Multifactorial skin barrier deficiency and atopic dermatitis: Essential topics to prevent the atopic march.

PubMed

Egawa, Gyohei; Kabashima, Kenji

2016-08-01

Atopic dermatitis (AD) is the most common inflammatory skin disease in the industrialized world and has multiple causes. Over the past decade, data from both experimental models and patients have highlighted the primary pathogenic role of skin barrier deficiency in patients with AD. Increased access of environmental agents into the skin results in chronic inflammation and contributes to the systemic "atopic (allergic) march." In addition, persistent skin inflammation further attenuates skin barrier function, resulting in a positive feedback loop between the skin epithelium and the immune system that drives pathology. Understanding the mechanisms of skin barrier maintenance is essential for improving management of AD and limiting downstream atopic manifestations. In this article we review the latest developments in our understanding of the pathomechanisms of skin barrier deficiency, with a particular focus on the formation of the stratum corneum, the outermost layer of the skin, which contributes significantly to skin barrier function. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Overall accessibility to traveling by rail for the elderly with and without functional limitations: the whole-trip perspective.

PubMed

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.

A framework for understanding semi-permeable barrier effects on migratory ungulates

USGS Publications Warehouse

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.

The angiopoietin1-Akt pathway regulates barrier function of the cultured spinal cord microvascular endothelial cells through Eps8.

PubMed

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.

Age-dependent changes at the blood-brain barrier. A Comparative structural and functional study in young adult and middle aged rats.

PubMed

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.

Bilayer Poly(Lactic-co-glycolic acid)/Nano-Hydroxyapatite Membrane with Barrier Function and Osteogenesis Promotion for Guided Bone Regeneration

PubMed Central

Fu, Li; Wang, Zhanfeng; Dong, Shujun; Cai, Yan; Ni, Yuxin; Zhang, Tianshou; Wang, Lin; Zhou, Yanmin

2017-01-01

Guided bone regeneration (GBR) is one such treatment that reconstructs neo-bone tissue by using a barrier membrane to prevent the invasion of soft tissue and to create a space for guiding new bone growth into the bone defect. Herein, we report a novel functionally graded bilayer membrane (FGBM) for GBR application. To fabricate the novel membrane, the composites of poly(lactic-co-glycolic acid) and nano-hydroxyapatite were prepared by phase inversion for the dense layer and by electrospinning for another porous layer, and their corresponding properties were evaluated including surface morphology, mechanics, degradability, cell barrier function, and in vitro osteogenic bioactivity. The results showed that PLGA with 5% nHA in dense layer could meet the requirement of mechanical strength and have excellent barrier function even on condition of post-degradation. Furthermore, PLGA with 30% nHA in porous layer could achieve the good physical and chemical properties. In addition, 30% nHA incorporation would enhance the in vitro mineralization, and have superior capabilities of cell adhesion, proliferation and differentiation compared to other groups. Therefore, the designed FGBM could potentially serve as a barrier for preferential tissue ingrowth and achieve a desirable therapeutic result for bone tissue regeneration. PMID:28772618

Beta-adrenergic stimulation contributes to maintenance of endothelial barrier functions under baseline conditions.

PubMed

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.

Solid lipid nanoparticles as a vehicle for brain-targeted drug delivery: two new strategies of functionalization with apolipoprotein E

NASA Astrophysics Data System (ADS)

Rute Neves, Ana; Fontes Queiroz, Joana; Weksler, Babette; Romero, Ignacio A.; Couraud, Pierre-Olivier; Reis, Salette

2015-12-01

Nanotechnology can be an important tool to improve the permeability of some drugs for the blood-brain barrier. In this work we created a new system to enter the brain by functionalizing solid lipid nanoparticles with apolipoprotein E, aiming to enhance their binding to low-density lipoprotein receptors on the blood-brain barrier endothelial cells. Solid lipid nanoparticles were successfully functionalized with apolipoprotein E using two distinct strategies that took advantage of the strong interaction between biotin and avidin. Transmission electron microscopy images revealed spherical nanoparticles, and dynamic light scattering gave a Z-average under 200 nm, a polydispersity index below 0.2, and a zeta potential between -10 mV and -15 mV. The functionalization of solid lipid nanoparticles with apolipoprotein E was demonstrated by infrared spectroscopy and fluorimetric assays. In vitro cytotoxic effects were evaluated by MTT and LDH assays in the human cerebral microvascular endothelial cells (hCMEC/D3) cell line, a human blood-brain barrier model, and revealed no toxicity up to 1.5 mg ml-1 over 4 h of incubation. The brain permeability was evaluated in transwell devices with hCMEC/D3 monolayers, and a 1.5-fold increment in barrier transit was verified for functionalized nanoparticles when compared with non-functionalized ones. The results suggested that these novel apolipoprotein E-functionalized nanoparticles resulted in dynamic stable systems capable of being used for an improved and specialized brain delivery of drugs through the blood-brain barrier.

Fatty acids are required for epidermal permeability barrier function.

PubMed

Mao-Qiang, M; Elias, P M; Feingold, K R

1993-08-01

The permeability barrier is mediated by a mixture of ceramides, sterols, and free fatty acids arranged as extracellular lamellar bilayers in the stratum corneum. Whereas prior studies have shown that cholesterol and ceramides are required for normal barrier function, definitive evidence for the importance of nonessential fatty acids is not available. To determine whether epidermal fatty acid synthesis also is required for barrier homeostasis, we applied 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an inhibitor of acetyl CoA carboxylase, after disruption of the barrier by acetone or tape stripping. TOFA inhibits epidermal fatty acid by approximately 50% and significantly delays barrier recovery. Moreover, coadministration of palmitate with TOFA normalizes barrier recovery, indicating that the delay is due to a deficiency in bulk fatty acids. Furthermore, TOFA treatment also delays the return of lipids to the stratum corneum and results in abnormalities in the structure of lamellar bodies, the organelle which delivers lipid to the stratum corneum. In addition, the organization of secreted lamellar body material into lamellar bilayers within the stratum corneum interstices is disrupted by TOFA treatment. Finally, these abnormalities in lamellar body and stratum corneum membrane structure are corrected by coapplication of palmitate with TOFA. These results demonstrate a requirement for bulk fatty acids in barrier homeostasis. Thus, inhibiting the epidermal synthesis of any of the three key lipids that form the extracellular, lipid-enriched membranes of the stratum corneum results in an impairment in barrier homeostasis.

Fatty acids are required for epidermal permeability barrier function.

PubMed Central

Mao-Qiang, M; Elias, P M; Feingold, K R

1993-01-01

The permeability barrier is mediated by a mixture of ceramides, sterols, and free fatty acids arranged as extracellular lamellar bilayers in the stratum corneum. Whereas prior studies have shown that cholesterol and ceramides are required for normal barrier function, definitive evidence for the importance of nonessential fatty acids is not available. To determine whether epidermal fatty acid synthesis also is required for barrier homeostasis, we applied 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an inhibitor of acetyl CoA carboxylase, after disruption of the barrier by acetone or tape stripping. TOFA inhibits epidermal fatty acid by approximately 50% and significantly delays barrier recovery. Moreover, coadministration of palmitate with TOFA normalizes barrier recovery, indicating that the delay is due to a deficiency in bulk fatty acids. Furthermore, TOFA treatment also delays the return of lipids to the stratum corneum and results in abnormalities in the structure of lamellar bodies, the organelle which delivers lipid to the stratum corneum. In addition, the organization of secreted lamellar body material into lamellar bilayers within the stratum corneum interstices is disrupted by TOFA treatment. Finally, these abnormalities in lamellar body and stratum corneum membrane structure are corrected by coapplication of palmitate with TOFA. These results demonstrate a requirement for bulk fatty acids in barrier homeostasis. Thus, inhibiting the epidermal synthesis of any of the three key lipids that form the extracellular, lipid-enriched membranes of the stratum corneum results in an impairment in barrier homeostasis. Images PMID:8102380

Overall Accessibility to Traveling by Rail for the Elderly with and without Functional Limitations: The Whole-Trip Perspective

PubMed Central

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

Anisotropic capillary barrier for waste site surface covers

DOEpatents

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.

Anisotropic capillary barrier for waste site surface covers

DOEpatents

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.

Energy Levels in Quantum Wells.

NASA Astrophysics Data System (ADS)

Zang, Jan Xin

Normalized analytical equations for eigenstates of an arbitrary one-dimensional configuration of square potentials in a well have been derived. The general formulation is used to evaluate the energy levels of a particle in a very deep potential well containing seven internal barriers. The configuration can be considered as a finite superlattice sample or as a simplified model for a sample with only several atom layers. The results are shown in graphical forms as functions of the height and width of the potential barriers and as functions of the ratio of the effective mass in barrier to the mass in well. The formation of energy bands and surface eigenstates from eigenstates of a deep single well, the coming close of two energy bands and a surface state which are separate ordinarily, and mixing of the wave function of a surface state with the bulk energy bands are seen. Then the normalized derivation is extended to study the effect of a uniform electric field applied across a one-dimensional well containing an internal configuration of square potentials The general formulation is used to calculate the electric field dependence of the energy levels of a deep well with five internal barriers. Typical results are shown in graphical forms as functions of the barrier height, barrier width, barrier effective mass and the field strength. The formation of Stark ladders and surface states from the eigenstates of a single deep well in an electric field, the localization process of wave functions with changing barrier height, width, and field strength and their anticrossing behaviors are seen. The energy levels of a hydrogenic impurity in a uniform medium and in a uniform magnetic field are calculated with variational methods. The energy eigenvalues for the eigenstates with major quantum number less than or equal to 3 are obtained. The results are consistent with previous results. Furthermore, the energy levels of a hydrogenic impurity at the bottom of a one-dimensional parabolic quantum well with a magnetic field normal to the plane of the well are calculated with the finite-basis-set variational method. The limit of small radial distance and the limit of great radial distance are considered to choose a set of proper basis functions. It is found that the energy levels increase with increasing parabolic parameter alpha and increase with increasing normalized magnetic field strength gamma except those levels with magnetic quantum number m < 0 at small gamma.

Examining the role of transfer coupling in sub-barrier fusion of Ti 46 , 50 + Sn 124

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, J. Felix; Allmond, J. M.; Gross, C. J.

2016-08-24

In this study, the presence of neutron transfer channels with positive Q values can enhance sub-barrier fusion cross sections. Recent measurements of the fusion excitation functions for 58Ni+ 132,124Sn found that the fusion enhancement due to the influence of neutron transfer is smaller than that in 40Ca + 132,124Sn although the Q values for multineutron transfer are comparable. The purpose of this study is to investigate the differences observed between the fusion of Sn + Ni and Sn + Ca. Methods: Fusion excitation functions for 46,50Ti + 124Sn have been measured at energies near the Coulomb barrier. As a result,more » a comparison of the barrier distributions for 46Ti+ 124Sn and 40Ca+ 124Sn shows that the 40Ca+ 124Sn system has a barrier strength resulting from the coupling to the very collective octupole state in 40Ca at an energy significantly lower than the uncoupled barrier. In conclusion, the large sub-barrier fusion enhancement in 40Ca induced reactions is attributed to both couplings to neutron transfer and inelastic excitation, with the octupole vibration of 40Ca playing a major role.« less

Hypoxanthine is a checkpoint stress metabolite in colonic epithelial energy modulation and barrier function.

PubMed

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.

Quantum finance Hamiltonian for coupon bond European and barrier options.

PubMed

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.

Resistin-like molecule β regulates innate colonic function: Barrier integrity and inflammation susceptibility

PubMed Central

Hogan, Simon P.; Seidu, Luqman; Blanchard, Carine; Groschwitz, Katherine; Mishra, Anil; Karow, Margaret L.; Ahrens, Richard; Artis, David; Murphy, Andrew J.; Valenzuela, David M.; Yancopoulos, George D.; Rothenberg, Marc E.

2007-01-01

Background: Resistin-like molecule (RELM) β is a cysteine-rich cytokine expressed in the gastrointestinal tract and implicated in insulin resistance and gastrointestinal nematode immunity; however, its function primarily remains an enigma. Objective: We sought to elucidate the function of RELM-β in the gastrointestinal tract. Methods: We generated RELM-β gene-targeted mice and examined colonic epithelial barrier function, gene expression profiles, and susceptibility to acute colonic inflammation. Results: We show that RELM-β is constitutively expressed in the colon by goblet cells and enterocytes and has a role in homeostasis, as assessed by alterations in colon mRNA transcripts and epithelial barrier function in the absence of RELM-β. Using acute colonic inflammatory models, we demonstrate that RELM-β has a central role in the regulation of susceptibility to colonic inflammation. Mechanistic studies identify that RELM-β regulates expression of type III regenerating gene (REG) (REG3β and γ), molecules known to influence nuclear factor κB signaling. Conclusions: These data define a critical role for RELM-β in the maintenance of colonic barrier function and gastrointestinal innate immunity. Clinical implications: These findings identify RELM-β as an important molecule in homeostatic gastrointestinal function and colonic inflammation, and as such, these results have implications for a variety of human inflammatory gastrointestinal conditions, including allergic gastroenteropathies. PMID:16815164

Damage and recovery of skin barrier function after glycolic acid chemical peeling and crystal microdermabrasion.

PubMed

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.

Accelerated barrier recovery and enhancement of the barrier integrity and properties by topical application of a pH 4 compared to a pH 5.8 w/o emulsion in aged skin.

PubMed

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.

Metabolic approaches to enhance transdermal drug delivery. 1. Effect of lipid synthesis inhibitors.

PubMed

Tsai, J C; Guy, R H; Thornfeldt, C R; Gao, W N; Feingold, K R; Elias, P M

1996-06-01

The intercellular domains of the stratum corneum, which contain a mixture of cholesterol, free fatty acids, and ceramides, mediate both the epidermal permeability barrier and the transdermal delivery of both lipophilic and hydrophilic molecules. Prior studies have shown that each of the three key lipid classes is required for normal barrier function. For example, selective inhibition of either cholesterol, fatty acid, or ceramide synthesis in the epidermis delays barrier recovery rates after barrier perturbation of hairless mouse skin in vivo. In this study, we investigated the potential of certain inhibitors of lipid synthesis to enhance the transdermal delivery of lidocaine or caffeine as a result of their capacity to perturb barrier homeostasis. After acetone disruption of the barrier, the extent of lidocaine delivery and the degree of altered barrier function paralleled each other. Moreover, the further alteration in barrier function produced by either the fatty acid synthesis inhibitor 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), the cholesterol synthesis inhibitor fluvastatin (FLU), or cholesterol sulfate (CS) resulted in a further increase in lidocaine absorption. Furthermore, coapplications of TOFA and CS together caused an additive increase in lidocaine uptake. Finally, a comparable increase in drug delivery occurred when the barrier was disrupted initially with DMSO instead of acetone; coapplications of TOFA and FLU together again delayed barrier recovery and increased drug delivery by about 8-fold vs delivery from a standard enhancing vehicle. Whereas these metabolic inhibitors also variably increased the octanol/water partitioning of the drugs studied (perhaps via complexion or pH alterations), physicochemical effects of the inhibitors alone did not alter drug uptake in intact skin; i.e., passive mechanisms alone cannot account for the net increase in drug delivery. Our results show that modulations of epidermal lipid biosynthesis, following application of conventional, chemical penetration enhancers, cause a further boost in drug delivery, attributable to the ability of these agents to alter both permeability barrier homeostasis and thermodynamics. This biochemical/metabolic approach provides a novel means to enhance transdermal drug delivery in conjunction with the concurrent or prior use of chemical enhancers.

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.

Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression

PubMed Central

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

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.

Assessing theoretical uncertainties in fission barriers of superheavy nuclei

DOE PAGES

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

Dilemmas of Korean Athletes With a Spinal Cord Injury to Participate in Sports: A Survey Based on the ICF Core Set for Spinal Cord Injury

PubMed Central

2016-01-01

Objective To explore the experiences of athletes with spinal cord injury (SCI) in Korea with respect to dilemmas of participating in sports with regards to the facilitators and barriers, using the International Classification of Functioning, Disability and Health (ICF). Methods The facilitators and barriers to sports participation of individuals with SCI were examined using 112 ICF categories. A questionnaire in dichotomous scale was answered, which covered the subjects 'Body functions', 'Body structures', 'Activity and participation' and 'Environmental factors'. Data analysis included the use of descriptive statistics to examine the frequency and magnitude of reported issues. Results Sixty-two community-dwelling participants were recruited. Frequently addressed barriers in 'Body functions' were mobility related problems such as muscle and joint problems, bladder and bowel functions, pressure ulcers, and pain. In 'Activity and participation', most frequently reported were mobility and self-care problems. Highly addressed barriers in 'Environmental factors' were sports facilities, financial cost, transportation problems and lack of information. Relationships such as peer, family and friends were the most important facilitators. Conclusion Numerous barriers still exist for SCI survivors to participate in sports, especially in the area of health care needs and environmental factors. Our results support the need for a multidisciplinary approach to promote sports participation. PMID:27847720

Hydrologic behavior of two engineered barriers following extreme wetting.

PubMed

Porro, I

2001-01-01

Many engineered barriers are expected to function for hundreds of years or longer. Over the course of time, it is likely that some barriers will experience infiltration to the point of breakthrough. This study compares the recovery from breakthrough of two storage-evapotranspiration type engineered barriers. Replicates of test plots comprising thick soil and capillary-biobarrier covers were wetted to breakthrough in 1997. Test plots were kept cleared of vegetation to maximize hydrologic stress during recovery. Following cessation of drainage resulting from the wetting irrigations, water storage levels in all plots were at elevated levels compared with pre-irrigation levels. As a result, infiltration of melting snow during the subsequent spring overloaded the storage capacity and produced drainage in all plots. Relatively rapid melting of accumulated snowfall produced the most significant infiltration events each year during the study. Capillary barriers yielded less total drainage than thick soil barriers. By limiting drainage, capillary barriers increased water storage in the upper portions of the test plots, which led to increased evaporation from the capillary barrier plots compared with thick soil plots. Increased evaporation in the capillary barrier plots allowed more water to infiltrate in the second season following the wetting tests without triggering drainage. All thick soil plots again yielded drainage in the second season. Within two years of intentionally induced breakthrough, evaporation alone (without transpiration) restored the capability of the capillary barrier covers to function as intended, although water storage in these covers remained at elevated levels.

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.

Contrasting effects of linaclotide and lubiprostone on restitution of epithelial cell barrier properties and cellular homeostasis after exposure to cell stressors

PubMed Central

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

Oral intake of beet extract provides protection against skin barrier impairment in hairless mice.

PubMed

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.

Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

PubMed

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.

South African Teachers' Attitudes toward Learners with Barriers to Learning: Attention-Deficit and Hyperactivity Disorder and Little or No Functional Speech

ERIC Educational Resources Information Center

Bornman, Juan; Donohue, Dana K.

2013-01-01

This study examined teachers' attitudes toward learners with two types of barriers to learning: a learner with attention-deficit and hyperactivity disorder (ADHD), and a learner with little or no functional speech (LNFS). The results indicated that although teachers reported that the learner with ADHD would be more disruptive in class and have a…

Characterization of the interaction between two food aroma components, alpha-pinene and ethyl butyrate, and ethylene-vinyl alcohol copolymer (EVOH) packaging films as a function of environmental humidity.

PubMed

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.

Selective Matrix (Hyaluronan) Interaction with CD44 and RhoGTPase Signaling Promotes Keratinocyte Functions and Overcomes Age-related Epidermal Dysfunction

PubMed Central

Bourguignon, Lilly Y.W.; Wong, Gabriel; Xia, Weiliang; Man, Mao-Qiang; Holleran, Walter M.; Elias, Peter M.

2013-01-01

Background Mouse epidermal chronologic aging is closely associated with aberrant matrix (hyaluronan, HA) -size distribution/production and impaired keratinocyte proliferation/differentiation, leading to a marked thinning of the epidermis with functional consequence that causes a slower recovery of permeability barrier function. Objective The goal of this study is to demonstrate mechanism-based, corrective therapeutic strategies using topical applications of small HA (HAS) and/or large HA (HAL) [or a sequential small HA (HAS) and large HA(HAL) (HAs-»HAL) treatment] as well as RhoGTPase signaling perturbation agents to regulate HA/CD44-mediated signaling, thereby restoring normal epidermal function, and permeability barrier homeostasis in aged mouse skin. Methods A number of biochemical, cell biological/molecular, pharmacological and physiological approaches were used to investigate matrix HA-CD44-mediated RhoGTPase signaling in regulating epidermal functions and skin aging. Results In this study we demonstrated that topical application of small HA (HAS) promotes keratinocyte proliferation and increases skin thickness, while it fails to upregulate keratinocyte differentiation or permeability barrier repair in aged mouse skin. In contrast, large HA (HAL) induces only minimal changes in keratinocyte proliferation and skin thickness, but restores keratinocyte differentiation and improves permeability barrier function in aged epidermis. Since neither HAS nor HAL corrects these epidermal defects in aged CD44 knock-out mice, CD44 likely mediates HA-associated epidermal functions in aged mouse skin. Finally, blockade of Rho-kinase activity with Y27632 or protein kinase-Nγ activity with Ro31-8220 significantly decreased the HA (HAS or HAL)-mediated changes in epidermal function in aged mouse skin. Conclusion The results of our study show first that HA application of different sizes regulates epidermal proliferation, differentiation and barrier function in aged mouse skin. Second, manipulation of matrix (HA) interaction with CD44 and RhoGTPase signaling could provide further novel therapeutic approaches that could be targeted for the treatment of various aging-related skin disorders. PMID:23790635

Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in murine epidermis. Modulation of enzyme content and activation state by barrier requirements.

PubMed Central

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

Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine

PubMed Central

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

Epithelial cell kinase-B61: an autocrine loop modulating intestinal epithelial migration and barrier function.

PubMed

Rosenberg, I M; Göke, M; Kanai, M; Reinecker, H C; Podolsky, D K

1997-10-01

Epithelial cell kinase (Eck) is a member of a large family of receptor tyrosine kinases whose functions remain largely unknown. Expression and regulation of Eck and its cognate ligand B61 were analyzed in the human colonic adenocarcinoma cell line Caco-2. Immunocytochemical staining demonstrated coexpression of Eck and B61 in the same cells, suggestive of an autocrine loop. Eck levels were maximal in preconfluent cells. In contrast, B61 levels were barely detectable in preconfluent cells and increased progressively after the cells reached confluence. Caco-2 cells cultured in the presence of added B61 showed a significant reduction in the levels of dipeptidyl peptidase and sucrase-isomaltase mRNA, markers of Caco-2 cell differentiation. Cytokines interleukin-1beta (IL-1beta), basic fibroblast growth factor, IL-2, epidermal growth factor, and transforming growth factor-beta modulated steady-state levels of Eck and B61 mRNA and regulated Eck activation as assessed by tyrosine phosphorylation. Functionally, stimulation of Eck by B61 resulted in increased proliferation, enhanced barrier function, and enhanced restitution of injured epithelial monolayers. These results suggest that the Eck-B61 interaction, a target of regulatory peptides, plays a role in intestinal epithelial cell development, migration, and barrier function, contributing to homeostasis and preservation of continuity of the epithelial barrier.

Shot Noise in Superconducting Wires Applied with a Periodic Electric Field.

PubMed

Chen, Qiao; Xu, Ning

2018-05-01

We have investigated the differential conductance and shot noise for the system of superconducting nanowires irradiated with a periodic electric field by nonequilibrium Green's functions. The numerical results show that the coupling between the Majorana bound states (MBSs) can be tuned by the periodic electric field. The width of barriers has huge influence on the coupling of MBSs, however, the separation between barriers affect the coupling faintly. The coupling increases with the width of barriers, the number of barriers and the strength of barriers. In addition, super-Poissonian shot noise emerges as the coupling increases.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Varinderjit; Vadas, J.; Steinbach, T. K.

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.

