towards medication and self-perceived stigma were the reasons for sub-optimal adherence, and (iv) long waiting period, doctor-patient relationship and less time devoted in counselling at the center contributed to missed visits. Mainstreaming ART can facilitate access and address 'missed doses' due to travel and migration. A 'morning' and 'evening' ART centre/s hours may reduce work absenteeism and help in time management. Proactive 'adherence probing' and probing on internalized stigma might optimize adherence. Adherence probing to prevent transitioning to suboptimal adherence among patients stable on ART is recommended.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Yablonsky, A. N., E-mail: yablonsk@ipmras.ru; Zhukavin, R. Kh.; Bekin, N. A.
For SiGe/Si(001) epitaxial structures with two nonequivalent SiGe quantum wells separated by a thin Si barrier, the spectral and time characteristics of interband photoluminescence corresponding to the radiative recombination of excitons in quantum wells are studied. For a series of structures with two SiGe quantum wells different in width, the characteristic time of tunneling of charge carriers (holes) from the narrow quantum well, distinguished by a higher exciton recombination energy, to the wide quantum well is determined as a function of the Si barrier thickness. It is shown that the time of tunneling of holes between the Si{sub 0.8}5Ge{sub 0.15}more » layers with thicknesses of 3 and 9 nm steadily decreases from ~500 to <5 ns, as the Si barrier thickness is reduced from 16 to 8 nm. At intermediate Si barrier thicknesses, an increase in the photoluminescence signal from the wide quantum well is observed, with a characteristic time of the same order of magnitude as the luminescence decay time of the narrow quantum well. This supports the observation of the effect of the tunneling of holes from the narrow to the wide quantum well. A strong dependence of the tunneling time of holes on the Ge content in the SiGe layers at the same thickness of the Si barrier between quantum wells is observed, which is attributed to an increase in the effective Si barrier height.« less
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Effects of financial disadvantage on use and non-use of after hours care in Australia.
Kelaher, Margaret; Dunt, David; Day, Susan; Feldman, Peter
2006-11-01
Policy addressing the provision of primary care after hours (AH) is currently in flux because of concerns about equity of access and cost. In this study we examine the effects of socioeconomic disadvantage on access to AH care and episodes of not seeking AH care when needed among users and non-users of AH care. The effects of health on these relationships were also explored. The total sample consisted of 5538 users of AH care and 891 non-users of AH care who were randomly selected for telephone interviews. Factors determining AH care included accessibility that is structural barriers to use of care such as distance and transport, as well as affordability and availability. Logistic regression was used to determine the impact of financial disadvantage on episodes of not seeking AH care. Barriers to use of AH care and household health were subsequently added to the models to assess their impact. The results suggested that there were inequities in access to AH care but these were a function of barriers to AH care use rather than financial disadvantage per se. Accessibility and availability were significant barriers to use of AH clinics among both user and non-user samples. Affordability was only a significant barrier among users of AH care. The study suggests that policy aimed at reducing these barriers may effectively address inequities in AH care but that to be optimally effective policy change would also need to be accompanied by changes in consumer awareness.
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Apoplastic Diffusion Barriers in Arabidopsis
Schreiber, Lukas; Franke, Rochus Benni; Geldner, Niko; Reina-Pinto, José J.; Kunst, Ljerka
2013-01-01
During the development of Arabidopsis and other land plants, diffusion barriers are formed in the apoplast of specialized tissues within a variety of plant organs. While the cuticle of the epidermis is the primary diffusion barrier in the shoot, the Casparian strips and suberin lamellae of the endodermis and the periderm represent the diffusion barriers in the root. Different classes of molecules contribute to the formation of extracellular diffusion barriers in an organ- and tissue-specific manner. Cutin and wax are the major components of the cuticle, lignin forms the early Casparian strip, and suberin is deposited in the stage II endodermis and the periderm. The current status of our understanding of the relationships between the chemical structure, ultrastructure and physiological functions of plant diffusion barriers is discussed. Specific aspects of the synthesis of diffusion barrier components and protocols that can be used for the assessment of barrier function and important barrier properties are also presented. PMID:24465172
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2012-01-01
Background Linaclotide has been proposed as a treatment for the same gastrointestinal indications for which lubiprostone has been approved, chronic idiopathic constipation and irritable bowel syndrome with constipation. Stressors damage the epithelial cell barrier and cellular homeostasis leading to loss of these functions. Effects of active linaclotide on repair of barrier and cell function in pig jejunum after ischemia and in T84 cells after treatment with proinflammatory cytokines, interferon-γ and tumor necrosis factor-α were examined. Comparison with effects of lubiprostone, known to promote repair of barrier function was carried out. Results In ischemia-damaged pig jejunum, using measurements of transepithelial resistance, 3H-mannitol fluxes, short-circuit current (Cl− secretion) and occludin localization, active linaclotide failed to effectively promote repair of the epithelial barrier or recovery of short-circuit current, whereas lubiprostone promoted barrier repair and increased short-circuit current. In control pig jejunum, 1 μM linaclotide and 1 μM lubiprostone both caused similar increases in short-circuit current (Cl− secretion). In T84 cells, using measurements of transepithelial resistance, fluxes of fluorescent macromolecules, occludin and mitochondrial membrane potential, active linaclotide was virtually ineffective against damage caused by interferon-γ and tumor necrosis factor-α, while lubiprostone protected or promoted repair of epithelial barrier and cell function. Barrier protection/repair by lubiprostone was inhibited by methadone, a ClC-2 inhibitor. Linaclotide, but not lubiprostone increased [cGMP]i as expected and [Ca2+]i and linaclotide depolarized while lubiprostone hyperpolarized the T84 plasma membrane potential suggesting that lubiprostone may lead to greater cellular stability compared to linaclotide. In T84 cells, as found with linaclotide but not with lubiprostone, transepithelial resistance was slightly but significantly decreased by guanylin, STa and 8-bromo cGMP and fluorescent dextran fluxes were increased by guanylin. However the physiological implications of these small but statistically significant changes remain unclear. Conclusions Considering the physiological importance of epithelial barrier function and cell integrity and the known impact of stressors, the finding that lubiprostone, but not active linaclotide, exhibits the additional distinct property of effective protection or repair of the epithelial barrier and cell function after stress suggests potential clinical importance for patients with impaired or compromised barrier function such as might occur in IBS. PMID:22553939
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Cuppoletti, John; Blikslager, Anthony T; Chakrabarti, Jayati; Nighot, Prashant K; Malinowska, Danuta H
2012-05-03
Linaclotide has been proposed as a treatment for the same gastrointestinal indications for which lubiprostone has been approved, chronic idiopathic constipation and irritable bowel syndrome with constipation. Stressors damage the epithelial cell barrier and cellular homeostasis leading to loss of these functions. Effects of active linaclotide on repair of barrier and cell function in pig jejunum after ischemia and in T84 cells after treatment with proinflammatory cytokines, interferon-γ and tumor necrosis factor-α were examined. Comparison with effects of lubiprostone, known to promote repair of barrier function was carried out. In ischemia-damaged pig jejunum, using measurements of transepithelial resistance, (3)H-mannitol fluxes, short-circuit current (Cl(-) secretion) and occludin localization, active linaclotide failed to effectively promote repair of the epithelial barrier or recovery of short-circuit current, whereas lubiprostone promoted barrier repair and increased short-circuit current. In control pig jejunum, 1 μM linaclotide and 1 μM lubiprostone both caused similar increases in short-circuit current (Cl(-) secretion). In T84 cells, using measurements of transepithelial resistance, fluxes of fluorescent macromolecules, occludin and mitochondrial membrane potential, active linaclotide was virtually ineffective against damage caused by interferon-γ and tumor necrosis factor-α, while lubiprostone protected or promoted repair of epithelial barrier and cell function. Barrier protection/repair by lubiprostone was inhibited by methadone, a ClC-2 inhibitor. Linaclotide, but not lubiprostone increased [cGMP]i as expected and [Ca(2+)]i and linaclotide depolarized while lubiprostone hyperpolarized the T84 plasma membrane potential suggesting that lubiprostone may lead to greater cellular stability compared to linaclotide. In T84 cells, as found with linaclotide but not with lubiprostone, transepithelial resistance was slightly but significantly decreased by guanylin, STa and 8-bromo cGMP and fluorescent dextran fluxes were increased by guanylin. However the physiological implications of these small but statistically significant changes remain unclear. Considering the physiological importance of epithelial barrier function and cell integrity and the known impact of stressors, the finding that lubiprostone, but not active linaclotide, exhibits the additional distinct property of effective protection or repair of the epithelial barrier and cell function after stress suggests potential clinical importance for patients with impaired or compromised barrier function such as might occur in IBS.
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Gutiérrez-Colina, Ana M; Eaton, Cyd K; Lee, Jennifer L; Reed-Knight, Bonney; Loiselle, Kristin; Mee, Laura L; LaMotte, Julia; Liverman, Rochelle; Blount, Ronald L
2016-08-01
OBJECTIVE : To evaluate levels of executive functioning in a sample of adolescent and young adult (AYA) transplant recipients, and to examine executive functioning in association with barriers to adherence and medication nonadherence. METHOD : In all, 41 caregivers and 39 AYAs were administered self- and proxy-report measures. RESULTS : AYA transplant recipients have significant impairments in executive functioning abilities. Greater dysfunction in specific domains of executive functioning was significantly associated with more barriers to adherence and greater medication nonadherence. CONCLUSION : AYA transplant recipients are at increased risk for executive dysfunction. The assessment of executive functioning abilities may guide intervention efforts designed to decrease barriers to adherence and promote developmentally appropriate levels of treatment responsibility. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Chou, Pang-Yun; Chen, Shih-Heng; Chen, Chih-Hao; Chen, Shih-Hsien; Fong, Yi Teng; Chen, Jyh-Ping
2017-11-01
In this study, we aimed to assess whether thermo-responsive in-situ forming hydrogels based on poly(N-isopropylacrylamide) (PNIPAM) could prevent post-operative peritendinous adhesion. The clinical advantages of the thermo-responsive hydrogels are acting as barrier material to block penetration of fibroblasts, providing mobility and flexibility during application and enabling injection through a small opening to fill spaces of any shape after surgery. The thermo-responsiveness of hydrogels was determined to ensure their clinic uses. By grafting hydrophilic biopolymers chitosan (CS) and hyaluronic acid (HA) to PNIPAM, the copolymer hydrogels show enhanced water retention and lubrication, while reduced volume shrinkage during phase transition. In cell culture experiments, the thermo-responsive hydrogel has good biocompatibility and reduces fibroblast penetration. In animal experiments, the effectiveness of preventing post-operative peritendinous adhesion was studied in a rabbit deep flexor tendon model. From gross examination, histology, bending angles of joints, tendon gliding excursion and pull-out force, HA-CS-PNIPAM (HACPN) was confirmed to be the best barrier material to prevent post-operative peritendinous adhesion compared to PNIPAM and CS-PNIPAM (CPN) hydrogels and a commercial barrier film Seprafilm®. There was no significant difference in the breaking strength of HACPN-treated tendons and spontaneously healed ones, indicating HACPN hydrogel application did not interfere with normal tendon healing. We conclude that HACPN hydrogel can provide the best functional outcomes to significantly prevent post-operative tendon adhesion in vivo. We prepared thermo-responsive in-situ forming hydrogels based on poly(N-isopropylacrylamide) (PNIPAM) to prevent post-operative peritendinous adhesion. The injectable barrier hydrogel could have better anti-adhesive properties than current commercial products by acting as barrier material to block penetration of fibroblasts, providing mobility and flexibility during application and enabling injection through a small opening to fill spaces of any shape after surgery. The effectiveness of preventing post-operative peritendinous adhesion was studied in a rabbit deep flexor tendon model. From gross examination, histology, bending angles of joints, tendon gliding excursion and pull-out force, HA-CS-PNIPAM (HACPN) was confirmed to be the best barrier material to prevent post-operative peritendinous adhesion compared to PNIPAM and CS-PNIPAM (CPN) hydrogels and a commercial barrier film Seprafilm®. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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Complementary Barrier Infrared Detector (CBIRD) Contact Methods
NASA Technical Reports Server (NTRS)
Ting, David Z.; Hill, Cory J.; Gunapala, Sarath D.
2013-01-01
The performance of the CBIRD detector is enhanced by using new device contacting methods that have been developed. The detector structure features a narrow gap adsorber sandwiched between a pair of complementary, unipolar barriers that are, in turn, surrounded by contact layers. In this innovation, the contact adjacent to the hole barrier is doped n-type, while the contact adjacent to the electron barrier is doped p-type. The contact layers can have wider bandgaps than the adsorber layer, so long as good electrical contacts are made to them. If good electrical contacts are made to either (or both) of the barriers, then one could contact the barrier(s) directly, obviating the need for additional contact layers. Both the left and right contacts can be doped either n-type or ptype. Having an n-type contact layer next to the electron barrier creates a second p-n junction (the first being the one between the hole barrier and the adsorber) over which applied bias could drop. This reduces the voltage drop over the adsorber, thereby reducing dark current generation in the adsorber region.
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Liu, Xinchun; Zhou, Xiaoshu; Yuan, Wei
2014-10-15
In mammalian central nervous system (CNS), the integrity of the blood-spinal cord barrier (BSCB), formed by tight junctions (TJs) between adjacent microvascular endothelial cells near the basement membrane of capillaries and the accessory structures, is important for relatively independent activities of the cellular constituents inside the spinal cord. The barrier function of the BSCB are tightly regulated and coordinated by a variety of physiological or pathological factors, similar with but not quite the same as its counterpart, the blood-brain barrier (BBB). Herein, angiopoietin 1 (Ang1), an identified ligand of the endothelium-specific tyrosine kinase receptor Tie-2, was verified to regulate barrier functions, including permeability, junction protein interactions and F-actin organization, in cultured spinal cord microvascular endothelial cells (SCMEC) of rat through the activity of Akt. Besides, these roles of Ang1 in the BSCB in vitro were found to be accompanied with an increasing expression of epidermal growth factor receptor pathway substrate 8 (Eps8), an F-actin bundling protein. Furthermore, the silencing of Eps8 by lentiviral shRNA resulted in an antagonistic effect vs. Ang1 on the endothelial barrier function of SCMEC. In summary, the Ang1-Akt pathway serves as a regulator in the barrier function modulation of SCMEC via the actin-binding protein Eps8. Copyright © 2014 Elsevier Inc. All rights reserved.
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Barrier-protective function of intestinal epithelial Toll-like receptor 2.
Cario, E
2008-11-01
The intestinal epithelial cell (IEC) barrier plays an important role in maintaining mucosal immune homeostasis. Dysregulated IEC barrier function appears to trigger and perpetuate inflammation in inflammatory bowel diseases (IBD). Novel risk variants in the Toll-like receptor 2 (TLR2) gene have previously been associated with a more severe disease phenotype in a subgroup of IBD patients. Recent studies have provided important insights of the commensal and host defense mechanisms to maintain functional barrier integrity of the intestinal epithelium through TLR2. Deficient TLR2 signaling may imbalance commensal-dependent intestinal epithelial barrier defense, facilitating mucosal injury and leading to increased susceptibility of colitis. Treatment with a synthetic TLR2 ligand significantly suppresses mucosal inflammation by efficiently protecting tight junction-associated integrity of the intestinal epithelium in vivo. These beneficial effects may be supplemented by TLR2-induced anti-inflammatory immune responses (such as interleukin-10 production) in lamina propria mononuclear cells. Thus, cell-specific TLR2 targeting may offer a novel therapeutic approach to human IBD therapy by protecting IEC barrier function.
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Minding and mending the gap: Social psychological interventions to reduce educational disparities.
Spitzer, Brian; Aronson, Joshua
2015-03-01
Achievement gaps continue to garner a great deal of attention both in academic and in popular circles. Many students continue to struggle despite broad educational reforms aimed at narrowing these gaps in learning and performance. In this article, we review a number of social psychological interventions that show promise in reducing gaps in achievement, not by addressing structural barriers to achievement, but by helping students cope with threats to their identity that impair intellectual functioning and motivation. For example, interventions involving meditation, role models, emotional reappraisal, growth mindsets, imagining possible selves, self-affirmations, belongingness and cooperative learning have been shown to ameliorate threats to identity and raise achievement. We describe and evaluate these social psychological interventions. Many achievement gaps involve a psychological predicament: a threat to one's social identity or to one's sense of belonging. Students' implicit theories - how they mind the gap - can act as barriers to their success. By helping students cope with these threats, these theory-based interventions represent a genuine advance in the way schools may reduce gaps in achievement. These interventions show how students' educational success depends partly on fluid aspects of context - how tasks are framed, who else is in the room, or what they believe about intelligence. Because of this fluidity, these interventions may not work in all settings. Achievement gaps are ultimately caused by a variety of factors, both objective and subjective that produce inequality. The research reviewed here suggests that even without changes in objective barriers to success, brief psychological interventions can narrow what many see as intractable gaps in academic achievement. © 2015 The British Psychological Society.
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Dimethyl fumarate reduces the risk of mycotoxins via improving intestinal barrier and microbiota
Ma, Ning; Wu, Yi; Xie, Fei; Du, Kexin; Wang, Yuan; Shi, Linxin; Ji, Linbao; Liu, Tianyi; Ma, Xi
2017-01-01
The effects of dimethyl fumarate (DMF) on mycotoxins and animal growth performance are well documented. However, its mechanism of anti-mildew effects is still unknown. The current study investigated how DMF detoxified the mycotoxin and improved the growth performance using BALB/c mice model, especially its effects on intestinal barrier function and gut micro-ecology. Our study also compared with the ultraviolet radiation (UR) treatment, a traditional anti-mildew control (TC). The results indicated that the DMF treatment had a lower contents of mycotoxin, better growth performance and improved mucosal morphology (P < 0.05), accompanied with the decreased intestinal permeability and the tighter gut barrier. Moreover, the efficiency of DMF was better than TC (P < 0.05). 16S rRNA gene sequence analysis revealed that the richness and diversity of bacteria was increased in DMF treatment. The most abundant OTUs belonged to Firmicutes and Bacteroidetes, and their changes in DMF were more moderate than the TC group, suggesting a more stable micro-ecology and the positive impact of DMF on the biodiversity of intestine. Specifically, the increased abundance of bacteria producing short-chain fatty acids (SCFAs), such as Gemella, Roseburia, Bacillus and Bacteroides in DMF group and prebiotics such as Lactobacillus in TC group, suggested a more healthier microbial composition and distribution. These findings supported that DMF had significant effects on animal's growth performance and intestinal barrier function by modulating the pathway of nutrient absorption and increasing the diversity and balance of gut microbes, which also illuminate that DMF is more efficient than traditional anti-mildew method. PMID:28574825
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Ren, Aixia; Zhang, Weiqiang; Thomas, Hugh Greg; Barish, Amy; Berry, Stephen; Kiel, Jeffrey S.
2011-01-01
Background To evaluate the efficacy and tolerability of a tannic acid-based medical food, Cesinex®, in the treatment of diarrhea, and to investigate the mechanisms underlying its antidiarrheal effect. Methods Cesinex® was prescribed to six children and four adults with diarrhea. Patient records were retrospectively reviewed for the primary outcome. Cesinex® and its major component, tannic acid, were tested for their effects on cholera toxin-induced intestinal fluid secretion in mouse. Polarized human gut epithelial cells (HT29-CL19A cells) were used to investigate the effects of tannic acid on epithelial barrier properties, transepithelial chloride secretion, and cell viability. Results Successful resolution of diarrheal symptoms was reported in nine of ten patients receiving Cesinex®. Treatment of HT29-CL19A cells with clinically relevant concentrations of tannic acid (0.01–1 mg/ml) significantly increased transepithelial resistance and inhibited the CFTR-dependent or the calcium-activated Cl− secretion. Tannic acid could also improve the impaired epithelial barrier function induced by TNFα and inhibited the disrupting effect of TNFα on the epithelial barrier function in these cells. CTX-induced mouse intestinal fluid secretion was significantly reduced by administration of Cesinex® or tannic acid. Cesinex® has high antioxidant capacity. Conclusions Cesinex® demonstrates an effective and safety profile in treatment of diarrhea. The broad-spectrum antidiarrheal effect of Cesinex® can be attributed to a combination of factors: its ability to improve the epithelial barrier properties, to inhibit intestinal fluid secretion, and the high antioxidant property. PMID:21748285
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Lee, Jounghee; Park, Sohyun
2015-01-01
Objectives The sodium content of meals provided at worksite cafeterias is greater than the sodium content of restaurant meals and home meals. The objective of this study was to assess the relationships between sodium-reduction practices, barriers, and perceptions among food service personnel. Methods We implemented a cross-sectional study by collecting data on perceptions, practices, barriers, and needs regarding sodium-reduced meals at 17 worksite cafeterias in South Korea. We implemented Chi-square tests and analysis of variance for statistical analysis. For post hoc testing, we used Bonferroni tests; when variances were unequal, we used Dunnett T3 tests. Results This study involved 104 individuals employed at the worksite cafeterias, comprised of 35 men and 69 women. Most of the participants had relatively high levels of perception regarding the importance of sodium reduction (very important, 51.0%; moderately important, 27.9%). Sodium reduction practices were higher, but perceived barriers appeared to be lower in participants with high-level perception of sodium-reduced meal provision. The results of the needs assessment revealed that the participants wanted to have more active education programs targeting the general population. The biggest barriers to providing sodium-reduced meals were use of processed foods and limited methods of sodium-reduced cooking in worksite cafeterias. Conclusion To make the provision of sodium-reduced meals at worksite cafeterias more successful and sustainable, we suggest implementing more active education programs targeting the general population, developing sodium-reduced cooking methods, and developing sodium-reduced processed foods. PMID:27169011
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Synchronization of cyclic power grids: Equilibria and stability of the synchronous state
NASA Astrophysics Data System (ADS)
Xi, Kaihua; Dubbeldam, Johan L. A.; Lin, Hai Xiang
2017-01-01
Synchronization is essential for the proper functioning of power grids; we investigate the synchronous states and their stability for cyclic power grids. We calculate the number of stable equilibria and investigate both the linear and nonlinear stabilities of the synchronous state. The linear stability analysis shows that the stability of the state, determined by the smallest nonzero eigenvalue, is inversely proportional to the size of the network. We use the energy barrier to measure the nonlinear stability and calculate it by comparing the potential energy of the type-1 saddles with that of the stable synchronous state. We find that the energy barrier depends on the network size (N) in a more complicated fashion compared to the linear stability. In particular, when the generators and consumers are evenly distributed in an alternating way, the energy barrier decreases to a constant when N approaches infinity. For a heterogeneous distribution of generators and consumers, the energy barrier decreases with N. The more heterogeneous the distribution is, the stronger the energy barrier depends on N. Finally, we find that by comparing situations with equal line loads in cyclic and tree networks, tree networks exhibit reduced stability. This difference disappears in the limit of N →∞ . This finding corroborates previous results reported in the literature and suggests that cyclic (sub)networks may be applied to enhance power transfer while maintaining stable synchronous operation.
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Diet, Microbiome, and the Intestinal Epithelium: An Essential Triumvirate?
Guzman, Javier Rivera; Conlin, Victoria Susan; Jobin, Christian
2013-01-01
The intestinal epithelium represents a critical barrier protecting the host against diverse luminal noxious agents, as well as preventing the uncontrolled uptake of bacteria that could activate an immune response in a susceptible host. The epithelial monolayer that constitutes this barrier is regulated by a meshwork of proteins that orchestrate complex biological function such as permeability, transepithelial electrical resistance, and movement of various macromolecules. Because of its key role in maintaining host homeostasis, factors regulating barrier function have attracted sustained attention from the research community. This paper will address the role of bacteria, bacterial-derived metabolism, and the interplay of dietary factors in controlling intestinal barrier function. PMID:23586037
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Thermal barrier coating on high temperature industrial gas turbine engines
NASA Technical Reports Server (NTRS)
Carlson, N.; Stoner, B. L.
1977-01-01
The thermal barrier coating used was a yttria stabilized zirconia material with a NiCrAlY undercoat, and the base engine used to establish improvements was the P&WA FT50A-4 industrial gas turbine engine. The design benefits of thermal barrier coatings include simplified cooling schemes and the use of conventional alloys in the engine hot section. Cooling flow reductions and improved heating rates achieved with thermal barrier coating result in improved performance. Economic benefits include reduced power production costs and reduced fuel consumption. Over the 30,000 hour life of the thermal barrier coated parts, fuel savings equivalent to $5 million are projected and specific power (megawatts/mass of engine airflow) improvements on the order of 13% are estimated.
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Containment of subsurface contaminants
Corey, J.C.
1994-09-06
A barrier is disclosed for reducing the spread of a plume of subsurface contaminants. The apparatus includes a well system for injecting a fluid, such as air, just outside and below the periphery of the plume. The fluid is injected at a pressure sufficient to lower the hydraulic conductivity of the soil from the point of injection to the surface thus establishing a curtain-like barrier to groundwater movement. The barrier is established upgradient of the plume to divert groundwater away, or preferably completely around the plume to reduce the flow of groundwater into or out of the plume. The barrier enables the remediation of the confined contamination and then, when the injection of the fluid is halted, the barrier quickly dissipates. 5 figs.
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Zhao, Tian-Yu; Su, Li-Ping; Ma, Chun-Ye; Zhai, Xiao-Han; Duan, Zhi-Jun; Zhu, Ying; Zhao, Gang; Li, Chun-Yan; Wang, Li-Xia; Yang, Dong
2015-07-08
Intestinal barrier dysfunction is not only the consequence of liver cirrhosis, but also an active participant in the development of liver cirrhosis. Previous studies showed that external administration of insulin-like growth factor 1 (IGF-1) improved intestinal barrier function in liver cirrhosis. However, the mechanism of IGF-1 on intestinal barrier in liver cirrhosis is not fully elucidated. The present study aims to investigate the mechanisms of IGF-1 improving intestinal barrier function via regulating tight junctions in intestines. We used carbon tetrachloride induced liver cirrhotic rats to investigate the effect of IGF-1 on intestinal claudin-1 and occludin expressions, serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, severity of liver fibrosis, portal pressures, enterocytic apoptosis and lipopolysaccharides (LPS) levels in portal vein. The changes of IGF-1 in serum during the development of rat liver cirrhosis were also evaluated. Additionally, we assessed the effect of IGF-1 on claudin-1 and occludin expressions, changes of transepithelial electrical resistance (TEER) and apoptosis in Caco-2 cells to confirm in vivo findings. Serum IGF-1 levels were decreased in the development of rat liver cirrhosis, and external administration of IGF-1 restored serum IGF-1 levels. External administration of IGF-1 reduced serum ALT and AST levels, severity of liver fibrosis, LPS levels in portal vein, enterocytic apoptosis and portal pressure in cirrhotic rats. External administration of IGF-1 increased the expressions of claudin-1 and occludin in enterocytes, and attenuated tight junction dysfunction in intestines of cirrhotic rats. LPS decreased TEER in Caco-2 cell monolayer. LPS also decreased claudin-1 and occludin expressions and increased apoptosis in Caco-2 cells. Furthermore, IGF-1 attenuated the effect of LPS on TEER, claudin-1 expression, occludin expression and apoptosis in Caco-2 cells. Tight junction dysfunction develops during the development of liver cirrhosis, and endotoxemia will develop subsequently. Correspondingly, increased endotoxin in portal system worsens tight junction dysfunction via decreasing intestinal occludin and claudin-1 expressions and increasing enterocytic apoptosis. Endotoxemia and intestinal barrier dysfunction form a vicious circle. External administration of IGF-1 breaks this vicious circle. Improvement of tight junctions might be one possible mechanism of the restoration of intestinal barrier function mediated by IGF-1.