Krüppel-like factor 5 is essential for maintenance of barrier function in mouse colon.

PubMed

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.

Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus

PubMed Central

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

Lithium diffusion at Si-C interfaces in silicon-graphene composites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Odbadrakh, Khorgolkhuu; McNutt, N. W.; Nicholson, D. M.

2014-08-04

Models of intercalated Li and its diffusion in Si-Graphene interfaces are investigated using density functional theory. Results suggest that the presence of interfaces alters the energetics of Li binding and diffusion significantly compared to bare Si or Graphene surfaces. Our results show that cavities along reconstructed Si surface provide diffusion paths for Li. Diffusion barriers calculated along these cavities are significantly lower than penetration barriers to bulk Si. Interaction with Si surface results in graphene defects, creating Li diffusion paths that are confined along the cavities but have still lower barrier than in bulk Si.

Abl Tyrosine Kinase Phosphorylates Nonmuscle Myosin Light Chain Kinase to Regulate Endothelial Barrier Function

PubMed Central

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

STM images and STS for a rectangular quantum corral constructed with δ-function barriers and the effect of an adsorbed atom on STM images and STS

NASA Astrophysics Data System (ADS)

Mitsuoka, Shigenori; Tamura, Akira

2012-04-01

Assuming that an electron confined by double δ-function barriers is in a quasi-stationary state, we derived eigenfunctions and eigenenergies of the electron. Applying this point of view to the electron confined in a rectangular quantum corral (QC), we obtained scanning tunneling microscopic (STM) images and scanning tunneling spectrum (STS). Our results are consistent with experimental ones, which confirms validity of the present model. Comparing with the treatment in which the corral potential is chosen to be of square-barrier type, the present treatment has an advantage that the eigenvalue equations are simple and the number of parameters that specify the potential barrier is only one except the bottom of the potential well. On the basis of a Dyson equation for the Green function we calculated STM images and STS of the QC having an adsorbed atom inside. Our results are consistent with experimental STM images and STS. In contrast to a previous viewpoint that the STS profile is reversed with that of the empty QC, we concluded the STS peaks of the adsorbed QC are shifted downward from those of the empty QC.

Probabilistic migration modelling focused on functional barrier efficiency and low migration concepts in support of risk assessment.

PubMed

Brandsch, Rainer

2017-10-01

Migration modelling provides reliable migration estimates from food-contact materials (FCM) to food or food simulants based on mass-transfer parameters like diffusion and partition coefficients related to individual materials. In most cases, mass-transfer parameters are not readily available from the literature and for this reason are estimated with a given uncertainty. Historically, uncertainty was accounted for by introducing upper limit concepts first, turning out to be of limited applicability due to highly overestimated migration results. Probabilistic migration modelling gives the possibility to consider uncertainty of the mass-transfer parameters as well as other model inputs. With respect to a functional barrier, the most important parameters among others are the diffusion properties of the functional barrier and its thickness. A software tool that accepts distribution as inputs and is capable of applying Monte Carlo methods, i.e., random sampling from the input distributions of the relevant parameters (i.e., diffusion coefficient and layer thickness), predicts migration results with related uncertainty and confidence intervals. The capabilities of probabilistic migration modelling are presented in the view of three case studies (1) sensitivity analysis, (2) functional barrier efficiency and (3) validation by experimental testing. Based on the predicted migration by probabilistic migration modelling and related exposure estimates, safety evaluation of new materials in the context of existing or new packaging concepts is possible. Identifying associated migration risk and potential safety concerns in the early stage of packaging development is possible. Furthermore, dedicated material selection exhibiting required functional barrier efficiency under application conditions becomes feasible. Validation of the migration risk assessment by probabilistic migration modelling through a minimum of dedicated experimental testing is strongly recommended.

Pericyte Derived Sphinogosine 1-Phosphate Induces the Expression of Adhesion Proteins and Modulates the Retinal Endothelial Cell Barrier

PubMed Central

McGuire, P.G.; Rangasamy, S.; Maestas, J.; Das, A.

2011-01-01

Objective The mechanisms that regulate the physical interaction of pericytes and endothelial cells and the effects of these interactions on interendothelial cell junctions are not well understood. We determined the extent to which vascular pericytes could regulate pericyte-endothelial adhesion and the consequences that this disruption might have on the function of the endothelial barrier. Methods and Results Human retinal microvascular endothelial cells were co-cultured with pericytes, and the effect on the monolayer resistance of endothelial cells and expression of the cell junction molecules N-cadherin and VE-cadherin were measured. The molecules responsible for the effect of pericytes or pericyte conditioned media on the endothelial resistance and cell junction molecules were further analyzed. Our results indicate that pericytes increase the barrier properties of endothelial cell monolayers. This barrier function is maintained through the secretion of pericyte-derived sphingosine 1-phosphate (S1P). S1P aids in maintenance of microvascular stability by up-regulating the expression of N-cadherin and VE-cadherin, and down-regulating the expression of angiopoietin 2. Conclusion Under normal circumstances, the retinal vascular pericytes maintain pericyte-endothelial contacts and vascular barrier function through the secretion of S1P. Alteration of pericyte-derived S1P production may be an important mechanism in the development of diseases characterized by vascular dysfunction and increased permeability. PMID:21940944

Factors influencing work functioning after cancer diagnosis: a focus group study with cancer survivors and occupational health professionals.

PubMed

Dorland, H F; Abma, F I; Roelen, C A M; Smink, J G; Ranchor, A V; Bültmann, U

2016-01-01

Cancer survivors (CSs) frequently return to work, but little is known about work functioning after return to work (RTW). We aimed to identify barriers and facilitators of work functioning among CSs. Three focus groups were conducted with CSs (n = 6, n = 8 and n = 8) and one focus group with occupational health professionals (n = 7). Concepts were identified by thematic analysis, using the Cancer and Work model as theoretical framework to structure the results. Long-lasting symptoms (e.g. fatigue), poor adaptation, high work ethics, negative attitude to work, ambiguous communication, lack of support and changes in the work environment were mentioned as barriers of work functioning. In contrast, staying at work during treatment, open dialogue, high social support, appropriate work accommodations and high work autonomy facilitated work functioning. Not only cancer-related symptoms affect work functioning of CSs after RTW but also psychosocial and work-related factors. The barriers and facilitators of work functioning should be further investigated in studies with a longitudinal design to examine work functioning over time.

Alterations in blood-brain barrier function following acute hypertension: comparison of the blood-to-brain transfer of horseradish peroxidase with that of alpha-aminisobutyric acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ellison, M.D.B.

The blood-brain barrier (BBB) selectively restricts the blood-to-brain passage of many solutes owing to unique properties of cerebrovascular endothelial cell membranes. To date, experimental study of the BBB has been accomplished primarily through the use of two different methodological approaches. Morphological studies have mostly employed large molecular weight (MW) tracers to detect morphological alterations underlying increased permeability. Physiological studies, employing smaller, more physiologic tracers have successfully described, quantitatively, certain functional aspects of blood-to-brain transfer. The current work attempts to merge these two approaches and to consider barrier function/dysfunction from both a morphological and a functional perspective. Specifically, the study comparesmore » in rats, following acute hypertension, the cerebrovascular passage of /sup 14/C-alpha-aminoisobutyric acid (AIB) and that of horseradish peroxidase (HRP). The blood-to-brain passage of AIB and HRP were compared following acute hypertension, with regard to both the distributions of the tracer extravasation patterns and the magnitude of tracer extravasation. The results of this study suggest that traditional morphological barrier studies alone do not reveal all aspects of altered barrier status and that multiple mechanisms underlying increased BBB permeability may operate simultaneously during BBB dysfunction.« less

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

PubMed Central

Kim, Seungbum; Goel, Ruby; Kumar, Ashok; Qi, Yanfei; Lobaton, Gil; Hosaka, Koji; Mohammed, Mohammed; Handberg, Eileen M.; Richards, Elaine M.; Pepine, Carl J.; Raizada, Mohan K.

2018-01-01

Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models. However, whether this association exists in humans is unknown. Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut–epithelial barrier function markers and microbiome composition could predict systolic BP (SBP). Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects. Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability. Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP. Zonulin strongly correlated with SBP (R2 = 0.5301, P<0.0001). Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001). The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP. These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans. They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN. PMID:29507058

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.

Bacillus cereus Induces Permeability of an In Vitro Blood-Retina Barrier▿

PubMed Central

Moyer, A. L.; Ramadan, R. T.; Thurman, J.; Burroughs, A.; Callegan, M. C.

2008-01-01

Most Bacillus cereus toxin production is controlled by the quorum-sensing-dependent, pleiotropic global regulator plcR, which contributes to the organism's virulence in the eye. The purpose of this study was to analyze the effects of B. cereus infection and plcR-regulated toxins on the barrier function of retinal pigment epithelium (RPE) cells, the primary cells of the blood-retina barrier. Human ARPE-19 cells were apically inoculated with wild-type or quorum-sensing-deficient B. cereus, and cytotoxicity was analyzed. plcR-regulated toxins were not required for B. cereus-induced RPE cytotoxicity, but these toxins did increase the rate of cell death, primarily by necrosis. B. cereus infection of polarized RPE cell monolayers resulted in increased barrier permeability, independent of plcR-regulated toxins. Loss of both occludin and ZO-1 expression occurred by 8 h postinfection, but alterations in tight junctions appeared to precede cytotoxicity. Of the several proinflammatory cytokines analyzed, only interleukin-6 was produced in response to B. cereus infection. These results demonstrate the deleterious effects of B. cereus infection on RPE barrier function and suggest that plcR-regulated toxins may not contribute significantly to RPE barrier permeability during infection. PMID:18268029

Bi-functional anodic TiO2 oxide: Nanotubes for wettability control and barrier oxide for uniform coloring

NASA Astrophysics Data System (ADS)

Kim, Sunkyu; Jung, Minkyeong; Kim, Moonsu; Choi, Jinsub

2017-06-01

A uniformly colored TiO2, on which the surface is functionalized with nanotubes to control wettability, was prepared by a two-step anodization; the first anodization was carried out to prepare nanotubes for a super-hydrophilic or -hydrophobic surface and the second anodization was performed to fabricate a thin film barrier oxide to ensure uniform coloring. The effect of the nanotubes on barrier oxide coloring was examined by spectrophotometry and UV-vis-IR spectroscopy. We found four different regimes governing the color changes in terms of anodization voltage, indicating that the color of the duplex TiO2 was primarily determined by the thickness of the barrier oxide layer formed during the second anodization step. The surface wettability, as confirmed by the water contact angle, revealed that the single barrier TiO2 yielded 74.6° ± 2.1, whereas the nanotubes on the barrier oxide imparted super-hydrophilic properties as a result of increasing surface roughness as well as imparting a higher hydrophobicity after organic acid treatment.

Barriers to and facilitators of the acceptance process for individuals with serious mental illness.

PubMed

Mizock, Lauren; Russinova, Zlatka; Millner, Uma Chandrika

2014-09-01

The process of acceptance of mental illness is a central component of recovery and has been linked to functioning, illness management, and quality of life. A number of barriers and facilitators have been theorized as impacting this process. This study was conducted with 30 participants with serious mental illness (a major psychiatric disorder with impairment in multiple areas of functioning) to elicit the barriers to and facilitators of the acceptance of mental illness. Grounded theory methodology was utilized to analyze the 30 semistructured interviews. Results revealed barriers to and facilitators of acceptance of mental illness at the micro level (cognitive, emotional, behavioral, identity-related), meso level (relational), and macro level (cultural, systemic). Clinical and research implications are discussed with regard to facilitating acceptance of mental illness. © The Author(s) 2014.

Spin accumulation in Si channels using CoFe/MgO/Si and CoFe/AlO{sub x}/Si tunnel contacts with high quality tunnel barriers prepared by radical-oxygen annealing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akushichi, T., E-mail: taiju.aku7@isl.titech.ac.jp; Shuto, Y.; Sugahara, S., E-mail: sugahara@isl.titech.ac.jp

We investigate spin injection into Si channels using three-terminal spin-accumulation (3T-SA) devices with high-quality CoFe/MgO/n-Si and CoFe/AlO{sub x}/n-Si tunnel spin-injectors whose tunnel barriers are formed by radical oxidation of Mg and Al thin films deposited on Si(100) substrates and successive annealing under radical-oxygen exposure. When the MgO and AlO{sub x} barriers are not treated by the radical-oxygen annealing, the Hanle-effect signals obtained from the 3T-SA devices are closely fitted by a single Lorentz function representing a signal due to trap spins. On the other hand, when the tunnel barriers are annealed under radical-oxygen exposure, the Hanle-effect signals can be accuratelymore » fitted by the superposition of a Lorentz function and a non-Lorentz function representing a signal due to accumulated spins in the Si channel. These results suggest that the quality improvement of tunnel barriers treated by radical-oxygen annealing is highly effective for spin-injection into Si channels.« less

Three-dimensional biomimetic vascular model reveals a RhoA, Rac1, and N-cadherin balance in mural cell-endothelial cell-regulated barrier function.

PubMed

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.

Anomalous anisotropies of fission fragments in near- and sub-barrier fusion-fussion reactions

NASA Astrophysics Data System (ADS)

Huanqiao, Zhang; Zuhua, Liu; Jincheng, Xu; Jun, Lu; Ming, Ruan; Kan, Xu

1992-03-01

Fission cross sections and angular distributions have been measured for the reactions of 16O + 232Th and238U, and19F + 208Pb and232Th at near- and sub-barrier energies. The fission excitation functions are rather well reproduced on the basis of Wong model or coupled channels theory. However, the models which reproduce the sub-barrier fusion cross sections fail to account for the experimental anisotropies of fission fragments. It is found that the observed anisotropies are much larger than expected. For the first time it has been observed that the anisotropies as a function of the center-of-mass energy show a peak centered near 4.5 MeV below the fusion barrier for several reaction systems. The present approaches fail to explain these anomalies. For 19F + 208Pb systems, our results confirm the prediction of an approximately constant value for the mean square spin of the compound nucleus produced in far sub-barrier fusion reaction.

Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus.

PubMed

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.

Neuroimmune Axes of the Blood–Brain Barriers and Blood–Brain Interfaces: Bases for Physiological Regulation, Disease States, and Pharmacological Interventions

PubMed Central

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

[Recent studies on corneal epithelial barrier function].

PubMed

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).

The pH of the main Brazilian commercial moisturizers and liquid soaps: considerations on the repair of the skin barrier.

PubMed

Gonçalves, Giovana M; Brianezi, Gabrielli; Miot, Hélio Amante

2017-01-01

The pH of the skin is slightly acidic (4.6 to 5.8) which is important for appropriate antibacterial, antifungal, constitution of barrier function, as well as structuring and maturation of the stratum corneum. This study aimed to evaluate the pH of the main commercial moisturizers and liquid soaps in Brazil. Thus, pH of the products was quantified by pH meter in three measurements. A total of 38 moisturizers and six commercial liquid soaps were evaluated. Mean pH of 63% and 50% of the moisturizing and liquid soaps presented results above 5.5, disfavoring repair, function, and synthesis of dermal barrier.

Nutrients affecting gastric barrier.

PubMed

Gasbarrini, Antonio; D'Aversa, Francesca; Di Rienzo, Teresa; Franceschi, Francesco

2014-01-01

The gastric barrier could be considered an active tissue involved in many synthetic and metabolic functions, as the immunological defense, by activating mucosal immune system. Barrier integrity results from a balance between protective and aggressive endogenous factors and from their interaction with exogenous factors (steroidal or nonsteroidal anti-inflammatory drugs, dietary nitrates, nitrites and/or NaCl, stress, Helicobacter pylori infection, food allergens and contaminants, metals, chemicals, radiation, smoking and alcohol intake). Nutrients represent the most important exogenous factors affecting gastric barrier because of the impact on people's everyday life. We report evidence from the literature about nutrients affecting gastric barrier and we investigate the possible effect that nutrients can play to determining or maintaining a gastric barrier dysfunction. © 2014 S. Karger AG, Basel.

Myosin Light Chain Kinase Mediates Intestinal Barrier Disruption following Burn Injury

PubMed Central

Chen, Chuanli; Wang, Pei; Su, Qin; Wang, Shiliang; Wang, Fengjun

2012-01-01

Background Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC) phosphorylation mediated by MLC kinase (MLCK) is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. Methodology/Principal Findings Male balb/c mice were assigned randomly to either sham burn (control) or 30% total body surface area (TBSA) full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg), an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC)-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression. Conclusions/Significance The MLCK-dependent MLC phosphorylation mediates intestinal epithelial barrier dysfunction after severe burn injury. It is suggested that MLCK-dependent MLC phosphorylation may be a critical target for the therapeutic treatment of intestinal epithelial barrier disruption after severe burn injury. PMID:22529961

Oxygen vacancy diffusion in bulk SrTiO3 from density functional theory calculations

DOE PAGES

Zhang, Lipeng; Liu, Bin; Zhuang, Houlong; ...

2016-04-01

Point defects and point defect diffusion contribute significantly to the properties of perovskite materials. However, even for the prototypical case of oxygen vacancies in SrTiO 3 (STO), predictions vary widely. Here we present a comprehensive and systematic study of the diffusion barriers for this material. We use density functional theory (DFT) and assess the role of different cell sizes, density functionals, and charge states. Our results show that vacancy-induced octahedral rotations, which are limited by the boundary conditions of the supercell, can significantly affect the computed oxygen vacancy diffusion energy barrier. The diffusion energy barrier of a charged oxygen vacancymore » is lower than that of a neutral one. Unexpectedly, we find that with increasing supercell size, the effects of the oxygen vacancy charge state, the type of DFT exchange and correlation functional on the energy barrier diminish, and the different DFT predictions asymptote to a value in the range of 0.39-0.49 eV. This work provides important insight and guidance that should be considered for investigations of point defect diffusion in other perovskite materials and in oxide superlattices.« less

I-V characteristics of graphene nanoribbon/h-BN heterojunctions and resonant tunneling.

PubMed

Wakai, Taiga; Sakamoto, Shoichi; Tomiya, Mitsuyoshi

2018-07-04

We present the first principle calculations of the electrical properties of graphene sheet/h-BN heterojunction (GS/h-BN) and 11-armchair graphene nanoribbon/h-BN heterojunction (11-AGNR/h-BN), which are carried out using the density functional theory (DFT) method and the non-equilibrium Green's function (NEGF) technique. Since 11-AGNR belongs to the conductive (3n-1)-family of AGNR, both are metallic nanomaterials with two transverse arrays of h-BN, which is a wide-gap semi-conductor. The two h-BN arrays act as double barriers. The transmission functions (TF) and I-[Formula: see text] characteristics of GS/h-BN and 11-AGNR/h-BN are calculated by DFT and NEGF, and they show that quantum double barrier tunneling occurs. The TF becomes very spiky in both materials, and it leads to step-wise I-[Formula: see text] characteristics rather than negative resistance, which is the typical behavior of double barriers in semiconductors. The results of our first principle calculations are also compared with 1D Dirac equation model for the double barrier system. The model explains most of the peaks of the transmission functions nearby the Fermi energy quite well. They are due to quantum tunneling.

Influence of functional food components on gut health.

PubMed

Wan, Murphy L Y; Ling, K H; El-Nezami, Hani; Wang, M F

2018-01-30

Intestinal epithelial cells (IECs) lining the gastrointestinal tract establish a barrier between external environments and the internal milieu. An intact intestinal barrier maintains gut health and overall good health of the body by preventing from tissue injury, pathogen infection and disease development. When the intestinal barrier function is compromised, bacterial translocation can occur. Our gut microbiota also plays a fundamentally important role in health, for example, by maintaining intestinal barrier integrity, metabolism and modulating the immune system, etc. Any disruption of gut microbiota composition (also termed dysbiosis) can lead to various pathological conditions. In short, intestinal barrier and gut microbiota are two crucial factors affecting gut health. The gastrointestinal tract is a complex environment exposed to many dietary components and commensal bacteria. Dietary components are increasingly recognized to play various beneficial roles beyond basic nutrition, resulting in the development of the functional food concepts. Various dietary modifiers, including the consumption of live bacteria (probiotics) and ingestible food constituents such as prebiotics, as well as polyphenols or synbiotics (combinations of probiotics and prebiotics) are the most well characterized dietary bioactive compounds and have been demonstrated to beneficially impact the gut health and the overall well-being of the host. In this review we depict the roles of intestinal epithelium and gut microbiota in mucosal defence responses and the influence of certain functional food components on the modulation of gut health, with a particular focus on probiotics, prebiotics and polyphenols.

In vitro models to estimate drug penetration through the compromised stratum corneum barrier.

PubMed

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.

Microbial induction of vascular pathology in the CNS.

PubMed

Kang, Silvia S; McGavern, Dorian B

2010-09-01

The central nervous system (CNS) is a finely tuned organ that participates in nearly every aspect of our day-to-day function. Neurons lie at the core of this functional unit and maintain an active dialogue with one another as well as their fellow CNS residents (e.g. astrocytes, oligodendrocytes, microglia). Because of this complex dialogue, it is essential that the CNS milieu be tightly regulated in order to permit uninterrupted and efficient neural chemistry. This is accomplished in part by anatomical barriers that segregate vascular components from the cerebral spinal fluid (CSF) and brain parenchyma. These barriers impede entry of noxious materials and enable the CNS to maintain requisite protein and ionic balances for constant electrochemical signaling. Under homeostatic conditions, the CNS is protected by the presence of specialized endothelium/epithelium, the blood brain barrier (BBB), and the blood-CSF barrier. However, following CNS infection these protective barriers can be comprised, sometimes resulting in severe neurological complications triggered by an imbalance or blockage of neural chemistry. In some instances, these disruptions are severe enough to be fatal. This review focuses on a selection of microbes (both viruses and parasites) that compromise vascular barriers and induce neurological complications upon gaining access to the CNS. Emphasis is placed on CNS diseases that result from a pathogenic interplay between host immune defenses and the invading microbe.

Microbial Induction of Vascular Pathology in the CNS

PubMed Central

Kang, Silvia S.

2016-01-01

The central nervous system (CNS) is a finely tuned organ that participates in nearly every aspect of our day-to-day function. Neurons lie at the core of this functional unit and maintain an active dialogue with one another as well as their fellow CNS residents (e.g. astrocytes, oligodendrocytes, microglia). Because of this complex dialogue, it is essential that the CNS milieu be tightly regulated in order to permit uninterrupted and efficient neural chemistry. This is accomplished in part by anatomical barriers that segregate vascular components from the cerebral spinal fluid (CSF) and brain parenchyma. These barriers impede entry of noxious materials and enable the CNS to maintain requisite protein and ionic balances for constant electrochemical signaling. Under homeostatic conditions, the CNS is protected by the presence of specialized endothelium/epithelium, the blood brain barrier (BBB), and the blood-CSF barrier. However, following CNS infection these protective barriers can be comprised, sometimes resulting in severe neurological complications triggered by an imbalance or blockage of neural chemistry. In some instances, these disruptions are severe enough to be fatal. This review focuses on a selection of microbes (both viruses and parasites) that compromise vascular barriers and induce neurological complications upon gaining access to the CNS. Emphasis is placed on CNS diseases that result from a pathogenic interplay between host immune defenses and the invading microbe. PMID:20401700

Albumin-associated free fatty acids induce macropinocytosis in podocytes

PubMed Central

Chung, Jun-Jae; Huber, Tobias B.; Gödel, Markus; Jarad, George; Hartleben, Björn; Kwoh, Christopher; Keil, Alexander; Karpitskiy, Aleksey; Hu, Jiancheng; Huh, Christine J.; Cella, Marina; Gross, Richard W.; Miner, Jeffrey H.; Shaw, Andrey S.

2015-01-01

Podocytes are specialized epithelial cells in the kidney glomerulus that play important structural and functional roles in maintaining the filtration barrier. Nephrotic syndrome results from a breakdown of the kidney filtration barrier and is associated with proteinuria, hyperlipidemia, and edema. Additionally, podocytes undergo changes in morphology and internalize plasma proteins in response to this disorder. Here, we used fluid-phase tracers in murine models and determined that podocytes actively internalize fluid from the plasma and that the rate of internalization is increased when the filtration barrier is disrupted. In cultured podocytes, the presence of free fatty acids (FFAs) associated with serum albumin stimulated macropinocytosis through a pathway that involves FFA receptors, the Gβ/Gγ complex, and RAC1. Moreover, mice with elevated levels of plasma FFAs as the result of a high-fat diet were more susceptible to Adriamycin-induced proteinuria than were animals on standard chow. Together, these results support a model in which podocytes sense the disruption of the filtration barrier via FFAs bound to albumin and respond by enhancing fluid-phase uptake. The response to FFAs may function in the development of nephrotic syndrome by amplifying the effects of proteinuria. PMID:25915582

Inflammatory Bowel Disease Therapies and Gut Function in a Colitis Mouse Model

PubMed Central

Nahidi, Lily; Leach, Steven T.; Mitchell, Hazel M.; Kaakoush, Nadeem O.; Lemberg, Daniel A.; Munday, John S.; Huinao, Karina; Day, Andrew S.

2013-01-01

Background. Exclusive enteral nutrition (EEN) is a well-established approach to the management of Crohn's disease. Aim. To determine effects of EEN upon inflammation and gut barrier function in a colitis mouse model. Methods. Interleukin-10-deficient mice (IL-10−/−) were inoculated with Helicobacter trogontum and then treated with EEN, metronidazole, hydrocortisone, or EEN and metronidazole combination. Blood and tissue were collected at 2 and 4 weeks with histology, mucosal integrity, tight junction integrity, inflammation, and H. trogontum load evaluated. Results. H. trogontum induced colitis in IL-10−/− mice with histological changes in the cecum and colon. Elevated mucosal IL-8 mRNA in infected mice was associated with intestinal barrier dysfunction indicated by decreased transepithelial electrical resistance and mRNA of tight junction proteins and increased short-circuit current, myosin light chain kinase mRNA, paracellular permeability, and tumor necrosis factor-α and myeloperoxidase plasma levels (P < 0.01 for all comparisons). EEN and metronidazole, but not hydrocortisone, treatments restored barrier function, maintained gut barrier integrity, and reversed inflammatory changes along with reduction of H. trogontum load (versus infected controls P < 0.05). Conclusion. H. trogontum infection in IL-10−/− mice induced typhlocolitis with intestinal barrier dysfunction. EEN and metronidazole, but not hydrocortisone, modulate barrier dysfunction and reversal of inflammatory changes. PMID:24027765

Novel routes of albumin passage across the glomerular filtration barrier.

PubMed

Castrop, H; Schießl, I M

2017-03-01

Albuminuria is a hallmark of kidney diseases of various aetiologies and an unambiguous symptom of the compromised integrity of the glomerular filtration barrier. Furthermore, there is increasing evidence that albuminuria per se aggravates the development and progression of chronic kidney disease. This review covers new aspects of the movement of large plasma proteins across the glomerular filtration barrier in health and disease. Specifically, this review focuses on the role of endocytosis and transcytosis of albumin by podocytes, which constitutes a new pathway of plasma proteins across the filtration barrier. Thus, we summarize what is known about the mechanisms of albumin endocytosis by podocytes and address the fate of the endocytosed albumin, which is directed to lysosomal degradation or transcellular movement with subsequent vesicular release into the urinary space. We also address the functional consequences of overt albumin endocytosis by podocytes, such as the formation of pro-inflammatory cytokines, which might eventually result in a deterioration of podocyte function. Finally, we consider the diagnostic potential of podocyte-derived albumin-containing vesicles in the urine as an early marker of a compromised glomerular barrier function. In terms of new technical approaches, the review covers how our knowledge of the movement of albumin across the glomerular filtration barrier has expanded by the use of new intravital imaging techniques. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Standards for the Protection of Skin Barrier Function.

PubMed

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.

Regulation of Endothelial Barrier Function by Cyclic Nucleotides: The Role of Phosphodiesterases

PubMed Central

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

Regulation of endothelial barrier function by cyclic nucleotides: the role of phosphodiesterases.

PubMed

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.

Impaired intestinal immune barrier and physical barrier function by phosphorus deficiency: Regulation of TOR, NF-κB, MLCK, JNK and Nrf2 signalling in grass carp (Ctenopharyngodon idella) after infection with Aeromonas hydrophila.

PubMed

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.

Tunneling of heat: Beyond linear response regime

NASA Astrophysics Data System (ADS)

Walczak, Kamil; Saroka, David

2018-02-01

We examine nanoscale processes of heat (energy) transfer as carried by electrons tunneling via potential barriers and molecular interconnects between two heat reservoirs (thermal baths). For that purpose, we use Landauer-type formulas to calculate thermal conductance and quadratic correction to heat flux flowing via quantum systems. As an input, we implement analytical expressions for transmission functions related to simple potential barriers and atomic bridges. Our results are discussed with respect to energy of tunneling electrons, temperature, the presence of resonant states, and specific parameters characterizing potential barriers as well as heat carriers. The simplicity of semi-analytical models developed by us allows to fit experimental data and extract crucial information about the values of model parameters. Further investigations are expected for more realistic transmission functions, while time-dependent aspects of nanoscale heat transfer may be addressed by using the concept of wave packets scattered on potential barriers and point-like defects within regular (periodic) nanostructures.

Interorganisational Integration: Healthcare Professionals’ Perspectives on Barriers and Facilitators within the Danish Healthcare System

PubMed Central

Godtfredsen, Nina Skavlan; Frølich, Anne

2016-01-01

Introduction: Despite many initiatives to improve coordination of patient pathways and intersectoral cooperation, Danish health care is still fragmented, lacking intra- and interorganisational integration. This study explores barriers to and facilitators of interorganisational integration as perceived by healthcare professionals caring for patients with chronic obstructive pulmonary disease within the Danish healthcare system. Methods: Seven focus groups were conducted in January through July 2014 with 21 informants from general practice, local healthcare centres and a pulmonary department at a university hospital in the Capital Region of Denmark. Results and discussion: Our results can be grouped into five influencing areas for interorganisational integration: communication/information transfer, committed leadership, patient engagement, the role and competencies of the general practitioner and organisational culture. Proposed solutions to barriers in each area hold the potential to improve care integration as experienced by individuals responsible for supporting and facilitating it. Barriers and facilitators to integrating care relate to clinical, professional, functional and normative integration. Especially, clinical, functional and normative integration seems fundamental to developing integrated care in practice from the perspective of healthcare professionals. PMID:27616948

Overview and introduction: The blood–brain barrier in health and disease

PubMed Central

Abbott, N. Joan; Friedman, Alon

2013-01-01

Summary This article introduces the special issue on “Blood–Brain Barrier and Epilepsy.” We review briefly current understanding of the structure and function of the blood–brain barrier (BBB), including its development and normal physiology, and ways in which it can be affected in pathology. The BBB formed by the endothelium of cerebral blood vessels is one of three main barrier sites protecting the central nervous system (CNS). The barrier is not a rigid structure, but a dynamic interface with a range of interrelated functions, resulting from extremely effective tight junctions, transendothelial transport systems, enzymes, and regulation of leukocyte permeation, which thereby generates the physical, transport, enzymatic, and immune regulatory functions of the BBB. The brain endothelial cells are important components of a “modular” structure, the neurovascular unit (NVU), with several associated cell types and extracellular matrix components. Modern methods have helped in identifying a range of proteins involved in barrier structure and function, and recent studies have revealed important stages, cell types, and signaling pathways important in BBB development. There is a growing list of CNS pathologies showing BBB dysfunction, with strong evidence that this can play a major role in certain disease etiologies. The articles that follow in this issue summarize in more detail reports and discussions of the recent international meeting on “BBB in Neurological Dysfunctions,” which took place recently at Ben-Gurion University of the Negev Desert Campus (Beer-Sheva, Israel), focusing on the link between experimental and clinical studies, and the ways in which these lead to improved drug treatments. PMID:23134489

Arctigenin from Fructus Arctii (Seed of Burdock) Reinforces Intestinal Barrier Function in Caco-2 Cell Monolayers

PubMed Central

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

The impact of aging on epithelial barriers.

PubMed

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.

Anti–IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus

PubMed Central

Zhang, Jiyong; Sadowska, Grazyna B.; Chen, Xiaodi; Park, Seon Yeong; Kim, Jeong-Eun; Bodge, Courtney A.; Cummings, Erin; Lim, Yow-Pin; Makeyev, Oleksandr; Besio, Walter G.; Gaitanis, John; Banks, William A.; Stonestreet, Barbara S.

2015-01-01

Impaired blood-brain barrier function represents an important component of hypoxic-ischemic brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-brain barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-brain barrier abnormalities have not been examined in the immature brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to brain ischemia. Anti–IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-brain barrier permeability was quantified using the blood-to-brain transfer constant in brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti–IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, brain parenchyma, and cerebrospinal fluid and decreases in brain IL-6 protein. Twenty-four hours after ischemia, anti–IL-6 mAb infusions attenuated ischemia-related increases in blood-brain barrier permeability and modulated tight junction and PLVAP protein expression in fetal brain. We conclude that inhibiting the effects of IL-6 protein with systemic infusions of neutralizing antibodies attenuates ischemia-related increases in blood-brain barrier permeability by inhibiting IL-6 and modulates tight junction proteins after ischemia.—Zhang, J., Sadowska, G. B., Chen, X., Park, S. Y., Kim, J.-E., Bodge, C. A., Cummings, E., Lim, Y.-P., Makeyev, O., Besio, W. G., Gaitanis, J., Banks, W. A., Stonestreet, B. S. Anti–IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus. PMID:25609424

Epidermal Permeability Barrier Recovery Is Delayed in Vitiligo-Involved Sites

PubMed Central

Liu, J.; Man, W.Y.; Lv, C.Z.; Song, S.P.; Shi, Y.J.; Elias, P.M.; Man, M.Q.

2010-01-01

Background/Objectives Prior studies have demonstrated that both the skin surface pH and epidermal permeability barrier function vary with skin pigmentation types. Although melanin deficiency is the main feature of vitiligo, alterations in cutaneous biophysical properties in vitiligo have not yet been well defined. In the present study, stratum corneum (SC) hydration, the skin surface pH and epidermal permeability barrier function in vitiligo were evaluated. Methods A total of 30 volunteers with vitiligo comprising 19 males and 11 females aged 13–51 years (mean age: 27.91 ± 2.06 years) were enrolled in this study. The skin surface pH, SC hydration, melanin/erythema index and transepidermal water loss (TEWL) were measured by respective probes connected to a Courage-Khazaka MPA5. SC integrity was determined by measuring the TEWL following each D-Squame application. The barrier recovery rate was assessed at 5 h following barrier disruption by repeated tape stripping. Results In addition to SC hydration, both melanin and erythema index were significantly lower in vitiligo lesions than in contralateral, nonlesional sites, while no difference in skin surface pH between vitiligo-involved and uninvolved areas was observed. In addition, neither the basal TEWL nor SC integrity in the involved areas differed significantly from that in the uninvolved areas. However, barrier recovery in vitiligo-involved sites was significantly delayed in comparison with uninvolved sites (40.83 ± 5.39% vs. 58.30 ± 4.71%; t = 2.441; p < 0.02). Conclusion Barrier recovery following tape stripping of the SC is delayed in vitiligo. Therefore, improvement in epidermal permeability barrier function may be an important unrecognized factor to be considered in treating patients with vitiligo. PMID:20185976

Trait Positive Affect Buffers the Effects of Acute Stress on Skin Barrier Recovery

PubMed Central

Robles, Theodore F.; Brooks, Kathryn P.; Pressman, Sarah D.

2010-01-01

Objective This study examines the role of self-reported trait positive affect (PA) on skin barrier recovery after skin disruption, and whether the role of trait PA in wound healing is consistent with the direct effects model or the stress-buffering model of PA and health. Design Sixty healthy participants (mean age 22.7 ± 3.9 years) completed a self-report measure of trait positive and negative affect, underwent a “tape-stripping” procedure that disrupts normal skin barrier function, and were randomly assigned to a Stress (Trier Social Stress Test) or No Stress (reading task) condition. Main Outcome Measures Skin barrier recovery was assessed by measuring transepidermal water loss up to 2 hr after skin disruption. Results Multilevel modeling indicated that greater trait PA was related to faster skin barrier recovery (p < .05). The effects of PA on skin barrier recovery were independent of levels of trait NA. Conclusion These findings suggest that trait PA may influence skin barrier recovery following a brief stressor. In addition, these results provide additional evidence that trait PA can positively impact objective health outcomes. PMID:19450044

A precise mass function in the excursion set approach

NASA Astrophysics Data System (ADS)

Del Popolo, Antonino

2017-04-01

In the present paper, using previous results from Del Popolo papers, we show how the mass function evolution can be obtained in the framework of a spherical collapse model, which has been modified to take account of dynamical friction, the cosmological constant, and angular momentum which proto-structures acquire through tidal interaction with neighbouring ones. We found an improved barrier which is in excellent agreement with simulations. The quoted barrier is used to calculated the mass function. In the case of the ΛCDM paradigm, our mass function is in good agreement (within some %) with the mass function of Klypin's Bolshoi simulation for the virial mass range 5 × 109 - 5 × 1014h-1M⊙, and 0 ≾ z ≿ 10. Similar agreement is obtained with Tinker's mass function, and Castorina's simulations.

Concerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors.

PubMed

Benedicto, Ignacio; Lehmann, Guillermo L; Ginsberg, Michael; Nolan, Daniel J; Bareja, Rohan; Elemento, Olivier; Salfati, Zelda; Alam, Nazia M; Prusky, Glen T; Llanos, Pierre; Rabbany, Sina Y; Maminishkis, Arvydas; Miller, Sheldon S; Rafii, Shahin; Rodriguez-Boulan, Enrique

2017-05-19

The outer blood-retina barrier is established through the coordinated terminal maturation of the retinal pigment epithelium (RPE), fenestrated choroid endothelial cells (ECs) and Bruch's membrane, a highly organized basement membrane that lies between both cell types. Here we study the contribution of choroid ECs to this process by comparing their gene expression profile before (P5) and after (P30) the critical postnatal period when mice acquire mature visual function. Transcriptome analyses show that expression of extracellular matrix-related genes changes dramatically over this period. Co-culture experiments support the existence of a novel regulatory pathway: ECs secrete factors that remodel RPE basement membrane, and integrin receptors sense these changes triggering Rho GTPase signals that modulate RPE tight junctions and enhance RPE barrier function. We anticipate our results will spawn a search for additional roles of choroid ECs in RPE physiology and disease.

Concerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors

PubMed Central

Benedicto, Ignacio; Lehmann, Guillermo L.; Ginsberg, Michael; Nolan, Daniel J.; Bareja, Rohan; Elemento, Olivier; Salfati, Zelda; Alam, Nazia M.; Prusky, Glen T.; Llanos, Pierre; Rabbany, Sina Y.; Maminishkis, Arvydas; Miller, Sheldon S.; Rafii, Shahin; Rodriguez-Boulan, Enrique

2017-01-01

The outer blood-retina barrier is established through the coordinated terminal maturation of the retinal pigment epithelium (RPE), fenestrated choroid endothelial cells (ECs) and Bruch's membrane, a highly organized basement membrane that lies between both cell types. Here we study the contribution of choroid ECs to this process by comparing their gene expression profile before (P5) and after (P30) the critical postnatal period when mice acquire mature visual function. Transcriptome analyses show that expression of extracellular matrix-related genes changes dramatically over this period. Co-culture experiments support the existence of a novel regulatory pathway: ECs secrete factors that remodel RPE basement membrane, and integrin receptors sense these changes triggering Rho GTPase signals that modulate RPE tight junctions and enhance RPE barrier function. We anticipate our results will spawn a search for additional roles of choroid ECs in RPE physiology and disease. PMID:28524846

Breakup and n -transfer effects on the fusion reactions Li,76+Sn,119120 around the Coulomb barrier

NASA Astrophysics Data System (ADS)

Fisichella, M.; Shotter, A. C.; Figuera, P.; Lubian, J.; Di Pietro, A.; Fernandez-Garcia, J. P.; Ferreira, J. L.; Lattuada, M.; Lotti, P.; Musumarra, A.; Pellegriti, M. G.; Ruiz, C.; Scuderi, V.; Strano, E.; Torresi, D.; Zadro, M.

2017-03-01

This paper presents values of complete fusion cross sections deduced from activation measurements for the reactions 6Li+120Sn and 7Li+119Sn , and for a projectile energy range from 17.5 to 28 MeV in the center-of-mass system. A new deconvolution analysis technique is used to link the basic activation data to the actual fusion excitation function. The complete fusion cross sections above the barrier are suppressed by about 70 % and 85 % with respect to the universal fusion function, used as a standard reference, in the 6Li and 7Li induced reactions, respectively. From a comparison of the excitation functions of the two systems at energies below the barrier, no significant differences can be observed, despite the two systems have different n -transfer Q values. This observation is supported by the results of coupled reaction channels (CRC) calculations.

Stratum corneum drying drives vertical compression and lipid organization and improves barrier function in vitro.

PubMed

Iwai, Ichiro; Kunizawa, Naomi; Yagi, Eiichiro; Hirao, Tetsuji; Hatta, Ichiro

2013-03-27

The stratum corneum dehydrates after exogenous hydration due to skincare or bathing. In this study, sheets of stratum corneum were isolated from reconstructed human epidermis and the barrier function and structure of these sheets were assessed during drying with the aim of improving our understanding of skincare. Water diffusion through the sheets of stratum corneum decreased with drying, accompanied by decreased thickness and increased visible light transmission through the sheets. Electron paramagnetic resonance revealed that the order parameter values of stratum corneum lipids increased with drying. X-ray diffraction analysis revealed increases in the diffraction intensity of lamellar structures, with an 11-12 nm periodicity and spacing of 0.42 nm for lattice structures with drying. These results suggest that the drying process improves the barrier function of the stratum corneum by organizing the intercellular lipids in a vertically compressed arrangement.

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.

Theoretical study on keto-enol tautomerisation of glutarimide for exploration of the isomerisation reaction pathway of glutamic acid in proteins using density functional theory

NASA Astrophysics Data System (ADS)

Fukuyoshi, Shuichi; Nakayoshi, Tomoki; Takahashi, Ohgi; Oda, Akifumi

2017-03-01

In order to elucidate the reason why glutamic acid residues have lesser racemisation reactivity than asparaginic acid, we investigated the racemisation energy barrier of piperidinedione, which is the presumed intermediate of the isomerisation reaction of L-Glu to D-Glu, by density functional theory calculations. In two-water-molecule-assisted racemisation, the activation barrier for keto-enol isomerisation was 28.1 kcal/mol. The result showed that the activation barrier for the racemisation of glutamic acid residues was not different from that for the racemisation of aspartic acid residues. Thus, glutamic acid residues can possibly cause the racemisation reaction if the cyclic intermediate stably exists.

The pH of the main Brazilian commercial moisturizers and liquid soaps: considerations on the repair of the skin barrier*

PubMed Central

Gonçalves, Giovana M; Brianezi, Gabrielli; Miot, Hélio Amante

2017-01-01

The pH of the skin is slightly acidic (4.6 to 5.8) which is important for appropriate antibacterial, antifungal, constitution of barrier function, as well as structuring and maturation of the stratum corneum. This study aimed to evaluate the pH of the main commercial moisturizers and liquid soaps in Brazil. Thus, pH of the products was quantified by pH meter in three measurements. A total of 38 moisturizers and six commercial liquid soaps were evaluated. Mean pH of 63% and 50% of the moisturizing and liquid soaps presented results above 5.5, disfavoring repair, function, and synthesis of dermal barrier. PMID:29166523

Could tight junctions regulate the barrier function of the aged skin?

PubMed

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.

Antibacterial [2-(Methacryloyloxy) ethyl] Trimethylammonium Chloride Functionalized Reduced Graphene Oxide/Poly(ethylene-co-vinyl alcohol) Multilayer Barrier Film for Food Packaging.

PubMed

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.

Pericyte-derived sphingosine 1-phosphate induces the expression of adhesion proteins and modulates the retinal endothelial cell barrier.

PubMed

McGuire, Paul G; Rangasamy, Sampathkumar; Maestas, Joann; Das, Arup

2011-12-01

The mechanisms that regulate the physical interaction of pericytes and endothelial cells and the effects of these interactions on interendothelial cell junctions are not well understood. We determined the extent to which vascular pericytes could regulate pericyte-endothelial adhesion and the consequences that this disruption might have on the function of the endothelial barrier. Human retinal microvascular endothelial cells were cocultured with pericytes, and the effect on the monolayer resistance of endothelial cells and expression of the cell junction molecules N-cadherin and VE-cadherin were measured. The molecules responsible for the effect of pericytes or pericyte-conditioned media on the endothelial resistance and cell junction molecules were further analyzed. Our results indicate that pericytes increase the barrier properties of endothelial cell monolayers. This barrier function is maintained through the secretion of pericyte-derived sphingosine 1-phosphate. Sphingosine 1-phosphate aids in maintenance of microvascular stability by upregulating the expression of N-cadherin and VE-cadherin, and downregulating the expression of angiopoietin 2. Under normal circumstances, the retinal vascular pericytes maintain pericyte-endothelial contacts and vascular barrier function through the secretion of sphingosine 1-phosphate. Alteration of pericyte-derived sphingosine 1-phosphate production may be an important mechanism in the development of diseases characterized by vascular dysfunction and increased permeability.

Chronic social stress in pigs impairs intestinal barrier and nutrient transporter function, and alters neuro-immune mediator and receptor expression

PubMed Central

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

The modulation of Schottky barriers of metal-MoS2 contacts via BN-MoS2 heterostructures.

PubMed

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.

Diabetic and sympathetic influences on the water permeability barrier function of human skin as measured using transepidermal water loss: A case-control study.

PubMed

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.

Reduction of diffusion barriers in isolated rat islets improves survival, but not insulin secretion or transplantation outcome

PubMed Central

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

Role of Vascular and Lymphatic Endothelial Cells in Hantavirus Pulmonary Syndrome Suggests Targeted Therapeutic Approaches

PubMed Central

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

Regulation of endothelial barrier function by p120-catenin∙VE-cadherin interaction

PubMed Central

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

Tight junctions and human diseases.

PubMed

Sawada, Norimasa; Murata, Masaki; Kikuchi, Keisuke; Osanai, Makoto; Tobioka, Hirotoshi; Kojima, Takashi; Chiba, Hideki

2003-09-01

Tight junctions are intercellular junctions adjacent to the apical end of the lateral membrane surface. They have two functions, the barrier (or gate) function and the fence function. The barrier function of tight junctions regulates the passage of ions, water, and various macromolecules, even of cancer cells, through paracellular spaces. The barrier function is thus relevant to edema, jaundice, diarrhea, and blood-borne metastasis. On the other hand, the fence function maintains cell polarity. In other words, tight junctions work as a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membrane. This function is deeply involved in cancer cell biology, in terms of loss of cell polarity. Of the proteins comprising tight junctions, integral membrane proteins occludin, claudins, and JAMs have been recently discovered. Of these molecules, claudins are exclusively responsible for the formation of tight-junction strands and are connected with the actin cytoskeleton mediated by ZO-1. Thus, both functions of tight junctions are dependent on the integrity of the actin cytoskeleton as well as ATP. Mutations in the claudin14 and the claudin16 genes result in hereditary deafness and hereditary hypomagnesemia, respectively. Some pathogenic bacteria and viruses target and affect the tight-junction function, leading to diseases. In this review, the relationship between tight junctions and human diseases is summarized.

Loss of tight junction barrier function and its role in cancer metastasis.