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Kortekaas Krohn, I; Callebaut, I; Alpizar, Y A; Steelant, B; Van Gerven, L; Skov, P S; Kasran, A; Talavera, K; Wouters, M M; Ceuppens, J L; Seys, S F; Hellings, P W
2018-05-01
Nasal hyperreactivity (NHR) is an important clinical feature of allergic rhinitis (AR). The efficacy of MP29-02 (azelastine hydrochloride (AZE) and fluticasone propionate [FP]) nasal spray on local inflammatory mediators and NHR in AR is unknown. We tested if MP29-02 decreases inflammatory mediators and NHR in AR and if this effect is due to restoration of nasal epithelial barrier function. A 4-week double-blinded placebo-controlled trial with MP29-02 treatment was conducted in 28 patients with house dust mite (HDM) AR. The presence of NHR was evaluated by measuring reduction in nasal flow upon cold dry air exposure. The effects of AZE ± FP on barrier integrity and airway inflammation were studied in a murine model of HDM-induced NHR and on reduced activation of murine sensory neurons and human mast cells. MP29-02 but not placebo reduced NHR (P < .0001 vs P = .21), levels of substance P (P = .026 vs P = .941), and β-hexosaminidase (P = .036 vs P = .632) in human nasal secretions. In wild-type C57BL6 mice, the reduction in β-hexosaminidase levels (P < .0001) by AZE + FP treatment upon HDM challenge was found in parallel with a decreased transmucosal passage (P = .0012) and completely reversed eosinophilic inflammation (P = .0013). In vitro, repeated applications of AZE + FP desensitized sensory neurons expressing the transient receptor potential channels TRPA1 and TRPV1. AZE + FP reduced MC degranulation to the same extent as AZE alone. MP29-02 treatment reduces inflammatory mediators and NHR in AR. The effects of AZE + FP on MC degranulation, nasal epithelial barrier integrity, and TRP channels provide novel insights into the pathophysiology of allergic rhinitis. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
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Gaudet, Andrew D; Mandrekar-Colucci, Shweta; Hall, Jodie C E; Sweet, David R; Schmitt, Philipp J; Xu, Xinyang; Guan, Zhen; Mo, Xiaokui; Guerau-de-Arellano, Mireia; Popovich, Phillip G
2016-08-10
Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers including inflammation. microRNA (miR)-155-5p is a small, noncoding RNA that negatively regulates mRNA translation. In macrophages, miR-155-5p is induced by inflammatory stimuli and elicits a response that could be toxic after SCI. miR-155 may also independently alter expression of genes that regulate axon growth in neurons. Here, we hypothesized that miR-155 deletion would simultaneously improve axon growth and reduce neuroinflammation after SCI by acting on both neurons and macrophages. New data show that miR-155 deletion attenuates inflammatory signaling in macrophages, reduces macrophage-mediated neuron toxicity, and increases macrophage-elicited axon growth by ∼40% relative to control conditions. In addition, miR-155 deletion increases spontaneous axon growth from neurons; adult miR-155 KO dorsal root ganglion (DRG) neurons extend 44% longer neurites than WT neurons. In vivo, miR-155 deletion augments conditioning lesion-induced intraneuronal expression of SPRR1A, a regeneration-associated gene; ∼50% more injured KO DRG neurons expressed SPRR1A versus WT neurons. After dorsal column SCI, miR-155 KO mouse spinal cord has reduced neuroinflammation and increased peripheral conditioning-lesion-enhanced axon regeneration beyond the epicenter. Finally, in a model of spinal contusion injury, miR-155 deletion improves locomotor function at postinjury times corresponding with the arrival and maximal appearance of activated intraspinal macrophages. In miR-155 KO mice, improved locomotor function is associated with smaller contusion lesions and decreased accumulation of inflammatory macrophages. Collectively, these data indicate that miR-155 is a novel therapeutic target capable of simultaneously overcoming neuron-intrinsic and neuron-extrinsic barriers to repair after SCI. Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers, including inflammation. Here, new data show that deleting microRNA-155 (miR-155) affects both mechanisms and improves repair and functional recovery after SCI. Macrophages lacking miR-155 have altered inflammatory capacity, which enhances neuron survival and axon growth of cocultured neurons. In addition, independent of macrophages, adult miR-155 KO neurons show enhanced spontaneous axon growth. Using either spinal cord dorsal column crush or contusion injury models, miR-155 deletion improves indices of repair and recovery. Therefore, miR-155 has a dual role in regulating spinal cord repair and may be a novel therapeutic target for SCI and other CNS pathologies. Copyright © 2016 the authors 0270-6474/16/368516-17$15.00/0.
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Thermal barrier coatings application in diesel engines
NASA Technical Reports Server (NTRS)
Fairbanks, J. W.
1995-01-01
Commercial use of thermal barrier coatings in diesel engines began in the mid 70's by Dr,. Ingard Kvernes at the Central Institute for Industrial Research in Oslo, Norway. Dr. Kvernes attributed attack on diesel engine valves and piston crowns encountered in marine diesel engines in Norwegian ships as hot-corrosion attributed to a reduced quality of residual fuel. His solution was to coat these components to reduce metal temperature below the threshold of aggressive hot-corrosion and also to provide protection. The Department of Energy has supported thermal barrier coating development for diesel engine applications. In the Clean Diesel - 50 Percent Efficient (CD-50) engine for the year 2000, thermal barrier coatings will be used on piston crowns and possibly other components. The primary purpose of the thermal barrier coatings will be to reduce thermal fatigue as the engine peak cylinder pressure will nearly be doubled. As the coatings result in higher available energy in the exhaust gas, efficiency gains are achieved through use of this energy by turbochargers, turbocompounding or thermoelectric generators.
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Fusion cross sections for reactions involving medium and heavy nucleus-nucleus systems
NASA Astrophysics Data System (ADS)
Atta, Debasis; Basu, D. N.
2014-12-01
Existing data on near-barrier fusion excitation functions of medium and heavy nucleus-nucleus systems have been analyzed by using a simple diffused-barrier formula derived assuming the Gaussian shape of the barrier-height distributions. The fusion cross section is obtained by folding the Gaussian barrier distribution with the classical expression for the fusion cross section for a fixed barrier. The energy dependence of the fusion cross section, thus obtained, provides good description to the existing data on near-barrier fusion and capture excitation functions for medium and heavy nucleus-nucleus systems. The theoretical values for the parameters of the barrier distribution are estimated which can be used for fusion or capture cross-section predictions that are especially important for planning experiments for synthesizing new superheavy elements.
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Song, Ji Youn; Kang, Hyun A; Kim, Mi-Yeon; Park, Young Min; Kim, Hyung Ok
2004-03-01
Superficial chemical peeling and microdermabrasion have become increasingly popular methods for producing facial rejuvenation. However, there are few studies reporting the skin barrier function changes after these procedures. To evaluate objectively the degree of damage visually and the time needed for the skin barrier function to recover after glycolic acid peeling and aluminum oxide crystal microdermabrasion using noninvasive bioengineering methods. Superficial chemical peeling using 30%, 50%, and 70% glycolic acid and aluminum oxide crystal microdermabrasion were used on the volar forearm of 13 healthy women. The skin response was measured by a visual observation and using an evaporimeter, corneometer, and colorimeter before and after peeling at set time intervals. Both glycolic acid peeling and aluminum oxide crystal microdermabrasion induced significant damage to the skin barrier function immediately after the procedure, and the degree of damage was less severe after the aluminum oxide crystal microdermabrasion compared with glycolic acid peeling. The damaged skin barrier function had recovered within 24 hours after both procedures. The degree of erythema induction was less severe after the aluminum oxide crystal microdermabrasion compared with the glycolic acid peeling procedure. The degree of erythema induced after the glycolic acid peeling procedure was not proportional to the peeling solution concentration used. The erythema subsided within 1 day after the aluminum oxide crystal microdermabrasion procedure and within 4 days after the glycolic acid peeling procedure. These results suggest that the skin barrier function is damaged after the glycolic acid peeling and aluminum oxide crystal microdermabrasion procedure but recovers within 1 to 4 days. Therefore, repeating the superficial peeling procedure at 2-week intervals will allow sufficient time for the damaged skin to recover its barrier function.
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Yeh, Po-An; Liu, Ya-Hsin; Chu, Wei-Chen; Liu, Jia-Yu; Sun, Y Henry
2018-05-02
Expansion of poly-glutamine (polyQ) stretches in several proteins has been linked to neurodegenerative diseases. The effects of polyQ-expanded proteins on neurons have been extensively studied, but their effects on glia remain unclear. We found that expression of distinct polyQ proteins exclusively in all glia or specifically in the blood-brain barrier (BBB) and blood-retina barrier (BRB) glia caused cell-autonomous impairment of BBB/BRB integrity, suggesting that BBB/BRB glia are most vulnerable to polyQ-expanded proteins. Furthermore, we also found that BBB/BRB leakage in Drosophila is reflected in reversed waveform polarity based on electroretinography (ERG), making ERG a sensitive method to detect BBB/BRB leakage. The polyQ-expanded protein Atxn3-84Q forms aggregates, induces BBB/BRB leakage, restricts Drosophila lifespan, and reduces the level of Repo (a pan-glial transcriptional factor required for glial differentiation). Expression of Repo in BBB/BRB glia can rescue BBB/BRB leakage, suggesting that the reduced expression of Repo is important for the effect of polyQ on BBB/BRB impairment. Coexpression of the chaperon HSP40 and HSP70 effectively rescues the effects of Atxn3-84Q, indicating that polyQ protein aggregation in glia is deleterious. Intriguingly, coexpression of wildtype Atxn3-27Q can also rescue BBB/BRB impairment, suggesting that normal polyQ protein may have a protective function.
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Total Quality Management (TQM): Group Dynamics Workshop
1990-05-15
interactions with other OSD decision-making bodies. " Remove barriers /facilitate implementation. " Direct action on unresolved process problems referred...TQM leadership. - Total Quality Management FUNCTIONS: * Translate goals to tangible internal initiatives. " Remove barriers . " Establish and...Quality Management FUNCTIONS: • Identify and remove barriers . " Develop practical process improvements. " Install solutions and measurement systems for
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Aghapour, Mahyar; Raee, Pourya; Moghaddam, Seyed Javad; Hiemstra, Pieter S; Heijink, Irene H
2018-02-01
The epithelial lining of the airway forms the first barrier against environmental insults, such as inhaled cigarette smoke, which is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). The barrier is formed by airway epithelial junctions, which are interconnected structures that restrict permeability to inhaled pathogens and environmental stressors. Destruction of the epithelial barrier not only exposes subepithelial layers to hazardous agents in the inspired air, but also alters the normal function of epithelial cells, which may eventually contribute to the development of COPD. Of note, disruption of epithelial junctions may lead to modulation of signaling pathways involved in differentiation, repair, and proinflammatory responses. Epithelial barrier dysfunction may be particularly relevant in COPD, where repeated injury by cigarette smoke exposure, pathogens, inflammatory mediators, and impaired epithelial regeneration may compromise the barrier function. In the current review, we discuss recent advances in understanding the mechanisms of barrier dysfunction in COPD, as well as the molecular mechanisms that underlie the impaired repair response of the injured epithelium in COPD and its inability to redifferentiate into a functionally intact epithelium.
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Universal potential-barrier penetration by initially confined wave packets
NASA Astrophysics Data System (ADS)
Granot, Er'El; Marchewka, Avi
2007-07-01
The dynamics of an initially sharp-boundary wave packet in the presence of an arbitrary potential barrier is investigated. It is shown that the penetration through the barrier is universal in the sense that it depends only on the values of the wave function and its derivatives at the boundary. The dependence on the derivatives vanishes at long distances from the barrier, where the dynamics is governed solely by the initial value of the wave function at the boundary.
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Lee, J Scott; Wang, Ruth X; Alexeev, Erica E; Lanis, Jordi M; Battista, Kayla D; Glover, Louise E; Colgan, Sean P
2018-04-20
Intestinal epithelial cells form a selectively permeable barrier to protect colon tissues from luminal microbiota and antigens and to mediate nutrient, fluid, and waste flux in the intestinal tract. Dysregulation of the epithelial cell barrier coincides with profound shifts in metabolic energy, especially in the colon, which exists in an energetically depleting state of physiological hypoxia. However, studies that systematically examine energy flux and adenylate metabolism during intestinal epithelial barrier development and restoration after disruption are lacking. Here, to delineate barrier-related energy flux, we developed an HPLC-based profiling method to track changes in energy flux and adenylate metabolites during barrier development and restoration. Cultured epithelia exhibited pooling of phosphocreatine and maintained ATP during barrier development. EDTA-induced epithelial barrier disruption revealed that hypoxanthine levels correlated with barrier resistance. Further studies uncovered that hypoxanthine supplementation improves barrier function and wound healing and that hypoxanthine appears to do so by increasing intracellular ATP, which improved cytoskeletal G- to F-actin polymerization. Hypoxanthine supplementation increased the adenylate energy charge in the murine colon, indicating potential to regulate adenylate energy charge-mediated metabolism in intestinal epithelial cells. Moreover, experiments in a murine colitis model disclosed that hypoxanthine loss during active inflammation correlates with markers of disease severity. In summary, our results indicate that hypoxanthine modulates energy metabolism in intestinal epithelial cells and is critical for intestinal barrier function. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
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Lee, Byeong Ryong; Kim, Tae Geun
2017-01-01
This article reports the electrical and optical properties of the reduced graphene oxide (RGO)/single-walled carbon nanotube (SWCNT) films using various p-type dopants and their application to GaN-based light-emitting diodes. To enhance the current injection and spreading of the RGO/SWCNT films on the light-emitting diodes (LEDs), we increased the work function (Φ) of the films using chemical doping with AuCl₃, poly(3,4-ethylenedioxythiophene) oxidized with poly(4-styrenesulfonate) (PEDOT:PSS) and MoO₃; thereby reduced the Schottky barrier height between the RGO/SWCNT films and p-GaN. By comparison, LEDs fabricated with work-function-tuned RGO/SWCNT film doped with MoO₃ exhibited the decrease of the forward voltage from 5.3 V to 5.02 V at 20 mA and the increase of the output power up to 1.26 times. We also analyzed the current injection mechanism using ultraviolet photoelectron spectroscopy and X-ray photoelectron spectroscopy.
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Wei, Jia; Zhou, Yu; Besner, Gail E
2015-07-01
Necrotizing enterocolitis (NEC) is associated with loss of neurons and glial cells in the enteric nervous system (ENS). Our goal was to determine whether enteric neural stem cell (NSC) transplantation, in conjunction with heparin-binding epidermal growth factor-like growth factor (HB-EGF), could protect against experimental NEC. In vitro, HB-EGF on NSC proliferation and migration, and the effects of receptors utilized by HB-EGF to exert these effects, were determined. In vivo, mouse pups were exposed to experimental NEC and treated with NSC alone, HB-EGF alone, NSC+HB-EGF, or HB-EGF overexpressing NSC. NSC engraftment and differentiation into neurons in the ENS, intestinal injury, intestinal permeability, and intestinal motility were determined. HB-EGF promoted NSC proliferation via ErbB-1 receptors and enhanced NSC migration via ErbB-1, ErbB-4, and Nardilysin receptors. HB-EGF significantly enhanced the engraftment of transplanted NSC into the ENS during NEC. NSC transplantation significantly reduced NEC incidence and improved gut barrier function and intestinal motility, and these effects were augmented by simultaneous administration of HB-EGF or by transplantation of HB-EGF overexpressing NSC. HB-EGF promotes NSC proliferation and migration. HB-EGF and NSC reduce intestinal injury and improve gut barrier function and intestinal motility in experimental NEC. Combined HB-EGF and NSC transplantation may represent a potential future therapy to prevent NEC.
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Water relations in cutover peatlands
NASA Astrophysics Data System (ADS)
Price, Jonathan S.; Ketcheson, Scott J.
Sphagnum mosses, the dominant peat-forming plant in many northern peatlands, generally do not regenerate spontaneously in mined peatlands because water transfer between the cutover peat and incipient moss diaspores cannot overcome the capillary barrier effect between the two hydraulically distinct layers. Artificial drainage networks established throughout peatlands, coupled with the removal of the acrotelm during the peat extraction process, drastically alter the natural system function through the exposure of more decomposed catotelm peat and increased compression, oxidation, and shrinkage, subsequently decreasing average pore diameter and enhancing this capillary barrier effect. Water table (WT) fluctuations, constrained within the reduced specific yield of the altered catotelm, exhibit increased variability and rapid decline. The increased effective stress caused by a declining WT can result in seasonal surface subsidence of 8 to 10 cm, thereby reducing saturated hydraulic conductivity by three orders of magnitude. Restoration efforts aim to alter the disturbed hydrological regime, creating conditions more favorable for the recolonization of Sphagnum mosses and the ultimate reestablishment of an upper acrotelm layer. Due to the large areal coverage and high organic carbon content, the response of peatlands to disturbances caused by resource extraction, and their return to functioning ecosystems, must be thoroughly addressed. This paper integrates both published and unpublished work to facilitate an overview of our understanding of the hydrological impact of peat cutting and its implications for restoration.
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Effect of a gap opening on the conductance of graphene with magnetic barrier structures
NASA Astrophysics Data System (ADS)
Esmailpour, Mohammad
2018-04-01
In the present study Klein tunneling in a single-layer gapped graphene was investigated by transfer matrix method under normal magnetic field for one and two magnetic barriers. Calculations show that electron transmission through a magnetic barrier is deflected to positive angles and reduces as the magnitude of magnetic field and especially the energy gap increases. This reduction is even more significant in larger fields so that after reaching a specific value of energy gap, an effective confinement for fermions and suppression of Klein tunneling is reached particularly in normal incidence and the conductance becomes zero. Unlike one barrier, the process of tunneling through two magnetic barriers induces symmetric transmission probability versus the incident angle; even, for lower energy gaps, electron transmission probability increases which in turn reduces total conductance via proper changes in the value of the magnetic field and energy gap. In general, it is concluded that confining electrons in asymmetric transmission through one barrier is conducted better than two barriers.
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Neoclassical theory inside transport barriers in tokamaks
NASA Astrophysics Data System (ADS)
Shaing, K. C.; Hsu, C. T.
2012-02-01
Inside the transport barriers in tokamaks, ion energy losses sometimes are smaller than the value predicted by the standard neoclassical theory. This improvement can be understood in terms of the orbit squeezing theory in addition to the sonic poloidal E ×B Mach number Up,m that pushes the tips of the trapped particles to the higher energy. In general, Up,m also includes the poloidal component of the parallel mass flow speed. These physics mechanisms are the corner stones for the transition theory of the low confinement mode (L-mode) to the high confinement mode (H-mode) in tokamaks. Here, detailed transport fluxes in the banana regime are presented using the parallel viscous forces calculated earlier. It is found, as expected, that effects of orbit squeezing and the sonic Up,m reduce the ion heat conductivity. The former reduces it by a factor of |S|3/2 and the later by a factor of R(Up ,m2)exp(-Up ,m2) with R(Up ,m2), a rational function. Here, S is the orbit squeezing factor.
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Reduction of proteinuria through podocyte alkalinization.
Altintas, Mehmet M; Moriwaki, Kumiko; Wei, Changli; Möller, Clemens C; Flesche, Jan; Li, Jing; Yaddanapudi, Suma; Faridi, Mohd Hafeez; Gödel, Markus; Huber, Tobias B; Preston, Richard A; Jiang, Jean X; Kerjaschki, Dontscho; Sever, Sanja; Reiser, Jochen
2014-06-20
Podocytes are highly differentiated cells and critical elements for the filtration barrier of the kidney. Loss of their foot process (FP) architecture (FP effacement) results in urinary protein loss. Here we show a novel role for the neutral amino acid glutamine in structural and functional regulation of the kidney filtration barrier. Metabolic flux analysis of cultured podocytes using genetic, toxic, and immunologic injury models identified increased glutamine utilization pathways. We show that glutamine uptake is increased in diseased podocytes to couple nutrient support to increased demand during the disease state of FP effacement. This feature can be utilized to transport increased amounts of glutamine into damaged podocytes. The availability of glutamine determines the regulation of podocyte intracellular pH (pHi). Podocyte alkalinization reduces cytosolic cathepsin L protease activity and protects the podocyte cytoskeleton. Podocyte glutamine supplementation reduces proteinuria in LPS-treated mice, whereas acidification increases glomerular injury. In summary, our data provide a metabolic opportunity to combat urinary protein loss through modulation of podocyte amino acid utilization and pHi. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
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Rodriguez, Kellie M
2013-02-01
Patients with diabetes are responsible for the vast majority of management requirements of their condition. However, their ability and motivation to engage in required self-management behaviors may be mitigated by multiple intrinsic and extrinsic factors. Intrinsic barriers include attitudes and health beliefs, limited diabetes knowledge and technical skill, reduced functional health literacy, and inadequate self-efficacy to promote positive behavior change. Extrinsic barriers include financial considerations, inadequate family and community support systems, ineffective clinical relationships, and limited access to effective diabetes health care delivery. Diabetes providers have opportunities for enhancing patient engagement with clinical recommendations and diabetes self-management through effective communication, including efforts to contextually assess patients' perceptions of diabetes and how the condition fits within the context of their changing lives. This article provides a conceptual framework for establishing and building an effective clinical alliance with patients with the goal of empowering them to take more control of their diabetes and reduce their risks for poor diabetes outcomes. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.
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Physical barrier to reduce WP mortalities of foraging waterfowl
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pochop, P.A.; Cummings, J.L.; Yoder, C.A.
White phosphorus (WP) has been identified as the cause of mortality to certain species of water-fowl at Eagle River Flats, a tidal marsh in Alaska, used as an ordinance impact area by the US Army. A blend of calcium bentonite/organo clays, gravel, and binding polymers was tested for effectiveness as a barrier to reduce duck foraging and mortality. Following the application of the barrier to one of two contaminated ponds, the authors observed greater duck foraging and higher mortality in the untreated pond and no mortality in the treated pond after a year of tidal inundations and ice effects. Emergentmore » vegetation recovered within a year of treatment. WP levels in the barrier were less than the method limit of detection, indicating no migration of WP into the materials. Barrier thickness remained relatively stable over a period of 4 years, and vegetation was found to be important in stabilizing the barrier material.« less
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Klem, John F; Kim, Jin K
2014-05-13
A two-color detector includes a first absorber layer. The first absorber layer exhibits a first valence band energy characterized by a first valence band energy function. A barrier layer adjoins the first absorber layer at a first interface. The barrier layer exhibits a second valence band energy characterized by a second valence band energy function. The barrier layer also adjoins a second absorber layer at a second interface. The second absorber layer exhibits a third valence band energy characterized by a third valence band energy function. The first and second valence band energy functions are substantially functionally or physically continuous at the first interface and the second and third valence band energy functions are substantially functionally or physically continuous at the second interface.
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Unipolar Barrier Dual-Band Infrared Detectors
NASA Technical Reports Server (NTRS)
Ting, David Z. (Inventor); Soibel, Alexander (Inventor); Khoshakhlagh, Arezou (Inventor); Gunapala, Sarath (Inventor)
2017-01-01
Dual-band barrier infrared detectors having structures configured to reduce spectral crosstalk between spectral bands and/or enhance quantum efficiency, and methods of their manufacture are provided. In particular, dual-band device structures are provided for constructing high-performance barrier infrared detectors having reduced crosstalk and/or enhance quantum efficiency using novel multi-segmented absorber regions. The novel absorber regions may comprise both p-type and n-type absorber sections. Utilizing such multi-segmented absorbers it is possible to construct any suitable barrier infrared detector having reduced crosstalk, including npBPN, nBPN, pBPN, npBN, npBP, pBN and nBP structures. The pBPN and pBN detector structures have high quantum efficiency and suppresses dark current, but has a smaller etch depth than conventional detectors and does not require a thick bottom contact layer.
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NASA Technical Reports Server (NTRS)
1993-01-01
In order to reduce heat transfer between a hot gas heat source and a metallic engine component, a thermal insulating layer of material is placed between them. This thermal barrier coating is applied by plasma spray processing the thin films. The coating has been successfully employed in aerospace applications for many years. Lewis Research Center, a leader in the development engine components coating technology, has assisted Caterpillar, Inc. in applying ceramic thermal barrier coatings on engines. Because these large engines use heavy fuels containing vanadium, engine valve life is sharply decreased. The barrier coating controls temperatures, extends valve life and reduces operating cost. Additional applications are currently under development.
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Crossing safety barriers: influence of children's morphological and functional variables.
Cordovil, Rita; Vieira, Filomena; Barreiros, João
2012-05-01
Thirty-three children between 3 and 6 years of age were asked to climb four different types of safety barriers. Morphological and functional variables of the children, which were expected to influence climbing or passing through skills, were collected. The influence of those variables on children's success rate and time to cross was tested. No barrier offered a total restraining efficacy. The horizontal bars barrier was crossed by 97% of the children. In the group of children that succeeded in crossing the four barriers, mean time to cross the most difficult barrier was 15 s. Age was the best predictor for success in crossing most barriers but morphology and strength were important predictors of time to cross. The influence of anthropometric variables in time to cross was dependent upon the characteristics of the barrier. A good design of safety barriers should consider children's age, morphology and strength. Copyright © 2011 Elsevier Ltd and The Ergonomics Society. All rights reserved.
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Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M; Mariani, John N; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S; John, Gareth R
2015-06-01
In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood-brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood-brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood-brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood-brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood-brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood-brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP as an astrocyte-derived permeability factor, and suggest TYMP and VEGFA together promote blood-brain barrier breakdown. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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NASA Astrophysics Data System (ADS)
Wittmann, Marion E.; Chandra, Sudeep; Reuter, John E.; Schladow, S. Geoffrey; Allen, Brant C.; Webb, Katie J.
2012-06-01
Anoxia can restrict species establishment in aquatic systems and the artificial promotion of these conditions can provide an effective control strategy for invasive molluscs. Low abundances (2-20 m-2) of the nonnative bivalve, Asian clam ( Corbicula fluminea), were first recorded in Lake Tahoe, CA-NV in 2002 and by 2010 nuisance-level population densities (>10,000 m-2) were observed. A non-chemical control method using gas impermeable benthic barriers to reduce dissolved oxygen (DO) concentrations available to C. fluminea was tested in this ultra-oligotrophic natural lake. In 2009, the impact of ethylene propylene diene monomer (EPDM) sheets (9 m2, n = 6) on C. fluminea beds was tested on 1-7 day intervals over a 56 day period (August-September). At an average water temperature of 18 °C, DO concentrations under these small barriers were reduced to zero after 72 h resulting in 100 % C. fluminea mortality after 28 days. In 2010, a large EPDM barrier (1,950 m2) was applied to C. fluminea populations for 120 days (July-November). C. fluminea abundances were reduced over 98 % after barrier removal, and remained significantly reduced (>90 %) 1 year later. Non-target benthic macroinvertebrate abundances were also reduced, with variable taxon-specific recolonization rates. High C. fluminea abundance under anoxic conditions increased the release of ammonium and soluble reactive phosphorus from the sediment substrate; but levels of unionized ammonia were low at 0.004-0.005 mg L-1. Prolonged exposure to anoxia using benthic barriers can provide an effective short term control strategy for C. fluminea.