PubMed

Martin, Tracey A; Jiang, Wen G

2009-04-01

As the most apical structure between epithelial and endothelial cells, tight junctions (TJ) are well known as functioning as a control for the paracellular diffusion of ions and certain molecules. It has however, become increasingly apparent that the TJ has a vital role in maintaining cell to cell integrity and that the loss of cohesion of the structure can lead to invasion and thus metastasis of cancer cells. This article will present data showing how modulation of expression of TJ molecules results in key changes in TJ barrier function leading to the successful metastasis of a number of different cancer types.

Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine.

PubMed

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.

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.

Corneal epithelial barrier function after oxybuprocaine provocation in diabetics.

PubMed

Stolwijk, T R; van Best, J A; Boor, J P; Lemkes, H H; Oosterhuis, J A

1990-03-01

Corneal epithelial permeability for fluorescein was determined after provocation by a local anesthetic in 18 non-insulin-dependent diabetes mellitus (NIDDM) patients, 23 insulin-dependent diabetes mellitus (IDDM) patients, and 22 healthy controls to evaluate the corneal epithelial barrier function in diabetes. All volunteers had Oxybuprocaine instilled into one eye and saline into the other eye. The epithelial permeability values were determined by fluorophotometry, and the ratio between both eyes was calculated for each individual. The mean permeability values of the saline-instilled eyes in the diabetic patients did not differ significantly from those in the healthy controls (P greater than 0.2). The individual ratios between Oxybuprocaine- and saline-instilled eyes in the NIDDM and IDDM patients differed significantly from those in the healthy controls (mean ratios: 2.6, 1.9, and 1.0, respectively; P less than 0.002). The permeability ratios and the percentage glycosylated hemoglobin (HbAlc) were linearly correlated in the NIDDM patients but not in the IDDM patients (r = 0.73, P less than 0.001, and r = 0.09, P greater than 0.68, respectively). The results showed that the corneal epithelial barrier function in the diabetic patients was not impaired compared with that in the healthy controls. After provocation by a local anesthetic, the barrier function was impaired in the diabetic patients only.

Schottky barrier amorphous silicon solar cell with thin doped region adjacent metal Schottky barrier

DOEpatents

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.

Flexible barrier film, method of forming same, and organic electronic device including same

DOEpatents

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.

Comparison of skin barrier function and sensory nerve electric current perception threshold between IgE-high extrinsic and IgE-normal intrinsic types of atopic dermatitis.

PubMed

Mori, T; Ishida, K; Mukumoto, S; Yamada, Y; Imokawa, G; Kabashima, K; Kobayashi, M; Bito, T; Nakamura, M; Ogasawara, K; Tokura, Y

2010-01-01

Background Two types of atopic dermatitis (AD) have been proposed, with different pathophysiological mechanisms underlying this seemingly heterogeneous disorder. The extrinsic type shows high IgE levels presumably as a consequence of skin barrier damage and feasible allergen permeation, whereas the intrinsic type exhibits normal IgE levels and is not mediated by allergen-specific IgE. Objectives To investigate the relationship between pruritus perception threshold and skin barrier function of patients with AD in a comparison between the extrinsic and intrinsic types. Methods Enrolled in this study were 32 patients with extrinsic AD, 17 with intrinsic AD and 24 healthy individuals. The barrier function of the stratum corneum was assessed by skin surface hydration and transepidermal water loss (TEWL), and pruritus perception was evaluated by the electric current perception threshold (CPT) of sensory nerves upon neuroselective transcutaneous electric stimulation. Results Skin surface hydration was significantly lower and TEWL was significantly higher in extrinsic AD than intrinsic AD or normal controls. Although there was no statistically significant difference in CPT among extrinsic AD, intrinsic AD and normal controls, CPT was significantly correlated with skin surface hydration and inversely with TEWL in intrinsic AD and normal controls, but not extrinsic AD. Finally, CPT was correlated with the visual analogue scale of itch in the nonlesional skin of patients with extrinsic but not intrinsic AD. Conclusions Patients with extrinsic AD have an impaired barrier, which increases the pre-existing pruritus but rather decreases sensitivity to external stimuli. In contrast, patients with intrinsic AD retain a normal barrier function and sensory reactivity to external pruritic stimuli.

Effects of Lactobacillus johnsonii and Lactobacillus reuteri on gut barrier function and heat shock proteins in intestinal porcine epithelial cells

PubMed Central

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

War experiences, general functioning and barriers to care among former child soldiers in Northern Uganda: the WAYS study.

PubMed

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.

Insulation Resistance Degradation in Ni-BaTiO3 Multilayer Ceramic Capacitors

NASA Technical Reports Server (NTRS)

Liu, Donhang (David)

2015-01-01

Insulation resistance (IR) degradation in Ni-BaTiO3 multilayer ceramic capacitors has been characterized by the measurement of both time to failure and direct-current (DC) leakage current as a function of stress time under highly accelerated life test conditions. The measured leakage current-time dependence data fit well to an exponential form, and a characteristic growth time ?SD can be determined. A greater value of tau(sub SD) represents a slower IR degradation process. Oxygen vacancy migration and localization at the grain boundary region results in the reduction of the Schottky barrier height and has been found to be the main reason for IR degradation in Ni-BaTiO3 capacitors. The reduction of barrier height as a function of time follows an exponential relation of phi (??)=phi (0)e(exp -2?t), where the degradation rate constant ??=??o??(????/????) is inversely proportional to the mean time to failure (MTTF) and can be determined using an Arrhenius plot. For oxygen vacancy electromigration, a lower barrier height phi(0) will favor a slow IR degradation process, but a lower phi(0) will also promote electronic carrier conduction across the barrier and decrease the insulation resistance. As a result, a moderate barrier height phi(0) (and therefore a moderate IR value) with a longer MTTF (smaller degradation rate constant ??) will result in a minimized IR degradation process and the most improved reliability in Ni-BaTiO3 multilayer ceramic capacitors.

Insulation Resistance Degradation in Ni-BaTiO3 Multilayer Ceramic Capacitors

NASA Technical Reports Server (NTRS)

Liu, Donhang David

2015-01-01

Insulation resistance (IR) degradation in NiBaTiO3 multilayer ceramic capacitors has been characterized by the measurement of both time to failure (TTF) and direct current leakage current as a function of stress time under highly accelerated life test conditions. The measured leakage current time dependence data fit well to an exponential form, and a characteristic growth time tau (sub SD) can be determined. A greater value of tau (sub SD) represents a slower IR degradation process. Oxygen vacancy migration and localization at the grain boundary region results in the reduction of the Schottky barrier height and has been found to be the main reason for IR degradation in NiBaTiO3 capacitors. The reduction of barrier height as a function oftime follows an exponential relation of phi (t ) = phi (0) e (exp -2Kt), where 13 the degradation rate constant K Koe (Ek/kT) is inversely proportional to the mean TTF (MTTF) and can be determined using an Arrhenius plot. For oxygen vacancy electromigration, a lower barrier height phi (0) will favor a slow IR degradation process, but a lower phi (0) will also promote electronic carrier conduction across the barrier and decrease the IR. As a result, a moderate barrier height phi (0) (and therefore a moderate IR value) with a longer MTTF (smaller degradation rate constant K) will result in a minimized IR degradation process and the most improved reliability in NiBaTiO3 multilayer ceramic capacitors.

Improvement of hydration and epidermal barrier function in human skin by a novel compound isosorbide dicaprylate.

PubMed

Chaudhuri, R K; Bojanowski, K

2017-10-01

The study involved the synthesis of a novel derivative of caprylic acid - isosorbide dicaprylate (IDC) - and the evaluation of its potential in improving water homoeostasis and epidermal barrier function in human skin. The effect of IDC on gene expression was assayed in skin organotypic cultures by DNA microarrays. The results were then confirmed for a few key genes by quantitative PCR, immuno- and cytochemistry. Final validation of skin hydration properties was obtained by four separate clinical studies. Level of hydration was measured by corneometer either by using 2% IDC lotion alone vs placebo or in combination with 2% glycerol lotion vs 2% glycerol only. A direct comparison in skin hydration between 2% IDC and 2% glycerol lotions was also carried out. The epidermal barrier function improvement was assessed by determining changes in transepidermal water loss (TEWL) on the arms before and after treatment with 2% IDC lotion versus placebo. IDC was found to upregulate the expression of AQP3, CD44 and proteins involved in keratinocyte differentiation as well as the formation and function of stratum corneum. A direct comparison between 2% IDC versus 2% glycerol lotions revealed a three-fold advantage of IDC in providing skin hydration. Severely dry skin treated with 2% IDC in combination with 2% glycerol showed 133% improvement, whereas 35% improvement was observed with moderately dry human skin. Topical isosorbide dicaprylate favourably modulates genes involved in the maintenance of skin structure and function, resulting in superior clinical outcomes. By improving skin hydration and epidermal permeability barrier, it offers therapeutic applications in skin ageing. © 2017 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Abnormal Barrier Function in Gastrointestinal Disorders.

PubMed

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.

Electrical properties and interface state energy distributions of Cr/n-Si Schottky barrier diode

NASA Astrophysics Data System (ADS)

Karataş, Şükrü; Yildirim, Nezir; Türüt, Abdülmecit

2013-12-01

In this study, the electrical characteristics of the Cr/n-type Si (MS) Schottky barrier diode have been investigated by the current-voltage (I-V) and capacitance-voltage (C-V) measurements at 300 K temperature. Using the thermionic emission theory, the values of ideality factor and the barrier height have been obtained to be 1.22, 0.71 and 1.01, 0.83 eV, from the results of the I-V and C-V measurements, respectively. The barrier height (Φb) and the series resistance (RS) obtained from Norde’s function have been compared with those obtained from Cheung functions, and a good agreement between the results of both methods was seen. The interface state density (NSS) calculated without the RS is obtained to be increasing exponentially with bias from 2.40 × 1012 cm-2 eV-1 in (EC-0.623) eV to 1.94 × 1014 cm-2 eV-1 in (EC-0.495) eV, also, the NSS obtained taking into account the RS has increased exponentially with bias from 2.07 × 1012 cm-2 eV-1 to 1.47 × 1014 cm-2 eV-1 in the same interval.

[Advance in studies on food allergy mechanism based on gut barrier].

PubMed

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.

Intraperitoneal adhesions--an ongoing challenge between biomedical engineering and the life sciences.

PubMed

Brochhausen, Christoph; Schmitt, Volker H; Rajab, Taufiek K; Planck, Constanze N E; Krämer, Bernhard; Wallwiener, Markus; Hierlemann, Helmut; Kirkpatrick, C James

2011-07-01

Peritoneal adhesions remain a relevant clinical problem despite the currently available prophylactic barrier materials. So far, the physical separation of traumatized serosa areas using barriers represents the most important clinical strategy for adhesion prevention. However, the optimal material has not yet been found. Further optimization or pharmacological functionalization of these barriers could give an innovative input for peritoneal adhesion prevention. Therefore, a more complete understanding of pathogenesis is required. On the basis of the pathophysiology of adhesion formation the main barriers currently in clinical practice as well as new innovations are discussed in the present review. Physiologically, mesothelial cells play a decisive role in providing a frictionless gliding surface on the serosa. Adhesion formation results from a cascade of events and is regulated by a variety of cellular and humoral factors. The main clinically applied strategy for adhesion prevention is based on the use of liquid or solid adhesion barriers to separate physically any denuded tissue. Both animal and human trials have not yet been able to identify the optimal barrier to prevent adhesion formation in a sustainable way. Therefore, further developments are required for effective prevention of postoperative adhesion formation. To reach this goal the combination of structural modification and pharmacological functionalization of barrier materials should be addressed. Achieving this aim requires the interaction between basic research, materials science and clinical expertise. Copyright © 2011 Wiley Periodicals, Inc.

An oncological view on the blood-testis barrier.

PubMed

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.

FABP4 induces asthmatic airway epithelial barrier dysfunction via ROS-activated FoxM1.

PubMed

Wu, Gaohui; Yang, Liteng; Xu, Yi; Jiang, Xiaohong; Jiang, Xiaomin; Huang, Lisha; Mao, Ling; Cai, Shaoxi

2018-01-01

Functional abnormal airway epithelial cells, along with activated inflammatory cells, resulting in chronic airway inflammation, are considered as the characteristic of asthma. Fatty Acid Binding Protein 4 (FABP4) takes part in glucose and lipid homeostasis, and also have an important role in allergic airway inflammation. However, whether FABP4 influence barrier function of airway epithelial cells is unknown. In vivo, a HDM-induced murine model of asthma was obtained to assessed airway inflammation and protein expression of E-cadherin and Forkhead Box M1 (FoxM1). In vitro, 16-HBE was cultured and was treated with hrFABP4, siFABP4, FABPF4 inhibitor BMS, or FoxM1 inhibitor RCM-1. IL-4, IL-5, and IL-13 level was determined by ELISA. Transepithelial electrical resistance (TER), paracellular permeability and E-cadherin-special immunofluorescence were measured to value airway epithelial barrier function. Intracellular ROS production was determined by DCF-DA fluorescence. FABP4 inhibitor BMS alleviate airway inflammation and destruction of E-cad in allergic mouse. Treatment with HDM or hrFABP4 aggravated inflammatory response, damaged airway epithelial barrier, which could be inhibited by siFABP4 and BMS. Treatment with HDM or hrFABP4 also enhanced levels of FoxM1, and Inhibited FoxM1 suppressed HDM- and hrFABP4-induced inflammation and airway epithelial barrier dysfunction. In addition, H 2 O 2 promoted FoxM1 expression, HDM and hrFABP4 induced-FoxM1 could be inhibited by NAC, leading to decreased inflammation and improved airway epithelial barrier. Upregulated ROS induced by FABP4 was of significance in activating FoxM1 leading to airway inflammation and epithelial barrier dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

Aging barriers influencing mobile health usability for older adults: A literature based framework (MOLD-US).

PubMed

Wildenbos, G A; Peute, Linda; Jaspers, Monique

2018-06-01

With the growing population of older adults as a potential user group of mHealth, the need increases for mHealth interventions to address specific aging characteristics of older adults. The existence of aging barriers to computer use is widely acknowledged. Yet, usability studies show that mHealth still fails to be appropriately designed for older adults and their expectations. To enhance designs of mHealth aimed at older adult populations, it is essential to gain insight into aging barriers that impact the usability of mHealth as experienced by these adults. This study aims to synthesize literature on aging barriers to digital (health) computer use, and explain, map and visualize these barriers in relation to the usability of mHealth by means of a framework. We performed a scoping review to synthesize and summarize reported physical and functional age barriers in relation to digital (mobile) health applications use. Aging barriers reported in the literature were mapped onto usability aspects categorized by Nielsen to explain their influence on user experience of mHealth. A framework (MOLD-US) was developed summarizing the evidence on the influence of aging barriers on mHealth use experienced by older adults. Four key categories of aging barriers influencing usability of mHealth were identified: cognition, motivation, physical ability and perception. Effective and satisfactory use of mHealth by older adults is complicated by cognition and motivation barriers. Physical ability and perceptual barriers further increase the risk of user errors and fail to notice important interaction tasks. Complexities of medical conditions, such as diminished eye sight related to diabetes or deteriorated motor skills as a result of rheumatism, can cause errors in user interaction. This research provides a novel framework for the exploration of aging barriers and their causes influencing mHealth usability in older adults. This framework allows for further systematic empirical testing and analysis of mHealth usability issues, as it enables results to be classified and interpreted based on impediments intrinsic to usability issues experienced by older adults. Importantly, the paper identifies a key need for future research on motivational barriers impeding mhealth use of older adults. More insights are needed in particular to disaggregating normal age related functional changes from specific medical conditions that influence experienced usefulness of mHealth by these adults. Copyright © 2018 Elsevier B.V. All rights reserved.

Starting a new conversation: Engaging Veterans with spinal cord injury in discussions of what function means to them, the barriers/facilitators they encounter, and the adaptations they use to optimize function.

PubMed

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.

The effects of polar excipients transcutol and dexpanthenol on molecular mobility, permeability, and electrical impedance of the skin barrier.

PubMed

Björklund, Sebastian; Pham, Quoc Dat; Jensen, Louise Bastholm; Knudsen, Nina Østergaard; Nielsen, Lars Dencker; Ekelund, Katarina; Ruzgas, Tautgirdas; Engblom, Johan; Sparr, Emma

2016-10-01

In the development of transdermal and topical products it is important to understand how formulation ingredients interact with the molecular components of the upper layer of the skin, the stratum corneum (SC), and thereby influence its macroscopic barrier properties. The aim here was to investigate the effect of two commonly used excipients, transcutol and dexpanthenol, on the molecular as well as the macroscopic properties of the skin membrane. Polarization transfer solid-state NMR methods were combined with steady-state flux and impedance spectroscopy measurements to investigate how these common excipients influence the molecular components of SC and its barrier function at strictly controlled hydration conditions in vitro with excised porcine skin. The NMR results provide completely new molecular insight into how transcutol and dexpanthenol affect specific molecular segments of both SC lipids and proteins. The presence of transcutol or dexpanthenol in the formulation at fixed water activity results in increased effective skin permeability of the model drug metronidazole. Finally, impedance spectroscopy data show clear changes of the effective skin capacitance after treatment with transcutol or dexpanthenol. Based on the complementary data, we are able to draw direct links between effects on the molecular properties and on the macroscopic barrier function of the skin barrier under treatment with formulations containing transcutol or dexpanthenol. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of sputtered lanthanum hexaboride film thickness on field emission from metallic knife edge cathodes

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.

Arsenic Compromises Conducting Airway Epithelial Barrier Properties in Primary Mouse and Immortalized Human Cell Cultures

PubMed Central

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

Butyrate protects against disruption of the blood-milk barrier and moderates inflammatory responses in a model of mastitis induced by lipopolysaccharide.

PubMed

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.

An alkaline phosphatase transport mechanism in the pathogenesis of Alzheimer's disease and neurodegeneration.

PubMed

Pike, Adrianne F; Kramer, Nynke I; Blaauboer, Bas J; Seinen, Willem; Brands, Ruud

2015-01-25

Systemic inflammation is associated with loss of blood-brain barrier integrity and neuroinflammation that lead to the exacerbation of neurodegenerative diseases. It is also associated specifically with the characteristic amyloid-β and tau pathologies of Alzheimer's disease. We have previously proposed an immunosurveillance mechanism for epithelial barriers involving negative feedback-regulated alkaline phosphatase transcytosis as an acute phase anti-inflammatory response that hangs in the balance between the resolution and the progression of inflammation. We now extend this model to endothelial barriers, particularly the blood-brain barrier, and present a literature-supported mechanistic explanation for Alzheimer's disease pathology with this system at its foundation. In this mechanism, a switch in the role of alkaline phosphatase from its baseline duties to a stopgap anti-inflammatory function results in the loss of alkaline phosphatase from cell membranes into circulation, thereby decreasing blood-brain barrier integrity and functionality. This occurs with impairment of both amyloid-β efflux and tau dephosphorylating activity in the brain as alkaline phosphatase is replenished at the barrier by receptor-mediated transport. We suggest systemic alkaline phosphatase administration as a potential therapy for the resolution of inflammation and the prevention of Alzheimer's disease pathology as well as that of other inflammation-related neurodegenerative diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Mechanisms of pertussis toxin-induced barrier dysfunction in bovine pulmonary artery endothelial cell monolayers.

PubMed

Patterson, C E; Stasek, J E; Schaphorst, K L; Davis, H W; Garcia, J G

1995-06-01

We have previously characterized several G proteins in endothelial cells (EC) as substrates for the ADP-ribosyltransferase activity of both pertussis (PT) and cholera toxin and described the modulation of key EC physiological responses, including gap formation and barrier function, by these toxins. In this study, we investigated the mechanisms involved in PT-mediated regulation of bovine pulmonary artery endothelial cells barrier function. PT caused a dose-dependent increase in albumin transfer, dependent upon action of the holotoxin, since neither the heat-inactivated PT, the isolated oligomer, nor the protomer induced EC permeability. PT-induced gap formation and barrier dysfunction were additive to either thrombin- or thrombin receptor-activating peptide-induced permeability, suggesting that thrombin and PT utilize distinct mechanisms. PT did not result in Ca2+ mobilization or alter either basal or thrombin-induced myosin light chain phosphorylation. However, PT stimulated protein kinase C (PKC) activation, and both PKC downregulation and PKC inhibition attenuated PT-induced permeability, indicating that PKC activity is involved in PT-induced barrier dysfunction. Like thrombin-induced permeability, the PT effect was blocked by prior increases in adenosine 3',5'-cyclic monophosphate. Thus PT-catalyzed ADP-ribosylation of a G protein (possibly other than Gi) may regulate cytoskeletal protein interactions, leading to EC barrier dysfunction.

Modelling the endothelial blood-CNS barriers: a method for the production of robust in vitro models of the rat blood-brain barrier and blood-spinal cord barrier

PubMed Central

2013-01-01

Background Modelling the blood-CNS barriers of the brain and spinal cord in vitro continues to provide a considerable challenge for research studying the passage of large and small molecules in and out of the central nervous system, both within the context of basic biology and for pharmaceutical drug discovery. Although there has been considerable success over the previous two decades in establishing useful in vitro primary endothelial cell cultures from the blood-CNS barriers, no model fully mimics the high electrical resistance, low paracellular permeability and selective influx/efflux characteristics of the in vivo situation. Furthermore, such primary-derived cultures are typically labour-intensive and generate low yields of cells, limiting scope for experimental work. We thus aimed to establish protocols for the high yield isolation and culture of endothelial cells from both rat brain and spinal cord. Our aim was to optimise in vitro conditions for inducing phenotypic characteristics in these cells that were reminiscent of the in vivo situation, such that they developed into tight endothelial barriers suitable for performing investigative biology and permeability studies. Methods Brain and spinal cord tissue was taken from the same rats and used to specifically isolate endothelial cells to reconstitute as in vitro blood-CNS barrier models. Isolated endothelial cells were cultured to expand the cellular yield and then passaged onto cell culture inserts for further investigation. Cell culture conditions were optimised using commercially available reagents and the resulting barrier-forming endothelial monolayers were characterised by functional permeability experiments and in vitro phenotyping by immunocytochemistry and western blotting. Results Using a combination of modified handling techniques and cell culture conditions, we have established and optimised a protocol for the in vitro culture of brain and, for the first time in rat, spinal cord endothelial cells. High yields of both CNS endothelial cell types can be obtained, and these can be passaged onto large numbers of cell culture inserts for in vitro permeability studies. The passaged brain and spinal cord endothelial cells are pure and express endothelial markers, tight junction proteins and intracellular transport machinery. Further, both models exhibit tight, functional barrier characteristics that are discriminating against large and small molecules in permeability assays and show functional expression of the pharmaceutically important P-gp efflux transporter. Conclusions Our techniques allow the provision of high yields of robust sister cultures of endothelial cells that accurately model the blood-CNS barriers in vitro. These models are ideally suited for use in studying the biology of the blood-brain barrier and blood-spinal cord barrier in vitro and for pre-clinical drug discovery. PMID:23773766

FISH OIL IMPROVES MOTOR FUNCTION, LIMITS BLOOD-BRAIN BARRIER DISRUPTION, AND REDUCES MMP9 GENE EXPRESSION IN A RAT MODEL OF JUVENILE TRAUMATIC BRAIN INJURY

PubMed Central

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

Fish oil improves motor function, limits blood-brain barrier disruption, and reduces Mmp9 gene expression in a rat model of juvenile traumatic brain injury.

PubMed

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.

Permeability of ergot alkaloids across the blood-brain barrier in vitro and influence on the barrier integrity

PubMed Central

Mulac, Dennis; Hüwel, Sabine; Galla, Hans-Joachim; Humpf, Hans-Ulrich

2012-01-01

Scope Ergot alkaloids are secondary metabolites of Claviceps spp. and they have been in the focus of research for many years. Experiments focusing on ergotamine as a former migraine drug referring to the ability to reach the brain revealed controversial results. The question to which extent ergot alkaloids are able to cross the blood-brain barrier is still not answered. Methods and results In order to answer this question we have studied the ability of ergot alkaloids to penetrate the blood-brain barrier in a well established in vitro model system using primary porcine brain endothelial cells. It could clearly be demonstrated that ergot alkaloids are able to cross the blood-brain barrier in high quantities in only a few hours. We could further identify an active transport for ergometrine as a substrate for the BCRP/ABCG2 transporter. Investigations concerning barrier integrity properties have identified ergocristinine as a potent substance to accumulate in these cells ultimately leading to a weakened barrier function. Conclusion For the first time we could show that the so far as biologically inactive described 8-(S) isomers of ergot alkaloids seem to have an influence on barrier integrity underlining the necessity for a risk assessment of ergot alkaloids in food and feed. PMID:22147614

Free energy profiles for two ubiquitous damaging agents: methylation and hydroxylation of guanine in B-DNA.

PubMed

Grüber, R; Aranda, J; Bellili, A; Tuñón, I; Dumont, E

2017-06-07

DNA methylation and hydroxylation are two ubiquitous reactions in DNA damage induction, yet insights are scarce concerning the free energy of activation within B-DNA. We resort to multiscale simulations to investigate the attack of a hydroxyl radical and of the primary diazonium onto a guanine embedded in a solvated dodecamer. Reaction free energy profiles characterize two strongly exergonic processes, yet allow unprecedented quantification of the barrier towards this damage reaction, not higher than 6 kcal mol -1 and sometimes inexistent, and of the exergonicities. In the case of the [G(C8)-OH]˙ intermediate, we challenge the functional dependence of such simulations: recently-proposed functionals, such as M06-2X and LC-BLYP, agree on a ∼4 kcal mol -1 barrier, whereas the hybrid GGA B3LYP functional predicts a barrier-less pathway. In the long term, multiscale approaches can help build up a unified panorama of DNA lesion induction. These results stress the importance of DFT/MM-MD simulations involving new functionals towards the sound modelling of biomolecule damage even in the ground state.

Non-Saccharomyces yeasts protect against epithelial cell barrier disruption induced by Salmonella enterica subsp. enterica serovar Typhimurium.

PubMed

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.

Barriers to activity and participation for stroke survivors in rural China.

PubMed

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.

A public health perspective to environmental barriers and accessibility problems for senior citizens living in ordinary housing.

PubMed

Granbom, Marianne; Iwarsson, Susanne; Kylberg, Marianne; Pettersson, Cecilia; Slaug, Björn

2016-08-11

Housing environments that hinder performance of daily activities and impede participation in social life have negative health consequences particularly for the older segment of the population. From a public health perspective accessible housing that supports active and healthy ageing is therefore crucial. The objective of the present study was to make an inventory of environmental barriers and investigate accessibility problems in the ordinary housing stock in Sweden as related to the functional capacity of senior citizens. Particular attention was paid to differences between housing types and building periods and to identify environmental barriers generating the most accessibility problems for sub-groups of senior citizens. Data on environmental barriers in dwellings from three databases on housing and health in old age was analysed (N = 1021). Four functional profiles representing large groups of senior citizens were used in analyses of the magnitude and severity of potential accessibility problems. Differences in terms of type of housing and building period were examined. High proportions of one-family houses as well as multi-dwellings had substantial numbers of environmental barriers, with significantly lower numbers in later building periods. Accessibility problems occurred already for senior citizens with few functional limitations, but more profound for those dependent on mobility devices. The most problematic housing sections were entrances in one-family houses and kitchens of multi-dwellings. Despite a high housing standard in the Swedish ordinary housing stock the results show substantial accessibility problems for senior citizens with functional limitations. To make housing accessible large-scale and systematic efforts are required.

Sun-Induced Changes in Stratum Corneum Function Are Gender and Dose Dependent in a Chinese Population

PubMed Central

Liu, Z.; Fluhr, J.W.; Song, S.P.; Sun, Z.; Wang, H.; Shi, Y.J.; Elias, P.M.; Man, M.-Q.

2010-01-01

Previous studies have demonstrated that UVB radiation changes the epidermal permeability barrier and stratum corneum (SC) hydration. It is well known that sun exposure causes erythema, sunburn and melanoma. However, whether daily sun exposure alters SC integrity and epidermal permeability barrier function is largely unknown, especially in Chinese subjects. In the present study, we assess the SC integrity, SC hydration and epidermal permeability barrier function following various doses of sun exposure. A total of 258 subjects (124 males and 134 females) aged 18–50 years were enrolled. A multifunctional skin physiology monitor (Courage & Khazaka MPA5) was used to measure SC hydration and transepidermal water loss (TEWL) on the forearms. In males, basal TEWL was higher with higher doses of sun exposure than with lower doses and control, whereas in females, basal TEWL was higher with lower doses of sun exposure than with higher doses and control. In the group with higher doses of sun exposure, TEWL in females was significantly lower than that in males. The barrier recovery was faster in females than in males in both control and lower-dose groups. In both males and females, barrier recovery was delayed with higher doses of sun exposure. In males, sun exposure did not alter SC hydration, while in females SC hydration was lower with lower doses of sun exposure as compared with control and higher doses of sun exposure. These results demonstrated that sun-induced changes in SC function and SC hydration vary with gender and the extent of sun exposure. PMID:20571289

DFT Virtual Screening Identifies Rhodium–Amidinate Complexes As Potential Homogeneous Catalysts for Methane-to-Methanol Oxidation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Ross; Nielsen, Robert J.; Goddard, William A.

2014-11-11

In the search for new organometallic catalysts for low-temperature selective conversion of CH4 to CH3OH, we apply quantum mechanical virtual screening to select the optimum combination of ligand and solvent on rhodium to achieve low barriers for CH4 activation and functionalization to recommend for experimental validation. Here, we considered Rh because its lower electronegativity compared with Pt and Pd may allow it to avoid poisoning by coordinating media. We report quantum mechanical predictions (including implicit and explicit solvation) of the mechanisms for RhIII(NN) and RhIII(NNF) complexes [where (NN) = bis(N-phenyl)benzylamidinate and (NNF) = bis(N-pentafluorophenyl)pentafluorobenzylamidinate] to catalytically activate and functionalize methanemore » using trifluoroacetic acid (TFAH) or water as a solvent. In particular, we designed the (NNF) ligand as a more electrophilic analogue to the (NN) ligand, and our results predict the lowest transition state barrier (ΔG‡ = 27.6 kcal/mol) for methane activation in TFAH from a pool of four different classes of ligands. To close the catalytic cycle, the functionalization of methylrhodium intermediates was also investigated, involving carbon–oxygen bond formation via SN2 attack by solvent, or SR2 attack by a vanadium oxo. Activation barriers for the functionalization of methylrhodium intermediates via nucleophilic attack are lower when the solvent is water, but CH4 activation barriers are higher. In addition, we have found a correlation between CH4 activation barriers and rhodium–methyl bond energies that allow us to predict the activation transition state energies for future ligands, as well.« less

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.

Edaravone Protects against Methylglyoxal-Induced Barrier Damage in Human Brain Endothelial Cells

PubMed Central

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

Fabrication and characterization of tunnel barriers in a multi-walled carbon nanotube formed by argon atom beam irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomizawa, H.; Department of Applied Physics, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585; Yamaguchi, T., E-mail: tyamag@riken.jp

We have evaluated tunnel barriers formed in multi-walled carbon nanotubes (MWNTs) by an Ar atom beam irradiation method and applied the technique to fabricate coupled double quantum dots. The two-terminal resistance of the individual MWNTs was increased owing to local damage caused by the Ar beam irradiation. The temperature dependence of the current through a single barrier suggested two different contributions to its Arrhenius plot, i.e., formed by direct tunneling through the barrier and by thermal activation over the barrier. The height of the formed barriers was estimated. The fabrication technique was used to produce coupled double quantum dots withmore » serially formed triple barriers on a MWNT. The current measured at 1.5 K as a function of two side-gate voltages resulted in a honeycomb-like charge stability diagram, which confirmed the formation of the double dots. The characteristic parameters of the double quantum dots were calculated, and the feasibility of the technique is discussed.« less

Systematics of capture and fusion dynamics in heavy-ion collisions

NASA Astrophysics Data System (ADS)

Wang, Bing; Wen, Kai; Zhao, Wei-Juan; Zhao, En-Guang; Zhou, Shan-Gui

2017-03-01

We perform a systematic study of capture excitation functions by using an empirical coupled-channel (ECC) model. In this model, a barrier distribution is used to take effectively into account the effects of couplings between the relative motion and intrinsic degrees of freedom. The shape of the barrier distribution is of an asymmetric Gaussian form. The effect of neutron transfer channels is also included in the barrier distribution. Based on the interaction potential between the projectile and the target, empirical formulas are proposed to determine the parameters of the barrier distribution. Theoretical estimates for barrier distributions and calculated capture cross sections together with experimental cross sections of 220 reaction systems with 182 ⩽ZPZT ⩽ 1640 are tabulated. The results show that the ECC model together with the empirical formulas for parameters of the barrier distribution work quite well in the energy region around the Coulomb barrier. This ECC model can provide prediction of capture cross sections for the synthesis of superheavy nuclei as well as valuable information on capture and fusion dynamics.

Regenerative switching CMOS system

DOEpatents

Welch, James D.

1998-01-01

Complementary Metal Oxide Semiconductor (CMOS) Schottky barrier Field Effect Transistor systems, which are a seriesed combination of N and P-Channel MOSFETS, in which Source Schottky barrier junctions of the N and P-Channel Schottky barrier MOSFETS are electically interconnected, (rather than the Drains as in conventional diffused junction CMOS), which Schottky barrier MOSFET system demonstrates Regenerative Inverting Switching Characteristics in use are disclosed. Both the N and P-Channel Schottky barrier MOSFET devices are unique in that they provide operational Drain Current vs. Drain to Source voltage as a function of Gate voltage only where the polarities of the Drain voltage and Gate voltage are opposite, referenced to the Source as a common terminal, and where the polarity of the voltage applied to the Gate is appropriate to cause Channel inversion. Experimentally derived results which demonstrate and verify the operation of N and P-Channel Schottky barrier MOSFETS actually fabricated on P and N-type Silicon respectively, by a common procedure using vacuum deposited Chromium as a Schottky barrier forming metal, are also provided.

Regenerative switching CMOS system

DOEpatents

Welch, J.D.

1998-06-02

Complementary Metal Oxide Semiconductor (CMOS) Schottky barrier Field Effect Transistor systems, which are a series combination of N and P-Channel MOSFETS, in which Source Schottky barrier junctions of the N and P-Channel Schottky barrier MOSFETS are electrically interconnected, (rather than the Drains as in conventional diffused junction CMOS), which Schottky barrier MOSFET system demonstrates Regenerative Inverting Switching Characteristics in use are disclosed. Both the N and P-Channel Schottky barrier MOSFET devices are unique in that they provide operational Drain Current vs. Drain to Source voltage as a function of Gate voltage only where the polarities of the Drain voltage and Gate voltage are opposite, referenced to the Source as a common terminal, and where the polarity of the voltage applied to the Gate is appropriate to cause Channel inversion. Experimentally derived results which demonstrate and verify the operation of N and P-Channel Schottky barrier MOSFETS actually fabricated on P and N-type Silicon respectively, by a common procedure using vacuum deposited Chromium as a Schottky barrier forming metal, are also provided. 14 figs.

Rifaximin Alters Intestinal Bacteria and Prevents Stress-Induced Gut Inflammation and Visceral Hyperalgesia in Rats

PubMed Central

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

Barriers and Facilitators to Implementing Functional Family Therapy in a Community Setting: Client and Practitioner Perspectives.

PubMed

McPherson, Kerri E; Kerr, Susan; Casey, Beth; Marshall, John

2017-10-01

While Functional Family Therapy (FFT) is known to be effective in addressing adolescent behavioral problems, there has been little exploration of issues relevant to its transport from the tightly controlled setting of clinical trials into routine service delivery. This study sought the views of key stakeholders, clients, and practitioners, on barriers and facilitators to the successful implementation of FFT. Undertaken in a community setting in Scotland, interviews were carried out with 12 adolescents, 14 parents/caregivers, and 6 practitioners. Results focus on: Referral process and pre-intervention contact; Engagement of families; Structure and delivery; Organizational factors. Although barriers to engagement were identified, FFT was viewed as an acceptable, appropriate and feasible intervention with the potential to improve adolescent wellbeing in 'real-world' settings. © 2017 American Association for Marriage and Family Therapy.

Association of Cell Surface Mucins with Galectin-3 Contributes to the Ocular Surface Epithelial Barrier*

PubMed Central

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

Intrinsic inhomogeneous barrier height at the n-TiO2/p-Si hole-blocking junction

NASA Astrophysics Data System (ADS)

Kumar, Mohit; Singh, Ranveer; Som, Tapobrata

2018-01-01

Using Kelvin probe force microscopy (KPFM) and temperature-dependent current-voltage characteristics, we study the charge transport across an n-TiO2/p-Si heterojunction. In particular, the KPFM result shows a variation in the work function at the TiO2 surface. On the other hand, temperature-dependent current-voltage characteristics depict a non-ideal hole-blocking behaviour of the same. In addition, the measured barrier height is found to decrease with temperature and does not follow the thermionic emission theory, strongly suggesting an inhomogeneous nature of the barrier. The observed barrier inhomogeneity is attributed to the nanoscale height modulation, arising due to the growth dynamics of TiO2 and corroborates well with the KPFM map. The presented results will open a new avenue to understand the charge transport in TiO2-based nanoscale devices.

The Drosophila blood-brain barrier: development and function of a glial endothelium.

PubMed

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.

Acute exposure to ergot alkaloids from endophyte-infected tall fescue does not alter absorptive or barrier function of the isolated bovine ruminal epithelium.

PubMed

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.

Temperature dependence of copper diffusion in different thickness amorphous tungsten/tungsten nitride layer

NASA Astrophysics Data System (ADS)

Asgary, Somayeh; Hantehzadeh, Mohammad Reza; Ghoranneviss, Mahmood

2017-11-01

The amorphous W/WN films with various thickness (10, 30 and 40 nm) and excellent thermal stability were successfully prepared on SiO2/Si substrate with evaporation and reactive evaporation method. The W/WN bilayer has technological importance because of its low resistivity, high melting point, and good diffusion barrier properties between Cu and Si. The thermal stability was evaluated by X-ray diffractometer (XRD) and Scanning Electron Microscope (SEM). In annealing process, the amorphous W/WN barrier crystallized and this phenomenon is supposed to be the start of Cu atoms diffusion through W/WN barrier into Si. With occurrence of the high-resistive Cu3Si phase, the W/WN loses its function as a diffusion barrier. The primary mode of Cu diffusion is the diffusion through grain boundaries that form during heat treatments. The amorphous structure with optimum thickness is the key factor to achieve a superior diffusion barrier characteristic. The results show that the failure temperature increased by increasing the W/WN film thickness from 10 to 30 nm but it did not change by increasing the W/WN film thickness from 30 to 40 nm. It is found that the 10 and 40 nm W/WN films are good diffusion barriers at least up to 800°C while the 30 nm W/WN film shows superior properties as a diffusion barrier, but loses its function as a diffusion barrier at about 900°C (that is 100°C higher than for 10 and 40 nm W/WN films).

Glial cell line-derived neurotrophic factor promotes barrier maturation and wound healing in intestinal epithelial cells in vitro.

PubMed

Meir, Michael; Flemming, Sven; Burkard, Natalie; Bergauer, Lisa; Metzger, Marco; Germer, Christoph-Thomas; Schlegel, Nicolas

2015-10-15

Recent data suggest that neurotrophic factors from the enteric nervous system are involved in intestinal epithelial barrier regulation. In this context the glial cell line-derived neurotrophic factor (GDNF) was shown to affect gut barrier properties in vivo directly or indirectly by largely undefined processes in a model of inflammatory bowel disease (IBD). We further investigated the potential role and mechanisms of GDNF in the regulation of intestinal barrier functions. Immunostaining of human gut specimen showed positive GDNF staining in enteric neuronal plexus and in enterocytes. In Western blots of the intestinal epithelial cell lines Caco2 and HT29B6, significant amounts of GDNF were detected, suggesting that enterocytes represent an additional source of GDNF. Application of recombinant GDNF on Caco2 and HT29B6 cells for 24 h resulted in significant epithelial barrier stabilization in monolayers with immature barrier functions. Wound-healing assays showed a significantly faster closure of the wounded areas after GDNF application. GDNF augmented cAMP levels and led to significant inactivation of p38 MAPK in immature cells. Activation of p38 MAPK signaling by SB-202190 mimicked GDNF-induced barrier maturation, whereas the p38 MAPK activator anisomycin blocked GDNF-induced effects. Increasing cAMP levels had adverse effects on barrier maturation, as revealed by permeability measurements. However, increased cAMP augmented the proliferation rate in Caco2 cells, and GDNF-induced proliferation of epithelial cells was abrogated by the PKA inhibitor H89. Our data show that enterocytes represent an additional source of GDNF synthesis. GDNF contributes to wound healing in a cAMP/PKA-dependent manner and promotes barrier maturation in immature enterocytes cells by inactivation of p38 MAPK signaling. Copyright © 2015 the American Physiological Society.

Anti-IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus.

PubMed

Zhang, Jiyong; Sadowska, Grazyna B; Chen, Xiaodi; Park, Seon Yeong; Kim, Jeong-Eun; Bodge, Courtney A; Cummings, Erin; Lim, Yow-Pin; Makeyev, Oleksandr; Besio, Walter G; Gaitanis, John; Banks, William A; Stonestreet, Barbara S

2015-05-01

Impaired blood-brain barrier function represents an important component of hypoxic-ischemic brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-brain barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-brain barrier abnormalities have not been examined in the immature brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to brain ischemia. Anti-IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-brain barrier permeability was quantified using the blood-to-brain transfer constant in brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti-IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, brain parenchyma, and cerebrospinal fluid and decreases in brain IL-6 protein. Twenty-four hours after ischemia, anti-IL-6 mAb infusions attenuated ischemia-related increases in blood-brain barrier permeability and modulated tight junction and PLVAP protein expression in fetal brain. We conclude that inhibiting the effects of IL-6 protein with systemic infusions of neutralizing antibodies attenuates ischemia-related increases in blood-brain barrier permeability by inhibiting IL-6 and modulates tight junction proteins after ischemia. © FASEB.

Electron Raman scattering in a strained ZnO/MgZnO double quantum well

NASA Astrophysics Data System (ADS)

Mojab-abpardeh, M.; Karimi, M. J.

2018-02-01

In this work, the electron Raman scattering in a strained ZnO / MgZnO double quantum wells is studied. The energy eigenvalues and the wave functions are obtained using the transfer matrix method. The effects of Mg composition, well width and barrier width on the internal electric field in well and barrier layers are investigated. Then, the influences of these parameters on the differential cross-section of electron Raman scattering are studied. Results indicate that the position, magnitude and the number of the peaks depend on the Mg composition, well width and barrier width.

Apoplastic Diffusion Barriers in Arabidopsis

PubMed Central

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

Contrasting effects of linaclotide and lubiprostone on restitution of epithelial cell barrier properties and cellular homeostasis after exposure to cell stressors.

PubMed

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.

Executive Functioning, Barriers to Adherence, and Nonadherence in Adolescent and Young Adult Transplant Recipients.

PubMed

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.

Evaluating the long-term hydrology of an evapotranspiration-capillary barrier with a 1000 year design life: HYDROLOGY OF A 1000 YEAR ETC BARRIER

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

Intestinal permeability in a patient with liver cirrhosis

PubMed Central

Aguirre Valadez, Jonathan Manuel; Rivera-Espinosa, Liliana; Méndez-Guerrero, Osvely; Chávez-Pacheco, Juan Luis; García Juárez, Ignacio; Torre, Aldo

2016-01-01

Liver cirrhosis is a worldwide public health problem, and patients with this disease are at high risk of developing complications, bacterial translocation from the intestinal lumen to the mesenteric nodes, and systemic circulation, resulting in the development of severe complications related to high mortality rate. The intestinal barrier is a structure with a physical and biochemical activity to maintain balance between the external environment, including bacteria and their products, and the internal environment. Patients with liver cirrhosis develop a series of alterations in different components of the intestinal barrier directly associated with the severity of liver disease that finally increased intestinal permeability. A “leaky gut” is an effect produced by damaged intestinal barrier; alterations in the function of tight junction proteins are related to bacterial translocation and their products. Instead, increasing serum proinflammatory cytokines and hemodynamics modification, which results in the appearance of complications of liver cirrhosis such as hepatic encephalopathy, variceal hemorrhage, bacterial spontaneous peritonitis, and hepatorenal syndrome. The intestinal microbiota plays a fundamental role in maintaining the proper function of the intestinal barrier; bacterial overgrowth and dysbiosis are two phenomena often present in people with liver cirrhosis favoring bacterial translocation. Increased intestinal permeability has an important role in the genesis of these complications, and treating it could be the base for prevention and partial treatment of these complications. PMID:27920543

Flow directionality, mountain barriers and functional traits determine diatom metacommunity structuring of high mountain streams.

PubMed

Dong, Xiaoyu; Li, Bin; He, Fengzhi; Gu, Yuan; Sun, Meiqin; Zhang, Haomiao; Tan, Lu; Xiao, Wen; Liu, Shuoran; Cai, Qinghua

2016-04-19

Stream metacommunities are structured by a combination of local (environmental filtering) and regional (dispersal) processes. The unique characters of high mountain streams could potentially determine metacommunity structuring, which is currently poorly understood. Aiming at understanding how these characters influenced metacommunity structuring, we explored the relative importance of local environmental conditions and various dispersal processes, including through geographical (overland), topographical (across mountain barriers) and network (along flow direction) pathways in shaping benthic diatom communities. From a trait perspective, diatoms were categorized into high-profile, low-profile and motile guild to examine the roles of functional traits. Our results indicated that both environmental filtering and dispersal processes influenced metacommunity structuring, with dispersal contributing more than environmental processes. Among the three pathways, stream corridors were primary pathway. Deconstructive analysis suggested different responses to environmental and spatial factors for each of three ecological guilds. However, regardless of traits, dispersal among streams was limited by mountain barriers, while dispersal along stream was promoted by rushing flow in high mountain stream. Our results highlighted that directional processes had prevailing effects on metacommunity structuring in high mountain streams. Flow directionality, mountain barriers and ecological guilds contributed to a better understanding of the roles that mountains played in structuring metacommunity.

Barrier-protective function of intestinal epithelial Toll-like receptor 2.

PubMed

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.

The Halo mass function from Excursion Set Theory. II. The Diffusing Barrier

NASA Astrophysics Data System (ADS)

Maggiore, Michele; Riotto, Antonio

2010-07-01

In excursion set theory, the computation of the halo mass function is mapped into a first-passage time process in the presence of a barrier, which in the spherical collapse model is a constant and in the ellipsoidal collapse model is a fixed function of the variance of the smoothed density field. However, N-body simulations show that dark matter halos grow through a mixture of smooth accretion, violent encounters, and fragmentations, and modeling halo collapse as spherical, or even as ellipsoidal, is a significant oversimplification. In addition, the very definition of what is a dark matter halo, both in N-body simulations and observationally, is a difficult problem. We propose that some of the physical complications inherent to a realistic description of halo formation can be included in the excursion set theory framework, at least at an effective level, by taking into account that the critical value for collapse is not a fixed constant δ c , as in the spherical collapse model, nor a fixed function of the variance σ of the smoothed density field, as in the ellipsoidal collapse model, but rather is itself a stochastic variable, whose scatter reflects a number of complicated aspects of the underlying dynamics. Solving the first-passage time problem in the presence of a diffusing barrier we find that the exponential factor in the Press-Schechter mass function changes from exp{-δ2 c /2σ2} to exp{-aδ2 c /2σ2}, where a = 1/(1 + DB ) and DB is the diffusion coefficient of the barrier. The numerical value of DB , and therefore the corresponding value of a, depends among other things on the algorithm used for identifying halos. We discuss the physical origin of the stochasticity of the barrier and, from recent N-body simulations that studied the properties of the collapse barrier, we deduce a value DB ~= 0.25. Our model then predicts a ~= 0.80, in excellent agreement with the exponential fall off of the mass function found in N-body simulations, for the same halo definition. Combining this result with the non-Markovian corrections computed in Paper I of this series, we derive an analytic expression for the halo mass function for Gaussian fluctuations and we compare it with N-body simulations.