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Wittmann, Marion E; Chandra, Sudeep; Reuter, John E; Schladow, S Geoffrey; Allen, Brant C; Webb, Katie J
2012-06-01
Anoxia can restrict species establishment in aquatic systems and the artificial promotion of these conditions can provide an effective control strategy for invasive molluscs. Low abundances (2-20 m(-2)) of the nonnative bivalve, Asian clam (Corbicula fluminea), were first recorded in Lake Tahoe, CA-NV in 2002 and by 2010 nuisance-level population densities (>10,000 m(-2)) were observed. A non-chemical control method using gas impermeable benthic barriers to reduce dissolved oxygen (DO) concentrations available to C. fluminea was tested in this ultra-oligotrophic natural lake. In 2009, the impact of ethylene propylene diene monomer (EPDM) sheets (9 m(2), n = 6) on C. fluminea beds was tested on 1-7 day intervals over a 56 day period (August-September). At an average water temperature of 18 °C, DO concentrations under these small barriers were reduced to zero after 72 h resulting in 100 % C. fluminea mortality after 28 days. In 2010, a large EPDM barrier (1,950 m(2)) was applied to C. fluminea populations for 120 days (July-November). C. fluminea abundances were reduced over 98 % after barrier removal, and remained significantly reduced (>90 %) 1 year later. Non-target benthic macroinvertebrate abundances were also reduced, with variable taxon-specific recolonization rates. High C. fluminea abundance under anoxic conditions increased the release of ammonium and soluble reactive phosphorus from the sediment substrate; but levels of unionized ammonia were low at 0.004-0.005 mg L(-1). Prolonged exposure to anoxia using benthic barriers can provide an effective short term control strategy for C. fluminea.
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Riaz, Atif; Zaidi, Shehla; Khowaja, Asif Raza
2015-03-06
A number of developing countries have contracted out public health facilities to the Non-Government Organizations (NGOs) in order to improve service utilization. However, there is a paucity of in-depth qualitative information on barriers to access services as a result of contracting from service users' perspective. The objective of this study was to explore perceived barriers to utilizing Maternal and Neonatal Health (MNH) services, in health facilities contracted out by government to NGO for service provision versus in those which are managed by government (non-contracted). A community-based qualitative exploratory study was conducted between April to September 2012 at two contracted-out and four matched non-contracted primary healthcare facilities in Thatta and Chitral, rural districts of Pakistan. Using semi-structured guide, the data were collected through thirty-six Focus Group Discussions (FGDs) conducted with mothers and their spouses in the catchment areas of selected facilities. Thematic analysis was performed using NVivo version 10.0 in which themes and sub-themes emerged. Key barriers reported in contracted sites included physical distance, user charges and familial influences. Whereas, poor functionality of health centres was the main barrier for non-contracted sites with other issues being comparatively less salient. Decision-making patterns for participants of both catchments were largely similar. Spouses and mother-in-laws particularly influenced the decision to utilize health facilities. Contracting out of health facility reduces supply side barriers to MNH services for the community served but distance, user charges and low awareness remain significant barriers. Contracting needs to be accompanied by measures for transportation in remote settings, oversight on user fee charges by contractor, and strong community-based behavior change strategies. © 2015 by Kerman University of Medical Sciences.
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Heat dissipation in controlled environment enclosures through the application of water screens
DOE Office of Scientific and Technical Information (OSTI.GOV)
Warrington, I.J.; Halligan, E.A.; Ruby, L.C.
1994-12-31
The use of plate glass-water thermal barriers in controlled environment facilities effectively reduces the thermal load within the plant growth chamber. This allows high PPFs to be provided for plant growth and development studies, adequate simulation of daily light integrals, and simulation of peak PPFs. Further, substantial amounts of incandescent lamp supplementation can be used to achieve simulation of daylight R:FR ratios which are needed to ensure adequate stem development in some species. While the focus in this paper has been on the use of entire thermal barriers which separate the lighting enclosure from the plant growth chamber, the samemore » principles apply to the use of water jackets for cooling individual lamps (such as can occur with xenon-arc lamps). In this instance, the barrier separating the lamps from the plant chamber can be much simpler (e.g., plexiglas) as the main function of the barrier is to separate the air ventilation of the lamp enclosure from the air system within the plant growth chamber. The main advantage of water as a thermal barrier is the negligible absorption of radiation in the photosynthetically-active and near infra-red wavebands. Consequently, plate glass-water barriers typically allow transmission of approximately 90% of radiation in these regions. While ventilated double and triple glazing systems appear to be attractive alternative to water barriers from an operating standpoint, their significant absorption in the biologically-important wavebands (7 - 12 %) with each glass layer and longer-wave cut-offs (typically 2500 - 4000 nm) makes them a much less attractive alternative. The data presented demonstrate clearly that measurement of PPF alone is not an adequate representation of the radiation environment being used in a controlled environment study.« less
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Riaz, Atif; Zaidi, Shehla; Khowaja, Asif Raza
2015-01-01
Background: A number of developing countries have contracted out public health facilities to the Non-Government Organizations (NGOs) in order to improve service utilization. However, there is a paucity of in-depth qualitative information on barriers to access services as a result of contracting from service users’ perspective. The objective of this study was to explore perceived barriers to utilizing Maternal and Neonatal Health (MNH) services, in health facilities contracted out by government to NGO for service provision versus in those which are managed by government (non-contracted). Methods: A community-based qualitative exploratory study was conducted between April to September 2012 at two contracted-out and four matched non-contracted primary healthcare facilities in Thatta and Chitral, rural districts of Pakistan. Using semi-structured guide, the data were collected through thirty-six Focus Group Discussions (FGDs) conducted with mothers and their spouses in the catchment areas of selected facilities. Thematic analysis was performed using NVivo version 10.0 in which themes and sub-themes emerged. Results: Key barriers reported in contracted sites included physical distance, user charges and familial influences. Whereas, poor functionality of health centres was the main barrier for non-contracted sites with other issues being comparatively less salient. Decision-making patterns for participants of both catchments were largely similar. Spouses and mother-in-laws particularly influenced the decision to utilize health facilities. Conclusion: Contracting out of health facility reduces supply side barriers to MNH services for the community served but distance, user charges and low awareness remain significant barriers. Contracting needs to be accompanied by measures for transportation in remote settings, oversight on user fee charges by contractor, and strong community-based behavior change strategies. PMID:25905478
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Grond, Susanne; Radner, Franz P.W.; Eichmann, Thomas O.; Kolb, Dagmar; Grabner, Gernot F.; Wolinski, Heimo; Gruber, Robert; Hofer, Peter; Heier, Christoph; Schauer, Silvia; Rülicke, Thomas; Hoefler, Gerald; Schmuth, Matthias; Elias, Peter M.; Lass, Achim; Zechner, Rudolf; Haemmerle, Guenter
2017-01-01
Adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) are limiting in cellular triglyceride catabolism. Although ATGL deficiency is compatible with normal skin development, mice globally lacking CGI-58 die postnatally and exhibit a severe epidermal permeability barrier defect, which may originate from epidermal and/or peripheral changes in lipid and energy metabolism. Here, we show that epidermis-specific disruption of CGI-58 is sufficient to provoke a defect in the formation of a functional corneocyte lipid envelope linked to impaired ω-O-acylceramide synthesis. As a result, epidermis-specific CGI-58-deficient mice show severe skin dysfunction, arguing for a tissue autonomous cause of disease development. Defective skin permeability barrier formation in global CGI-58-deficient mice could be reversed via transgenic restoration of CGI-58 expression in differentiated but not basal keratinocytes suggesting that CGI-58 is essential for lipid metabolism in suprabasal epidermal layers. The compatibility of ATGL deficiency with normal epidermal function indicated that CGI-58 may stimulate an epidermal triglyceride lipase beyond ATGL required for the adequate provision of fatty acids as a substrate for ω-O-acylceramide synthesis. Pharmacological inhibition of ATGL enzyme activity similarly reduced triglyceride-hydrolytic activities in wild-type and CGI-58 overexpressing epidermis implicating that CGI-58 participates in ω-O-acylceramide biogenesis independent of its role as a coactivator of epidermal triglyceride catabolism. PMID:27725204
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Rosero, Olivér; Ónody, Péter; Molnár, Dávid; Lotz, Gábor; Turóczi, Zsolt; Fülöp, András; Garbaisz, Dávid; Harsányi, László; Szijártó, Attila
2014-01-01
Mesenteric ischemia-reperfusion (IR) is associated with impairment of the gut barrier function and the initiation of a proinflammatory cascade with life-threatening results. Therefore methods directed to ameliorate IR injury are of great importance. We aimed at describing the effects of postconditioning (PC) on the alterations of the intestinal mucosal function and the inflammatory response upon mesenteric IR. Methods. Male Wistar rats were gavaged with green fluorescent protein-expressing E. coli suspensions. Animals were randomized into three groups (n = 15), sham-operated, IR-, and PC-groups, and underwent 60 minutes of superior mesenteric artery occlusion, followed by 6 hours of reperfusion. Postconditioning was performed at the onset of reperfusion. Blood and tissue samples were taken at the end of reperfusion, for histological, bacteriological, and plasma examinations. Results. The PC-group presented a more favorable claudin-2, claudin-3, claudin-4, and zonula occludens-1 membrane expression profile, and significantly lower rates of bacterial translocation to distant organs and plasma D-lactate levels compared to the IR-group. Histopathological lesions, plasma I-FABP, IL-6, and TNF-α levels were significantly lower in the PC-group compared to the IR-group. Conclusion. The use of postconditioning improved the integrity of the intestinal mucosal barrier upon mesenteric IR, and thus reduced the incidence of bacterial translocation and development of a systemic inflammatory response. PMID:24955347
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Liu, Kai-Ming; Chen, Yi-Ju; Shen, Li-Fen; Haddad, Amir N S; Song, I-Wen; Chen, Li-Ying; Chen, Yu-Ju; Wu, Jer-Yuarn; Yen, Jeffrey J Y; Chen, Yuan-Tsong
2015-11-01
Many biochemical pathways involved in hair and skin development have not been investigated. Here, we reported on the lesions and investigated the mechanism underlying hair and skin abnormalities in Zdhhc13(skc4) mice with a deficiency in DHHC13, a palmitoyl-acyl transferase encoded by Zdhhc13. Homozygous affected mice showed ragged and dilapidated cuticle of the hair shaft (CUH, a hair anchoring structure), poor hair anchoring ability, and premature hair loss at early telogen phase of the hair cycle, resulting in cyclic alopecia. Furthermore, the homozygous affected mice exhibited hyperproliferation of the epidermis, disturbed cornification, fragile cornified envelope (CE, a skin barrier structure), and impaired skin barrier function. Biochemical investigations revealed that cornifelin, which contains five palmitoylation sites at cysteine residues (C58, C59, C60, C95, and C101), was a specific substrate of DHHC13 and that it was absent in the CUH and CE structures of the affected mice. Furthermore, cornifelin levels were markedly reduced when two palmitoylated cysteines were replaced with serine (C95S and C101S). Taken together, our results suggest that DHHC13 is important for hair anchoring and skin barrier function and that cornifelin deficiency contributes to cyclic alopecia and skin abnormalities in Zdhhc13(skc4) mice.
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Rosero, Olivér; Ónody, Péter; Kovács, Tibor; Molnár, Dávid; Lotz, Gábor; Tóth, Szilárd; Turóczi, Zsolt; Fülöp, András; Garbaisz, Dávid; Harsányi, László; Szijártó, Attila
2014-01-01
Mesenteric ischemia-reperfusion (IR) is associated with impairment of the gut barrier function and the initiation of a proinflammatory cascade with life-threatening results. Therefore methods directed to ameliorate IR injury are of great importance. We aimed at describing the effects of postconditioning (PC) on the alterations of the intestinal mucosal function and the inflammatory response upon mesenteric IR. Male Wistar rats were gavaged with green fluorescent protein-expressing E. coli suspensions. Animals were randomized into three groups (n = 15), sham-operated, IR-, and PC-groups, and underwent 60 minutes of superior mesenteric artery occlusion, followed by 6 hours of reperfusion. Postconditioning was performed at the onset of reperfusion. Blood and tissue samples were taken at the end of reperfusion, for histological, bacteriological, and plasma examinations. The PC-group presented a more favorable claudin-2, claudin-3, claudin-4, and zonula occludens-1 membrane expression profile, and significantly lower rates of bacterial translocation to distant organs and plasma D-lactate levels compared to the IR-group. Histopathological lesions, plasma I-FABP, IL-6, and TNF- α levels were significantly lower in the PC-group compared to the IR-group. The use of postconditioning improved the integrity of the intestinal mucosal barrier upon mesenteric IR, and thus reduced the incidence of bacterial translocation and development of a systemic inflammatory response.
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Exactly solvable Schrödinger equation with double-well potential for hydrogen bond
NASA Astrophysics Data System (ADS)
Sitnitsky, A. E.
2017-05-01
We construct a double-well potential for which the Schrödinger equation can be exactly solved via reducing to the confluent Heun's one. Thus the wave function is expressed via the confluent Heun's function. The latter is tabulated in Maple so that the obtained solution is easily treated. The potential is infinite at the boundaries of the final interval that makes it to be highly suitable for modeling hydrogen bonds (both ordinary and low-barrier ones). We exemplify theoretical results by detailed treating the hydrogen bond in KHCO3 and show their good agreement with literature experimental data.
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Volynets, Valentina; Louis, Sandrine; Pretz, Dominik; Lang, Lisa; Ostaff, Maureen J; Wehkamp, Jan; Bischoff, Stephan C
2017-05-01
Background: The consumption of a Western-style diet (WSD) and high fructose intake are risk factors for metabolic diseases. The underlying mechanisms are largely unclear. Objective: To unravel the mechanisms by which a WSD and fructose promote metabolic disease, we investigated their effects on the gut microbiome and barrier function. Methods: Adult female C57BL/6J mice were fed a sugar- and fat-rich WSD or control diet (CD) for 12 wk and given access to tap water or fructose-supplemented water. The microbiota was analyzed with the use of 16S rRNA gene sequencing. Barrier function was studied with the use of permeability tests, and endotoxin, mucus thickness, and gene expressions were measured. Results: The WSD increased body weight gain but not endotoxin translocation compared with the CD. In contrast, high fructose intake increased endotoxin translocation 2.6- and 3.8-fold in the groups fed the CD + fructose and WSD + fructose, respectively, compared with the CD group. The WSD + fructose treatment also induced a loss of mucus thickness in the colon (-46%) and reduced defensin expression in the ileum and colon. The lactulose:mannitol ratio in the WSD + fructose mice was 1.8-fold higher than in the CD mice. Microbiota analysis revealed that fructose, but not the WSD, increased the Firmicutes:Bacteroidetes ratio by 88% for CD + fructose and 63% for WSD + fructose compared with the CD group. Bifidobacterium abundance was greater in the WSD mice than in the CD mice (63-fold) and in the WSD + fructose mice than in the CD + fructose mice (330-fold). Conclusions: The consumption of a WSD or high fructose intake differentially affects gut permeability and the microbiome. Whether these differences are related to the distinct clinical outcomes, whereby the WSD primarily promotes weight gain and high fructose intake causes barrier dysfunction, needs to be investigated in future studies. © 2017 American Society for Nutrition.
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Erman, Andreja; Kerec Kos, Mojca; Žakelj, Simon; Resnik, Nataša; Romih, Rok; Veranič, Peter
2013-11-01
High transepithelial electrical resistance (TEER) demonstrates a functional permeability barrier of the normal urothelium, which is maintained by a layer of highly differentiated superficial cells. When the barrier is challenged, a quick regeneration is induced. We used side-by-side diffusion chambers as an ex vivo system to determine the time course of functional and structural urothelial regeneration after chitosan-induced injury. The exposure of the urothelium to chitosan caused a 60 % decrease in TEER, the exposure of undifferentiated urothelial cells to the luminal surface and leaky tight junctions. During the regeneration period (350 min), TEER recovered to control values after approximately 200 min, while structural regeneration continued until 350 min after injury. The tight junctions are the earliest and predominant component of the barrier to appear, while complete barrier regeneration is achieved by delayed superficial cell terminal differentiation. The barrier function and the structure of untreated urothelium were unaffected in side-by-side diffusion chambers for at least 6 h. The urinary bladder tissue excised from an animal thus retains the ability to maintain and restore the transepithelial barrier and cellular ultrastructure for a sufficient period to allow for studies of regeneration in ex vivo conditions.
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Hoehn, Jessica L; Riekert, Kristin A; Borrelli, Belinda; Rand, Cynthia S; Eakin, Michelle N
2016-08-01
To identify barriers and motivators for reducing secondhand smoke exposure (SHSe) for families of African-American, low-income, urban children. Audiotaped intervention sessions of 52 African-American caregivers of Head Start children who reported being a smoker and/or had at least one smoker in the home were randomly sampled from a larger trial examining the effectiveness of a motivational-interviewing intervention in reducing child's SHSe. Counseling sessions were qualitatively coded to identify barriers and motivators to implementing a home smoking ban or quitting smoking. African-American families identified several themes that were either or both barriers and motivators for SHSe reduction, including: asking others not to smoke, other family living in the home, neighborhood safety, absence of childcare, cost/availability of cessation tools, physician support and prevention of health problems. Urban, low-income African-American families face numerous barriers to reducing SHSe. Families were able to identify many motivators for reducing SHSe, suggesting an awareness of the importance for SHSe reduction but uncertainty in their confidence to change behaviors. Counseling should include tailoring to be most effective in supporting health behavior change. Greater emphasis on motivators is needed, such as low-cost/free cessation tools, engagement from physicians and greater involvement of extended family members. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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Hoehn, Jessica L.; Riekert, Kristin A.; Borrelli, Belinda; Rand, Cynthia S.; Eakin, Michelle N.
2016-01-01
Objective: To identify barriers and motivators for reducing secondhand smoke exposure (SHSe) for families of African-American, low-income, urban children. Method: Audiotaped intervention sessions of 52 African-American caregivers of Head Start children who reported being a smoker and/or had at least one smoker in the home were randomly sampled from a larger trial examining the effectiveness of a motivational-interviewing intervention in reducing child’s SHSe. Counseling sessions were qualitatively coded to identify barriers and motivators to implementing a home smoking ban or quitting smoking. Results: African-American families identified several themes that were either or both barriers and motivators for SHSe reduction, including: asking others not to smoke, other family living in the home, neighborhood safety, absence of childcare, cost/availability of cessation tools, physician support and prevention of health problems. Discussion: Urban, low-income African-American families face numerous barriers to reducing SHSe. Families were able to identify many motivators for reducing SHSe, suggesting an awareness of the importance for SHSe reduction but uncertainty in their confidence to change behaviors. Counseling should include tailoring to be most effective in supporting health behavior change. Greater emphasis on motivators is needed, such as low-cost/free cessation tools, engagement from physicians and greater involvement of extended family members. PMID:27329373
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Rhinovirus Delays Cell Repolarization in a Model of Injured/Regenerating Human Airway Epithelium
Faris, Andrea N.; Ganesan, Shyamala; Chattoraj, Asamanja; Chattoraj, Sangbrita S.; Comstock, Adam T.; Unger, Benjamin L.; Hershenson, Marc B.
2016-01-01
Rhinovirus (RV), which causes exacerbation in patients with chronic airway diseases, readily infects injured airway epithelium and has been reported to delay wound closure. In this study, we examined the effects of RV on cell repolarization and differentiation in a model of injured/regenerating airway epithelium (polarized, undifferentiated cells). RV causes only a transient barrier disruption in a model of normal (mucociliary-differentiated) airway epithelium. However, in the injury/regeneration model, RV prolongs barrier dysfunction and alters the differentiation of cells. The prolonged barrier dysfunction caused by RV was not a result of excessive cell death but was instead associated with epithelial-to-mesenchymal transition (EMT)-like features, such as reduced expression of the apicolateral junction and polarity complex proteins, E-cadherin, occludin, ZO-1, claudins 1 and 4, and Crumbs3 and increased expression of vimentin, a mesenchymal cell marker. The expression of Snail, a transcriptional repressor of tight and adherence junctions, was also up-regulated in RV-infected injured/regenerating airway epithelium, and inhibition of Snail reversed RV-induced EMT-like features. In addition, compared with sham-infected cells, the RV-infected injured/regenerating airway epithelium showed more goblet cells and fewer ciliated cells. Inhibition of epithelial growth factor receptor promoted repolarization of cells by inhibiting Snail and enhancing expression of E-cadherin, occludin, and Crumbs3 proteins, reduced the number of goblet cells, and increased the number of ciliated cells. Together, these results suggest that RV not only disrupts barrier function, but also interferes with normal renewal of injured/regenerating airway epithelium by inducing EMT-like features and subsequent goblet cell hyperplasia. PMID:27119973
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Vishwanath, Sollapura J.; Kosma, Dylan K.; Pulsifer, Ian P.; Scandola, Sabine; Pascal, Stéphanie; Joubès, Jérôme; Dittrich-Domergue, Franziska; Lessire, René; Rowland, Owen; Domergue, Frédéric
2013-01-01
Suberin is found in a variety of tissues, such as root endoderms and periderms, storage tuber periderms, tree cork layer, and seed coats. It acts as a hydrophobic barrier to control the movement of water, gases, and solutes as well as an antimicrobial barrier. Suberin consists of polymerized phenolics, glycerol, and a variety of fatty acid derivatives, including primary fatty alcohols. We have conducted an in-depth analysis of the distribution of the C18:0 to C22:0 fatty alcohols in Arabidopsis (Arabidopsis thaliana) roots and found that only 20% are part of the root suberin polymer, together representing about 5% of its aliphatic monomer composition, while the remaining 80% are found in the nonpolymeric (soluble) fraction. Down-regulation of Arabidopsis FATTY ACYL REDUCTASE1 (FAR1), FAR4, and FAR5, which collectively produce the fatty alcohols found in suberin, reduced their levels by 70% to 80% in (1) the polymeric and nonpolymeric fractions from roots of tissue culture-grown plants, (2) the suberin-associated root waxes from 7-week-old soil-grown plants, and (3) the seed coat suberin polymer. By contrast, the other main monomers of suberin were not altered, indicating that reduced levels of fatty alcohols did not influence the suberin polymerization process. Nevertheless, the 75% reduction in total fatty alcohol and diol loads in the seed coat resulted in increased permeability to tetrazolium salts and a higher sensitivity to abscisic acid. These results suggest that fatty alcohols and diols play an important role in determining the functional properties of the seed coat suberin barrier. PMID:24019425
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Gpr124 is essential for blood-brain barrier integrity in central nervous system disease.
Chang, Junlei; Mancuso, Michael R; Maier, Carolina; Liang, Xibin; Yuki, Kanako; Yang, Lu; Kwong, Jeffrey W; Wang, Jing; Rao, Varsha; Vallon, Mario; Kosinski, Cynthia; Zhang, J J Haijing; Mah, Amanda T; Xu, Lijun; Li, Le; Gholamin, Sharareh; Reyes, Teresa F; Li, Rui; Kuhnert, Frank; Han, Xiaoyuan; Yuan, Jenny; Chiou, Shin-Heng; Brettman, Ari D; Daly, Lauren; Corney, David C; Cheshier, Samuel H; Shortliffe, Linda D; Wu, Xiwei; Snyder, Michael; Chan, Pak; Giffard, Rona G; Chang, Howard Y; Andreasson, Katrin; Kuo, Calvin J
2017-04-01
Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt-β-catenin signaling. Constitutive activation of Wnt-β-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124-CKO mice, with rescue of the endothelial gene tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption.
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Martin-Jaular, Lorena; Ferrer, Mireia; Calvo, Maria; Rosanas-Urgell, Anna; Kalko, Susana; Graewe, Stefanie; Soria, Guadalupe; Cortadellas, Núria; Ordi, Jaume; Planas, Anna; Burns, James; Heussler, Volker; del Portillo, Hernando A
2011-01-01
Knowledge of the dynamic features of the processes driven by malaria parasites in the spleen is lacking. To gain insight into the function and structure of the spleen in malaria, we have implemented intravital microscopy and magnetic resonance imaging of the mouse spleen in experimental infections with non-lethal (17X) and lethal (17XL) Plasmodium yoelii strains. Noticeably, there was higher parasite accumulation, reduced motility, loss of directionality, increased residence time and altered magnetic resonance only in the spleens of mice infected with 17X. Moreover, these differences were associated with the formation of a strain-specific induced spleen tissue barrier of fibroblastic origin, with red pulp macrophage-clearance evasion and with adherence of infected red blood cells to this barrier. Our data suggest that in this reticulocyte-prone non-lethal rodent malaria model, passage through the spleen is different from what is known in other Plasmodium species and open new avenues for functional/structural studies of this lymphoid organ in malaria. PMID:20923452
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Schweitzer, Kelly S; Hatoum, Hadi; Brown, Mary Beth; Gupta, Mehak; Justice, Matthew J; Beteck, Besem; Van Demark, Mary; Gu, Yuan; Presson, Robert G; Hubbard, Walter C; Petrache, Irina
2011-12-01
The epithelial and endothelial cells lining the alveolus form a barrier essential for the preservation of the lung respiratory function, which is, however, vulnerable to excessive oxidative, inflammatory, and apoptotic insults. Whereas profound breaches in this barrier function cause pulmonary edema, more subtle changes may contribute to inflammation. The mechanisms by which cigarette smoke (CS) exposure induce lung inflammation are not fully understood, but an early alteration in the epithelial barrier function has been documented. We sought to investigate the occurrence and mechanisms by which soluble components of mainstream CS disrupt the lung endothelial cell barrier function. Using cultured primary rat microvascular cell monolayers, we report that CS induces endothelial cell barrier disruption in a dose- and time-dependent manner of similar magnitude to that of the epithelial cell barrier. CS exposure triggered a mechanism of neutral sphingomyelinase-mediated ceramide upregulation and p38 MAPK and JNK activation that were oxidative stress dependent and that, along with Rho kinase activation, mediated the endothelial barrier dysfunction. The morphological changes in endothelial cell monolayers induced by CS included actin cytoskeletal rearrangement, junctional protein zonula occludens-1 loss, and intercellular gap formation, which were abolished by the glutathione modulator N-acetylcysteine and ameliorated by neutral sphingomyelinase inhibition. The direct application of ceramide recapitulated the effects of CS, by disrupting both endothelial and epithelial cells barrier, by a mechanism that was redox and apoptosis independent and required Rho kinase activation. Furthermore, ceramide induced dose-dependent alterations of alveolar microcirculatory barrier in vivo, measured by two-photon excitation microscopy in the intact rat. In conclusion, soluble components of CS have direct endothelial barrier-disruptive effects that could be ameliorated by glutathione modulators or by inhibitors of neutral sphingomyelinase, p38 MAPK, JNK, and Rho kinase. Amelioration of endothelial permeability may alleviate lung and systemic vascular dysfunction associated with smoking-related chronic obstructive lung diseases.
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Yang, Yang; Qiu, Yuan; Wang, Wensheng; Xiao, Weidong; Liang, Hongyin; Zhang, Chaojun; Yang, Hanwenbo; Teitelbaum, Daniel H; Sun, Li-Hua; Yang, Hua
2014-01-01
Intestinal barrier function failure from ischemia/reperfusion (I/R) and acute hypoxia has been implicated as a critical determinant in the predisposition to intestinal inflammation and a number of inflammatory disorders. Here, we identified the role of Adenosine A2B receptor (A2BAR) in the regulation of intestinal barrier function under I/R and acute hypoxic conditions. C57BL/6J mice were used, and were randomized into three groups: Sham, I/R, IR+PSB1115 (a specific A2BAR antagonist) groups. After surgery, the small bowel was harvested for immunohistochemical staining, RNA and protein content, and intestinal permeability analyses. Using an epithelial cell culture model, we investigated the influence of hypoxia on the epithelial function, and the role of A2BAR in the expressions of tight junction and epithelial permeability. The expressions of Claudin-1, occludin and ZO-1 were detected by RT-PCR and Western-Blot. Epithelial barrier function was assessed with transepithelial resistance (TER). The A2BAR antagonist, PSB1115, significantly increased tight junction protein expression after intestinal I/R or acute hypoxia conditions. PSB1115 also attenuated the disrupted distribution of TJ proteins. Furthermore, inhibition of A2BAR attenuated the decrease in TER induced by I/R or acute hypoxic conditions, and maintained intestinal barrier function. Antagonism of A2BAR activity improves intestinal epithelial structure and barrier function in a mouse model of intestinal I/R and a cell model of acute hypoxia. These findings support a potentially destructive role for A2BAR under intestinal I/R and acute hypoxic conditions.
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Nanoscopic compartmentalization of membrane protein motion at the axon initial segment.
Albrecht, David; Winterflood, Christian M; Sadeghi, Mohsen; Tschager, Thomas; Noé, Frank; Ewers, Helge
2016-10-10
The axon initial segment (AIS) is enriched in specific adaptor, cytoskeletal, and transmembrane molecules. During AIS establishment, a membrane diffusion barrier is formed between the axonal and somatodendritic domains. Recently, an axonal periodic pattern of actin, spectrin, and ankyrin forming 190-nm-spaced, ring-like structures has been discovered. However, whether this structure is related to the diffusion barrier function is unclear. Here, we performed single-particle tracking time-course experiments on hippocampal neurons during AIS development. We analyzed the mobility of lipid-anchored molecules by high-speed single-particle tracking and correlated positions of membrane molecules with the nanoscopic organization of the AIS cytoskeleton. We observe a strong reduction in mobility early in AIS development. Membrane protein motion in the AIS plasma membrane is confined to a repetitive pattern of ∼190-nm-spaced segments along the AIS axis as early as day in vitro 4, and this pattern alternates with actin rings. Mathematical modeling shows that diffusion barriers between the segments significantly reduce lateral diffusion along the axon. © 2016 Albrecht et al.
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Ab initio study of the mechanism of bottom-up synthesis of graphene nanoribbons
NASA Astrophysics Data System (ADS)
Xiao, Zhongcan; Ma, Chuanxu; Zhang, Honghai; Liang, Liangbo; Huang, Jingsong; Lu, Wenchang; Hong, Kunlun; Li, An-Ping; Bernholc, Jerry
Graphene nanoribbons (GNRs) can be fabricated with atomic precision by using molecular precursors deposited on a metal substrate, and potentially form the basis for future molecular-scale electronics. The precursor molecules are first annealed to form a polymer, and further annealing at a higher temperature leads to the formation of a GNR. We systematically study the reaction pathways of this cyclodehydrogenation process, using density functional theory and the nudged elastic band method. We find that the Au substrate reduces the reaction barriers for key steps in the cyclodehydrogenation process: cyclization, hydrogen migration and desorption. Furthermore, our calculations explain recent experiments showing that an STM-tip can induce local polymer-to-GNR transition, which can be used to fabricate atomically precise heterojunctions: at a negative bias, the STM tip injects excess holes into the polymer HOMO state, lowering the energy barrier in agreement with Woodward-Hoffmann rules. At a positive bias, when excess electrons are injected into the LUMO state, the energy barrier is not significantly lowered and the transition is not observed.
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Anne Timm; Eric Hallerman; Andy Dolloff; Mark Hudy; Randall Kolka
2016-01-01
The overall goal of the study was to evaluate effects of landscape features, barriers, on Brook Trout Salvelinus fontinalis population genetics and to identify a potential barrier height threshold where genetic diversity was reduced upstream of the barrier and differentiation and relatedness increase. We screened variation at eight...
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Use of a spiral rectal diaphragm technique to control anal sphincter incontinence in a cat.
Pavletic, Michael; Mahn, Matt; Duddy, Jean
2012-09-15
A 10-year-old castrated male domestic shorthair cat was examined for a mass involving the right anal sac region. The mass was diagnosed as a fibrosarcoma, and resulted in progressive tenesmus, requiring repeated resection. Surgical removal of the fibrosarcoma was performed on 4 occasions, including complete resection of the anal sphincter muscles and portions of the rectum. A perineal urethrostomy was required during the third surgical procedure secondary to tumor invasion of the preputial tissues. To reduce involuntary loss of feces, the remaining rectal wall was rotated approximately 225° prior to surgical closure during the second, third, and fourth surgical procedures. This procedure created a natural spiral diaphragm within the rectal lumen. The elastic spiral barrier reduced inadvertent fecal loss and facilitated fecal distention of the terminal portion of the colon, allowing the patient to anticipate the impending passage of feces and to use the litter tray on a daily basis. With complete loss of the terminal portion of the rectum and anal sphincter muscles, spiraling the rectum created a deformable threshold barrier to reduce excessive loss of stool secondary to fecal incontinence. On the basis of the positive outcome in this patient, this novel technique may be a useful option to consider for the treatment of cats with loss of anal sphincter function.
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Smad4 deletion in blood vessel endothelial cells promotes ovarian cancer metastasis.
Yang, Jie; Wang, Ya; Zeng, Zhen; Qiao, Long; Zhuang, Liang; Gao, Qinglei; Ma, Ding; Huang, Xiaoyuan
2017-05-01
SMAD4 is a critical co-smad in signal transduction pathways activated in response to transforming growth factor-β (TGF-β)-related ligands, regulating cell growth and differentiation. The roles played by SMAD4 inactivation in tumors highlighted it as a tumor-suppressor gene. Herein, we report that loss of SMAD4 expression in vascular endothelial cells promotes ovarian cancer invasion. SiRNA transfer of this gene in the HUVEC reduced SMAD4 protein expression and function. Although it reduced the vessel endothelial cell tubule formation in vitro and in vivo, it did not affect the tumor growth significantly in vivo. However, it weakened the barrier integrity in endothelial cells and increased vessel permeability and the ovarian cancer liver metastasis. We documented reduced angiogenesis and increased invasion histologically and by intravital microscopy, and gained mechanistic insight at the messenger and gene level. Finally, we found a negative reciprocal regulation between SMAD4 and FYN. FYN is one of the Src family kinases (SFK), activation of which can cause dissociation of cell-cell junctions and adhesion, resulting in paracellular hypermeability. Upon SMAD4 deletion, we detected high expression levels of FYN in vessel endothelial cells, suggesting the mechanism of the ovarian tumor cells cross the endothelial barrier and transform to an invasive phenotype.
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Direct hydride shift mechanism and stereoselectivity of P450nor confirmed by QM/MM calculations.
Krámos, Balázs; Menyhárd, Dóra K; Oláh, Julianna
2012-01-19
Nitric oxide reductase (P450(nor)) found in Fusarium oxysporum catalyzes the reduction of nitric oxide to N(2)O in a multistep process. The reducing agent, NADH, is bound in the distal pocket of the enzyme, and direct hydride transfer occurs from NADH to the nitric oxide bound heme enzyme, forming intermediate I. Here we studied the possibility of hydride transfer from NADH to both the nitrogen and oxygen of the heme-bound nitric oxide, using quantum chemical and combined quantum mechanics/molecular mechanics (QM/MM) calculations, on two different protein models, representing both possible stereochemistries, a syn- and an anti-NADH arrangement. All calculations clearly favor hydride transfer to the nitrogen of nitric oxide, and the QM-only barrier and kinetic isotope effects are good agreement with the experimental values of intermediate I formation. We obtained higher barriers in the QM/MM calculations for both pathways, but hydride transfer to the nitrogen of nitric oxide is still clearly favored. The barriers obtained for the syn, Pro-R conformation of NADH are lower and show significantly less variation than the barriers obtained in the case of anti conformation. The effect of basis set and wide range of functionals on the obtained results are also discussed.
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The Role of Moisturizers in Addressing Various Kinds of Dermatitis: A Review
Indrastuti, Niken; Danarti, Retno; Saefudin, Tatan
2017-01-01
Moisturizer is a major component of basic daily skin care, particularly in presence of epidermal barrier alteration and reduced epidermal water content. It is an important part of a dermatologist’s strategy to maintain skin health as well as treating various dermatoses which co-exist with skin dryness and are linked to impaired skin barrier function, such as in atopic disorders as well as other types of dermatitis. Mastering the knowledge regarding mechanism of action, application, dosage, adverse effects as well as specific clinical usage of moisturizers is a must for a dermatologist in order to support their use, particularly for evidence-based, therapeutic purposes. This review discusses the use of moisturizer both for skin health maintenance as well as a definitive or adjuvant therapy for many kinds of dermatitis. PMID:29229630
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lenly J. Weathers; Lynn E. Katz
2002-05-29
The use of zero valent iron, permeable reactive barriers (PRBs) for groundwater remediation continues to increase. AN exciting variation of this technology involves introducing anaerobic bacteria into these barriers so that both biological and abiotic pollutant removal processes are functional. This work evaluated the hypothesis that a system combining a mixed culture of sulfate reducing bacteria (SRB) with zero valent iron would have a greater cr(VI) removal efficiency and a greater total Cr(VI) removal capacity than a zero valent iron system without the microorganisms. Hence, the overall goal of this research was to compare the performance of these types ofmore » systems with regard to their Cr(VI) removal efficiency and total Cr(VI) removal capacity. Both batch and continuous flow reactor systems were evaluated.« less
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Grantee Spotlight: Marvella Ford, Ph.D. - Reducing Barriers to Surgical Cancer Care among African Am
Drs. Marvella E. Ford and Nestor F. Esnaola were awarded a five-year NIH/NIMHD R01 grant to evaluate a patient navigation intervention to reduce barriers to surgical cancer care and improving surgical resection rates in African Americans with lung cancer.
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Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo
2016-06-01
Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.
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Influence of solid noise barriers on near-road and on-road air quality
NASA Astrophysics Data System (ADS)
Baldauf, Richard W.; Isakov, Vlad; Deshmukh, Parikshit; Venkatram, Akula; Yang, Bo; Zhang, K. Max
2016-03-01
Public health concerns regarding adverse health effects for populations spending significant amounts of time near high traffic roadways has increased substantially in recent years. Roadside features, including solid noise barriers, have been investigated as potential methods that can be implemented in a relatively short time period to reduce air pollution exposures from nearby traffic. A field study was conducted to determine the influence of noise barriers on both on-road and downwind pollutant concentrations near a large highway in Phoenix, Arizona, USA. Concentrations of nitrogen dioxide, carbon monoxide, ultrafine particles, and black carbon were measured using a mobile platform and fixed sites along two limited-access stretches of highway that contained a section of noise barrier and a section with no noise barrier at-grade with the surrounding terrain. Results of the study showed that pollutant concentrations behind the roadside barriers were significantly lower relative to those measured in the absence of barriers. The reductions ranged from 50% within 50 m from the barrier to about 30% as far as 300 m from the barrier. Reductions in pollutant concentrations generally began within the first 50 m of the barrier edge; however, concentrations were highly variable due to vehicle activity behind the barrier and along nearby urban arterial roadways. The concentrations on the highway, upwind of the barrier, varied depending on wind direction. Overall, the on-road concentrations in front of the noise barrier were similar to those measured in the absence of the barrier, contradicting previous modeling results that suggested roadside barriers increase pollutant levels on the road. Thus, this study suggests that noise barriers do reduce potential pollutant exposures for populations downwind of the road, and do not likely increase exposures to traffic-related pollutants for vehicle passengers on the highway.
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NASA Astrophysics Data System (ADS)
Kim, Sang-Jo; Lee, Kwang Jae; Park, Seong-Ju
2018-06-01
We numerically investigated the effects of trapezoidal quantum barriers (QBs) on efficiency droop in InGaN/GaN multiple quantum well (MQW) light-emitting diodes (LEDs). Simulations showed that the electrostatic field in QWs of LEDs with trapezoidal barriers is reduced because of the reduced sheet charge density at the QW-QB interface caused by the thin GaN layer in trapezoidal QBs. Additionally, the InGaN grading region in trapezoidal QBs suppresses hot carrier transport and this enhances efficient carrier injection into the QWs. The electroluminescence intensity of an LED with trapezoidal QBs is increased by 10.2% and 6.7% at 245 A cm‑2 when compared with the intensities of LEDs with square-type GaN barriers and multilayer barriers, respectively. The internal quantum efficiency (IQE) droop of an LED with trapezoidal QBs is 16% at 300 A cm‑2, while LEDs with square-type GaN barriers and multilayer barriers have IQE droop of 31% and 24%, respectively. This IQE droop alleviation in LEDs with trapezoidal QBs is attributed to the reduced energy band bending, efficient hole injection, and more uniform hole distribution in the MQWs that results from reduction of the piezoelectric field by the trapezoidal QBs. These results indicate that the trapezoidal QB in MQWs is promising for enhanced efficiency in high-power GaN-based LEDs.
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Containment wells to form hydraulic barriers along site boundaries.
Vo, D; Ramamurthy, A S; Qu, J; Zhao, X P
2008-12-15
In the field, aquifer remediation methods include pump and treat procedures based on hydraulic control systems. They are used to reduce the level of residual contamination present in the soil and soil pores of aquifers. Often, physical barriers are erected along the boundaries of the target (aquifer) site to reduce the leakage of the released soil contaminant to the surrounding regions. Physical barriers are expensive to build and dismantle. Alternatively, based on simple hydraulic principles, containment wells or image wells injecting clear water can be designed and built to provide hydraulic barriers along the contaminated site boundaries. For brevity, only one pattern of containment well system that is very effective is presented in detail. The study briefly reports about the method of erecting a hydraulic barrier around a contaminated region based on the simple hydraulic principle of images. During the clean-up period, hydraulic barriers can considerably reduce the leakage of the released contaminant from the target site to surrounding pristine regions. Containment wells facilitate the formation of hydraulic barriers. Hence, they control the movement of contaminants away from the site that is being remedied. However, these wells come into play, only when the pumping operation for cleaning up the site is active. After operation, they can be filled with soil to permit the natural ground water movement. They can also be used as monitoring wells.
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Huby, Maria P.; Duan, Chaojun; Baer, Lisa; Peng, Zhanglong; Kozar, Rosemary A.; Doursout, Marie-Francoise; Holcomb, John B.; Wade, Charles E.; Ko, Tien C.
2015-01-01
Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use of fresh frozen plasma (FFP) in patients requiring massive transfusion is associated with improved outcomes. FFP contains significant amounts of adiponectin, which is known to have vascular protective function. We hypothesize that FFP improves vascular barrier function largely via adiponectin. Plasma adiponectin levels were measured in 19 severely injured patients in hemorrhagic shock (HS). Compared to normal individuals, plasma adiponectin levels decreased to 49% in HS patients prior to resuscitation (p<0.05) and increased to 64% post resuscitation (but not significant). In a HS mouse model, we demonstrated a similar decrease in plasma adiponectin to 54% but a significant increase to 79% by FFP resuscitation compared to baseline (p<0.05). HS disrupted lung vascular barrier function, leading to an increase in permeability. FFP resuscitation reversed these HS-induced effects. Immunodepletion of adiponectin from FFP abolished FFP's effects on blocking endothelial hyperpermeability in vitro, and on improving lung vascular barrier function in HS mice. Replenishment with adiponectin rescued FFP's effects. These findings suggest that adiponectin is an important component in FFP resuscitation contributing to the beneficial effects on vascular barrier function after HS. PMID:26263440
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Grether-Beck, Susanne; Felsner, Ingo; Brenden, Heidi; Kohne, Zippora; Majora, Marc; Marini, Alessandra; Jaenicke, Thomas; Rodriguez-Martin, Marina; Trullas, Carles; Hupe, Melanie; Elias, Peter M.; Krutmann, Jean
2012-01-01
Urea is an endogenous metabolite, known to enhance stratum corneum hydration. Yet, topical urea anecdotally also improves permeability barrier function, and it appears to exhibit antimicrobial activity. Hence, we hypothesized that urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. In 21 human volunteers, topical urea improved barrier function in parallel with enhanced antimicrobial peptide (LL-37 and β-defensin-2) expression. Urea both stimulates expression of, and is transported into keratinocytes by two urea transporters, UT-A1 and UT-A2, and by aquaporin 3, 7 and 9. Inhibitors of these urea transporters block the downstream biological effects of urea, which include increased mRNA and protein levels for: (i) transglutaminase-1, involucrin, loricrin and filaggrin; (ii) epidermal lipid synthetic enzymes, and (iii) cathelicidin/LL-37 and β-defensin-2. Finally, we explored the potential clinical utility of urea, showing that topical urea applications normalized both barrier function and antimicrobial peptide expression in a murine model of atopic dermatitis (AD). Together, these results show that urea is a small-molecule regulator of epidermal permeability barrier function and antimicrobial peptide expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with potential therapeutic applications in diseased skin. PMID:22418868
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Saunders, Norman R; Dziegielewska, Katarzyna M; Unsicker, Klaus; Ek, C Joakim
2016-11-01
The brain functions within a specialized environment tightly controlled by brain barrier mechanisms. Understanding the regulation of barrier formation is important for understanding brain development and may also lead to finding new ways to deliver pharmacotherapies to the brain; access of many potentially promising drugs is severely hindered by these barrier mechanisms. The cellular composition of the neurovascular unit of the blood-brain barrier proper and their effects on regulation of its function are beginning to be understood. One hallmark of the neurovascular unit in the adult is the astroglial foot processes that tightly surround cerebral blood vessels. However their role in barrier formation is still unclear. In this study we examined barrier function in newborn, juvenile and adult mice lacking fibroblast growth factor-2 (FGF-2), which has been shown to result in altered astroglial differentiation during development. We show that during development of FGF-2 deficient mice the astroglial contacts with cerebral blood vessels are delayed compared with wild-type animals. However, this delay did not result in changes to the permeability properties of the blood brain barrier as assessed by exclusion of either small or larger sized molecules at this interface. In addition cerebral vessels were positive for tight-junction proteins and we observed no difference in the ultrastructure of the tight-junctions. The results indicate that the direct contact of astroglia processes to cerebral blood vessels is not necessary for either the formation of the tight-junctions or for basic permeability properties and function of the blood-brain barrier. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1201-1212, 2016. © 2016 Wiley Periodicals, Inc.
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NASA Astrophysics Data System (ADS)
Malinina, A. A.; Malinin, A. N.
2013-12-01
Results are presented from studies of the optical characteristics and parameters of plasma of a dielectric barrier discharge in a mixture of mercury dibromide vapor with neon—the working medium of a non-coaxial exciplex gas-discharge emitter. The electron energy distribution function, the transport characteristics, the specific power losses for electron processes, the electron density and temperature, and the rate constants for the processes of elastic and inelastic electron scattering by the working mixture components are determined as functions of the reduced electric field. The rate constant of the process leading to the formation of exciplex mercury monobromide molecules is found to be 1.6 × 10-14 m3/s for a reduced electric field of E/ N = 15 Td, at which the maximum emission intensity in the blue-green spectral region (λmax = 502 nm) was observed in this experiment.
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Structure of the CLC-1 chloride channel from Homo sapiens.
Park, Eunyong; MacKinnon, Roderick
2018-05-29
CLC channels mediate passive Cl - conduction, while CLC transporters mediate active Cl - transport coupled to H + transport in the opposite direction. The distinction between CLC-0/1/2 channels and CLC transporters seems undetectable by amino acid sequence. To understand why they are different functionally we determined the structure of the human CLC-1 channel. Its 'glutamate gate' residue, known to mediate proton transfer in CLC transporters, adopts a location in the structure that appears to preclude it from its transport function. Furthermore, smaller side chains produce a wider pore near the intracellular surface, potentially reducing a kinetic barrier for Cl - conduction. When the corresponding residues are mutated in a transporter, it is converted to a channel. Finally, Cl - at key sites in the pore appear to interact with reduced affinity compared to transporters. Thus, subtle differences in glutamate gate conformation, internal pore diameter and Cl - affinity distinguish CLC channels and transporters. © 2018, Park & MacKinnon.
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Krüppel-like factor 5 is essential for maintenance of barrier function in mouse colon.
Liu, Yang; Chidgey, Martyn; Yang, Vincent W; Bialkowska, Agnieszka B
2017-11-01
Krüppel-like factor 5 (KLF5) is a member of the zinc finger family of transcription factors that regulates homeostasis of the intestinal epithelium. Previous studies suggested an indispensable role of KLF5 in maintaining intestinal barrier function. In the current study, we investigated the mechanisms by which KLF5 regulates colonic barrier function in vivo and in vitro. We used an inducible and a constitutive intestine-specific Klf5 knockout mouse models ( Villin-CreER T2 ;Klf5 fl/fl designated as Klf5 ΔIND and Villin-Cre;Klf5 fl/fl as Klf5 ΔIS ) and studied an inducible KLF5 knockdown in Caco-2 BBe cells using a lentiviral Tet-on system (Caco-2 BBe KLF5ΔIND ). Specific knockout of Klf5 in colonic tissues, either inducible or constitutive, resulted in increased intestinal permeability. The phenotype was accompanied by a significant reduction in Dsg2 , which encodes desmoglein-2, a desmosomal cadherin, at both mRNA and protein levels. Transmission electron microscopy showed alterations of desmosomal morphology in both KLF5 knockdown Caco-2 BBe cells and Klf5 knockout mouse colonic tissues. Inducible knockdown of KLF5 in Caco-2BBe cells grown on Transwell plates led to impaired barrier function as evidenced by decreased transepithelial electrical resistance and increased paracellular permeability to fluorescein isothiocyanate-4 kDa dextran. Furthermore, DSG2 was significantly decreased in KLF5 knockdown cells, and DSG2 overexpression partially rescued the impaired barrier function caused by KLF5 knockdown. Electron microscopy studies demonstrated altered desmosomal morphology after KLF5 knockdown. In combination with chromatin immunoprecipitation analysis and promoter study, our data show that KLF5 regulates intestinal barrier function by mediating the transcription of DSG2 , a gene encoding a major component of desmosome structures. NEW & NOTEWORTHY The study is original research on the direct function of a Krüppel-like factor on intestinal barrier function, which is commonly exerted by cell junctions, including tight junctions, adherens junctions, and desmosomes. Numerous previous studies were focused on tight junctions and adherens junctions. However, this study provided a new perspective on how the intestinal barrier function is regulated by KLF5 through DSG2, a component of desmosome complexes. Copyright © 2017 the American Physiological Society.
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Foster, Kylie J.; Miklavcic, Stanley J.
2017-01-01
In this paper, we present a detailed and comprehensive mathematical model of active and passive ion and water transport in plant roots. Two key features are the explicit consideration of the separate, but interconnected, apoplastic, and symplastic transport pathways for ions and water, and the inclusion of both active and passive ion transport mechanisms. The model is used to investigate the respective roles of the endodermal Casparian strip and suberin lamellae in the salt stress response of plant roots. While it is thought that these barriers influence different transport pathways, it has proven difficult to distinguish their separate functions experimentally. In particular, the specific role of the suberin lamellae has been unclear. A key finding based on our simulations was that the Casparian strip is essential in preventing excessive uptake of Na+ into the plant via apoplastic bypass, with a barrier efficiency that is reflected by a sharp gradient in the steady-state radial distribution of apoplastic Na+ across the barrier. Even more significantly, this function cannot be replaced by the action of membrane transporters. The simulations also demonstrated that the positive effect of the Casparian strip of controlling Na+ uptake, was somewhat offset by its contribution to the osmotic stress component: a more effective barrier increased the detrimental osmotic stress effect. In contrast, the suberin lamellae were found to play a relatively minor, even non-essential, role in the overall response to salt stress, with the presence of the suberin lamellae resulting in only a slight reduction in Na+ uptake. However, perhaps more significantly, the simulations identified a possible role of suberin lamellae in reducing plant energy requirements by acting as a physical barrier to preventing the passive leakage of Na+ into endodermal cells. The model results suggest that more and particular experimental attention should be paid to the properties of the Casparian strip when assessing the salt tolerance of different plant varieties and species. Indeed, the Casparian strip appears to be a more promising target for plant breeding and plant genetic engineering efforts than the suberin lamellae for the goal of improving salt tolerance. PMID:28804493
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Self-reported physical activity in patients on chronic hemodialysis: correlates and barriers.
Bossola, Maurizio; Pellu, Valentina; Di Stasio, Enrico; Tazza, Luigi; Giungi, Stefania; Nebiolo, Pier Eugenio
2014-01-01
The knowledge of the barriers that are associated with decreased physical activity (PA) in patients on chronic hemodialysis (PCH) may be of primary importance for the nephrologists. Thus, we aimed to assess the barriers associated with the absent or reduced PA in PCH of a Mediterranean country. Patients were invited to answer the question 'How often do you exercise during your leisure time?'. Also, patients included in the study were asked to answer questions regarding barriers to physical activity lower than desired. We studied 105 patients. Forty (38.1%) patients reported to never exercise, 6 (5.7%) reported to exercise less than once/week, 4 (3.8%) once/week, 23 (21.9%) two to three times/week, 12 (11.4%) four to five times/week and 20 (19%) daily. Overall, 46 (43.8%) patients never exercised or exercised less than once/week ('inactive') and 59 (56.2%) did exercise more often ('active'). At the multivariate analysis, reduced walking ability, fatigue on the non-dialysis days, and shortness of breath were independently and negatively associated with PA. The same results were found when the reduced model of the multivariate logistic backward regression was built introducing in the model also clinical and laboratory variables. In PCH, fatigue on the non-dialysis days, reduced walking ability, and shortness of breath are barriers independently associated to decreased PA. Knowledge about the causes and mechanisms that generate these barriers has to be acquired. © 2014 S. Karger AG, Basel.
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Brufau, M Teresa; Campo-Sabariz, Joan; Bou, Ricard; Carné, Sergi; Brufau, Joaquim; Vilà, Borja; Marqués, Ana M; Guardiola, Francesc; Ferrer, Ruth; Martín-Venegas, Raquel
2016-08-01
One promising strategy for reducing human salmonellosis induced by Salmonella Enteritidis is to supplement animal diets with natural feed additives such as mannan oligosaccharides (MOSs). We sought to investigate the potential role of Salmosan (S-βGM), an MOS product extremely rich in β-galactomannan, in preventing epithelial barrier function disruption induced by S. Enteritidis colonization in an in vitro model of intestinal Caco-2 cells in culture. Differentiated Caco-2 cells were incubated for 3 h with S. Enteritidis at a multiplicity of infection of 10 in the absence or presence of 500 μg S-βGM/mL. Paracellular permeability (PP) was assessed by transepithelial electrical resistance (TER), d-mannitol, and fluorescein isothiocyanate-dextran (FD-4) flux. Tight junction proteins and cytoskeletal actin were also localized by confocal microscopy. Reactive oxygen species (ROS) and lipid peroxidation products were evaluated. Scanning and transmission electron microscopy were used to visualize S. Enteritidis adhesion to, and invasion of, the Caco-2 cell cultures. Compared with controls, TER was significantly reduced by 30%, and d-mannitol and FD-4 flux were significantly increased by 374% and 54% in S. Enteritidis-infected cultures, respectively. The presence of S-βGM in infected cultures induced total recoveries of TER and FD-4 flux to values that did not differ from the control and a partial recovery of d-mannitol flux. These effects were confirmed by immunolocalization of actin, zonula occludens protein 1, and occludin. Similar results were obtained for Salmonella Dublin. The protection of S-βGM on PP in infected cultures may be associated with a total recovery of ROS production to values that did not differ from the control. Moreover, S-βGM has the capacity to agglutinate bacteria, leading to a significant reduction of 32% in intracellular S Enteritidis. The results demonstrate that S-βGM contributes to protecting epithelial barrier function in a Caco-2 cell model disrupted by S. Enteritidis. © 2016 American Society for Nutrition.