Epithelial-specific A2B adenosine receptor signaling protects the colonic epithelial barrier during acute colitis

PubMed Central

Aherne, CM; Saeedi, B; Collins, CB; Masterson, JC; McNamee, EN; Perrenoud, L; Rapp, CR; Curtis, VF; Bayless, A; Fletcher, A; Glover, LE; Evans, CM; Jedlicka, P; Furuta, GT; de Zoeten, EF; Colgan, SP; Eltzschig, HK

2015-01-01

Central to inflammatory bowel disease (IBD) pathogenesis is loss of mucosal barrier function. Emerging evidence implicates extracellular adenosine signaling in attenuating mucosal inflammation. We hypothesized that adenosine-mediated protection from intestinal barrier dysfunction involves tissue-specific signaling through the A2B adenosine receptor (Adora2b) at the intestinal mucosal surface. To address this hypothesis, we combined pharmacologic studies and studies in mice with global or tissue-specific deletion of the Adora2b receptor. Adora2b−/− mice experienced a significantly heightened severity of colitis, associated with a more acute onset of disease and loss of intestinal epithelial barrier function. Comparison of mice with Adora2b deletion on vascular endothelial cells (Adora2bfl/flVeCadCre+) or intestinal epithelia (Adora2bfl/flVillinCre+) revealed a selective role for epithelial Adora2b signaling in attenuating colonic inflammation. In vitro studies with Adora2b knockdown in intestinal epithelial cultures or pharmacologic studies highlighted Adora2b-driven phosphorylation of vasodilator-stimulated phosphoprotein (VASP) as a specific barrier repair response. Similarly, in vivo studies in genetic mouse models or treatment studies with an Adora2b agonist (BAY 60-6583) recapitulate these findings. Taken together, our results suggest that intestinal epithelial Adora2b signaling provides protection during intestinal inflammation via enhancing mucosal barrier responses. PMID:25850656

Up-regulation of the tight-junction protein ZO-1 by substance P and IGF-1 in A431 cells.

PubMed

Ko, Ji-Ae; Murata, Shizuka; Nishida, Teruo

2009-08-01

The formation of a barrier by tight junctions is important in epithelia of various tissues. Substance P (SP) and insulin-like growth factor (IGF)-1 synergistically promote barrier function in the corneal epithelium. We have now examined the effects of SP and IGF-1 on expression of the tight-junction protein zonula occludens (ZO)-1 in A431 human epidermoid carcinoma cells. Reverse transcription-polymerase chain reaction (RT-PCR) and immunoblot analyses revealed that SP and IGF-1 increased the amounts of ZO-1 mRNA and protein in these cells in a concentration-dependent manner, with neither SP nor IGF-1 alone having such an effect. The SP- and IGF-1-induced up-regulation of ZO-1 was accompanied by phosphorylation of extracellular signal-regulated kinase (ERK), and both of these effects were blocked by PD98059, an inhibitor of ERK activation. SP and IGF-1 also increased the transepithelial electrical resistance (TER) (an indicator of barrier function) of an A431 cell monolayer in a manner sensitive to PD98059. Our results thus suggest that the synergistic induction of ZO-1 expression by SP and IGF-1 may promote barrier function in skin epithelial cells. (c) 2009 John Wiley & Sons, Ltd.

Skin barrier function recovery after diamond microdermabrasion.

PubMed

Kim, Hei Sung; Lim, Sook Hee; Song, Ji Youn; Kim, Mi-Yeon; Lee, Ji Ho; Park, Jong Gap; Kim, Hyung Ok; Park, Young Min

2009-10-01

Microdermabrasion is a popular method for facial rejuvenation and is performed worldwide. Despite its extensive usage, there are few publications on skin barrier change after microdermabrasion and none concerning diamond microdermabrasion. Our object was to see changes in transepidermal water loss (TEWL), hydration and erythema of the face following diamond microdermabrasion. Twenty-eight patients were included in this spilt face study. TEWL, stratum corneum hydration and the degree of erythema were measured from the right and left sides of the face (forehead and cheek) at baseline. One side of the face was treated with diamond microdermabrasion and the other side was left untreated. Measurements were taken right after the procedure and repeated at set time intervals. Diamond microdermabrasion was associated with a statistically significant increase in TEWL immediately after the procedure and at 24 h. However, on day 2, levels of TEWL were back to baseline. An increase in hydration and erythema was observed right after microdermabrasion, but both returned to baseline on day 1. The results show that skin barrier function of the forehead and cheek recovers within 2 days of diamond microdermabrasion. Diamond microdermabrasion performed on a weekly basis, as presently done, is expected to allow sufficient time for the damaged skin to recover its barrier function in most parts of the face.

Simulation study of light transport in laser-processed LYSO:Ce detectors with single-side readout

NASA Astrophysics Data System (ADS)

Bläckberg, L.; El Fakhri, G.; Sabet, H.

2017-11-01

A tightly focused pulsed laser beam can locally modify the crystal structure inside the bulk of a scintillator. The result is incorporation of so-called optical barriers with a refractive index different from that of the crystal bulk, that can be used to redirect the scintillation light and control the light spread in the detector. We here systematically study the scintillation light transport in detectors fabricated using the laser induced optical barrier technique, and objectively compare their potential performance characteristics with those of the two mainstream detector types: monolithic and mechanically pixelated arrays. Among countless optical barrier patterns, we explore barriers arranged in a pixel-like pattern extending all-the-way or half-way through a 20 mm thick LYSO:Ce crystal. We analyze the performance of the detectors coupled to MPPC arrays, in terms of light response functions, flood maps, line profiles, and light collection efficiency. Our results show that laser-processed detectors with both barrier patterns constitute a new detector category with a behavior between that of the two standard detector types. Results show that when the barrier-crystal interface is smooth, no DOI information can be obtained regardless of barrier refractive index (RI). However, with a rough barrier-crystal interface we can extract multiple levels of DOI. Lower barrier RI results in larger light confinement, leading to better transverse resolution. Furthermore we see that the laser-processed crystals have the potential to increase the light collection efficiency, which could lead to improved energy resolution and potentially better timing resolution due to higher signals. For a laser-processed detector with smooth barrier-crystal interfaces the light collection efficiency is simulated to  >42%, and for rough interfaces  >73%. The corresponding numbers for a monolithic crystal is 39% with polished surfaces, and 71% with rough surfaces, and for a mechanically pixelated array 35% with polished pixel surfaces and 59% with rough surfaces.

Simulation study of light transport in laser-processed LYSO:Ce detectors with single-side readout.

PubMed

Bläckberg, L; El Fakhri, G; Sabet, H

2017-10-19

A tightly focused pulsed laser beam can locally modify the crystal structure inside the bulk of a scintillator. The result is incorporation of so-called optical barriers with a refractive index different from that of the crystal bulk, that can be used to redirect the scintillation light and control the light spread in the detector. We here systematically study the scintillation light transport in detectors fabricated using the laser induced optical barrier technique, and objectively compare their potential performance characteristics with those of the two mainstream detector types: monolithic and mechanically pixelated arrays. Among countless optical barrier patterns, we explore barriers arranged in a pixel-like pattern extending all-the-way or half-way through a 20 mm thick LYSO:Ce crystal. We analyze the performance of the detectors coupled to MPPC arrays, in terms of light response functions, flood maps, line profiles, and light collection efficiency. Our results show that laser-processed detectors with both barrier patterns constitute a new detector category with a behavior between that of the two standard detector types. Results show that when the barrier-crystal interface is smooth, no DOI information can be obtained regardless of barrier refractive index (RI). However, with a rough barrier-crystal interface we can extract multiple levels of DOI. Lower barrier RI results in larger light confinement, leading to better transverse resolution. Furthermore we see that the laser-processed crystals have the potential to increase the light collection efficiency, which could lead to improved energy resolution and potentially better timing resolution due to higher signals. For a laser-processed detector with smooth barrier-crystal interfaces the light collection efficiency is simulated to  >42%, and for rough interfaces  >73%. The corresponding numbers for a monolithic crystal is 39% with polished surfaces, and 71% with rough surfaces, and for a mechanically pixelated array 35% with polished pixel surfaces and 59% with rough surfaces.

Effects of Lactobacillus johnsonii and Lactobacillus reuteri on gut barrier function and heat shock proteins in intestinal porcine epithelial cells.

PubMed

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.

Altered Expression of ZO-1 and ZO-2 in Sertoli Cells and Loss of Blood-Testis Barrier Integrity in Testicular Carcinoma In Situ1

PubMed Central

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

Regulation of feto-maternal barrier by matriptase- and PAR-2-mediated signaling is required for placental morphogenesis and mouse embryonic survival.

PubMed

Szabo, Roman; Peters, Diane E; Kosa, Peter; Camerer, Eric; Bugge, Thomas H

2014-07-01

The development of eutherian mammalian embryos is critically dependent on the selective bi-directional transport of molecules across the placenta. Here, we uncover two independent and partially redundant protease signaling pathways that include the membrane-anchored serine proteases, matriptase and prostasin, and the G protein-coupled receptor PAR-2 that mediate the establishment of a functional feto-maternal barrier. Mice with a combined matriptase and PAR-2 deficiency do not survive to term and the survival of matriptase-deficient mice heterozygous for PAR-2 is severely diminished. Embryos with the combined loss of PAR-2 and matriptase or PAR-2 and the matriptase partner protease, prostasin, uniformly die on or before embryonic day 14.5. Despite the extensive co-localization of matriptase, prostasin, and PAR-2 in embryonic epithelia, the overall macroscopic and histological analysis of the double-deficient embryos did not reveal any obvious developmental abnormalities. In agreement with this, the conditional deletion of matriptase from the embryo proper did not affect the prenatal development or survival of PAR-2-deficient mice, indicating that the critical redundant functions of matriptase/prostasin and PAR-2 are limited to extraembryonic tissues. Indeed, placentas of the double-deficient animals showed decreased vascularization, and the ability of placental epithelium to establish a functional feto-maternal barrier was severely diminished. Interestingly, molecular analysis suggested that the barrier defect was associated with a selective deficiency in the expression of the tight junction protein, claudin-1. Our results reveal unexpected complementary roles of matriptase-prostasin- and PAR-2-dependent proteolytic signaling in the establishment of placental epithelial barrier function and overall embryonic survival.

Regulation of Feto-Maternal Barrier by Matriptase- and PAR-2-Mediated Signaling Is Required for Placental Morphogenesis and Mouse Embryonic Survival

PubMed Central

Szabo, Roman; Peters, Diane E.; Kosa, Peter; Camerer, Eric; Bugge, Thomas H.

2014-01-01

The development of eutherian mammalian embryos is critically dependent on the selective bi-directional transport of molecules across the placenta. Here, we uncover two independent and partially redundant protease signaling pathways that include the membrane-anchored serine proteases, matriptase and prostasin, and the G protein-coupled receptor PAR-2 that mediate the establishment of a functional feto-maternal barrier. Mice with a combined matriptase and PAR-2 deficiency do not survive to term and the survival of matriptase-deficient mice heterozygous for PAR-2 is severely diminished. Embryos with the combined loss of PAR-2 and matriptase or PAR-2 and the matriptase partner protease, prostasin, uniformly die on or before embryonic day 14.5. Despite the extensive co-localization of matriptase, prostasin, and PAR-2 in embryonic epithelia, the overall macroscopic and histological analysis of the double-deficient embryos did not reveal any obvious developmental abnormalities. In agreement with this, the conditional deletion of matriptase from the embryo proper did not affect the prenatal development or survival of PAR-2-deficient mice, indicating that the critical redundant functions of matriptase/prostasin and PAR-2 are limited to extraembryonic tissues. Indeed, placentas of the double-deficient animals showed decreased vascularization, and the ability of placental epithelium to establish a functional feto-maternal barrier was severely diminished. Interestingly, molecular analysis suggested that the barrier defect was associated with a selective deficiency in the expression of the tight junction protein, claudin-1. Our results reveal unexpected complementary roles of matriptase-prostasin- and PAR-2-dependent proteolytic signaling in the establishment of placental epithelial barrier function and overall embryonic survival. PMID:25078604

A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors

NASA Astrophysics Data System (ADS)

Xu, Hui; Li, Zhongyu; Yu, Yue; Sizdahkhani, Saman; Ho, Winson S.; Yin, Fangchao; Wang, Li; Zhu, Guoli; Zhang, Min; Jiang, Lei; Zhuang, Zhengping; Qin, Jianhua

2016-11-01

The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes-permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research.

Self-consistent many-electron theory of electron work functions and surface potential characteristics for selected metals

NASA Technical Reports Server (NTRS)

Smith, J. R.

1969-01-01

Electron work functions, surface potentials, and electron number density distributions and electric fields in the surface region of 26 metals were calculated from first principles within the free electron model. Calculation proceeded from an expression of the total energy as a functional of the electron number density, including exchange and correlation energies, as well as a first inhomogeneity term. The self-consistent solution was obtained via a variational procedure. Surface barriers were due principally to many-body effects; dipole barriers were small only for some alkali metals, becoming quite large for the transition metals. Surface energies were inadequately described by this model, which neglects atomistic effects. Reasonable results were obtained for electron work functions and surface potential characteristics, maximum electron densities varying by a factor of over 60.

Diet, Microbiome, and the Intestinal Epithelium: An Essential Triumvirate?

PubMed Central

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

Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures.

PubMed

Schweitzer, Kelly S; Chen, Steven X; Law, Sarah; Van Demark, Mary; Poirier, Christophe; Justice, Matthew J; Hubbard, Walter C; Kim, Elena S; Lai, Xianyin; Wang, Mu; Kranz, William D; Carroll, Clinton J; Ray, Bruce D; Bittman, Robert; Goodpaster, John; Petrache, Irina

2015-07-15

The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1-20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10-20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.

Platinum-catalyzed hydrolysis etching of SiC in water: A density functional theory study

NASA Astrophysics Data System (ADS)

Van Bui, Pho; Toh, Daisetsu; Isohashi, Ai; Matsuyama, Satoshi; Inagaki, Kouji; Sano, Yasuhisa; Yamauchi, Kazuto; Morikawa, Yoshitada

2018-05-01

A comprehensive study of the physicochemical interactions and the reaction mechanism of SiC etching with water by Pt catalysts can reveal key details about the surface treatment and catalytic phenomena at interfaces. Therefore, density functional theory simulations were performed to study the kinetics of Pt-assisted water dissociation and breaking of a Si–C bond compared to the HF-assisted mechanism. These calculations carefully considered the elastic and chemical interaction energies at the Pt–SiC interface, activation barriers of Si–C bond dissociation, and the catalytic role of Pt. It was found that the Pt-catalyzed etching of SiC in water is initiated via hydrolysis reactions that break the topmost Si–C bonds. The activation barrier strongly depends on the elastic and chemical interactions. However, chemical interactions are a dominant factor and mainly contribute to the lowering of the activation barrier, resulting in an increased rate of reaction.

Symbiotic Bacterial Metabolites Regulate Gastrointestinal Barrier Function via the Xenobiotic Sensor PXR and Toll-like Receptor 4

PubMed Central

Venkatesh, Madhukumar; Mukherjee, Subhajit; Wang, Hongwei; Li, Hao; Sun, Katherine; Benechet, Alaxandre P.; Qiu, Zhijuan; Maher, Leigh; Redinbo, Matthew R.; Phillips, Robert S.; Fleet, James C.; Kortagere, Sandhya; Mukherjee, Paromita; Fasano, Alessio; Le Ven, Jessica; Nicholson, Jeremy K.; Dumas, Marc E.; Khanna, Kamal M.; Mani, Sridhar

2014-01-01

SUMMARY Intestinal microbial metabolites are conjectured to affect mucosal integrity through an incompletely characterized mechanism. Here we showed microbial-specific indoles regulated intestinal barrier function through the xenobiotic sensor, pregnane X receptor (PXR). Indole 3-propionic acid (IPA), in the context of indole, is as a ligand for PXR in vivo, and IPA down-regulated enterocyte TNF–α while up-regulated junctional protein-coding mRNAs. PXR-deficient (Nr1i2−/−) mice showed a distinctly “leaky” gut physiology coupled with up-regulation of the Toll-like receptor (TLR) signaling pathway. These defects in the epithelial barrier were corrected in Nr1i2−/−Tlr4−/− mice. Our results demonstrate that a direct chemical communication between the intestinal symbionts and PXR regulates mucosal integrity through a pathway which involves luminal sensing and signaling by TLR4. PMID:25065623

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.

Hybrid functional studies of stability and diffusion of hydrogen in Mg-doped GaN

NASA Astrophysics Data System (ADS)

Park, Ji-Sang; Chang, K. J.

2012-02-01

Nitride semiconductors are known to suffer from low p-type doping efficiency due to the high activation energy of Mg acceptors and the compensation of hole carriers. To enhance hole carrier concentration, the hydrogen co-doping method is widely used, in which hydrogen is intentionally doped with Mg dopants and removed by subsequent thermal annealing. In this work, we perform first-principles density functional calculations to study the stability and diffusion of hydrogen in Mg-doped GaN. For the exchange-correlation potential, we employ both the generalized gradient approximation (GGA) proposed by Perdew, Burke, and Ernzerhof and the hybrid density functional of Heyd, Scuseria, and Ernzerhof. We examine the diffusion pathways and dissociation barriers of H from the Mg-H complex using the nudged elastic band and dimer methods. We compare the results of the GGA and hybrid density functional calculations for the stability of various H interstitial configurations and the migration barriers for H diffusion. Finally, using the calculated migration barriers as inputs, we perform kinetic Monte Carlo simulations for the dissociation of the Mg-H complex and find that the Mg acceptors are activated by thermal annealing up to 700-800 ^oC, in good agreement with experiments.

Room temperature current-voltage (I-V) characteristics of Ag/InGaN/n-Si Schottky barrier diode

NASA Astrophysics Data System (ADS)

Erdoğan, Erman; Kundakçı, Mutlu

2017-02-01

Metal-semiconductors (MSs) or Schottky barrier diodes (SBDs) have a significant potential in the integrated device technology. In the present paper, electrical characterization of Ag/InGaN/n-Si Schottky diode have been systematically carried out by simple Thermionic method (TE) and Norde function based on the I-V characteristics. Ag ohmic and schottky contacts are deposited on InGaN/n-Si film by thermal evaporation technique under a vacuum pressure of 1×10-5 mbar. Ideality factor, barrier height and series resistance values of this diode are determined from I-V curve. These parameters are calculated by TE and Norde methods and findings are given in a comparetive manner. The results show the consistency for both method and also good agreement with other results obtained in the literature. The value of ideality factor and barrier height have been determined to be 2.84 and 0.78 eV at room temperature using simple TE method. The value of barrier height obtained with Norde method is calculated as 0.79 eV.

Cobalt chloride compromises transepithelial barrier properties of CaCo-2 BBe human gastrointestinal epithelial cell layers.

PubMed

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.

Total Quality Management (TQM): Group Dynamics Workshop

DTIC Science & Technology

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

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

Airway Epithelial Barrier Dysfunction in Chronic Obstructive Pulmonary Disease: Role of Cigarette Smoke Exposure.

PubMed

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.

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.

[Immune dysfunction and cognitive deficit in stress and physiological aging. Part II: New approaches to cognitive disorder prevention and treatment ].

PubMed

Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

2014-01-01

Long-term stress as well as physiological aging result in similar immunological and hormonal disturbances including hypothalamic-pituitary-adrenal) axis depletion, aberrant immune response (regulatory T-cells, Tregs, and T(h17)-lymphocyte accumulation) and decreased dehydroepian-drosterone synthesis both in the brain and in the adrenal glands. Since the main mechanisms of inflammation control, "prompt" (stress hormones) and "delayed" (Tregs), are broken, serum cytokine levels increase and become sufficient for blood-brain-barrier disruption. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Structural and functional alterations of blood-brain-barrier as well as stress- (or age-) induced neuroinflammation promote influx of bone marrow derived dendritic cells and lymphocyte effectors into the brain parenchyma. Thereafter, mass intrusion ofpro-inflammatory mediators and immune cells having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets: 1) reduction of excessive Treg accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement of blood-brain-barrier function.

A novel method for calculating the energy barriers for carbon diffusion in ferrite under heterogeneous stress

NASA Astrophysics Data System (ADS)

Tchitchekova, Deyana S.; Morthomas, Julien; Ribeiro, Fabienne; Ducher, Roland; Perez, Michel

2014-07-01

A novel method for accurate and efficient evaluation of the change in energy barriers for carbon diffusion in ferrite under heterogeneous stress is introduced. This method, called Linear Combination of Stress States, is based on the knowledge of the effects of simple stresses (uniaxial or shear) on these diffusion barriers. Then, it is assumed that the change in energy barriers under a complex stress can be expressed as a linear combination of these already known simple stress effects. The modifications of energy barriers by either uniaxial traction/compression and shear stress are determined by means of atomistic simulations with the Climbing Image-Nudge Elastic Band method and are stored as a set of functions. The results of this method are compared to the predictions of anisotropic elasticity theory. It is shown that, linear anisotropic elasticity fails to predict the correct energy barrier variation with stress (especially with shear stress) whereas the proposed method provides correct energy barrier variation for stresses up to ˜3 GPa. This study provides a basis for the development of multiscale models of diffusion under non-uniform stress.

A novel method for calculating the energy barriers for carbon diffusion in ferrite under heterogeneous stress.

PubMed

Tchitchekova, Deyana S; Morthomas, Julien; Ribeiro, Fabienne; Ducher, Roland; Perez, Michel

2014-07-21

A novel method for accurate and efficient evaluation of the change in energy barriers for carbon diffusion in ferrite under heterogeneous stress is introduced. This method, called Linear Combination of Stress States, is based on the knowledge of the effects of simple stresses (uniaxial or shear) on these diffusion barriers. Then, it is assumed that the change in energy barriers under a complex stress can be expressed as a linear combination of these already known simple stress effects. The modifications of energy barriers by either uniaxial traction/compression and shear stress are determined by means of atomistic simulations with the Climbing Image-Nudge Elastic Band method and are stored as a set of functions. The results of this method are compared to the predictions of anisotropic elasticity theory. It is shown that, linear anisotropic elasticity fails to predict the correct energy barrier variation with stress (especially with shear stress) whereas the proposed method provides correct energy barrier variation for stresses up to ∼3 GPa. This study provides a basis for the development of multiscale models of diffusion under non-uniform stress.

Maximum dose angle for oblique incidence on primary beam protective barriers in the design of medical radiation therapy facilities.