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Bone marrow-CNS connections: Implications in the pathogenesis of diabetic retinopathy
Douglas, Yellowlees; Bhatwadekar, Ashay D.; Shaw, Lynn C.; Carnegie, Debra; Caballero, Sergio; Li, Quihong; Calzi, Sergio Li; Raizada, Mohan K.; Stitt, Alan W.; Grant, Maria B.
2013-01-01
Diabetic retinopathy is the fourth most common cause of blindness in adults. Current therapies, including anti-VEGF therapy, have partial efficacy in arresting the progression of proliferative diabetic retinopathy and diabetic macular edema. This review provides an overview of a novel, innovative approach to viewing diabetic retinopathy as the result of an inflammatory cycle that affects the bone marrow (BM) and the central and sympathetic nervous systems. Diabetes associated inflammation may be the result of BM neuropathy which skews haematopoiesis towards generation of increased inflammatory cells but also reduced production of endothelial progenitor cells responsible for maintaining healthy endothelial function and renewal. The resulting systemic inflammation further impacts the hypothalamus, promoting insulin resistance and diabetes, and initiates an inflammatory cascade that adversely impacts both macrovascular and microvascular complications, including diabetic retinopathy (DR). This review examines the idea of using anti-inflammatory agents that cross not only the blood-retinal barrier to enter the retina but also have the capability to target the central nervous system and cross the blood-brain barrier to reduce neuroinflammation. This neuroinflammation in key sympathetic centers serves to not only perpetuate BM pathology but promote insulin resistance which is characteristic of type 2 diabetic patients (T2D) but is also seen in T1D. A case series of morbidly obese T2D patients with retinopathy and neuropathy treated with minocycline, a well-tolerated antibiotic that crosses both the blood-retina and blood-brain barrier is presented. Our results indicates that minocycine shows promise for improving visual acuity, reducing pain from peripheral neuropathy, promoting weight loss and improving blood pressure control and we postulate that these observed beneficial effects are due to a reduction of chronic inflammation. PMID:22609081
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List, Karin; Szabo, Roman; Molinolo, Alfredo; Nielsen, Boye Schnack; Bugge, Thomas H.
2006-01-01
The membrane serine protease matriptase is required for epidermal barrier function, hair formation, and thymocyte development in mice, and dysregulated matriptase expression causes epidermal squamous cell carcinoma. To elucidate the specific functions of matriptase in normal and aberrant epidermal differentiation, we used enzymatic gene trapping combined with immunohistochemical, ultrastructural, and barrier function assays to delineate the spatio-temporal expression and function of matriptase in mouse keratinized tissue development, homeostasis, and malignant transformation. In the interfollicular epidermis, matriptase expression was restricted to postmitotic transitional layer keratinocytes undergoing terminal differentiation. Matriptase was also expressed in keratinizing oral epithelium, where it was required for oral barrier function, and in thymic epithelium. In all three tissues, matriptase colocalized with profilaggrin. In staged embryos, the onset of epidermal matriptase expression coincided with that of profilaggrin expression and acquisition of the epidermal barrier. In marked contrast to stratifying keritinized epithelium, matripase expression commenced already in undifferentiated and rapidly proliferating profilaggrin-negative matrix cells and displayed hair growth cycle-dependent expression. Exposure of the epidermis to carcinogens led to the gradual appearance of matriptase in a keratin-5-positive proliferative cell compartment during malignant progression. Combined with previous studies, these data suggest that matriptase has diverging functions in the genesis of stratified keratinized epithelium, hair follicles, and squamous cell carcinoma. PMID:16651618
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List, Karin; Szabo, Roman; Molinolo, Alfredo; Nielsen, Boye Schnack; Bugge, Thomas H
2006-05-01
The membrane serine protease matriptase is required for epidermal barrier function, hair formation, and thymocyte development in mice, and dysregulated matriptase expression causes epidermal squamous cell carcinoma. To elucidate the specific functions of matriptase in normal and aberrant epidermal differentiation, we used enzymatic gene trapping combined with immunohistochemical, ultrastructural, and barrier function assays to delineate the spatio-temporal expression and function of matriptase in mouse keratinized tissue development, homeostasis, and malignant transformation. In the interfollicular epidermis, matriptase expression was restricted to postmitotic transitional layer keratinocytes undergoing terminal differentiation. Matriptase was also expressed in keratinizing oral epithelium, where it was required for oral barrier function, and in thymic epithelium. In all three tissues, matriptase colocalized with profilaggrin. In staged embryos, the onset of epidermal matriptase expression coincided with that of profilaggrin expression and acquisition of the epidermal barrier. In marked contrast to stratifying keritinized epithelium, matripase expression commenced already in undifferentiated and rapidly proliferating profilaggrin-negative matrix cells and displayed hair growth cycle-dependent expression. Exposure of the epidermis to carcinogens led to the gradual appearance of matriptase in a keratin-5-positive proliferative cell compartment during malignant progression. Combined with previous studies, these data suggest that matriptase has diverging functions in the genesis of stratified keratinized epithelium, hair follicles, and squamous cell carcinoma.
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Fredenburgh, Laura E.; Velandia, Margarita M. Suarez; Ma, Jun; Olszak, Torsten; Cernadas, Manuela; Englert, Joshua A.; Chung, Su Wol; Liu, Xiaoli; Begay, Cynthia; Padera, Robert F.; Blumberg, Richard S.; Walsh, Stephen R.; Baron, Rebecca M.; Perrella, Mark A.
2011-01-01
Sepsis remains the leading cause of death in critically ill patients despite modern advances in critical care. Intestinal barrier dysfunction may lead to secondary bacterial translocation and the development of the multiple organ dysfunction syndrome during sepsis. Cyclooxygenase-2 (COX-2) is highly upregulated in the intestine during sepsis and we hypothesized that it may be critical in the maintenance of intestinal epithelial barrier function during peritonitis-induced polymicrobial sepsis. COX-2−/− and COX-2+/+ BALB/c mice underwent cecal ligation and puncture (CLP) or sham surgery. Mice chimeric for COX-2 were derived by bone marrow transplantation and underwent CLP. C2BBe1 cells, an intestinal epithelial cell line, were treated with the COX-2 inhibitor NS-398, PGD2, or vehicle and stimulated with cytokines. COX-2−/− mice developed exaggerated bacteremia and increased mortality compared with COX-2+/+ mice following CLP. Mice chimeric for COX-2 exhibited the recipient phenotype suggesting that epithelial COX-2 expression in the ileum attenuates bacteremia following CLP. Absence of COX-2 significantly increased epithelial permeability of the ileum and reduced expression of the tight junction proteins zonula occludens-1 (ZO-1), occludin, and claudin-1 in the ileum following CLP. Furthermore, PGD2 attenuated cytokine-induced hyperpermeability and ZO-1 downregulation in NS-398-treated C2BBe1 cells. Our findings reveal that absence of COX-2 is associated with enhanced intestinal epithelial permeability and leads to exaggerated bacterial translocation and increased mortality during peritonitis-induced sepsis. Taken together, our results suggest that epithelial expression of COX-2 in the ileum is a critical modulator of tight junction protein expression and intestinal barrier function during sepsis. PMID:21967897
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Runtsch, Marah C; Hu, Ruozhen; Alexander, Margaret; Wallace, Jared; Kagele, Dominique; Petersen, Charisse; Valentine, John F; Welker, Noah C; Bronner, Mary P; Chen, Xinjian; Smith, Daniel P; Ajami, Nadim J; Petrosino, Joseph F; Round, June L; O'Connell, Ryan M
2015-10-06
Host-microbial interactions within the mammalian intestines must be properly regulated in order to promote host health and limit disease. Because the microbiota provide constant immunological signals to intestinal tissues, a variety of regulatory mechanisms have evolved to ensure proper immune responses to maintain homeostasis. However, many of the genes that comprise these regulatory pathways, including immune-modulating microRNAs (miRNAs), have not yet been identified or studied in the context of intestinal homeostasis. Here, we investigated the role of microRNA-146a (miR-146a) in regulating intestinal immunity and barrier function and found that this miRNA is expressed in a variety of gut tissues in adult mice. By comparing intestinal gene expression in WT and miR-146a-/- mice, we demonstrate that miR-146a represses a subset of gut barrier and inflammatory genes all within a network of immune-related signaling pathways. We also found that miR-146a restricts the expansion of intestinal T cell populations, including Th17, Tregs, and Tfh cells. GC B cells, Tfh ICOS expression, and the production of luminal IgA were also reduced by miR-146a in the gut. Consistent with an enhanced intestinal barrier, we found that miR-146a-/- mice are resistant to DSS-induced colitis, a model of Ulcerative Colitis (UC), and this correlated with elevated colonic miR-146a expression in human UC patients. Taken together, our data describe a role for miR-146a in constraining intestinal barrier function, a process that alters gut homeostasis and enhances at least some forms of intestinal disease in mice.
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Runtsch, Marah C.; Hu, Ruozhen; Alexander, Margaret; Wallace, Jared; Kagele, Dominique; Petersen, Charisse; Valentine, John F.; Welker, Noah C.; Bronner, Mary P.; Chen, Xinjian; Smith, Daniel P.; Ajami, Nadim J.; Petrosino, Joseph F.; Round, June L.; O'Connell, Ryan M.
2015-01-01
Host-microbial interactions within the mammalian intestines must be properly regulated in order to promote host health and limit disease. Because the microbiota provide constant immunological signals to intestinal tissues, a variety of regulatory mechanisms have evolved to ensure proper immune responses to maintain homeostasis. However, many of the genes that comprise these regulatory pathways, including immune-modulating microRNAs (miRNAs), have not yet been identified or studied in the context of intestinal homeostasis. Here, we investigated the role of microRNA-146a (miR-146a) in regulating intestinal immunity and barrier function and found that this miRNA is expressed in a variety of gut tissues in adult mice. By comparing intestinal gene expression in WT and miR-146a−/− mice, we demonstrate that miR-146a represses a subset of gut barrier and inflammatory genes all within a network of immune-related signaling pathways. We also found that miR-146a restricts the expansion of intestinal T cell populations, including Th17, Tregs, and Tfh cells. GC B cells, Tfh ICOS expression, and the production of luminal IgA were also reduced by miR-146a in the gut. Consistent with an enhanced intestinal barrier, we found that miR-146a−/− mice are resistant to DSS-induced colitis, a model of Ulcerative Colitis (UC), and this correlated with elevated colonic miR-146a expression in human UC patients. Taken together, our data describe a role for miR-146a in constraining intestinal barrier function, a process that alters gut homeostasis and enhances at least some forms of intestinal disease in mice. PMID:26456940
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Azouz, Nurit P; Ynga-Durand, Mario A; Caldwell, Julie M; Jain, Ayushi; Rochman, Mark; Fischesser, Demetria M; Ray, Leanne M; Bedard, Mary C; Mingler, Melissa K; Forney, Carmy; Eilerman, Matthew; Kuhl, Jonathan T; He, Hua; Biagini Myers, Jocelyn M; Mukkada, Vincent A; Putnam, Philip E; Khurana Hershey, Gurjit K; Kottyan, Leah C; Wen, Ting; Martin, Lisa J; Rothenberg, Marc E
2018-06-06
Loss of barrier integrity has an important role in eliciting type 2 immune responses, yet the molecular events that initiate and connect this with allergic inflammation remain unclear. We reveal an endogenous, homeostatic mechanism that controls barrier function and inflammatory responses in esophageal allergic inflammation. We show that a serine protease inhibitor, SPINK7 (serine peptidase inhibitor, kazal type 7), is part of the differentiation program of human esophageal epithelium and that SPINK7 depletion occurs in a human allergic, esophageal condition termed eosinophilic esophagitis. Experimental manipulation strategies reducing SPINK7 in an esophageal epithelial progenitor cell line and primary esophageal epithelial cells were sufficient to induce barrier dysfunction and transcriptional changes characterized by loss of cellular differentiation and altered gene expression known to stimulate allergic responses (for example, FLG and SPINK5 ). Epithelial silencing of SPINK7 promoted production of proinflammatory cytokines including thymic stromal lymphopoietin (TSLP). Loss of SPINK7 increased the activity of urokinase plasminogen-type activator (uPA), which in turn had the capacity to promote uPA receptor-dependent eosinophil activation. Treatment of epithelial cells with the broad-spectrum antiserine protease, α1 antitrypsin, reversed the pathologic features associated with SPINK7 silencing. The relevance of this pathway in vivo was supported by finding genetic epistasis between variants in TSLP and the uPA-encoding gene, PLAU We propose that the endogenous balance between SPINK7 and its target proteases is a key checkpoint in regulating mucosal differentiation, barrier function, and inflammatory responses and that protein replacement with antiproteases may be therapeutic for select allergic diseases. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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Li, Baohai; Kamiya, Takehiro; Kalmbach, Lothar; Yamagami, Mutsumi; Yamaguchi, Katsushi; Shigenobu, Shuji; Sawa, Shinichiro; Danku, John M C; Salt, David E; Geldner, Niko; Fujiwara, Toru
2017-03-06
The formation of Casparian strips and suberin lamellae at the endodermis limits the free diffusion of nutrients and harmful substances via the apoplastic space between the soil solution and the stele in roots [1-3]. Casparian strips are ring-like lignin polymers deposited in the middle of anticlinal cell walls between endodermal cells and fill the gap between them [4-6]. Suberin lamellae are glycerolipid polymers covering the endodermal cells and likely function as a barrier to limit transmembrane movement of apoplastic solutes into the endodermal cells [7, 8]. However, the current knowledge on the formation of these two distinct endodermal barriers and their regulatory role in nutrient transport is still limited. Here, we identify an uncharacterized gene, LOTR1, essential for Casparian strip formation in Arabidopsis thaliana. The lotr1 mutants display altered localization of CASP1, an essential protein for Casparian strip formation [9], disrupted Casparian strips, ectopic suberization of endodermal cells, and low accumulation of shoot calcium (Ca). Degradation by expression of a suberin-degrading enzyme in the mutants revealed that the ectopic suberization at the endodermal cells limits Ca transport through the transmembrane pathway, thereby causing reduced Ca delivery to the shoot. Moreover, analysis of the mutants showed that suberin lamellae function as an apoplastic diffusion barrier to the stele at sites of lateral root emergence where Casparian strips are disrupted. Our findings suggest that the transmembrane pathway through unsuberized endodermal cells, rather than the sites of lateral root emergence, mediates the transport of apoplastic substances such as Ca into the xylem. Copyright © 2017 Elsevier Ltd. All rights reserved.
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DOT National Transportation Integrated Search
2013-07-01
A Manual for Assessing Safety Hardware (MASH) Test Level 4 (TL-4) energy-absorbing, urban roadside/median barrier was developed to reduce lateral vehicle accelerations below those observed during similar crashes into permanent concrete barriers. Seve...
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Bernard, Didem; Selden, Thomas; Yeh, Susan
2016-04-01
People with functional limitations and chronic conditions account for the greatest resource use within the health care system. To examine financial burdens and barriers to care among nonelderly adults, focusing on the role of functional limitations and chronic conditions. High financial burden is defined as medical spending exceeding 20 percent of family income. Financial barriers are defined as delaying care/being unable to get care for financial reasons, and reporting that delaying care/going without was a big problem. Data are from the Medical Expenditure Panel Survey (2008-2012). Functional limitations are associated with increased prevalence of financial burdens. Among single adults, the frequency of high burdens is 20.3% for those with functional limitations, versus 7.8% for those without. Among those with functional limitations, those with 3 or more chronic conditions are twice as likely to have high burdens compared to those without chronic conditions (22.2% versus 11.1%, respectively). Similar patterns occur among persons in multi-person families whose members have functional limitations and chronic conditions. Having functional limitations and chronic conditions is also strongly associated with financial barriers to care: 40.2% among the uninsured, 21.9% among those with public coverage, and 13.6% among those with private group insurance were unable to get care. Functional limitations and chronic conditions are associated with increased prevalence of burdens and financial barriers in all insurance categories, with the exception that an association between functional limitations and the prevalence of burdens was not observed for public coverage. Published by Elsevier Inc.
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Fusion enhancement at near and sub-barrier energies in 19O + 12C
Singh, Varinderjit; Vadas, J.; Steinbach, T. K.; ...
2016-12-12
Measuring the fusion excitation function for an isotopic chain of projectile nuclei provides a stringent test of a microscopic description of fusion. We report the first measurement of the fusion excitation function at near-barrier energies for the 19O+ 12C system. The measured excitation function is compared with the fusion excitation function of 18O+ 12C. A significant enhancement in the fusion probability of 19O ions with a 12C target as compared to 18O ions is observed. As a result, the experimental cross-sections observed at near-barrier energies are compared with a state-of-the-art microscopic model.
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Zou, Yaotian; Tarko, Andrew P
2018-02-01
The objective of this study was to develop crash modification factors (CMFs) and estimate the average crash costs applicable to a wide range of road-barrier scenarios that involved three types of road barriers (concrete barriers, W-beam guardrails, and high-tension cable barriers) to produce a suitable basis for comparing barrier-oriented design alternatives and road improvements. The intention was to perform the most comprehensive and in-depth analysis allowed by the cross-sectional method and the crash data available in Indiana. To accomplish this objective and to use the available data efficiently, the effects of barrier were estimated on the frequency of barrier-relevant (BR) crashes, the types of harmful events and their occurrence during a BR crash, and the severity of BR crash outcomes. The harmful events component added depth to the analysis by connecting the crash onset with its outcome. Further improvement of the analysis was accomplished by considering the crash outcome severity of all the individuals involved in a crash and not just drivers, utilizing hospital data, and pairing the observations with and without road barriers along same or similar road segments to better control the unobserved heterogeneity. This study confirmed that the total number of BR crashes tended to be higher where medians had installed barriers, mainly due to collisions with barriers and, in some cases, with other vehicles after redirecting vehicles back to traffic. These undesirable effects of barriers were surpassed by the positive results of reducing cross-median crashes, rollover events, and collisions with roadside hazards. The average cost of a crash (unit cost) was reduced by 50% with cable barriers installed in medians wider than 50ft. A similar effect was concluded for concrete barriers and guardrails installed in medians narrower than 50ft. The studied roadside guardrails also reduced the unit cost by 20%-30%. Median cable barriers were found to be the most effective among all the studied barriers due to the smaller increase in the crash frequency caused by these barriers and the less severe injury outcomes. More specifically, the occupants of vehicles colliding with near-side cable barriers tended to have less severe injuries than occupants of vehicles entering the median from median's farther side. The near-side cable barriers provided protection against rollover inside the median and against a potentially dangerous collision with or running over the median drain; therefore, the greatest safety benefit can be expected where cable barriers are installed at both edges of the median. The CMFs and unit crash costs for 48 road-barrier scenarios produced in this study are included in this paper. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Quantum finance Hamiltonian for coupon bond European and barrier options.
Baaquie, Belal E
2008-03-01
Coupon bond European and barrier options are financial derivatives that can be analyzed in the Hamiltonian formulation of quantum finance. Forward interest rates are modeled as a two-dimensional quantum field theory and its Hamiltonian and state space is defined. European and barrier options are realized as transition amplitudes of the time integrated Hamiltonian operator. The double barrier option for a financial instrument is "knocked out" (terminated with zero value) if the price of the underlying instrument exceeds or falls below preset limits; the barrier option is realized by imposing boundary conditions on the eigenfunctions of the forward interest rates' Hamiltonian. The price of the European coupon bond option and the zero coupon bond barrier option are calculated. It is shown that, is general, the constraint function for a coupon bond barrier option can -- to a good approximation -- be linearized. A calculation using an overcomplete set of eigenfunctions yields an approximate price for the coupon bond barrier option, which is given in the form of an integral of a factor that results from the barrier condition times another factor that arises from the payoff function.
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Modeling the impact of solid noise barriers on near road air quality
Studies based on field measurements, wind tunnel experiments, and controlled tracer gas releases indicate that solid, roadside noise barriers can lead to reductions in downwind near-road air pollutant concentrations. A tracer gas study showed that a solid barrier reduced pollutan...
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Oral intake of beet extract provides protection against skin barrier impairment in hairless mice.
Kawano, Ken-Ichi; Umemura, Kazuo
2013-05-01
The epidermis acts as a functional barrier against the external environment. Disturbances in the function of this barrier cause water loss and increase the chances of penetration by various irritable stimuli, leading to skin diseases such as dry skin, atopic dermatitis, and psoriasis. Ceramides are a critical natural element of the protective epidermal barrier. The aim of this study was to evaluate whether the oral intake of beet (Beta vulgaris) extract, a natural product rich in glucosylceramide (GlcCer), may prevent disturbance in skin barrier function. When HR-1 hairless mice were fed a special diet (HR-AD), transepidermal water loss (TEWL) from the dorsal skin increased, with a compensatory increase in water intake after 5 weeks. Mice fed with HR-AD had dry skin with erythema and showed increased scratching behaviour. Histological examinations revealed a remarkable increase in the thickness of the skin at 8 weeks. Supplemental addition of beet extract, which contained GlcCer at a final concentration of 0.1%, significantly prevented an increase TEWL, water intake, cumulative scratching time, and epidermal thickness at 8 weeks. These results indicate that oral intake of beet extract shows potential for preventing skin diseases associated with impaired skin barrier function. Copyright © 2012 John Wiley & Sons, Ltd.
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MO-D-213-07: RadShield: Semi- Automated Calculation of Air Kerma Rate and Barrier Thickness
DOE Office of Scientific and Technical Information (OSTI.GOV)
DeLorenzo, M; Wu, D; Rutel, I
2015-06-15
Purpose: To develop the first Java-based semi-automated calculation program intended to aid professional radiation shielding design. Air-kerma rate and barrier thickness calculations are performed by implementing NCRP Report 147 formalism into a Graphical User Interface (GUI). The ultimate aim of this newly created software package is to reduce errors and improve radiographic and fluoroscopic room designs over manual approaches. Methods: Floor plans are first imported as images into the RadShield software program. These plans serve as templates for drawing barriers, occupied regions and x-ray tube locations. We have implemented sub-GUIs that allow the specification in regions and equipment for occupancymore » factors, design goals, number of patients, primary beam directions, source-to-patient distances and workload distributions. Once the user enters the above parameters, the program automatically calculates air-kerma rate at sampled points beyond all barriers. For each sample point, a corresponding minimum barrier thickness is calculated to meet the design goal. RadShield allows control over preshielding, sample point location and material types. Results: A functional GUI package was developed and tested. Examination of sample walls and source distributions yields a maximum percent difference of less than 0.1% between hand-calculated air-kerma rates and RadShield. Conclusion: The initial results demonstrated that RadShield calculates air-kerma rates and required barrier thicknesses with reliable accuracy and can be used to make radiation shielding design more efficient and accurate. This newly developed approach differs from conventional calculation methods in that it finds air-kerma rates and thickness requirements for many points outside the barriers, stores the information and selects the largest value needed to comply with NCRP Report 147 design goals. Floor plans, parameters, designs and reports can be saved and accessed later for modification and recalculation. We have confirmed that this software accurately calculates air-kerma rates and required barrier thicknesses for diagnostic radiography and fluoroscopic rooms.« less
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Adsorption and oxidation of SO2 by graphene oxides: A van der Waals density functional theory study
NASA Astrophysics Data System (ADS)
Zhang, Huijuan; Cen, Wanglai; Liu, Jie; Guo, Jiaxiu; Yin, Huaqiang; Ning, Ping
2015-01-01
Carbon materials have been used for low temperature (20-150 °C) catalytic removal of SO2 from the coal-burned flue gases for a long time, but the mechanism at atomic level is still controversial. Density functional theory was used to investigate the adsorption and oxidation of SO2 on elaborated graphene oxides (GOs) to discover the insights. It is found that the hydroxyl groups on GO surface possess bi-functional effects: both enhancing the adsorption of SO2 through H-bonding interaction and reducing the reaction barrier for its oxidation to SO3. The promotion of oxidation is related to a pre-activation of the surface epoxy group. Based on Bader population, charge difference and electron localization function analysis, a charge transfer channel is proposed to explain the pre-activation.
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Hyaluronan-Inorganic Nanohybrid Materials for Biomedical Applications.
Cai, Zhixiang; Zhang, Hongbin; Wei, Yue; Cong, Fengsong
2017-06-12
Nanomaterials, including gold, silver, and magnetic nanoparticles, carbon, and mesoporous materials, possess unique physiochemical and biological properties, thus offering promising applications in biomedicine, such as in drug delivery, biosensing, molecular imaging, and therapy. Recent advances in nanotechnology have improved the features and properties of nanomaterials. However, these nanomaterials are potentially cytotoxic and demonstrate a lack of cell-specific function. Thus, they have been functionalized with various polymers, especially polysaccharides, to reduce toxicity and improve biocompatibility and stability under physiological conditions. In particular, nanomaterials have been widely functionalized with hyaluronan (HA) to enhance their distribution in specific cells and tissues. This review highlights the most recent advances on HA-functionalized nanomaterials for biotechnological and biomedical applications, as nanocarriers in drug delivery, contrast agents in molecular imaging, and diagnostic agents in cancer therapy. A critical evaluation of barriers affecting the use of HA-functionalized nanomaterials is also discussed, and insights into the outlook of the field are explored.
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The relationship between skin function, barrier properties, and body-dependent factors.
Dąbrowska, A K; Spano, F; Derler, S; Adlhart, C; Spencer, N D; Rossi, R M
2018-05-01
Skin is a multilayer interface between the body and the environment, responsible for many important functions, such as temperature regulation, water transport, sensation, and protection from external triggers. This paper provides an overview of principal factors that influence human skin and describes the diversity of skin characteristics, its causes and possible consequences. It also discusses limitations in the barrier function of the skin, describing mechanisms of absorption. There are a number of in vivo investigations focusing on the diversity of human skin characteristics with reference to barrier properties and body-dependent factors. Skin properties vary among individuals of different age, gender, ethnicity, and skin types. In addition, skin characteristics differ depending on the body site and can be influenced by the body-mass index and lifestyle. Although one of the main functions of the skin is to act as a barrier, absorption of some substances remains possible. Various factors can alter human skin properties, which can be reflected in skin function and the quality of everyday life. Skin properties and function are strongly interlinked. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Lee, Linda L.; Puchowicz, Michelle; Golub, Mari S.; Befroy, Douglas E.; Wilson, Dennis W.; Anderson, Steven; Cline, Gary; Bini, Jason; Borkowski, Kamil; Knotts, Trina A.; Rutledge, John C.
2018-01-01
Recent work suggests that diet affects brain metabolism thereby impacting cognitive function. Our objective was to determine if a western diet altered brain metabolism, increased blood-brain barrier (BBB) transport and inflammation, and induced cognitive impairment in C57BL/6 (WT) mice and low-density lipoprotein receptor null (LDLr -/-) mice, a model of hyperlipidemia and cognitive decline. We show that a western diet and LDLr -/- moderately influence cognitive processes as assessed by Y-maze and radial arm water maze. Also, western diet significantly increased BBB transport, as well as microvessel factor VIII in LDLr -/- and microglia IBA1 staining in WT, both indicators of activation and neuroinflammation. Interestingly, LDLr -/- mice had a significant increase in 18F- fluorodeoxyglucose uptake irrespective of diet and brain 1H-magnetic resonance spectroscopy showed increased lactate and lipid moieties. Metabolic assessments of whole mouse brain by GC/MS and LC/MS/MS showed that a western diet altered brain TCA cycle and β-oxidation intermediates, levels of amino acids, and complex lipid levels and elevated proinflammatory lipid mediators. Our study reveals that the western diet has multiple impacts on brain metabolism, physiology, and altered cognitive function that likely manifest via multiple cellular pathways. PMID:29444171
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Proksch, E; Elias, P M; Feingold, K R
1990-01-01
Epidermal cholesterol biosynthesis is regulated by barrier function. We quantitated the amount and activation state (phosphorylation-dephosphorylation) of the rate-limiting enzyme, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, in epidermis before and after barrier disruption. In murine epidermis we found high enzyme activity (1.75 +/- 0.02 nmol/min per mg protein). After acute barrier disruption, enzyme activity began to increase after 1.5 h, reaching a maximum increase by 2.5 h, and returned to normal by 15 h. Chronic barrier disruption increased total enzyme activity by 83%. In normal epidermis, measurement of HMG CoA reductase activity in microsomes isolated in NaF- vs. NaCl-containing buffers demonstrated that 46 +/- 2% of the enzyme was in the active form. After acute or chronic barrier disruption, a marked increase in the percentage of HMG CoA reductase in the active form was observed. Acute disruption increased enzyme activation state as early as 15 min, reaching a maximum after 2.5 h, with an increase still present at 15 h, indicating that changes in activation state had a close temporal relationship with barrier function. Increases in total HMG CoA reductase activity occurred only after profound barrier disruption, whereas changes in activation state occur with lesser degrees of barrier disruption. Artificial correction of barrier function prevented the increase in total HMG CoA reductase activity, and partially prevented the increase in enzyme activation. These results show that barrier requirements regulate epidermal cholesterol synthesis by modulating both the HMG CoA reductase amount and activation state. Images PMID:2312730
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Novel attributes of bandstructure effect on the performance of germanium Schottky barrier MOSFET
NASA Astrophysics Data System (ADS)
Ahangari, Zahra
2018-07-01
A detailed study of the bandstructure effect on the performance of a double-gate germanium Schottky barrier MOSFET (Ge-SBFET) is investigated. An accurate calculation of the thickness-dependent 2D bandstructure is employed within a 20 orbital sp 3 d 5 s* tight-binding formalism, and the quantum transport of the carriers is elucidated based on the non-equilibrium Green’s function formalism. Quantum confinement considerably changes the bandstructure profile of the Ge-SBFET and causes the energy difference of the | {{Γ }}-L| valleys to rearrange. For a channel thickness of about 1.5 nm, the two-fold X 2 type valleys with major axes at the {{Γ }} point form a subband with minimum energy, and the | {{Γ }}-L| energy split is reduced to 13 meV, which compensates for the lack of density of states in the nanoscale regime. Moreover, the strong transverse confinement of the ultra-thin body Ge-SBFET increases the effective Schottky barrier height and a parabolic potential profile with discrete resonant states is formed along the current transport direction, mainly at low drain voltages. Resonant tunnelling creates oscillations in the transfer characteristic, especially at low temperatures and at a reduced value of drain voltages. The impact of the physical and structural parameters, which may affect the resonant tunnelling in a Ge-SBFET, is thoroughly analysed. The results in this paper pave the way towards elucidating the applications of nanoscale Ge-SBFETs.
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Predictors of women's exercise maintenance after cardiac rehabilitation.
Moore, Shirley M; Dolansky, Mary A; Ruland, Cornelia M; Pashkow, Fredric J; Blackburn, Gordon G
2003-01-01
Less than 50% of persons who participate in cardiac rehabilitation (CR) programs maintain an exercise regimen for as long as 6 months after completion. This study was conducted to identify factors that predict women's exercise following completion of a CR program. In this prospective, descriptive study, a convenience sample of 60 women were recruited at completion of a phase II CR program. Exercise was measured using a heart rate wristwatch monitor over 3 months. Predictor variables collected at the time of the subjects' enrollment were age, body mass index, cardiac functional status, comorbidity, muscle or joint pain, motivation, mood state, social support, self-efficacy, perceived benefits or barriers, and prior exercise. Of women, 25% did not exercise at all following completion of a CR program and only 48% of the subjects were exercising at 3 months. Different predictors were found of the various dimensions of exercise maintenance. Predictors of exercise frequency were comorbidity and instrumental social support. Instrumental social support was the only predictor of exercise persistence. Comorbidity was the only predictor of exercise intensity. The only predictor of the total amount of exercise was benefits or barriers. Interventions aimed at increasing women's exercise should focus on increasing their problem-solving abilities to reduce barriers to exercise and increase social support by family and friends. Because comorbidity was a significant predictor of exercise, women should be encouraged to use exercise techniques that reduce impact on muscles and joints (eg, swimming) or exercising for short periods several times a day.
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Jansen, Jens Einar; Wøldike, Peter Michael; Haahr, Ulrik Helt; Simonsen, Erik
2015-03-01
Delays in initiating treatment are associated with poor clinical and functional outcomes, yet there remains unclarity as to what facilitates and what acts as barriers to accessing appropriate support for first-episode psychosis. To explore this we examined service users' views of their illness trajectory and help-seeking behavior. To describe service-users' experiences with and understanding of their illness and pathway to care, including their need for treatment, the role of their relatives and experience with the treatment service. In-depth interviews were conducted with eleven randomly selected service users (median age 20, range 15-24, 6 males, 5 females) diagnosed with a first-episode psychosis and currently enrolled in treatment for this disorder. Fear of stigma, lack of knowledge about mental illness and normalisation of symptoms were barriers to accessing appropriate treatment, while support from significant others and information accessed by internet were reported as important elements in seeking appropriate treatment. The findings regarding barriers to treatment are in accordance with themes found in earlier studies and serve to validate these. Our study highlights the need to include psychological factors such as normalisation of symptoms and fear of stigma when attempting to reduce DUP in early psychosis, in addition to initiatives to reduce service delays. Also, a greater use of the potentials inherent in Internet and social media platforms seems important in this regard.
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Tong, Nianting; Zhang, Zhenzhen; Zhang, Wei; Qiu, Yating; Gong, Yuanyuan; Yin, Lili; Qiu, Qinghua; Wu, Xingwei
2013-01-01
Retinal swelling, leading to irreversible visual impairment, is an important early complication in retinal ischemia/reperfusion (I/R) injury. Diosmin, a naturally occurring flavonoid glycoside, has been shown to have antioxidative and anti-inflammatory effects against I/R injury. The present study was performed to evaluate the retinal microvascular protective effect of diosmin in a model of I/R injury. Unilateral retinal I/R was induced by increasing intraocular pressure to 110 mm Hg for 60 min followed by reperfusion. Diosmin (100 mg/kg) or vehicle solution was administered intragastrically 30 min before the onset of ischemia and then daily after I/R injury until the animals were sacrificed. Rats were evaluated for retinal functional injury by electroretinogram (ERG) just before sacrifice. Retinas were harvested for HE staining, immunohistochemistry assay, ELISA, and western blotting analysis. Evans blue (EB) extravasation was determined to assess blood-retinal barrier (BRB) disruption and the structure of tight junctions (TJ) was examined by transmission electron microscopy. Diosmin significantly ameliorated the reduction of b-wave, a-wave, and b/a ratio in ERG, alleviated retinal edema, protected the TJ structure, and reduced EB extravasation. All of these effects of diosmin were associated with increased zonular occluden-1 (ZO-1) and occludin protein expression and decreased VEGF/PEDF ratio. Maintenance of TJ integrity and reduced permeability of capillaries as well as improvements in retinal edema were observed with diosmin treatment, which may contribute to preservation of retinal function. This protective effect of diosmin may be at least partly attributed to its ability to regulate the VEGF/PEDF ratio.
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Xu, Wei; Hong, Seok Jong; Zeitchek, Michael; Cooper, Garry; Jia, Shengxian; Xie, Ping; Qureshi, Hannan A; Zhong, Aimei; Porterfield, Marshall D; Galiano, Robert D; Surmeier, D James; Mustoe, Thomas A
2015-03-01
Although it is known that the inflammatory response that results from disruption of epithelial barrier function after injury results in excessive scarring, the upstream signals remain unknown. It has also been observed that epithelial disruption results in reduced hydration status and that the use of occlusive dressings that prevent water loss from wounds decreases scar formation. We hypothesized that hydration status changes sodium homeostasis and induces sodium flux in keratinocytes, which result in activation of pathways responsible for keratinocyte-fibroblast signaling and ultimately lead to activation of fibroblasts. Here, we demonstrate that perturbations in epithelial barrier function lead to increased sodium flux in keratinocytes. We identified that sodium flux in keratinocytes is mediated by epithelial sodium channels (ENaCs) and causes increased secretion of proinflammatory cytokines, which activate fibroblast via the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathway. Similar changes in signal transduction and sodium flux occur by increased sodium concentration, which simulates reduced hydration, in the media in epithelial cultures or human ex vivo skin cultures. Blockade of ENaC, prostaglandin synthesis, or PGE2 receptors all reduce markers of fibroblast activation and collagen synthesis. In addition, employing a validated in vivo excessive scar model in the rabbit ear, we demonstrate that utilization of either an ENaC blocker or a COX-2 inhibitor results in a marked reduction in scarring. Other experiments demonstrate that the activation of COX-2 in response to increased sodium flux is mediated through the PIK3/Akt pathway. Our results indicate that ENaC responds to small changes in sodium concentration with inflammatory mediators and suggest that the ENaC pathway is a potential target for a strategy to prevent fibrosis.
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Cultural Barriers to Change in Assessment Practices in Higher Education
ERIC Educational Resources Information Center
Jenkins, Deborah Bainer
2007-01-01
The culture at the authors' institution raised barriers to changing from traditional assessment to portfolio assessment in the doctoral program. A Culture of Independence presented barriers of time and functional inadequacy. A Culture of Compliance raised trust, group process, and membership issues. These barriers were managed and overcome using…
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NASA Astrophysics Data System (ADS)
Devitt, Catherine; O'Neill, Eoin; Waldron, Richard
2016-04-01
Septic systems that are malfunctioning, improperly sited or designed, present a contamination risk to drinking water sources, and subsequently, to human health. However, the international literature identifies gaps in householder knowledge regarding the function and maintenance requirements of septic systems, and also the potential health and environmental risk implications. Allied with householder fears related to the financial cost of risk management, these factors tend to reduce concern to recognise a malfunctioning system. In the Republic of Ireland, three-quarters of households in rural areas utilise an individual domestic wastewater treatment system (or septic system). Consequently, a significant portion of rural households that rely on groundwater sources via private-well use are at risk. Ireland reports one of the highest crude incidence rates of Verotoxigenic Escherichia coli (VTEC) infection in the European Union, and waterborne transmission related to contact with untreated or poorly treated water from private water sources is a factor in its transmission. Following recent Irish legislative change that places a duty of care on individual householders to ensure a proper system functioning, this exploratory study examines perceptions towards the risk management of septic systems among Irish householders. Using qualitative research methods, four focus groups selected on the basis of geographical variation, and two semi-structured interviews were conducted. While most householders agreed that poorly maintained septic systems represented a threat to the environment and to public health, none reported to having a regular maintenance routine in place. Thematic analysis revealed the drivers and barriers to septic system maintenance, and preferences of householders pertaining to communication on septic systems. The Health Belief Model is employed to help understand results. Results suggest that householder capacity to engage in regular risk management is reduced by limited perceptions of risk susceptibility and severity, impeding cues to action and barrier concerns. Understanding societal perceptions is central to effectively engaging with the public, and informing an improved approach to future pro-environmental engagement and behaviour.
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Loma, P; Guzman-Aranguez, A; Pérez de Lara, M J; Pintor, J
2015-01-01
Background and Purpose Here, we have studied the effects of the dinucleotide P1, P4-Di (adenosine-5′) tetraphosphate (Ap4A) on corneal barrier function conferred by the tight junction (TJ) proteins and its possible involvement in ocular drug delivery and therapeutic efficiency. Experimental Approach Experiments in vitro were performed using human corneal epithelial cells (HCLEs) treated with Ap4A (100 μM) for 5 min. Western blot analysis and transepithelial electrical resistance (TEER) were performed to study the TJ protein levels and barrier function respectively. Intracellular pathways involved were determined using an ERK inhibitor and P2Y2 receptor siRNAs. In in vivo assays with New Zealand rabbits, TJ integrity was examined by zonula occludens-1 (ZO-1) staining. The hypotensive compound 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) was used to assess improved delivery, measuring its levels by HPLC and measuring intraocular pressure using 5-MCA-NAT, P2Y receptor antagonists and P2Y2 siRNAs. Key Results Two hours after Ap4A pretreatment, TJ protein levels in HCLE cells were reduced around 40% compared with control. TEER values were significantly reduced at 2 and 4 h (68 and 52% respectively). TJ reduction and ERK activation were blocked by the ERK inhibitor U012 and P2Y2 siRNAs. In vivo, topical application of Ap4A disrupted ZO-1 membrane distribution. 5-MCA-NAT levels in the aqueous humour were higher when Ap4A was previously instilled and its hypotensive effect was also increased. This action was reversed by P2Y receptor antagonists and P2Y2 siRNA. Conclusions and Implications Ap4A increased corneal epithelial barrier permeability. Its application could improve ocular drug delivery and consequently therapeutic efficiency. PMID:25297531
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Barrier properties of cultured retinal pigment epithelium.
Rizzolo, Lawrence J
2014-09-01
The principal function of an epithelium is to form a dynamic barrier that regulates movement between body compartments. Each epithelium is specialized with barrier functions that are specific for the tissues it serves. The apical surface commonly faces a lumen, but the retinal pigment epithelium (RPE) appears to be unique by a facing solid tissue, the sensory retina. Nonetheless, there exists a thin (subretinal) space that can become fluid filled during pathology. RPE separates the subretinal space from the blood supply of the outer retina, thereby forming the outer blood-retinal barrier. The intricate interaction between the RPE and sensory retina presents challenges for learning how accurately culture models reflect native behavior. The challenge is heightened by findings that detail the variation of RPE barrier proteins both among species and at different stages of the life cycle. Among the striking differences is the expression of claudin family members. Claudins are the tight junction proteins that regulate ion diffusion across the spaces that lie between the cells of a monolayer. Claudin expression by RPE varies with species and life-stage, which implies functional differences among commonly used animal models. Investigators have turned to transcriptomics to supplement functional studies when comparing native and cultured tissue. The most detailed studies of the outer blood-retinal barrier have focused on human RPE with transcriptome and functional studies reported for human fetal, adult, and stem-cell derived RPE. Copyright © 2014 Elsevier Ltd. All rights reserved.
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A Key Claudin Extracellular Loop Domain is Critical for Epithelial Barrier Integrity
Mrsny, Randall J.; Brown, G. Thomas; Gerner-Smidt, Kirsten; Buret, Andre G.; Meddings, Jon B.; Quan, Clifford; Koval, Michael; Nusrat, Asma
2008-01-01
Intercellular tight junctions (TJs) regulate epithelial barrier properties. Claudins are major structural constituents of TJs and belong to a large family of tetra-spanning membrane proteins that have two predicted extracellular loops (ELs). Given that claudin-1 is widely expressed in epithelia, we further defined the role of its EL domains in determining TJ function. The effects of several claudin-1 EL mimetic peptides on epithelial barrier structure and function were examined. Incubation of model human intestinal epithelial cells with a 27-amino acid peptide corresponding to a portion of the first EL domain (Cldn-153–80) reversibly interfered with epithelial barrier function by inducing the rearrangement of key TJ proteins: occludin, claudin-1, junctional adhesion molecule-A, and zonula occludens-1. Cldn-153–80 associated with both claudin-1 and occludin, suggesting both the direct interference with the ability of these proteins to assemble into functional TJs and their close interaction under physiological conditions. These effects were specific for Cldn-153–80, because peptides corresponding to other claudin-1 EL domains failed to influence TJ function. Furthermore, the oral administration of Cldn-153–80 to rats increased paracellular gastric permeability. Thus, the identification of a critical claudin-1 EL motif, Cldn-153–80, capable of regulating TJ structure and function, offers a useful adjunct to treatments that require drug delivery across an epithelial barrier. PMID:18349130
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Defenders and Challengers of Endothelial Barrier Function
Rahimi, Nader
2017-01-01
Regulated vascular permeability is an essential feature of normal physiology and its dysfunction is associated with major human diseases ranging from cancer to inflammation and ischemic heart diseases. Integrity of endothelial cells also play a prominent role in the outcome of surgical procedures and organ transplant. Endothelial barrier function and integrity are regulated by a plethora of highly specialized transmembrane receptors, including claudin family proteins, occludin, junctional adhesion molecules (JAMs), vascular endothelial (VE)-cadherin, and the newly identified immunoglobulin (Ig) and proline-rich receptor-1 (IGPR-1) through various distinct mechanisms and signaling. On the other hand, vascular endothelial growth factor (VEGF) and its tyrosine kinase receptor, VEGF receptor-2, play a central role in the destabilization of endothelial barrier function. While claudins and occludin regulate cell–cell junction via recruitment of zonula occludens (ZO), cadherins via catenin proteins, and JAMs via ZO and afadin, IGPR-1 recruits bullous pemphigoid antigen 1 [also called dystonin (DST) and SH3 protein interacting with Nck90/WISH (SH3 protein interacting with Nck)]. Endothelial barrier function is moderated by the function of transmembrane receptors and signaling events that act to defend or destabilize it. Here, I highlight recent advances that have provided new insights into endothelial barrier function and mechanisms involved. Further investigation of these mechanisms could lead to the discovery of novel therapeutic targets for human diseases associated with endothelial dysfunction. PMID:29326721
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Rifaximin Exerts Beneficial Effects Independent of its Ability to Alter Microbiota Composition.
Kang, Dae J; Kakiyama, Genta; Betrapally, Naga S; Herzog, Jeremy; Nittono, Hiroshi; Hylemon, Phillip B; Zhou, Huiping; Carroll, Ian; Yang, Jing; Gillevet, Patrick M; Jiao, Chunhua; Takei, Hajime; Pandak, William M; Iida, Takashi; Heuman, Douglas M; Fan, Sili; Fiehn, Oliver; Kurosawa, Takao; Sikaroodi, Masoumeh; Sartor, R B; Bajaj, Jasmohan S
2016-08-25
Rifaximin has clinical benefits in minimal hepatic encephalopathy (MHE) but the mechanism of action is unclear. The antibiotic-dependent and -independent effects of rifaximin need to be elucidated in the setting of MHE-associated microbiota. To assess the action of rifaximin on intestinal barrier, inflammatory milieu and ammonia generation independent of microbiota using rifaximin. Four germ-free (GF) mice groups were used (1) GF, (2) GF+rifaximin, (3) Humanized with stools from an MHE patient, and (4) Humanized+rifaximin. Mice were followed for 30 days while rifaximin was administered in chow at 100 mg/kg from days 16-30. We tested for ammonia generation (small-intestinal glutaminase, serum ammonia, and cecal glutamine/amino-acid moieties), systemic inflammation (serum IL-1β, IL-6), intestinal barrier (FITC-dextran, large-/small-intestinal expression of IL-1β, IL-6, MCP-1, e-cadherin and zonulin) along with microbiota composition (colonic and fecal multi-tagged sequencing) and function (endotoxemia, fecal bile acid deconjugation and de-hydroxylation). All mice survived until day 30. In the GF setting, rifaximin decreased intestinal ammonia generation (lower serum ammonia, increased small-intestinal glutaminase, and cecal glutamine content) without changing inflammation or intestinal barrier function. Humanized microbiota increased systemic/intestinal inflammation and endotoxemia without hyperammonemia. Rifaximin therapy significantly ameliorated these inflammatory cytokines. Rifaximin also favorably impacted microbiota function (reduced endotoxin and decreased deconjugation and formation of potentially toxic secondary bile acids), but not microbial composition in humanized mice. Rifaximin beneficially alters intestinal ammonia generation by regulating intestinal glutaminase expression independent of gut microbiota. MHE-associated fecal colonization results in intestinal and systemic inflammation in GF mice, which is also ameliorated with rifaximin.
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Riddle, M A; Leckman, J F; Cohen, D J; Anderson, M; Ort, S I; Caruso, K A; Shaywitz, B A
1986-01-01
Central dopaminergic (DA) function in children and adults was assessed by monitoring plasma-free levels of the dopamine metabolite homovanillic acid (pHVA) before and after a single oral dose and chronic oral administration of debrisoquin. Debrisoquin inhibits peripheral metabolism of dopamine to HVA and does not cross the blood-brain barrier. By reducing peripheral formation of HVA through the use of debrisoquin, the remaining HVA in plasma more accurately reflects central DA activity. Debrisoquin administration resulted in marked reductions of pHVA in each of 12 patients studied. Eleven of the 12 subjects tolerated debrisoquin without physical or behavioral side effects. The debrisoquin administration method appears to be a safe and potentially valid technique for evaluating aspects of central dopaminergic function in children and adults.
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Effect of a 308-nm excimer laser on atopic dermatitis-like skin lesions in NC/Nga mice.
Oh, Chang Taek; Kwon, Tae-Rin; Seok, Joon; Choi, Eun Ja; Kim, Soon Re; Jang, Yu-Jin; Mun, Seog Kyun; Kim, Chan Woong; Lee, Sungeun; Lee, Jongmin; Kim, Myeung Nam; Choi, Sun Young; Kim, Beom Joon
2016-08-01
Atopic dermatitis (AD) is a common inflammatory skin disease that can affect all age groups. It has a relapsing course, which dramatically affects the quality of life of patients. A 308-nm excimer laser has been reported to be a safe and effective treatment for inflammatory skin diseases, although the range of potential application has not been fully explored. The purpose of this study was to evaluate the therapeutic effects of a 308-nm laser on AD-like skin lesions in NC/Nga mice. Dermatophagoides farinae-exposed NC/Nga mice with a clinical score of 12 were treated with either a 308-nm excimer laser or narrowband-UVB (NB-UVB). The effects of the 308-nm excimer laser were evaluated by dermatitis scores, skin histology, skin barrier function, and immunological parameters, including IgE and Th2-mediated cytokines. The 308-nm excimer laser significantly reduced the severity of skin lesions and decreased the total serum levels of IgE and Th2-mediated cytokines. The excimer laser also significantly reduced the inflammatory cellular infiltrate into AD-induced skin lesions. Moreover, treatment with the 308-nm excimer laser led to recovery of skin barrier function in AD-induced skin lesions. The 308-nm excimer laser can be considered a valid and safe therapeutic option for the treatment of localized AD. Lasers Surg. Med. 48:629-637, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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Liévin-Le Moal, Vanessa
2013-06-01
Some water-borne protozoan parasites induce diseases through their membrane-associated functional structures and virulence factors that hijack the host cellular molecules and signalling pathways leading to structural and functional lesions in the intestinal barrier. In this Microreview we analyse the insights on the mechanisms of pathogenesis of Entamoeba intestinalis, Giardia and Cryptosporidium observed in the human colon carcinoma fully differentiated colon cancer cell lines, cell subpopulations and clones expressing the structural and functional characteristics of highly specialized fully differentiated epithelial cells lining the intestinal epithelium and mimicking structurally and functionally an intestinal barrier. © 2013 John Wiley & Sons Ltd.
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Gut barrier in health and disease: focus on childhood.
Viggiano, D; Ianiro, G; Vanella, G; Bibbò, S; Bruno, G; Simeone, G; Mele, G
2015-01-01
The gut barrier is a functional unit, organized as a multi-layer system, made up of two main components: a physical barrier surface, which prevents bacterial adhesion and regulates paracellular diffusion to the host tissues, and a deep functional barrier, that is able to discriminate between pathogens and commensal microorganisms, organizing the immune tolerance and the immune response to pathogens. Other mechanisms, such as gastric juice and pancreatic enzymes (which both have antibacterial properties) participate in the luminal integrity of the gut barrier. From the outer layer to the inner layer, the physical barrier is composed of gut microbiota (that competes with pathogens to gain space and energy resources, processes the molecules necessary to mucosal integrity and modulates the immunological activity of deep barrier), mucus (which separates the intraluminal content from more internal layers and contains antimicrobial products and secretory IgA), epithelial cells (which form a physical and immunological barrier) and the innate and adaptive immune cells forming the gut-associated lymphoid tissue (which is responsible for antigen sampling and immune responses). Disruption of the gut barrier has been associated with many gastrointestinal diseases, but also with extra-intestinal pathological condition, such as type 1 diabetes mellitus, allergic diseases or autism spectrum disorders. The maintenance of a healthy intestinal barrier is therefore of paramount importance in children, for both health and economic reasons. Many drugs or compounds used in the treatment of gastrointestinal disorders act through the restoration of a normal intestinal permeability. Several studies have highlighted the role of probiotics in the modulation and reduction of intestinal permeability, considering the strong influence of gut microbiota in the modulation of the function and structure of gut barrier, but also on the immune response of the host. To date, available weapons for the maintenance and repair of gut barrier are however few, even if promising. Considerable efforts, including both a better understanding of the gut barrier features and mechanisms in health and disease, and the development of new pharmacological approaches for the modulation of gut barrier components, are needed for the prevention and treatment of gastrointestinal and extraintestinal diseases associated with gut barrier impairment.
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Genova, Jennifer L.; Fehon, Richard G.