PubMed

Fondevila, Damián; Arbiser, Silvio; Sansogne, Rosana; Brunetto, Mónica; Dosoretz, Bernardo

2008-05-01

Primary barrier determinations for the shielding of medical radiation therapy facilities are generally made assuming normal beam incidence on the barrier, since this is geometrically the most unfavorable condition for that shielding barrier whenever the occupation line is allowed to run along the barrier. However, when the occupation line (for example, the wall of an adjacent building) runs perpendicular to the barrier (especially roof barrier), then two opposing factors come in to play: increasing obliquity angle with respect to the barrier increases the attenuation, while the distance to the calculation point decreases, hence, increasing the dose. As a result, there exists an angle (alpha(max)) for which the equivalent dose results in a maximum, constituting the most unfavorable geometric condition for that shielding barrier. Based on the usual NCRP Report No. 151 model, this article presents a simple formula for obtaining alpha(max), which is a function of the thickness of the barrier (t(E)) and the equilibrium tenth-value layer (TVL(e)) of the shielding material for the nominal energy of the beam. It can be seen that alpha(max) increases for increasing TVL(e) (hence, beam energy) and decreases for increasing t(E), with a range of variation that goes from 13 to 40 deg for concrete barriers thicknesses in the range of 50-300 cm and most commercially available teletherapy machines. This parameter has not been calculated in the existing literature for radiotherapy facilities design and has practical applications, as in calculating the required unoccupied roof shielding for the protection of a nearby building located in the plane of the primary beam rotation.

Longitudinal Evaluation of the Skin Microbiome and Association with Microenvironment and Treatment in Canine Atopic Dermatitis.

PubMed

Bradley, Charles W; Morris, Daniel O; Rankin, Shelley C; Cain, Christine L; Misic, Ana M; Houser, Timothy; Mauldin, Elizabeth A; Grice, Elizabeth A

2016-06-01

Host-microbe interactions may play a fundamental role in the pathogenesis of atopic dermatitis, a chronic relapsing inflammatory skin disorder characterized by universal colonization with Staphylococcus species. To examine the relationship between epidermal barrier function and the cutaneous microbiota in atopic dermatitis, this study used a spontaneous model of canine atopic dermatitis. In a cohort of 14 dogs with canine atopic dermatitis, the skin microbiota were longitudinally evaluated with parallel assessment of skin barrier function at disease flare, during antimicrobial therapy, and post-therapy. Sequencing of the bacterial 16S ribosomal RNA gene showed decreased bacterial diversity and increased proportions of Staphylococcus (S. pseudintermedius in particular) and Corynebacterium species compared with a cohort of healthy control dogs (n = 16). Treatment restored bacterial diversity with decreased proportions of Staphylococcus species, concurrent with decreased canine atopic dermatitis severity. Skin barrier function, as measured by corneometry, pH, and transepidermal water loss also normalized with treatment. Bacterial diversity correlated with transepidermal water loss and pH level but not with corneometry results. These findings provide insights into the relationship between the cutaneous microbiome and skin barrier function in atopic dermatitis, show the impact of antimicrobial therapy on the skin microbiome, and highlight the utility of canine atopic dermatitis as a spontaneous nonrodent model of atopic dermatitis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Contacting co-culture of human retinal microvascular endothelial cells alters barrier function of human embryonic stem cell derived retinal pigment epithelial cells.

PubMed

Skottman, H; Muranen, J; Lähdekorpi, H; Pajula, E; Mäkelä, K; Koivusalo, L; Koistinen, A; Uusitalo, H; Kaarniranta, K; Juuti-Uusitalo, K

2017-10-01

Here we evaluated the effects of human retinal microvascular endothelial cells (hREC) on mature human embryonic stem cell (hESC) derived retinal pigment epithelial (RPE) cells. The hESC-RPE cells (Regea08/017, Regea08/023 or Regea11/013) and hREC (ACBRI 181) were co-cultured on opposite sides of transparent membranes for up to six weeks. Thereafter barrier function, small molecule permeability, localization of RPE and endothelial cell marker proteins, cellular fine structure, and growth factor secretion of were evaluated. After co-culture, the RPE specific CRALBP and endothelial cell specific von Willebrand factor were appropriately localized. In addition, the general morphology, pigmentation, and fine structure of hESC-RPE cells were unaffected. Co-culture increased the barrier function of hESC-RPE cells, detected both with TEER measurements and cumulative permeability of FD4 - although the differences varied among the cell lines. Co-culturing significantly altered VEGF and PEDF secretion, but again the differences were cell line specific. The results of this study showed that co-culture with hREC affects hESC-RPE functionality. In addition, co-culture revealed drastic cell line specific differences, most notably in growth factor secretion. This model has the potential to be used as an in vitro outer blood-retinal barrier model for drug permeability testing. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Barrier distributions and signatures of transfer channels in the Ca40+Ni58,64 fusion reactions at energies around and below the Coulomb barrier

NASA Astrophysics Data System (ADS)

Bourgin, D.; Courtin, S.; Haas, F.; Stefanini, A. M.; Montagnoli, G.; Goasduff, A.; Montanari, D.; Corradi, L.; Fioretto, E.; Huiming, J.; Scarlassara, F.; Rowley, N.; Szilner, S.; Mijatović, T.

2014-10-01

Background: The nuclear structure of colliding nuclei is known to influence the fusion process. Couplings of the relative motion to nuclear shape deformations and vibrations lead to an enhancement of the sub-barrier fusion cross section in comparison with the predictions of one-dimensional barrier penetration models. This enhancement is explained by coupled-channels calculations including these couplings. The sub-barrier fusion cross section is also affected by nucleon transfer channels between the colliding nuclei. Purpose: The aim of the present experiment is to investigate the influence of the projectile and target nuclear structures on the fusion cross sections in the Ca40+Ni58 and Ca40+Ni64 systems. Methods: The experimental and theoretical fusion excitation functions as well as the barrier distributions were compared for these two systems. Coupled-channels calculations were performed using the ccfull code. Results: Good agreement was found between the measured and calculated fusion cross sections for the Ca40+Ni58 system. The situation is different for the Ca40+Ni64 system where the coupled-channels calculations with no nucleon transfer clearly underestimate the fusion cross sections below the Coulomb barrier. The fusion excitation function was, however, well reproduced at low and high energies by including the coupling to the neutron pair-transfer channel in the calculations. Conclusions: The nuclear structure of the colliding nuclei influences the fusion cross sections below the Coulomb barrier for both Ca40+Ni58,64 systems. Moreover, we highlighted the effect of the neutron pair-transfer channel on the fusion cross sections in Ca40+Ni64.

Two-color infrared detector

DOEpatents

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.

Crossing safety barriers: influence of children's morphological and functional variables.

PubMed

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.

Lactobacillus plantarum Enhanced IL-22 Production in Natural Killer (NK) Cells That Protect the Integrity of Intestinal Epithelial Cell Barrier Damaged by Enterotoxigenic Escherichia coli.

PubMed

Qiu, Yueqin; Jiang, Zongyong; Hu, Shenglan; Wang, Li; Ma, Xianyong; Yang, Xuefen

2017-11-13

Interleukin (IL)-22-producing Natural Killer (NK) cells protect the gut epithelial cell barrier from pathogens. A strain of probiotics, Lactobacillus plantarum (L. plantarum, LP), was previously found by our laboratory to significantly improve the mucosal barrier integrity and function of the small intestine in pigs. However, it was unclear whether LP benefited the intestinal mucosal barrier via interactions with the intestinal NK cells. The present study, therefore, was focused on the therapeutic effect of NK cells that were stimulated by LP on attenuating enterotoxigenic Escherichia coli (ETEC)-induced the damage to the integrity of the epithelial cell barrier. The results showed that LP can efficiently increase protein levels of the natural cytotoxicity receptor (NCR) family, and the expression levels of IL-22 mRNA and protein in NK cells. Transfer of NK cells stimulated by LP conferred protection against ETEC K88-induced intestinal epithelial barrier damage in NCM460 cells. We found that NK cells stimulated by LP could partially offset the reduction in NCM460 cell monolayers transepithelial electrical resistance (TEER) caused by ETEC K88, and increase ZO-1 and occludin mRNA and protein expressions by ETEC K88-infected NCM460 cells. Furthermore, adding NK cells that were stimulated by LP to ETEC K88-infected NCM460cells, IL-22R1, p-Stat3, and p-Tyk2 expression by NCM460 cells was increased. Mechanistic experiment showed that NK cells stimulated by LP lost the function of maintaining TEER of NCM460 cells challenged with ETEC K88, when polyclonal anti-IL-22 antibody was used to block IL-22 production. Collectively, our results suggested that LP stimulation of NK could enhance IL-22 production, which might be able to provide defense against ETEC-induced damage to the integrity of intestinal epithelial barrier.

Metformin Improves Ileal Epithelial Barrier Function in Interleukin-10 Deficient Mice

PubMed Central

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

Tight junction proteins contribute to barrier properties in human pleura.

PubMed

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.

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

Hydroxide Degradation Pathways for Substituted Benzyltrimethyl Ammonium: A DFT Study

DOE PAGES

Long, Hai; Pivovar, Bryan S.

2014-11-01

The stability of cations used in the alkaline exchange membranes has been a major challenge. In this paper, degradation energy barriers were investigated by density functional theory for substituted benzyltrimethyl ammonium (BTMA+) cations. Findings show that electron-donating substituent groups at meta-position(s) of the benzyl ring could result in increased degradation barriers. However, after investigating more than thirty substituted BTMA+ cations, the largest improvement in degradation barrier found was only 6.7 kJ/mol. This suggests a modest (8×) improvement in stability for this type of approach may be possible, but for anything greater other approaches will need to be pursued.

The morphologic changes in lamellar bodies and intercorneocyte lipids after tape stripping and occlusion with a water vapor-impermeable membrane.

PubMed

Jiang, S; Koo, S W; Lee, S H

1998-03-01

It has been reported that artificial restoration of barrier function by a water vapor-impermeable membrane after tape stripping induces barrier abrogation in hairless mice, impeding rather than enhancing barrier recovery. To address this issue, we examined the morphologic changes in the epidermis after tape stripping and occlusion with a water vapor-impermeable membrane in murine skin. Male hairless mice were used for all studies of barrier perturbation and occlusion. Barrier disruption was achieved by repeated application of cellophane tape. Immediately after tape stripping the animals were wrapped in a tightly fitting water vapor-impermeable membrane. Transepidermal water loss (TEWL) was measured 20 min after tape stripping and 14, 24, 36, 48 and 60 h after occlusion. For electron microscopy the samples were treated with osmium tetroxide (OsO4) or ruthenium tetroxide (RuO4). When tape-stripped animals were wrapped in a water vapor-impermeable membrane, thereby preventing water flux, barrier function did not recover normally. These results demonstrate that an artificial block to TEWL with an impermeable membrane did not enhance barrier recovery. By electron microscopy many transitional cells and lacunae of various sizes were seen within the intercellular spaces of the stratum corneum after occlusion following tape stripping. Occlusion also caused alterations in both lipid lamellar membrane structures in the stratum corneum interstices and the lamellar bodies in the cytosol of granulocytes and transitional cells. Secreted lamellar body contents also appeared to be abnormal in the stratum corneum-stratum granulosum junction.

Improving Dispersion and Barrier Properties of Polyketone/Graphene Nanoplatelet Composites via Noncovalent Functionalization Using Aminopyrene.

PubMed

Cho, Jaehyun; Jeon, Ikseong; Kim, Seong Yun; Lim, Soonho; Jho, Jae Young

2017-08-23

A series of polyketone (PK) nanocomposite films with varying content of noncovalently functionalized graphene nanoplatelet with 1-aminopyrene (GNP/APy) is prepared by solution blending with a solvent of hexafluoro-2-propanol. GNP/APy, prepared by a facile method, can effectively induce specific interaction such as hydrogen bonding between the amine functional group of GNP/APy and the carbonyl functional group of the PK matrix. With comparison of GNP and GNP/Py as reference materials, intensive investigation on filler-matrix interaction is achieved. In addition, the dispersion state of the functionalized GNP (f-GNPs; GNP/Py and GNP/APy) in the PK matrix is analyzed by three-dimensional nondestructive X-ray microcomputed tomography, and the increased dispersion state of those fillers results in significant improvement in the water vapor transmission rate (WVTR). The enhancement in WVTR of the PK/GNP/APy nanocomposite film at 1 wt % loading of filler leads to a barrier performance approximately 2 times larger compared to that of PK/GNP nanocomposite film and an approximately 92% reduction in WVTR compared to the case of pristine PK film. We expect that this facile method of graphene functionalization to enhance graphene dispersibility as well as interfacial interaction with the polymer matrix will be widely utilized to expand the potential of graphene materials to barrier film applications.

Glucocorticoid action in human corneal epithelial cells establishes roles for corticosteroids in wound healing and barrier function of the eye.

PubMed

Kadmiel, Mahita; Janoshazi, Agnes; Xu, Xiaojiang; Cidlowski, John A

2016-11-01

Glucocorticoids play diverse roles in almost all physiological systems of the body, including both anti-inflammatory and immunosuppressive roles. Synthetic glucocorticoids are one of the most widely prescribed drugs and are used in the treatment of conditions such as autoimmune diseases, allergies, ocular disorders and certain types of cancers. In the interest of investigating glucocorticoid actions in the cornea of the eye, we established that multiple cell types in mouse corneas express functional glucocorticoid receptor (GR) with corneal epithelial cells having robust expression. To define glucocorticoid actions in a cell type-specific manner, we employed immortalized human corneal epithelial (HCE) cell line to define the glucocorticoid transcriptome and elucidated its functions in corneal epithelial cells. Over 4000 genes were significantly regulated within 6 h of dexamethasone treatment, and genes associated with cell movement, cytoskeletal remodeling and permeability were highly regulated. Real-time in vitro wound healing assays revealed that glucocorticoids delay wound healing by attenuating cell migration. These functional alterations were associated with cytoskeletal remodeling at the wounded edge of a scratch-wounded monolayer. However, glucocorticoid treatment improved the organization of tight-junction proteins and enhanced the epithelial barrier function. Our results demonstrate that glucocorticoids profoundly alter corneal epithelial gene expression and many of these changes likely impact both wound healing and epithelial cell barrier function. Published by Elsevier Ltd.

Stability diagrams for the surface patterns of GaN(0001bar) as a function of Schwoebel barrier height

NASA Astrophysics Data System (ADS)

Krzyżewski, Filip; Załuska-Kotur, Magdalena A.

2017-01-01

Height and type of Schwoebel barriers (direct or inverse) decides about the character of the surface instability. Different surface morphologies are presented. Step bunches, double steps, meanders, mounds and irregular patterns emerge at the surface as a result of step (Schwoebel) barriers at some temperature or miscut values. The study was carried out on the two-component kinetic Monte Carlo (kMC) model of GaN(0001bar) surface grown in nitrogen rich conditions. Diffusion of gallium adatoms over N-polar surface is slow and nitrogen adatoms are almost immobile. We show that in such conditions surfaces remain smooth when gallium adatoms diffuse in the presence of low inverse Schwoebel barrier. It is illustrated by adequate stability diagrams for surface morphologies.

Spin-resolved conductance of Dirac electrons through multibarrier arrays

NASA Astrophysics Data System (ADS)

Dahal, Dipendra; Gumbs, Godfrey; Iurov, Andrii

We use a transfer matrix method to calculate the transmission coefficient of Dirac electrons through an arbitrary number of square potential barrier in gapped monolayer graphene(MLG) and bilayer graphene (BLG). The widths of barriers may not be chosen equal. The shift in the angle of incidence and the width of the barrier required for resonance are investigated numerically for both MLG and BLG. We compare the effects due to energy gap on these two transmission coefficient for each of these two structures (MLG and BLG). We present our results as functions of barrier width, height as well as incoming electron energy as well as band gap and examine the conditions for which perfect reflection or transmission occurs. Our transmission data are further used to calculate conductivity.

Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye

PubMed Central

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

Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye.

PubMed

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.

Mutation of EpCAM leads to intestinal barrier and ion transport dysfunction.

PubMed

Kozan, Philip A; McGeough, Matthew D; Peña, Carla A; Mueller, James L; Barrett, Kim E; Marchelletta, Ronald R; Sivagnanam, Mamata

2015-05-01

Congenital tufting enteropathy (CTE) is a devastating diarrheal disease seen in infancy that is typically associated with villous changes and the appearance of epithelial tufts. We previously found mutations in epithelial cell adhesion molecule (EpCAM) to be causative in CTE. We developed a knock-down cell model of CTE through transfection of an EpCAM shRNA construct into T84 colonic epithelial cells to elucidate the in vitro role of EpCAM in barrier function and ion transport. Cells with EpCAM deficiency exhibited decreased electrical resistance, increased permeability, and decreased ion transport. Based on mutations in CTE patients, an in vivo mouse model was developed, with tamoxifen-inducible deletion of exon 4 in Epcam resulting in mutant protein with decreased expression. Tamoxifen treatment of Epcam (Δ4/Δ4) mice resulted in pathological features of villous atrophy and epithelial tufts, similar to those in human CTE patients, within 4 days post induction. Epcam (Δ4/Δ4) mice also showed decreased expression of tight junctional proteins, increased permeability, and decreased ion transport in the intestines. Taken together, these findings reveal mechanisms that may underlie disease in CTE. Knock-down EpCAM cell model of congenital tufting enteropathy was developed. In vivo inducible mouse model was developed resulting in mutant EpCAM protein. Cells with EpCAM deficiency demonstrated barrier and ion transport dysfunction. Tamoxifen-treated Epcam (Δ4/Δ4) mice demonstrated pathological features. Epcam (Δ4/Δ4) mice showed improper barrier function and ion transport.

Localization or tunneling in asymmetric double-well potentials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Dae-Yup, E-mail: dsong@sunchon.ac.kr

An asymmetric double-well potential is considered, assuming that the wells are parabolic around the minima. The WKB wave function of a given energy is constructed inside the barrier between the wells. By matching the WKB function to the exact wave functions of the parabolic wells on both sides of the barrier, for two almost degenerate states, we find a quantization condition for the energy levels which reproduces the known energy splitting formula between the two states. For the other low-lying non-degenerate states, we show that the eigenfunction should be primarily localized in one of the wells with negligible magnitude inmore » the other. Using Dekker’s method (Dekker, 1987), the present analysis generalizes earlier results for weakly biased double-well potentials to systems with arbitrary asymmetry.« less

Correlative study of functional and structural regeneration of urothelium after chitosan-induced injury.

PubMed

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.

Intestinal barrier function of Atlantic salmon (Salmo salar L.) post smolts is reduced by common sea cage environments and suggested as a possible physiological welfare indicator

PubMed Central

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

Acute treatment with kerosene damages the dermal barrier and alters the distribution of topically applied benzo(a)pyrene in mice.

PubMed

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.

Mechanisms of lung endothelial barrier disruption induced by cigarette smoke: role of oxidative stress and ceramides.

PubMed

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.

Barriers in access to home care services among ethnic minority and Dutch elderly--a qualitative study.

PubMed

Suurmond, Jeanine; Rosenmöller, Doenja L; El Mesbahi, Hakima; Lamkaddem, Majda; Essink-Bot, Marie-Louise

2016-02-01

Ethnic minority elderly have a high prevalence of functional limitations and chronic conditions compared to Dutch elderly. However, their use of home care services is low compared to Dutch elderly. Explore the barriers to access to home care services for Turkish, Moroccan Surinamese and ethnic Dutch elderly. Qualitative semi-structured group interviews and individual interviews. The Netherlands. Seven group interviews (n=50) followed by individual interviews (n=5) were conducted, in the preferred language of the participants. Results were ordered and reported according to a framework of access to health care services. This framework describes five dimensions of accessibility to generate access to health care services, from the perspective of the users: ability to perceive health needs, ability to seek health care, ability to reach, ability to pay and ability to engage. This study shows that while barriers are common among all groups, several specific barriers in access to home care services exist for ethnic minority elderly. Language and communication barriers as well as limited networks and a preference for informal care seem to mutually enforce each other, resulting in many barriers during the navigation process to home care. In order to provide equal access to home care for all who need it, the language and communication barriers should be tackled by home care services and home care nurses. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adenosine A2B receptor modulates intestinal barrier function under hypoxic and ischemia/reperfusion conditions.

PubMed

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.

Evaluation of the activity and safety of CS21 barrier genital gel® compared to topical aciclovir and placebo in symptoms of genital herpes recurrences: a randomized clinical trial.

PubMed

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.

Remediation of groundwater contaminated with the lead-phenol binary system by granular dead anaerobic sludge-permeable reactive barrier.

PubMed

Faisal, Ayad A H; Abd Ali, Ziad T

2017-10-01

Computer solutions (COMSOL) Multiphysics 3.5a software was used for simulating the one-dimensional equilibrium transport of the lead-phenol binary system including the sorption process through saturated sandy soil as the aquifer and granular dead anaerobic sludge (GDAS) as the permeable reactive barrier. Fourier-transform infrared spectroscopy analysis proved that the carboxylic and alcohol groups are responsible for the bio-sorption of lead onto GDAS, while phosphines, aromatic and alkane are the functional groups responsible for the bio-sorption of phenol. Batch tests have been performed to characterize the equilibrium sorption properties of the GDAS and sandy soil in lead and/or phenol containing aqueous solutions. Numerical and experimental results proved that the barrier plays a potential role in the restriction of the contaminant plume migration and there is a linear relationship between longevity and thickness of the barrier. A good agreement between these results was recognized with root mean squared error not exceeding 0.04.

The TNF-α/NF-κB signaling pathway has a key role in methamphetamine–induced blood–brain barrier dysfunction

PubMed Central

Coelho-Santos, Vanessa; Leitão, Ricardo A; Cardoso, Filipa L; Palmela, Inês; Rito, Manuel; Barbosa, Marcos; Brito, Maria A; Fontes-Ribeiro, Carlos A; Silva, Ana P

2015-01-01

Methamphetamine (METH) is a psychostimulant that causes neurologic and psychiatric abnormalities. Recent studies have suggested that its neurotoxicity may also result from its ability to compromise the blood–brain barrier (BBB). Herein, we show that METH rapidly increased the vesicular transport across endothelial cells (ECs), followed by an increase of paracellular transport. Moreover, METH triggered the release of tumor necrosis factor-alpha (TNF-α), and the blockade of this cytokine or the inhibition of nuclear factor-kappa B (NF-κB) pathway prevented endothelial dysfunction. Since astrocytes have a crucial role in modulating BBB function, we further showed that conditioned medium obtained from astrocytes previously exposed to METH had a negative impact on barrier properties also via TNF-α/NF-κB pathway. Animal studies corroborated the in vitro results. Overall, we show that METH directly interferes with EC properties or indirectly via astrocytes through the release of TNF-α and subsequent activation of NF-κB pathway culminating in barrier dysfunction. PMID:25899299

Simultaneous assessment of glomerular filtration and barrier function in live zebrafish

PubMed Central

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

Fission barriers of light nuclei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grotowski, K.; Pl-dash-baraneta, R.; Blann, M.

1989-04-01

Experimental fission excitation functions for compound nuclei /sup 52/Fe, /sup 49/Cr, /sup 46/V, and /sup 44/Ti formed in heavy-ion reactions are analyzed in the Hauser-Feshbach/Bohr-Wheeler formalism using fission barriers based on the rotating liquid drop model of Cohen et al. and on the rotating finite range model of Sierk. We conclude that the rotating finite range approach gives better reproduction of experimental fission yields, consistent with results found for heavier systems.

Hyaluronan 35kDa treatment protects mice from Citrobacter rodentium infection and induces epithelial tight junction protein ZO-1 in vivo.

PubMed

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.

Multiple Rap1 effectors control Epac1-mediated tightening of endothelial junctions.

PubMed

Pannekoek, Willem-Jan; Vliem, Marjolein J; Bos, Johannes L

2018-02-17

Epac1 and Rap1 mediate cAMP-induced tightening of endothelial junctions. We have previously found that one of the mechanisms is the inhibition of Rho-mediated tension in radial stress fibers by recruiting the RhoGAP ArhGAP29 in a complex containing the Rap1 effectors Rasip1 and Radil. However, other mechanisms have been proposed as well, most notably the induction of tension in circumferential actin cables by Cdc42 and its GEF FGD5. Here, we have investigated how Rap1 controls FGD5/Cdc42 and how this interconnects with Radil/Rasip1/ArhGAP29. Using endothelial barrier measurements, we show that Rho inhibition is not sufficient to explain the barrier stimulating effect of Rap1. Indeed, Cdc42-mediated tension is induced at cell-cell contacts upon Rap1 activation and this is required for endothelial barrier function. Depletion of potential Rap1 effectors identifies AF6 to mediate Rap1 enhanced tension and concomitant Rho-independent barrier function. When overexpressed in HEK293T cells, AF6 is found in a complex with FGD5 and Radil. From these results we conclude that Rap1 utilizes multiple pathways to control tightening of endothelial junctions, possibly through a multiprotein effector complex, in which AF6 functions to induce tension in circumferential actin cables.