2003-01-01
One essential function of epithelia is to form a barrier between the apical and basolateral surfaces of the epithelium. In vertebrate epithelia, the tight junction is the primary barrier to paracellular flow across epithelia, whereas in invertebrate epithelia, the septate junction (SJ) provides this function. In this study, we identify new proteins that are required for a functional paracellular barrier in Drosophila. In addition to the previously known components Coracle (COR) and Neurexin (NRX), we show that four other proteins, Gliotactin, Neuroglian (NRG), and both the α and β subunits of the Na+/K+ ATPase, are required for formation of the paracellular barrier. In contrast to previous reports, we demonstrate that the Na pump is not localized basolaterally in epithelial cells, but instead is concentrated at the SJ. Data from immunoprecipitation and somatic mosaic studies suggest that COR, NRX, NRG, and the Na+/K+ ATPase form an interdependent complex. Furthermore, the observation that NRG, a Drosophila homologue of vertebrate neurofascin, is an SJ component is consistent with the notion that the invertebrate SJ is homologous to the vertebrate paranodal SJ. These findings have implications not only for invertebrate epithelia and barrier functions, but also for understanding of neuron–glial interactions in the mammalian nervous system. PMID:12782686
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Genova, Jennifer L; Fehon, Richard G
2003-06-09
One essential function of epithelia is to form a barrier between the apical and basolateral surfaces of the epithelium. In vertebrate epithelia, the tight junction is the primary barrier to paracellular flow across epithelia, whereas in invertebrate epithelia, the septate junction (SJ) provides this function. In this study, we identify new proteins that are required for a functional paracellular barrier in Drosophila. In addition to the previously known components Coracle (COR) and Neurexin (NRX), we show that four other proteins, Gliotactin, Neuroglian (NRG), and both the alpha and beta subunits of the Na+/K+ ATPase, are required for formation of the paracellular barrier. In contrast to previous reports, we demonstrate that the Na pump is not localized basolaterally in epithelial cells, but instead is concentrated at the SJ. Data from immunoprecipitation and somatic mosaic studies suggest that COR, NRX, NRG, and the Na+/K+ ATPase form an interdependent complex. Furthermore, the observation that NRG, a Drosophila homologue of vertebrate neurofascin, is an SJ component is consistent with the notion that the invertebrate SJ is homologous to the vertebrate paranodal SJ. These findings have implications not only for invertebrate epithelia and barrier functions, but also for understanding of neuron-glial interactions in the mammalian nervous system.
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ERIC Educational Resources Information Center
Wilson, Coralie Joy; Deane, Frank P.; Marshall, Kellie L.; Dalley, Andrew
2008-01-01
The "Building Bridges to General Practice" (BBGP) program is an outreach initiative. It aims to reduce young peoples' perceived knowledge- and belief-based barriers to engaging in treatment and to increase their behavioral intentions to consult a general medical practitioner (GP) for physical and psychological problems. By increasing…
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-09-06
... reduce the level of infrastructure rebuilt on the barrier islands and allow natural processes to... to enhance visitor education, research, and resource protection opportunities. The seashore would be... barrier islands and coastal environments. Interpretive programs would focus on illustrating how barrier...
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Structure of a CLC chloride ion channel by cryo-electron microscopy
Park, Eunyong; Campbell, Ernest B.; MacKinnon, Roderick
2017-01-01
CLC proteins transport chloride (Cl−) ions across cellular membranes to regulate muscle excitability, electrolyte movement across epithelia, and acidification of intracellular organelles. Some CLC proteins are channels that conduct Cl− ions passively, whereas others are secondary active transporters that exchange two Cl− ions for one H+. The structural basis underlying these distinctive transport mechanisms is puzzling because CLC channels and transporters are expected to share the same architecture based on sequence homology. To solve this puzzle we determined the structure of a mammalian CLC channel (CLC-K) using cryo-electron microscopy. A conserved loop in the Cl− transport pathway shows a structure markedly different from that of CLC transporters. Consequently, the cytosolic constriction for Cl− passage is widened in CLC-K such that the kinetic barrier previously postulated for Cl−/H+ transporter function would be reduced. Thus, reduction of a kinetic barrier in CLC channels enables fast flow of Cl− down its electrochemical gradient. PMID:28002411
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Interferon-λ restricts West Nile virus neuroinvasion by tightening the blood-brain barrier.
Lazear, Helen M; Daniels, Brian P; Pinto, Amelia K; Huang, Albert C; Vick, Sarah C; Doyle, Sean E; Gale, Michael; Klein, Robyn S; Diamond, Michael S
2015-04-22
Although interferon-λ [also known as type III interferon or interleukin-28 (IL-28)/IL-29] restricts infection by several viruses, its inhibitory mechanism has remained uncertain. We used recombinant interferon-λ and mice lacking the interferon-λ receptor (IFNLR1) to evaluate the effect of interferon-λ on infection with West Nile virus, an encephalitic flavivirus. Cell culture studies in mouse keratinocytes and dendritic cells showed no direct antiviral effect of exogenous interferon-λ, even though expression of interferon-stimulated genes was induced. We observed no differences in West Nile virus burden between wild-type and Ifnlr1(-/-) mice in the draining lymph nodes, spleen, or blood. We detected increased West Nile virus infection in the brain and spinal cord of Ifnlr1(-/-) mice, yet this was not associated with a direct antiviral effect in mouse neurons. Instead, we observed an increase in blood-brain barrier permeability in Ifnlr1(-/-) mice. Treatment of mice with pegylated interferon-λ2 resulted in decreased blood-brain barrier permeability, reduced West Nile virus infection in the brain without affecting viremia, and improved survival against lethal virus challenge. An in vitro model of the blood-brain barrier showed that interferon-λ signaling in mouse brain microvascular endothelial cells increased transendothelial electrical resistance, decreased virus movement across the barrier, and modulated tight junction protein localization in a protein synthesis- and signal transducer and activator of transcription 1 (STAT1)-independent manner. Our data establish an indirect antiviral function of interferon-λ in which noncanonical signaling through IFNLR1 tightens the blood-brain barrier and restricts viral neuroinvasion and pathogenesis. Copyright © 2015, American Association for the Advancement of Science.
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Kho, Dan T; Johnson, Rebecca H; O'Carroll, Simon J; Angel, Catherine E; Graham, E Scott
2017-09-21
Herein we demonstrate the sensitive nature of human blood-brain barrier (BBB) endothelial cells to sodium azide and its gaseous product. Sodium azide is known to be acutely cytotoxic at low millimolar concentrations, hence its use as a biological preservative (e.g., in antibodies). Loss of barrier integrity was noticed in experiments using Electric Cell-substrate Impedance Sensing (ECIS) biosensor technology, to measure endothelial barrier integrity continuously in real-time. Initially the effect of sodium azide was observed as an artefact where it was present in antibodies being employed in neutralisation experiments. This was confirmed where antibody clones that were azide-free did not mediate loss of barrier function. A delayed loss of barrier function in neighbouring wells implied the influence of a liberated gaseous product. ECIS technology demonstrated that the BBB endothelial cells had a lower level of direct sensitivity to sodium azide of ~3 µM. Evidence of gaseous toxicity was consistently observed at 30 µM and above, with disrupted barrier function and cell death in neighbouring wells. We highlight the ability of this cellular biosensor technology to reveal both the direct and gaseous toxicity mediated by sodium azide. The sensitivity and temporal dimension of ECIS technology was instrumental in these observations. These findings have substantial implications for the wide use of sodium azide in biological reagents, raising issues of their application in live-cell assays and with regard to the protection of the user. This research also has wider relevance highlighting the sensitivity of brain endothelial cells to a known mitochondrial disruptor. It is logical to hypothesise that BBB endothelial dysfunction due to mitochondrial dys-regulation could have an important but underappreciated role in a range of neurological diseases.
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The effects of hypertension on the cerebral circulation
Pires, Paulo W.; Dams Ramos, Carla M.; Matin, Nusrat
2013-01-01
Maintenance of brain function depends on a constant blood supply. Deficits in cerebral blood flow are linked to cognitive decline, and they have detrimental effects on the outcome of ischemia. Hypertension causes alterations in cerebral artery structure and function that can impair blood flow, particularly during an ischemic insult or during periods of low arterial pressure. This review will focus on the historical discoveries, novel developments, and knowledge gaps in 1) hypertensive cerebral artery remodeling, 2) vascular function with emphasis on myogenic reactivity and endothelium-dependent dilation, and 3) blood-brain barrier function. Hypertensive artery remodeling results in reduction in the lumen diameter and an increase in the wall-to-lumen ratio in most cerebral arteries; this is linked to reduced blood flow postischemia and increased ischemic damage. Many factors that are increased in hypertension stimulate remodeling; these include the renin-angiotensin-aldosterone system and reactive oxygen species levels. Endothelial function, vital for endothelium-mediated dilation and regulation of myogenic reactivity, is impaired in hypertension. This is a consequence of alterations in vasodilator mechanisms involving nitric oxide, epoxyeicosatrienoic acids, and ion channels, including calcium-activated potassium channels and transient receptor potential vanilloid channel 4. Hypertension causes blood-brain barrier breakdown by mechanisms involving inflammation, oxidative stress, and vasoactive circulating molecules. This exposes neurons to cytotoxic molecules, leading to neuronal loss, cognitive decline, and impaired recovery from ischemia. As the population ages and the incidence of hypertension, stroke, and dementia increases, it is imperative that we gain a better understanding of the control of cerebral artery function in health and disease. PMID:23585139
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Clearance of amyloid-β peptide across the choroid plexus in Alzheimer's disease.
Alvira-Botero, Ximena; Carro, Eva M
2010-12-01
Aging and several neurodegenerative diseases bring about changes in the anatomy and physiology of the choroid plexus. The identification of specific membrane receptors that bind and internalize extracellular ligands has revolutionized the traditional roles of this tissue. Amyloid beta peptide (Aβ), the major constituent of the amyloid core of senile plaques in patients with Alzheimer's disease (AD) is known to contribute to disease neuropathology and progression. Recent emphasis on comorbidity of AD and a deficient clearance of Aβ across the blood-brain barrier and blood-cerebrospinal fluid barrier have highlighted the importance of brain Aβ clearance in AD. The megalin receptor has also been implicated in the pathogenesis of AD. Faulty Aβ clearance from the brain across the choroid plexus epithelium by megalin appears to mediate focal Aβ accumulation in AD. Patients with AD have reduced levels of megalin at the choroid plexus, which in turn seem to increase brain levels of Aβ through a decreased efflux of brain Aβ. Therapies that increase megalin expression at the choroid plexus could potentially control accumulation of brain Aβ. This review covers in depth the anatomy and function of the choroid plexus, focusing on the brain barrier at the choroid plexus, as it actively participates in Aβ clearance. In addition, we describe the role of the choroid plexus in brain functions, aging and AD, as well as the role of megalin in the process of Aβ clearance. Finally, we present current data on the use of choroid plexus cells to repair the damaged brain.
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Karpurapu, Manjula; Lee, Yong Gyu; Qian, Ziqing; Wen, Jin; Ballinger, Megan N.; Rusu, Luiza; Chung, Sangwoon; Deng, Jing; Qian, Feng; Reader, Brenda F.; Nirujogi, Teja Srinivas; Park, Gye Young; Pei, Dehua; Christman, John W.
2018-01-01
Specific therapies targeting cellular and molecular events of sepsis induced Acute Lung Injury (ALI) pathogenesis are lacking. We have reported a pivotal role for Nuclear Factors of Activated T cells (NFATc3) in regulating macrophage phenotype during sepsis induced ALI and subsequent studies demonstrate that NFATc3 transcriptionally regulates macrophage CCR2 and TNFα gene expression. Mouse pulmonary microvascular endothelial cell monolayer maintained a tighter barrier function when co-cultured with LPS stimulated NFATc3 deficient macrophages whereas wild type macrophages caused leaky monolayer barrier. More importantly, NFATc3 deficient mice showed decreased neutrophilic lung inflammation, improved alveolar capillary barrier function, arterial oxygen saturation and survival benefit in lethal CLP sepsis mouse models. In addition, survival of wild type mice subjected to the lethal CLP sepsis was not improved with broad-spectrum antibiotics, whereas the survival of NFATc3 deficient mice was improved to 40–60% when treated with imipenem. Passive adoptive transfer of NFATc3 deficient macrophages conferred protection against LPS induced ALI in wild type mice. Furthermore, CP9-ZIZIT, a highly potent, cell-permeable peptide inhibitor of Calcineurin inhibited NFATc3 activation. CP9-ZIZIT effectively reduced sepsis induced inflammatory cytokines and pulmonary edema in mice. Thus, this study demonstrates that inhibition of NFATc3 activation by CP9-ZIZIT provides a potential therapeutic option for attenuating sepsis induced ALI/pulmonary edema. PMID:29535830
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Allsopp, Philip; Possemiers, Sam; Campbell, David; Oyarzábal, Iván Saldaña; Gill, Chris; Rowland, Ian
2013-08-01
Linear inulin-type fructan (ITF) prebiotics have a putative role in the prevention of colorectal cancer, whereas relatively little is known about branched fructans. This study aims to investigate the fermentation properties and potential prebiotic activity of branched fructans derived from Agave angustifolia Haw, using the Simulator of Human Intestinal Microbial Ecosystem (SHIME) model. The proximal, transverse and distal vessels were used to investigate fructan fermentation throughout the colon and to assess the alterations of the microbial composition and fermentation metabolites (short chain fatty acids and ammonia). The influence on bioactivity of the fermentation supernatant was assessed by MTT, Comet and transepithelial electrical resistance (TER), respectively. Addition of Agave fructan to the SHIME model significantly increased (P < 0.05), bifidobacteria populations (proximal and transverse), SCFA concentrations (proximal, transverse and distal) and decreased ammonia concentrations in the distal vessel. Furthermore, the fermentation supernatant significantly (P < 0.05) increased the TER of a Caco-2 cell monolayer (%) and decreased fluorescein-based paracellular flux, suggesting enhanced barrier function and reduced epithelial barrier permeability (proximal and distal vessel). While cytotoxicity and genotoxicity remained unaltered in response to the presence of Agave fructans. To conclude, branched Agave fructans show indications of prebiotic activity, particularly in relation to colon health by exerting a positive influence on gut barrier function, an important aspect of colon carcinogenesis. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.
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Proksch, E; Nissen, H P
2002-12-01
Dexpanthenol-containing creams have been widely used for treatment of lesions (superficial wounds) of the skin and mucous membranes. Dexpanthenol is converted in tissues to pantothenic acid, a component of coenzyme A. Coenzyme A catalyses early steps in the synthesis of fatty acids and sphingolipids which are of crucial importance for stratum corneum lipid bilayers and cell membrane integrity. In the present study, the effects were examined of a dexpanthenol-containing cream on skin barrier repair, stratum corneum hydration, skin roughness, and inflammation after sodium lauryl sulphate (SLS)-induced irritation. Irritation was induced by application of SLS in patch test chambers. The dexpanthenol-contaming cream or the vehicle were applied twice daily and barrier repair, hydration, roughness, and inflammation of the skin were determined by using biophysical methods. Significantly accelerated skin barrier repair was found in treatments with the dexpanthenol-containing cream (verum) compared with vehicle-treated (placebo) or untreated skin. Both verum and placebo showed an increase in stratum corneum hydration, but significantly more so with the dexpanthenol-containing cream. Both creams reduced skin roughness, but again the verum was superior. The dexpanthenol-containing cream significantly reduced skin redness as a sign of inflammation in contrast to the vehicle, which produced no effect. Treatment with a dexpanthenol-containing cream showed significantly enhanced skin barrier repair and stratum corneum hydration, while reducing skin roughness and inflammation.
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Density functional theory study of acetaldehyde hydrodeoxygenation on MoO3
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mei, Donghai; Karim, Ayman M.; Wang, Yong
2011-04-06
Periodic spin-polarized density functional theory calculations were performed to investigate acetaldehyde (CH3CHO) hydrodeoxygenation on the reduced molybdenum trioxide (MoO3) surface. The perfect O-terminated α-MoO3(010) surface is reduced to generate an oxygen defect site in the presence of H2. H2 dissociatively adsorbs at the surface oxygen sites forming two surface hydroxyls, which can recombine into a water molecule weakly bound at the Mo site. A terminal oxygen (Ot) defect site thus forms after water desorption. CH3CHO adsorbs at the O-deficient Mo site via either the sole O-Mo bond or the O-Mo and the C-O double bonds. The possible reaction pathways ofmore » the adsorbed CH3CHO with these two configurations were thoroughly examined using the dimer searching method. Our results show that the ideal deoxygenation of CH3CHO leading to ethylene (C2H4) on the reduced MoO3(010) surface is feasible. The adsorbed CH3CHO first dehydrogenate into CH2CHO by reacting with a neighboring terminal Ot. The hydroxyl (OtH) then hydrogenates CH2CHO into CH2CH2O to complete the hydrogen transfer cycle with an activation barrier of 1.39 eV. The direct hydrogen transfer from CH3CHO to CH2CH2O is unlikely due to the high barrier of 2.00 eV. The produced CH2CH2O readily decomposes into C2H4 that directly releases to the gas phase, and regenerates the Ot atom on the Mo site. As a result, the reduced MoO3(010) surface is reoxidized to the perfect MoO3(010) surface after CH3CHO deoxygenation. Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy.« less
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NASA Astrophysics Data System (ADS)
Hutauruk, Sindak
2017-09-01
The frequent congestion causes accumulation of vehicles at the intersection of roads cutting off railroads, reducing the functionality of highway services, the loss of vehicle functions as a means of transportation, waste of fuel energy, and CO2 increase in intersections. The occurrence of congestion caused by the absence of integration of traffic light controls by opening and closing the railway barrier, therefore need to be done integrated control especially during and after a while train crossing the highway. The case raised in this study is the crossroads Prof. H.M. Jalan Yamin with Gaharu road in Medan. Researchers tried to solve the problem by designing and creating a tool that would coordinate and regulate traffic lights with railroad doors, thus reducing congestion for 23 minutes, reducing fuel by as much as 60,340 liters per day, thereby reducing CO2 exhaust gases in the area. This tool uses microcontroller as its control center. This design is done with a miniature simulation, meaning it is not done in the actual situation, but the field conditions can be represented in the simulation in the form of miniature.
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Intestinal epithelial barrier function and tight junction proteins with heat and exercise
Zuhl, Micah N.; Moseley, Pope L.
2015-01-01
A single layer of enterocytes and tight junctions (intercellular multiprotein complexes) form the intestinal epithelial barrier that controls transport of molecules through transcellular and paracellular pathways. A dysfunctional or “leaky” intestinal tight junction barrier allows augmented permeation of luminal antigens, endotoxins, and bacteria into the blood stream. Various substances and conditions have been shown to affect the maintenance of the intestinal epithelial tight junction barrier. The primary focus of the present review is to analyze the effects of exertional or nonexertional (passive hyperthermia) heat stress on tight junction barrier function in in vitro and in vivo (animals and humans) models. Our secondary focus is to review changes in tight junction proteins in response to exercise or hyperthermic conditions. Finally, we discuss some pharmacological or nutritional interventions that may affect the cellular mechanisms involved in maintaining homeostasis of the intestinal epithelial tight junction barrier during heat stress or exercise. PMID:26359485
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Intestinal epithelial barrier function and tight junction proteins with heat and exercise.
Dokladny, Karol; Zuhl, Micah N; Moseley, Pope L
2016-03-15
A single layer of enterocytes and tight junctions (intercellular multiprotein complexes) form the intestinal epithelial barrier that controls transport of molecules through transcellular and paracellular pathways. A dysfunctional or "leaky" intestinal tight junction barrier allows augmented permeation of luminal antigens, endotoxins, and bacteria into the blood stream. Various substances and conditions have been shown to affect the maintenance of the intestinal epithelial tight junction barrier. The primary focus of the present review is to analyze the effects of exertional or nonexertional (passive hyperthermia) heat stress on tight junction barrier function in in vitro and in vivo (animals and humans) models. Our secondary focus is to review changes in tight junction proteins in response to exercise or hyperthermic conditions. Finally, we discuss some pharmacological or nutritional interventions that may affect the cellular mechanisms involved in maintaining homeostasis of the intestinal epithelial tight junction barrier during heat stress or exercise. Copyright © 2016 the American Physiological Society.
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Lee, Byeong Ryong; Kim, Tae Geun
2016-06-01
This paper reports the electrical and optical properties of the reduced graphene oxide (RGO)/single-walled carbon nanotube (SWNT) films using various p-type dopants and its application to GaN-based light-emitting diodes. To enhance the current injection and spreading of the RGO/SWNT films on the light-emitting diodes (LEDs), we increased the work function (φ) of the films using chemical doping with AuCl3, poly(3,4-ethylenedioxythiophene) oxidized with poly(4-styrenesulfonate) ( PSS) and MoO3; thereby reduced the Schottky barrier height between the RGO/SWNT films and p-GaN. By comparison, LEDs fabricated with work-function-tuned RGO/SWNT film doped with MoO3 exhibited the decrease of the forward voltage from 5.3 V to 5.02 V at 20 mA and the increase of the output power up to 1.26 times. We also analyzed the current injection mechanism using ultraviolet photoelectron spectroscopy and X-ray photoelectron spectroscopy.
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Substrate doping: A strategy for enhancing reactivity on gold nanocatalysts by tuning sp bands
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mammen, Nisha; Narasimhan, Shobhana; Gironcoli, Stefano de
2015-10-14
We suggest that the reactivity of Au nanocatalysts can be greatly increased by doping the oxide substrate on which they are placed with an electron donor. To demonstrate this, we perform density functional theory calculations on a model system consisting of a 20-atom gold cluster placed on a MgO substrate doped with Al atoms. We show that not only does such substrate doping switch the morphology of the nanoparticles from the three-dimensional tetrahedral form to the two-dimensional planar form, but it also significantly lowers the barrier for oxygen dissociation by an amount proportional to the dopant concentration. At a dopingmore » level of 2.78%, the dissociation barrier is reduced by more than half, which corresponds to a speeding up of the oxygen dissociation rate by five orders of magnitude at room temperature. This arises from a lowering in energy of the s and p states of Au. The d states are also lowered in energy, however, this by itself would have tended to reduce reactivity. We propose that a suitable measure of the reactivity of Au nanoparticles is the difference in energy of sp and d states.« less
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Safety-Net Hospitals Face More Barriers Yet Use Fewer Strategies to Reduce Readmissions
Figueroa, Jose F.; Joynt, Karen E.; Zhou, Xiner; Orav, E. John; Jha, Ashish K.
2016-01-01
Objective U.S. hospitals that care for vulnerable populations, “safety-net hospitals” (SNHs), are more likely to incur penalties under the Hospital Readmissions Reduction Program (HRRP), which penalizes hospitals with higher-than-expected readmissions. Understanding whether SNHs face unique barriers to reducing readmissions or whether they underuse readmission-prevention strategies is important. Design We surveyed leadership at 1,600 U.S. acute care hospitals, of whom 980 participated, between June 2013–January 2014. Responses on 28 questions on readmission-related barriers and strategies were compared between SNHs and non-SNHs, adjusting for non-response and sampling strategy. We further compared responses between high-performing SNHs and low-performing SNHs. Results We achieved a 62% response rate. SNHs were more likely to report patient-related barriers, including lack of transportation, homelessness, and language barriers compared to non-SNHs (p-values<0.001). Despite reporting more barriers, SNHs were less likely to use e-tools to share discharge summaries (70.1% vs. 73.7%, p<0.04) or verbally communicate (31.5% vs. 39.8%, p<0.001) with outpatient providers, track readmissions by race/ethnicity (23.9% vs. 28.6%, p<0.001), or enroll patients in post-discharge programs (13.3% vs. 17.2%, p<0.001). SNHs were also less likely to use discharge coordinators, pharmacists, and post-discharge programs. When we examined the use of strategies within SNHs, we found trends to suggest that high-performing SNHs were more likely to use several readmission strategies. Conclusions Despite reporting more barriers to reducing readmissions, SNHs were less likely to use readmission-reduction strategies. This combination of higher barriers and lower use of strategies may explain why SNHs have higher rates of readmissions and penalties under the HRRP. PMID:28060053
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Fernando, Antonio T; Consedine, Nathan S
2017-06-01
Compassion is an expectation of patients, regulatory bodies, and physicians themselves. Most research has, however, studied compassion fatigue rather than compassion itself and has concentrated on the role of the physician. The Transactional Model of Physician Compassion suggests that physician, patient, external environment, and clinical factors are all relevant. Because these factors vary both across different specialities and among physicians with differing degrees of experience, barriers to compassion are also likely to vary. We describe barriers to physician compassion as a function of specialization (psychiatry, general practice, surgery, internal medicine, and pediatrics) and physician experience. We used a cross-sectional study using demographic data, specialization, practice parameters, and the Barriers to Physician Compassion Questionnaire. Nonrandom convenience sampling was used to recruit 580 doctors, of whom 444 belonged to the targeted speciality groups. The sample was characterized before conducting a factorial Multivariate Analysis of Covariance and further post hoc analyses. A 5 (speciality grouping) × 2 (more vs. less physician experience) Multivariate Analysis of Covariance showed that the barriers varied as a function of both speciality and experience. In general, psychiatrists reported lower barriers, whereas general practitioners and internal medicine specialists generally reported greater barriers. Barriers were generally greater among less experienced doctors. Documenting and investigating barriers to compassion in different speciality groups have the potential to broaden current foci beyond the physician and inform interventions aimed at enhancing medical compassion. In addition, certain aspects of the training or practice of psychiatry that enhance compassion may mitigate barriers to compassion in other specialities. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.
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Lee, Sang Eun; Lee, Seung Hun
2018-06-01
Epidermal barrier formation and the maintenance of barrier homeostasis are essential to protect us from the external environments and organisms. Moreover, impaired keratinocytes differentiation and dysfunctional skin barrier can be the primary causes or aggravating factors for many inflammatory skin diseases including atopic dermatitis and psoriasis. Therefore, understanding the regulation mechanisms of keratinocytes differentiation and skin barrier homeostasis is important to understand many skin diseases and establish an effective treatment strategy. Calcium ions (Ca 2+ ) and their concentration gradient in the epidermis are essential in regulating many skin functions, including keratinocyte differentiation, skin barrier formation, and permeability barrier homeostasis. Recent studies have suggested that the intracellular Ca 2+ stores such as the endoplasmic reticulum (ER) are the major components that form the epidermal calcium gradient and the ER calcium homeostasis is crucial for regulating keratinocytes differentiation, intercellular junction formation, antimicrobial barrier, and permeability barrier homeostasis. Thus, both Ca 2+ release from intracellular stores, such as the ER and Ca 2+ influx mechanisms are important in skin barrier. In addition, growing evidences identified the functional existence and the role of many types of calcium channels which mediate calcium flux in keratinocytes. In this review, the origin of epidermal calcium gradient and their role in the formation and regulation of skin barrier are focused. We also focus on the role of ER calcium homeostasis in skin barrier. Furthermore, the distribution and role of epidermal calcium channels, including transient receptor potential channels, store-operated calcium entry channel Orai1, and voltage-gated calcium channels in skin barrier are discussed.
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Mato, M; Ookawara, S; Sakamoto, A; Aikawa, E; Ogawa, T; Mitsuhashi, U; Masuzawa, T; Suzuki, H; Honda, M; Yazaki, Y; Watanabe, E; Luoma, J; Yla-Herttuala, S; Fraser, I; Gordon, S; Kodama, T
1996-01-01
The transport of solutes between blood and brain is regulated by a specific barrier. Capillary endothelial cells of brain are known to mediate barrier function and facilitate transport. Here we report that specific cells surrounding arterioles, known as Mato's fluorescent granular perithelial (FGP) cells or perivascular microglial cells, contribute to the barrier function. Immunohistochemical and in situ hybridization studies indicate that, in normal brain cortex, type I and type II macrophage scavenger receptors are expressed only in FGP/perivascular microglial cells, and surface markers of macrophage lineage are also detected on them. These cells mediate the uptake of macromolecules, including modified low density lipoprotein, horseradish peroxidase, and ferritin injected either into the blood or into the cerebral ventricles. Accumulation of scavenged materials with aging or after the administration of a high-fat diet results in the formation of honeycomb-like foam cells and the narrowing of the lumen of arterioles in the brain cortex. These results indicate involvement of FGP/perivascular microglial cells in the barrier and scavenger functions in the central nervous system. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:8622926
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Zhao, Shulan; Lian, Fei; Duo, Lian
2011-01-01
A column experiment with horizontal permeable barriers was conducted to investigate phytoextraction of heavy metals by Lolium perenne L. from municipal solid waste compost following EDTA application, as well as to study the effects of L. perenne and permeable barriers on preventing metal from leaching. In columns with barriers, EDTA addition yielded maximum concentrations of Cu, Zn and Pb of 155, 541 and 33.5 mg kg(-1) in shoot, respectively. This led to 4.2, 2.1 and 7.4 times higher concentrations of Cu, Zn and Pb compared to treatment with no chelating agent, respectively. In treatments with 10 mmol kg(-1) EDTA, the barriers reduced leaching of Cu, Zn and Pb by approximately three times, respectively, resulting in leaching of total initial Cu, Zn and Pb by 27.3%, 25.2% and 28.8%, respectively, after four times' irrigation. These results indicate that L. perenne and permeable barriers are effective to reduce leaching of heavy metals and minimize the risk of contaminating groundwater in EDTA-enhanced phytoremediation. Thus these findings highlight that turfgrass and permeable barriers can effectively prevent metal leaching. Copyright © 2010 Elsevier Ltd. All rights reserved.
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Common Perceived Barriers and Facilitators for Reducing Sedentary Behaviour among Office Workers
Kallings, Lena V.; Blom, Victoria; Forsell, Yvonne; Ekblom, Maria M.
2018-01-01
Qualitative studies identified barriers and facilitators associated with work-related sedentary behaviour. The objective of this study was to determine common perceived barriers and facilitators among office workers, assess subgroup differences, and describe sedentary behaviour. From two Swedish companies, 547 office workers (41 years (IQR = 35–48), 65% women, 66% highly educated) completed questionnaires on perceived barriers and facilitators, for which subgroup differences in age, gender, education, and workplace sedentary behaviour were assessed. Sedentary behaviour was measured using inclinometers (n = 311). The most frequently reported barrier was sitting is a habit (67%), which was reported more among women than men (Χ2 = 5.14, p = 0.03) and more among highly sedentary office workers (Χ2 = 9.26, p < 0.01). The two other most reported barriers were that standing is uncomfortable (29%) and standing is tiring (24%). Facilitators with the most support were the introduction of either standing- or walking-meetings (respectively 33% and 29%) and more possibilities or reminders for breaks (31%). The proportion spent sedentary was 64% at the workplace, 61% on working days, and 57% on non-working days. This study provides a detailed understanding of office workers’ ideas about sitting and means to reduce sitting. We advise to include the supported facilitators and individualized support in interventions to work towards more effective strategies to reduce sedentary behaviour. PMID:29670047
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Common Perceived Barriers and Facilitators for Reducing Sedentary Behaviour among Office Workers.
Nooijen, Carla F J; Kallings, Lena V; Blom, Victoria; Ekblom, Örjan; Forsell, Yvonne; Ekblom, Maria M
2018-04-18
Qualitative studies identified barriers and facilitators associated with work-related sedentary behaviour. The objective of this study was to determine common perceived barriers and facilitators among office workers, assess subgroup differences, and describe sedentary behaviour. From two Swedish companies, 547 office workers (41 years (IQR = 35–48), 65% women, 66% highly educated) completed questionnaires on perceived barriers and facilitators, for which subgroup differences in age, gender, education, and workplace sedentary behaviour were assessed. Sedentary behaviour was measured using inclinometers ( n = 311). The most frequently reported barrier was sitting is a habit (67%), which was reported more among women than men (Χ² = 5.14, p = 0.03) and more among highly sedentary office workers (Χ² = 9.26, p < 0.01). The two other most reported barriers were that standing is uncomfortable (29%) and standing is tiring (24%). Facilitators with the most support were the introduction of either standing- or walking-meetings (respectively 33% and 29%) and more possibilities or reminders for breaks (31%). The proportion spent sedentary was 64% at the workplace, 61% on working days, and 57% on non-working days. This study provides a detailed understanding of office workers’ ideas about sitting and means to reduce sitting. We advise to include the supported facilitators and individualized support in interventions to work towards more effective strategies to reduce sedentary behaviour.
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Temperature dependent current transport of Pd/ZnO nanowire Schottky diodes
NASA Astrophysics Data System (ADS)
Gayen, R. N.; Bhattacharyya, S. R.; Jana, P.
2014-09-01
Zinc oxide (ZnO) nanowire based Schottky barrier diodes are fabricated by depositing Pd metal contact on top of vertically well-aligned ZnO nanowire arrays. A vertical array of ZnO nanowires on indium tin oxide (ITO) coated glass substrates is synthesized by hybrid wet chemical route. Scanning electron microscopy (SEM), x-ray diffraction (XRD) and x-ray photoelectron spectroscopy (XPS) measurement confirm the formation of stoichiometric well-aligned hexagonal (h-ZnO) nanowire arrays with wurtzite structure. Temperature dependent current-voltage (I-V) measurements on palladium-ZnO (Pd/ZnO) nanowire Schottky junctions in the temperature range 303-383 K exhibit excellent rectifying character. From these nonlinear I-V plots, different electrical parameters of diode-like reverse saturation current, barrier height and ideality factor are determined as a function of temperature assuming pure thermionic emission model. The ideality factor is found to decrease while the barrier height increases with the increase in temperature. The series resistance values calculated from Cheung’s functions also show temperature dependency. Such behavior can be attributed to the presence of defects that traps carriers, and barrier height inhomogeneity at the interface of the barrier junction. After barrier height inhomogeneity correction, considering a Gaussian distributed barrier height fluctuation across the Pd/ZnO interface, the estimated values of mean barrier height and modified Richardson constant are more closely matched to the theoretically predicted value for Pd/ZnO Schottky barrier diodes. The variation of density of interface states as a function of interface state energy is also calculated.
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The intestinal barrier in multiple sclerosis: implications for pathophysiology and therapeutics.
Camara-Lemarroy, Carlos R; Metz, Luanne; Meddings, Jonathan B; Sharkey, Keith A; Wee Yong, V
2018-05-30
Biological barriers are essential for the maintenance of homeostasis in health and disease. Breakdown of the intestinal barrier is an essential aspect of the pathophysiology of gastrointestinal inflammatory diseases, such as inflammatory bowel disease. A wealth of recent studies has shown that the intestinal microbiome, part of the brain-gut axis, could play a role in the pathophysiology of multiple sclerosis. However, an essential component of this axis, the intestinal barrier, has received much less attention. In this review, we describe the intestinal barrier as the physical and functional zone of interaction between the luminal microbiome and the host. Besides its essential role in the regulation of homeostatic processes, the intestinal barrier contains the gut mucosal immune system, a guardian of the integrity of the intestinal tract and the whole organism. Gastrointestinal disorders with intestinal barrier breakdown show evidence of CNS demyelination, and content of the intestinal microbiome entering into the circulation can impact the functions of CNS microglia. We highlight currently available studies suggesting that there is intestinal barrier dysfunction in multiple sclerosis. Finally, we address the mechanisms by which commonly used disease-modifying drugs in multiple sclerosis could alter the intestinal barrier and the microbiome, and we discuss the potential of barrier-stabilizing strategies, including probiotics and stabilization of tight junctions, as novel therapeutic avenues in multiple sclerosis.
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Anisotropic capillary barrier for waste site surface covers
Stormont, J.C.
1996-08-27
Waste sites are capped or covered upon closure. The cover structure incorporates a number of different layers each having a contributory function. One such layer is the barrier layer. Traditionally the barriers have been compacted soil and geosynthetics. These types of barriers have not been successfully implemented in unsaturated ground conditions like those found in dry climates. Capillary barriers have been proposed as barrier layers in dry environments, but the divergence length of these barriers has been found to be inadequate. An alternative to the capillary barrier is a anisotropic capillary barrier. An anisotropic capillary barrier has an increased divergence length which results in more water being diverted laterally preventing the majority of water from percolating in a downward direction through the barrier. 10 figs.
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Anisotropic capillary barrier for waste site surface covers
Stormont, John C.
1996-01-01
Waste sites are capped or covered upon closure. The cover structure incorporates a number of different layers each having a contributory function. One such layer is the barrier layer. Traditionally the barriers have been compacted soil and geosynthetics. These types of barriers have not been successfully implemented in unsaturated ground conditions like those found in dry climates. Capillary barriers have been proposed as barrier layers in dry environments, but the divergence length of these barriers has been found to be inadequate. An alternative to the capillary barrier is a anisotropic capillary barrier. An anisotropic capillary barrier has an increased divergence length which results in more water being diverted laterally preventing the majority of water from percolating in a downward direction through the barrier.
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NASA Astrophysics Data System (ADS)
Lademann, J.; Richter, H.; Astner, S.; Patzelt, A.; Knorr, F.; Sterry, W.; Antoniou, Ch
2008-04-01
Normal skin barrier function is an essential aspect of skin homeostasis and regeneration. Dynamic inflammatory, proliferative and neoplastic skin processes such as wound healing, psoriasis and contact dermatitis are associated with a significant disruption of the skin barrier. In recent years, there has been increasing interest in evaluating cosmetic and pharmacologic products for their ability to restore these protective properties. The gold standard for characterization of barrier function has been the measurement of the transepidermal water loss, however the disadvantage of this method is its interference with several endogenous and exogenous factors such as hydration, perspiration and topically applied substances. This study was aimed to test the clinical applicability of a fluorescence confocal laser scanning microscope (LSM) for a systematic morphologic analysis of the structure, integrity and thickness of the stratum corneum in 10 otherwise healthy volunteers. The influence of skin treatment with commercial moisturizing cream on skin barrier function was evaluated in serial non-invasive examinations. Our findings showed that in vivo LSM may represent a simple and efficient method for the characterization of skin barrier properties, such as the thickness and hydration of the stratum corneum.
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Sugita, Kazunari; Steer, Catherine A; Martinez-Gonzalez, Itziar; Altunbulakli, Can; Morita, Hideaki; Castro-Giner, Francesc; Kubo, Terufumi; Wawrzyniak, Paulina; Rückert, Beate; Sudo, Katsuko; Nakae, Susumu; Matsumoto, Kenji; O'Mahony, Liam; Akdis, Mübeccel; Takei, Fumio; Akdis, Cezmi A
2018-01-01
Bronchial epithelial barrier leakiness and type 2 innate lymphoid cells (ILC2s) have been separately linked to asthma pathogenesis; however, the influence of ILC2s on the bronchial epithelial barrier has not been investigated previously. We investigated the role of ILC2s in the regulation of bronchial epithelial tight junctions (TJs) and barrier function both in bronchial epithelial cells of asthmatic patients and healthy subjects and general innate lymphoid cell- and ILC2-deficient mice. Cocultures of human ILC2s and bronchial epithelial cells were used to determine transepithelial electrical resistance, paracellular flux, and TJ mRNA and protein expressions. The effect of ILC2s on TJs was examined by using a murine model of IL-33-induced airway inflammation in wild-type, recombination-activating gene 2 (Rag2) -/- , Rag2 -/- Il2rg -/- , and Rora sg/sg mice undergoing bone marrow transplantation to analyze the in vivo relevance of barrier disruption by ILC2s. ILC2s significantly impaired the epithelial barrier, as demonstrated by reduced transepithelial electrical resistance and increased fluorescein isothiocyanate-dextran permeability in air-liquid interface cultures of human bronchial epithelial cells. This was in parallel to decreased mRNAs and disrupted protein expression of TJ proteins and was restored by neutralization of IL-13. Intranasal administration of recombinant IL-33 to wild-type and Rag2 -/- mice lacking T and B cells triggered TJ disruption, whereas Rag2 -/- Il2rg -/- and Rora sg/sg mice undergoing bone marrow transplantation that lack ILC2s did not show any barrier leakiness. Direct nasal administration of IL-13 was sufficient to induce deficiency in the TJ barrier in the bronchial epithelium of mice in vivo. These data highlight an essential mechanism in asthma pathogenesis by demonstrating that ILC2s are responsible for bronchial epithelial TJ barrier leakiness through IL-13. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Sinko, Robert; Bažant, Zdeněk P.; Keten, Sinan
2018-01-01
The Pickett effect describes the excess non-additive strain developed during drying of a nanoporous solid material under creep. One explanation for its origins, developed using micromechanical models, is the progressive relaxation of internally developed microprestress. However, these models have not explicitly considered the effects of this microprestress on nanoscale energy barriers that govern the relative motion and displacement between nanopore walls during deformation. Here, we evaluate the nanoscale effects of transverse microprestresses on the drying creep behaviour of a nanoscale slit pore using coarse-grained molecular dynamics. We find that the underlying energy barrier depends exponentially on the transverse microprestress, which is attributed to changes in the effective viscosity and degree of nanoconfinement of molecules in the water interlayer. Specifically, as the transverse microprestress is relaxed (i.e. its magnitude decreases), the activation energy barrier is reduced, thereby leading to an acceleration of the creep behaviour and a stronger Pickett effect. Based on our simulation results, we introduce a new microprestress-dependent energy term into our existing Arrhenius model, which describes the relative displacement of pore walls as a function of the underlying activation energy barriers. Our findings further verify the existing micromechanical theories for the origin of the Pickett effect and establish a quantitative relationship between the transverse microprestress and the intensity of the Pickett effect.
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Quispe Calla, N E; Vicetti Miguel, R D; Boyaka, P N; Hall-Stoodley, L; Kaur, B; Trout, W; Pavelko, S D; Cherpes, T L
2016-11-01
Depot-medroxyprogesterone acetate (DMPA) is a hormonal contraceptive especially popular in areas with high prevalence of HIV and other sexually transmitted infections (STI). Although observational studies identify DMPA as an important STI risk factor, mechanisms underlying this connection are undefined. Levonorgestrel (LNG) is another progestin used for hormonal contraception, but its effect on STI susceptibility is much less explored. Using a mouse model of genital herpes simplex virus type 2 (HSV-2) infection, we herein found that DMPA and LNG similarly reduced genital expression of the desmosomal cadherin desmoglein-1α (DSG1α), enhanced access of inflammatory cells to genital tissue by increasing mucosal epithelial permeability, and increased susceptibility to viral infection. Additional studies with uninfected mice revealed that DMPA-mediated increases in mucosal permeability promoted tissue inflammation by facilitating endogenous vaginal microbiota invasion. Conversely, concomitant treatment of mice with DMPA and intravaginal estrogen restored mucosal barrier function and prevented HSV-2 infection. Evaluating ectocervical biopsy tissue from women before and 1 month after initiating DMPA remarkably revealed that inflammation and barrier protection were altered by treatment identically to changes seen in progestin-treated mice. Together, our work reveals DMPA and LNG diminish the genital mucosal barrier; a first-line defense against all STI, but may offer foundation for new contraceptive strategies less compromising of barrier protection.
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Monitoring the Vadose Zone Moisture Regime Below a Surface Barrier
NASA Astrophysics Data System (ADS)
Zhang, Z. F.; Strickland, C. E.; Field, J. G.
2009-12-01
A 6000 m2 interim surface barrier has been constructed over a portion of the T Tank Farm in the Depart of Energy’s Hanford site. The purpose of using a surface barrier was to reduce or eliminate the infiltration of meteoric precipitation into the contaminated soil zone due to past leaks from Tank T-106 and hence to reduce the rate of movement of the plume. As part of the demonstration effort, vadose zone moisture is being monitored to assess the effectiveness of the barrier on the reduction of soil moisture flow. A vadose zone monitoring system was installed to measure soil water conditions at four horizontal locations (i.e., instrument Nests A, B, C, and D) outside, near the edge of, and beneath the barrier. Each instrument nest consists of a capacitance probe with multiple sensors, multiple heat-dissipation units, and a neutron probe access tube used to measure soil-water content and soil-water pressure. Nest A serves as a control by providing subsurface conditions outside the influence of the surface barrier. Nest B provides subsurface measurements to assess barrier edge effects. Nests C and D are used to assess the impact of the surface barrier on soil-moisture conditions beneath it. Monitoring began in September 2006 and continues to the present. To date, the monitoring system has provided high-quality data. Results show that the soil beneath the barrier has been draining from the shallower depth. The lack of climate-caused seasonal variation of soil water condition beneath the barrier indicates that the surface barrier has minimized water exchange between the soil and the atmosphere.
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Energy barrier analysis of Nd-Fe-B thin films
NASA Astrophysics Data System (ADS)
Goto, R.; Okamoto, S.; Kikuchi, N.; Kitakami, O.
2015-05-01
The magnetization reversal mechanism of a permanent magnet has long been a controversial issue, which is closely related to the so-called coercivity problem. It is well known that the energy barrier for magnetization reversal contains essential information on reversal process. In this study, we propose a method to analyze the energy barrier function for the magnetization reversal. Preferentially (001) oriented Nd-Fe-B films with and without a Nd overlayer are used as model magnets. By combining the magnetic viscosity and time dependent coercivity measurements, the barrier function has been successfully evaluated. As a result, although the Nd-Fe-B films with and without Nd overlayer exhibit different magnetic behaviors, the power indices for their energy barrier are almost the same, suggesting that the magnetization reversal proceeds in a similar mode.
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Cording, Jimmi; Günther, Ramona; Vigolo, Emilia; Tscheik, Christian; Winkler, Lars; Schlattner, Isabella; Lorenz, Dorothea; Haseloff, Reiner F; Schmidt-Ott, Kai M; Wolburg, Hartwig; Blasig, Ingolf E
2015-11-01
Tight junctions (TJs) seal paracellular clefts in epithelia/endothelia and form tissue barriers for proper organ function. TJ-associated marvel proteins (TAMPs; tricellulin, occludin, marvelD3) are thought to be relevant to regulation. Under normal conditions, tricellulin tightens tricellular junctions against macromolecules. Traces of tricellulin occur in bicellular junctions. As pathological disturbances have not been analyzed, the structure and function of human tricellulin, including potentially redox-sensitive Cys sites, were investigated under reducing/oxidizing conditions at 3- and 2-cell contacts. Ischemia, hypoxia, and reductants redistributed tricellulin from 3- to 2-cell contacts. The extracellular loop 2 (ECL2; conserved Cys321, Cys335) trans-oligomerized between three opposing cells. Substitutions of these residues caused bicellular localization. Cys362 in transmembrane domain 4 contributed to bicellular heterophilic cis-interactions along the cell membrane with claudin-1 and marvelD3, while Cys395 in the cytosolic C-terminal tail promoted homophilic tricellullar cis-interactions. The Cys sites included in homo-/heterophilic bi-/tricellular cis-/trans-interactions contributed to cell barrier tightness for small/large molecules. Tricellulin forms TJs via trans- and cis-association in 3-cell contacts, as demonstrated electron and quantified fluorescence microscopically; it tightens 3- and 2-cell contacts. Tricellulin's ECL2 specifically seals 3-cell contacts redox dependently; a structural model is proposed. TAMP ECL2 and claudins' ECL1 share functionally and structurally similar features involved in homo-/heterophilic tightening of cell-cell contacts. Tricellulin is a specific redox sensor and sealing element at 3-cell contacts and may compensate as a redox mediator for occludin loss at 2-cell contacts in vivo and in vitro. Molecular interaction mechanisms were proposed that contribute to tricellulin's function. In conclusion, tricellulin is a junctional redox regulator for ischemia-related alterations.
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Bourke, Claire D.; Mountford, Adrian P.
2015-01-01
The skin provides an important first line of defence and immunological barrier to invasive pathogens, but immune responses must also be regulated to maintain barrier function and ensure tolerance of skin surface commensal organisms. In schistosomiasis-endemic regions, populations can experience repeated percutaneous exposure to schistosome larvae, however little is known about how repeated exposure to pathogens affects immune regulation in the skin. Here, using a murine model of repeated infection with Schistosoma mansoni larvae, we show that the skin infection site becomes rich in regulatory IL-10, whilst in its absence, inflammation, neutrophil recruitment, and local lymphocyte proliferation is increased. Whilst CD4+ T cells are the primary cellular source of regulatory IL-10, they expressed none of the markers conventionally associated with T regulatory (Treg) cells (i.e. FoxP3, Helios, Nrp1, CD223, or CD49b). Nevertheless, these IL-10+ CD4+ T cells in the skin from repeatedly infected mice are functionally suppressive as they reduced proliferation of responsive CD4+ T cells from the skin draining lymph node. Moreover, the skin of infected Rag-/- mice had impaired IL-10 production and increased neutrophil recruitment. Finally, we show that the mechanism behind IL-10 production by CD4+ T cells in the skin is due to a combination of an initial (day 1) response specific to skin commensal bacteria, and then over the following days schistosome-specific CD4+ T cell responses, which together contribute towards limiting inflammation and tissue damage following schistosome infection. We propose CD4+ T cells in the skin that do not express markers of conventional T regulatory cell populations have a significant role in immune regulation after repeated pathogen exposure and speculate that these cells may also help to maintain skin barrier function in the context of repeated percutaneous insult by other skin pathogens. PMID:25974019
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Pre-coalescence scaling of graphene island sizes
NASA Astrophysics Data System (ADS)
Das, Shantanu; Drucker, Jeff
2018-05-01
Graphene grown using cold-wall chemical vapor deposition on Cu surfaces follows a classical nucleation and growth mechanism. Following nucleation at the earliest growth stages, isolated crystallites grow, impinge, and coalesce to form a continuous layer. During the pre-coalescence growth regime, the size distributions of graphene crystallites exhibit scaling of the form N(s) = θ/⟨s⟩2 g(s/⟨s⟩), where s is the island area, θ is the graphene coverage, ⟨s⟩ is the average island area, N is the areal density, and g(x) is a scaling function. For graphene grown on Cu surfaces that have been annealed in a reducing Ar + H2 ambient, excellent data collapse onto a universal Avrami scaling function is observed irrespective of graphene coverage, surface roughness, or Cu grain size. This result is interpreted to indicate attachment-limited growth and desorption of diffusing C-containing species. Graphene grown on Cu surfaces that were annealed in a non-reducing environment exhibits a qualitatively different scaling function, indicating diffusion-limited growth with a lower attachment barrier combined with C detachment from the graphene edges.
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ERIC Educational Resources Information Center
Hoehn, Jessica L.; Riekert, Kristin A.; Borrelli, Belinda; Rand, Cynthia S.; Eakin, Michelle N.
2016-01-01
Objective: To identify barriers and motivators for reducing secondhand smoke exposure (SHSe) for families of African-American, low-income, urban children. Method: Audiotaped intervention sessions of 52 African-American caregivers of Head Start children who reported being a smoker and/or had at least one smoker in the home were randomly sampled…
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Helminths and intestinal barrier function
McKay, Derek M.; Shute, Adam; Lopes, Fernando
2017-01-01
ABSTRACT Approximately one-sixth of the worlds' population is infected with helminths and this class of parasite takes a major toll on domestic livestock. The majority of species of parasitic helminth that infect mammals live in the gut (the only niche for tapeworms) where they contact the hosts' epithelial cells. Here, the helminth-intestinal epithelial interface is reviewed in terms of the impact on, and regulation of epithelial barrier function, both intrinsic (epithelial permeability) and extrinsic (mucin, bacterial peptides, commensal bacteria) elements of the barrier. The data available on direct effects of helminths on epithelial permeability are scant, fragmentary and pales in comparison with knowledge of mobilization of immune reactions and effector cells in response to helminth parasites and how these impact intestinal barrier function. The interaction of helminth-host and helminth-host-bacteria is an important determinant of gut form and function and precisely defining these interactions will radically alter our understanding of normal gut physiology and pathophysiological reactions, revealing new approaches to infection with parasitic helminths, bacterial pathogens and idiopathic auto-inflammatory disease. PMID:28452686
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THE PERMEABILITY OF RAT TRANSITIONAL EPITHELIUM
Hicks, R. M.
1966-01-01
Permeability barriers must exist in transitional epithelium to prevent the free flow of water from underlying blood capillaries through the epithelium into the hypertonic urine, and such a barrier has now been demonstrated in isolated bladders. This barrier is passive in function and can be destroyed by damaging the luminal surface of the transitional epithelium with sodium hydroxide and 8 M urea solutions, by digesting it with trypsin, lecithinase C, and lecithinase D, or by treating it with lipid solvents such as Triton x 100 and saponin. From this it is concluded that the barrier depends on the integrity of lipoprotein cell membranes. The barrier function is also destroyed by sodium thioglycollate solutions, and electron microscope investigations show that sodium thioglycollate damages the thick asymmetric membrane which limits the luminal face of the superficial squamous cell. Cytochemical staining shows the epithelium to contain disulfide and thiol groups and to have a concentration of these groups at the luminal margin of the superficial cells. It thus appears that the permeability barrier also depends on the presence of disulfide bridges in the epithelium, and it is presumed that these links are located in keratin. Because of the effect of thioglycollates, both on the barrier function and on the morphology of the membrane, it is suggested that keratin may be incorporated in the thick barrier membrane. It is proposed that the cells lining the urinary bladder and ureters should be regarded as a keratinizing epitheluim. PMID:5901498
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Barriers to Successful Treatment Completion in Child Sexual Abuse Survivors
ERIC Educational Resources Information Center
McPherson, Paul; Scribano, Philip; Stevens, Jack
2012-01-01
Child sexual abuse (CSA) often requires psychological treatment to address the symptoms of victim trauma. Barriers to entry and completion of counseling services can compromise long-term well-being. An integrated medical and mental health evaluation and treatment model of a child advocacy center (CAC) has the potential to reduce barriers to mental…
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Adolescents' Views of Food and Eating: Identifying Barriers to Healthy Eating
ERIC Educational Resources Information Center
Stevenson, Clifford; Doherty, Glenda; Barnett, Julie; Muldoon, Orla T.; Trew, Karen
2007-01-01
Contemporary Western society has encouraged an obesogenic culture of eating amongst youth. Multiple factors may influence an adolescent's susceptibility to this eating culture, and thus act as a barrier to healthy eating. Given the increasing prevalence of obesity amongst adolescents, the need to reduce these barriers has become a necessity.…
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Nutrition: Unique to Older Adults
... with supplements may help reduce falls. Social and Economic Barriers to Good Nutrition : Researchers have found that people in lower social or economic situations have some predictable barriers to eating a ...
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The gut microbiota and gastrointestinal surgery.
Guyton, Kristina; Alverdy, John C
2017-01-01
Surgery involving the gastrointestinal tract continues to prove challenging because of the persistence of unpredictable complications such as anastomotic leakage and life-threatening infections. Removal of diseased intestinal segments results in substantial catabolic stress and might require complex reconstructive surgery to maintain the functional continuity of the intestinal tract. As gastrointestinal surgery necessarily involves a breach of an epithelial barrier colonized by microorganisms, preoperative intestinal antisepsis is used to reduce infection-related complications. The current approach to intestinal antisepsis varies widely across institutions and countries with little understanding of its mechanism of action, effect on the gut microbiota and overall efficacy. Many of the current approaches to intestinal antisepsis before gastrointestinal surgery run counter to emerging concepts of intestinal microbiota contributing to immune function and recovery from injury. Here, we review evidence outlining the role of gut microbiota in recovery from gastrointestinal surgery, particularly in the development of infections and anastomotic leak. To make surgery safer and further reduce complications, a molecular, genetic and functional understanding of the response of the gastrointestinal tract to alterations in its microbiota is needed. Methods can then be developed to preserve the health-promoting functions of the microbiota while at the same time suppressing their harmful effects.