E. coli O124 K72 alters the intestinal barrier and the tight junctions proteins of guinea pig intestine.

PubMed

Ren, Xiaomeng; Zhu, Yanyan; Gamallat, Yaser; Ma, Shenhao; Chiwala, Gift; Meyiah, Abdo; Xin, Yi

2017-10-01

Our research group previously isolated and identified a strain of pathogenic Escherichia coli from clinical samples called E. coli O124 K72. The present study was aimed at determining the potential effects of E. coli O124 K72 on intestinal barrier functions and structural proteins integrity in guinea pig. Guinea pigs were grouped into three groups; control (CG); E. coli O124 K72 (E. coli); and probiotics Lactobacillus rhamnosus (LGG). Initially, we create intestinal dysbiosis by giving all animals Levofloxacin for 10days, but the control group (CG) received the same volume of saline. Then, the animals received either E. coli O124 K72 (E. coli) or Lactobacillus rhamnosus (LGG) according to their assigned group. E. coli O124 K72 treatment significantly affected colon morphology and distorted intestinal barrier function by up-regulating Claudin2 and down-regulating Occludin. In addition, E. coli upregulated the mRNA expression of MUC1, MUC2, MUC13 and MUC15. Furthermore, suspected tumor was found in the E. coli treated animals. Our results suggested that E. coli O124 K72 strain has adverse effects on intestinal barrier functions and is capable of altering integrity of structural proteins in guinea pig model while at same time it may have a role in colon carcinogenesis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function after Hemorrhagic Shock

PubMed Central

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

Potential Applications of Phyto-Derived Ceramides in Improving Epidermal Barrier Function.

PubMed

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.

Helminthic therapy: improving mucosal barrier function

PubMed Central

Wolff, Martin J.; Broadhurst, Mara J.

2014-01-01

The epidemiology of autoimmune diseases and helminth infections led to suggestions that helminths could improve inflammatory conditions, which was then tested using animal models. This has translated to clinical investigations aimed at the safe and controlled reintroduction of helminthic exposure to patients suffering from autoimmune diseases (so-called “helminthic therapy”) in an effort to mitigate the inflammatory response. In this review, we will summarize the results of recent clinical trials of helminthic therapy, with particular attention to mechanisms of action. Whereas previous reviews have emphasized immune regulatory mechanisms activated by helminths, we propose that enhancement of mucosal barrier function may have an equally important role in improving conditions of inflammatory bowel diseases. PMID:22464690

Delineation of Matriptase Protein Expression by Enzymatic Gene Trapping Suggests Diverging Roles in Barrier Function, Hair Formation, and Squamous Cell Carcinogenesis

PubMed Central

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

Delineation of matriptase protein expression by enzymatic gene trapping suggests diverging roles in barrier function, hair formation, and squamous cell carcinogenesis.

PubMed

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.

DFT studies on the heterogeneous oxidation of SO2 by oxygen functional groups on graphene.

PubMed

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.

Glial-derived neurotrophic factor is essential for blood-nerve barrier functional recovery in an experimental murine model of traumatic peripheral neuropathy.

PubMed

Dong, Chaoling; Helton, E Scott; Zhou, Ping; Ouyang, Xuan; d'Anglemont de Tassigny, Xavier; Pascual, Alberto; López-Barneo, José; Ubogu, Eroboghene E

2018-06-18

There is emerging evidence that glial-derived neurotrophic factor (GDNF) is a potent inducer of restrictive barrier function in tight junction-forming microvascular endothelium and epithelium, including the human blood-nerve barrier (BNB) in vitro. We sought to determine the role of GDNF in restoring BNB function in vivo by evaluating sciatic nerve horseradish peroxidase (HRP) permeability in tamoxifen-inducible GDNF conditional knockout (CKO) adult mice following non-transecting crush injury via electron microscopy, with appropriate wildtype (WT) and heterozygous (HET) littermate controls. A total of 24 age-, genotype- and sex-matched mice >12 weeks of age were injected with 30 mg/kg HRP via tail vein injection 7 or 14 days following unilateral sciatic nerve crush, and both sciatic nerves were harvested 30 minutes later for morphometric assessment by light and electron microscopy. The number and percentage of HRP-permeable endoneurial microvessels were ascertained to determine the effect of GDNF in restoring barrier function in vivo. Following sciatic nerve crush, there was significant upregulation in GDNF protein expression in WT and HET mice that was abrogated in CKO mice. GDNF significantly restored sciatic nerve BNB HRP impermeability to near normal levels by day 7, with complete restoration seen by day 14 in WT and HET mice. A significant recovery lag was observed in CKO mice. This effect was independent on VE-Cadherin or claudin-5 expression on endoneurial microvessels. These results imply an important role of GDNF in restoring restrictive BNB function in vivo, suggesting a potential strategy to re-establish the restrictive endoneurial microenvironment following traumatic peripheral neuropathies.

"State of the Art" of technical protection measures in Austria and the effectiveness documented during bedload and debris flow events

NASA Astrophysics Data System (ADS)

Moser, Markus; Mehlhorn, Susanne; Rudolf-Miklau, Florian; Suda, Jürgen

2017-04-01

Since the beginning of systematic torrent control in Austria 130 years ago, barriers are constructed for protection purposes. Until the end of the 1960s, solid barriers were built at the exits of depositional areas to prevent dangerous debris flows from reaching high consequence areas. The development of solid barriers with large slots or slits to regulate sediment transport began with the use of reinforced concrete during the 1970s (Rudolf-Miklau, Suda 2011). In order to dissipate the energy of debris flows debris flow breakers have been designed since the 1980s. By slowing and depositing the surge front of the debris flow, downstream reaches of the stream channel and settlement areas should be exposed to considerably lower dynamic impact. In the past, the technological development of these constructions was only steered by the experiences of the engineering practice while an institutionalized process of standardization comparable to other engineering branches was not existent. In future all structures have to be designed and dimensioned according to the EUROCODE standards. This was the reason to establish an interdisciplinary working group (ON-K 256) at the Austrian Standards Institute (ASI), which has managed to developed comprehensive new technical standards for torrent control engineering, including load models, design, dimensioning and life cycle assessment of torrent control works (technical standard ONR 24800 - series). Extreme torrential events comprise four definable displacement processes floods; fluvial solid transport; hyper-concentrated solid transport (debris floods) and debris flow (stony debris flow or mud-earth flow). As a rule, the design of the torrential barriers has to follow its function (Kettl, 1984). Modern protection concepts in torrent control are scenario-oriented and try to optimize different functions in a chain of protections structures (function chain). More or less the first step for the designing the optimal construction type is the definition of the displacement processes for each torrent section. The criteria for each process are defined in the technical standard ONR 24800 - series in Austria. According to ONR 24800 the functions of torrential barriers can be divided in process control functional types (retention; dosing and filtering; energy dissipation). The last step is the designing of the construction type. Bedload and debris events in Austria showed the functionality of the barriers. On the basis of these findings and results, some recommendations were derived to improve the function fulfilment of the technical protection measures.

Financial burdens and barriers to care among nonelderly adults: The role of functional limitations and chronic conditions.

PubMed

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.

Sept7b is essential for pronephric function and development of left-right asymmetry in zebrafish embryogenesis.

PubMed

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.

Kinetic Monte Carlo Simulation of Oxygen Diffusion in Ytterbium Disilicate

NASA Astrophysics Data System (ADS)

Good, Brian

2015-03-01

Ytterbium disilicate is of interest as a potential environmental barrier coating for aerospace applications, notably for use in next generation jet turbine engines. In such applications, the diffusion of oxygen and water vapor through these coatings is undesirable if high temperature corrosion is to be avoided. In an effort to understand the diffusion process in these materials, we have performed kinetic Monte Carlo simulations of vacancy-mediated oxygen diffusion in Ytterbium Disilicate. Oxygen vacancy site energies and diffusion barrier energies are computed using Density Functional Theory. We find that many potential diffusion paths involve large barrier energies, but some paths have barrier energies smaller than one electron volt. However, computed vacancy formation energies suggest that the intrinsic vacancy concentration is small in the pure material, with the result that the material is unlikely to exhibit significant oxygen permeability.

Functionality of cooperation between health, welfare and education sectors serving children and families

PubMed Central

Kanste, Outi; Halme, Nina; Perälä, Marja-Leena

2013-01-01

Introduction Children and their families use a lot of different services, which poses challenges in terms of cooperation between service providers. The purpose of the study was to evaluate and compare the functioning of this cooperation between services for children and families in Finland's mainland municipalities from the viewpoints of employees and managers. Method The study was carried out using a cross-sectional survey design. Data were gathered using two postal surveys from employees and managers working in health care, social welfare and educational settings. The data consisted of responses from 457 employees and 327 managers. Results Employees working in primary health care and education services assessed cooperation as working better than did those working in social welfare, special health care or mental health and substance abuse services. Well-functioning cooperation at the operational and strategic level was related to good awareness of services and to agreed and well-functioning cooperation practices with few barriers to cooperation. Employees were more critical than managers concerning the occurrence of barriers and about the agreed cooperation practices. Conclusions Successful cooperation in providing services for children and families requires an awareness of services, management structures that support cooperation, agreed practices and efforts to overcome barriers to cooperation. PMID:24363637

Modelling the endothelial blood-CNS barriers: a method for the production of robust in vitro models of the rat blood-brain barrier and blood-spinal cord barrier.

PubMed

Watson, P Marc D; Paterson, Judy C; Thom, George; Ginman, Ulrika; Lundquist, Stefan; Webster, Carl I

2013-06-18

Modelling the blood-CNS barriers of the brain and spinal cord in vitro continues to provide a considerable challenge for research studying the passage of large and small molecules in and out of the central nervous system, both within the context of basic biology and for pharmaceutical drug discovery. Although there has been considerable success over the previous two decades in establishing useful in vitro primary endothelial cell cultures from the blood-CNS barriers, no model fully mimics the high electrical resistance, low paracellular permeability and selective influx/efflux characteristics of the in vivo situation. Furthermore, such primary-derived cultures are typically labour-intensive and generate low yields of cells, limiting scope for experimental work. We thus aimed to establish protocols for the high yield isolation and culture of endothelial cells from both rat brain and spinal cord. Our aim was to optimise in vitro conditions for inducing phenotypic characteristics in these cells that were reminiscent of the in vivo situation, such that they developed into tight endothelial barriers suitable for performing investigative biology and permeability studies. Brain and spinal cord tissue was taken from the same rats and used to specifically isolate endothelial cells to reconstitute as in vitro blood-CNS barrier models. Isolated endothelial cells were cultured to expand the cellular yield and then passaged onto cell culture inserts for further investigation. Cell culture conditions were optimised using commercially available reagents and the resulting barrier-forming endothelial monolayers were characterised by functional permeability experiments and in vitro phenotyping by immunocytochemistry and western blotting. Using a combination of modified handling techniques and cell culture conditions, we have established and optimised a protocol for the in vitro culture of brain and, for the first time in rat, spinal cord endothelial cells. High yields of both CNS endothelial cell types can be obtained, and these can be passaged onto large numbers of cell culture inserts for in vitro permeability studies. The passaged brain and spinal cord endothelial cells are pure and express endothelial markers, tight junction proteins and intracellular transport machinery. Further, both models exhibit tight, functional barrier characteristics that are discriminating against large and small molecules in permeability assays and show functional expression of the pharmaceutically important P-gp efflux transporter. Our techniques allow the provision of high yields of robust sister cultures of endothelial cells that accurately model the blood-CNS barriers in vitro. These models are ideally suited for use in studying the biology of the blood-brain barrier and blood-spinal cord barrier in vitro and for pre-clinical drug discovery.

Intraepithelial gammadelta+ lymphocytes maintain the integrity of intestinal epithelial tight junctions in response to infection.

PubMed

Dalton, Jane E; Cruickshank, Sheena M; Egan, Charlotte E; Mears, Rainy; Newton, Darren J; Andrew, Elizabeth M; Lawrence, Beth; Howell, Gareth; Else, Kathryn J; Gubbels, Marc-Jan; Striepen, Boris; Smith, Judith E; White, Stanley J; Carding, Simon R

2006-09-01

Intestinal epithelial integrity and permeability is dependent on intercellular tight junction (TJ) complexes. How TJ integrity is regulated remains unclear, although phosphorylation and dephosphorylation of the integral membrane protein occludin is an important determinant of TJ formation and epithelial permeability. We have investigated the role intestinal intraepithelial lymphocytes (iIELs) play in regulating epithelial permeability in response to infection. Recombinant strains of Toxoplasma gondii were used to assess intestinal epithelial barrier function and TJ integrity in mice with intact or depleted populations of iIELs. Alterations in epithelial permeability were correlated with TJ structure and the state of phosphorylation of occludin. iIEL in vivo reconstitution experiments were used to identify the iIELs required to maintain epithelial permeability and TJ integrity. In the absence of gammadelta+ iIELs, intestinal epithelial barrier function and the ability to restrict epithelial transmigration of Toxoplasma and the unrelated intracellular bacterial pathogen Salmonella typhimurium was severely compromised. Leaky epithelium in gammadelta+ iIEL-deficient mice was associated with the absence of phosphorylation of serine residues of occludin and lack of claudin 3 and zona occludens-1 proteins in TJ complexes. These deficiencies were attributable to the absence of a single subset of gammadelta T-cell receptor (TCR-Vgamma7+) iIELs that, after reconstituting gammadelta iIEL-deficient mice, restored epithelial barrier function and TJ complexes, resulting in increased resistance to infection. These findings identify a novel role for gammadelta+ iIELs in maintaining TJ integrity and epithelial barrier function that have implications for understanding the pathogenesis of intestinal inflammatory diseases associated with disruption of TJ complexes.

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.

Reevaluation of the non-lesional dry skin in atopic dermatitis by acute barrier disruption: an abnormal permeability barrier homeostasis with defective processing to generate ceramide.

PubMed

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.

Stage-dependency of apoptosis and the blood-testis barrier in the dogfish shark (Squalus acanthias): cadmium-induced changes as assessed by vital fluorescence techniques.

PubMed

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.

In Vitro Effects of Preserved and Unpreserved Anti-Allergic Drugs on Human Corneal Epithelial Cells

PubMed Central

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

Vocal Fold Epithelial Barrier in Health and Injury A Research Review

PubMed Central

Levendoski, Elizabeth Erickson; Leydon, Ciara; Thibeault, Susan L.

2015-01-01

Purpose Vocal fold epithelium is composed of layers of individual epithelial cells joined by junctional complexes constituting a unique interface with the external environment. This barrier provides structural stability to the vocal folds and protects underlying connective tissue from injury while being nearly continuously exposed to potentially hazardous insults including environmental or systemic-based irritants such as pollutants and reflux, surgical procedures, and vibratory trauma. Small disruptions in the epithelial barrier may have a large impact on susceptibility to injury and overall vocal health. The purpose of this article is to provide a broad-based review of our current knowledge of the vocal fold epithelial barrier. Methods A comprehensive review of the literature was conducted. Details of the structure of the vocal fold epithelial barrier are presented and evaluated in the context of function in injury and pathology. The importance of the epithelial-associated vocal fold mucus barrier is also introduced. Results/Conclusions Information presented in this review is valuable for clinicians and researchers as it highlights the importance of this understudied portion of the vocal folds to overall vocal health and disease. Prevention and treatment of injury to the epithelial barrier is a significant area awaiting further investigation. PMID:24686981

Time dependent semiclassical tunneling through one dimensional barriers using only real valued trajectories

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herman, Michael F.

2015-10-28

The time independent semiclassical treatment of barrier tunneling has been understood for a very long time. Several semiclassical approaches to time dependent tunneling through barriers have also been presented. These typically involve trajectories for which the position variable is a complex function of time. In this paper, a method is presented that uses only real valued trajectories, thus avoiding the complications that can arise when complex trajectories are employed. This is accomplished by expressing the time dependent wave packet as an integration over momentum. The action function in the exponent in this expression is expanded to second order in themore » momentum. The expansion is around the momentum, p{sub 0{sup *}}, at which the derivative of the real part of the action is zero. The resulting Gaussian integral is then taken. The stationary phase approximation requires that the derivative of the full action is zero at the expansion point, and this leads to a complex initial momentum and complex tunneling trajectories. The “pseudo-stationary phase” approximation employed in this work results in real values for the initial momentum and real valued trajectories. The transmission probabilities obtained are found to be in good agreement with exact quantum results.« less

Spintronics with multiferroics

NASA Astrophysics Data System (ADS)

Béa, H.; Gajek, M.; Bibes, M.; Barthélémy, A.

2008-10-01

In this paper, we review the recent research on the functionalization of multiferroics for spintronics applications. We focus more particularly on antiferromagnetic and ferroelectric BiFeO3 and its integration in several types of architectures. For instance, when used as a tunnel barrier, BiFeO3 allows the observation of a large tunnel magnetoresistance with Co and (La,Sr)MnO3 ferromagnetic electrodes. Also, its antiferromagnetic and magnetoelectric properties have been exploited to induce an exchange coupling with a ferromagnet. The mechanisms of such an exchange coupling open ways to electrically control magnetization and possibly the logic state of spintronics devices. We also discuss recent results concerning the use of ferromagnetic and ferroelectric (La,Bi)MnO3 as an active tunnel barrier in magnetic tunnel junctions with Au and (La,Sr)MnO3 electrodes. A four-resistance-state device has been obtained, with two states arising from a spin filtering effect due to the ferromagnetic character of the barrier and two resulting from the ferroelectric behavior of the (La,Bi)MnO3 ultrathin film. These results show that the additional degree of freedom provided by the ferroelectric polarization brings novel functionalities to spintronics, either as a extra order parameter for multiple-state memory elements, or as a handle for gate-controlled magnetic memories.

AKAP9, a Regulator of Microtubule Dynamics, Contributes to Blood-Testis Barrier Function

PubMed Central

Venkatesh, Deepak; Mruk, Dolores; Herter, Jan M.; Cullere, Xavier; Chojnacka, Katarzyna; Cheng, C. Yan; Mayadas, Tanya N.

2017-01-01

The blood-testis barrier (BTB), formed between adjacent Sertoli cells, undergoes extensive remodeling to facilitate the transport of preleptotene spermatocytes across the barrier from the basal to apical compartments of the seminiferous tubules for further development and maturation into spermatozoa. The actin cytoskeleton serves unique structural and supporting roles in this process, but little is known about the role of microtubules and their regulators during BTB restructuring. The large isoform of the cAMP-responsive scaffold protein AKAP9 regulates microtubule dynamics and nucleation at the Golgi. We found that conditional deletion of Akap9 in mice after the initial formation of the BTB at puberty leads to infertility. Akap9 deletion results in marked alterations in the organization of microtubules in Sertoli cells and a loss of barrier integrity despite a relatively intact, albeit more apically localized F-actin and BTB tight junctional proteins. These changes are accompanied by a loss of haploid spermatids due to impeded meiosis. The barrier, however, progressively reseals in older Akap9 null mice, which correlates with a reduction in germ cell apoptosis and a greater incidence of meiosis. However, spermiogenesis remains defective, suggesting additional roles for AKAP9 in this process. Together, our data suggest that AKAP9 and, by inference, the regulation of the microtubule network are critical for BTB function and subsequent germ cell development during spermatogenesis. PMID:26687990

The relationship between skin function, barrier properties, and body-dependent factors.

PubMed

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.

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…

Intestinal Alkaline Phosphatase Regulates Tight Junction Protein Levels

PubMed Central

Liu, Wei; Hu, Dong; Huo, Haizhong; Zhang, Weifeng; Adiliaghdam, Fatemeh; Morrison, Sarah; Ramirez, Juan M; Gul, Sarah S; Hamarneh, Sulaiman R; Hodin, Richard A

2017-01-01

BACKGROUND Intestinal alkaline phosphatase (IAP) plays a pivotal role in maintaining gut health and well-being. Oral supplementation with IAP in mice improves gut barrier function and prevents luminal proinflammatory factors from gaining access to the circulation. In this study, we sought to explore the relationship between IAP and tight junction protein (TJP) expression and function. STUDY DESIGN The effect of IAP deletion on TJP levels was studied in mouse embryonic fibroblasts (MEFs) generated from IAP-knockout and wild type mice. Regulation of TJPs by IAP was assayed in the human colon cancer Caco-2 and T84 cells by overexpressing the human IAP gene. Tight junction protein levels and localization were measured by using RT q-PCR and antibodies targeting the specific TJPs. Finally, the effect of IAP on inflammation-induced intestinal permeability was measured by in vitro trans-well epithelial electrical resistance (TEER). RESULTS Intestinal alkaline phosphatase gene deletion in MEFs resulted in significantly lower levels of ZO-1, ZO-2, and Occludin compared with levels in wild-type control cells; IAP over-expression in Caco-2 and T84 cells resulted in approximate 2-fold increases in the mRNA levels of ZO-1 and ZO-2. The IAP treatment ameliorated lipopolysaccharide-induced increased permeability in the Caco-2 trans-well system. Furthermore, IAP treatment preserved the localization of the ZO-1 and Occludin proteins during inflammation and was also associated with improved epithelial barrier function. CONCLUSIONS Intestinal alkaline phosphatase is a major regulator of gut mucosal permeability and appears to work at least partly through improving TJP levels and localization. These data provide a strong foundation to develop IAP as a novel therapy to maintain gut barrier function. PMID:27106638

An isotope dilution gas chromatography/mass spectrometry method for trace analysis of xylene and its metabolites in tissues following threshold limit value exposures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pyon, K.H.; Kracko, D.A.; Strunk, M.R.

1995-12-01

The existence of a nose-brain barrier that functions to protect the central nervous system (CNS) from inhaled toxicants has been postulated. Just as a blood-brain barrier protects the CNS from systemic toxicants, the nose-brain barrier may have similar characteristic functions. One component of interest is nasal xenobiotic metabolism and its effect on the transport of pollutants into the CNS at environmentally plausible levels of exposure. Previous results have shown that inhaled xylene are dimethyl phenol (DMP) and methyl benzyl alcohol (MBA), and the nonvolatile metabolites are toluic acid (TA) and methyl hippuric acid (MHA). The nonvolatile metabolites of xylene, alongmore » with a small quantity of volatiles, representing either parent xylene or volatile metabolites, are transported via the olfactory epithelium to the glomeruli within the olfactory bulbs of the brain. Further work will be done to establish the linearity for each analyte at the actual highest detection limit of the GC/MS.« less

Curcumin-mediated regulation of intestinal barrier function: The mechanism underlying its beneficial effects.

PubMed

Ghosh, Siddhartha S; He, Hongliang; Wang, Jing; Gehr, Todd W; Ghosh, Shobha

2018-01-02

Curcumin has anti-inflammatory, anti-oxidant and anti-proliferative properties established largely by in vitro studies. Accordingly, oral administration of curcumin beneficially modulates many diseases including diabetes, fatty-liver disease, atherosclerosis, arthritis, cancer and neurological disorders such as depression, Alzheimer's or Parkinson's disease. However, limited bioavailability and inability to detect curcumin in circulation or target tissues has hindered the validation of a causal role. We established curcumin-mediated decrease in the release of gut bacteria-derived lipopolysaccharide (LPS) into circulation by maintaining the integrity of the intestinal barrier function as the mechanism underlying the attenuation of metabolic diseases (diabetes, atherosclerosis, kidney disease) by curcumin supplementation precluding the need for curcumin absorption. In view of the causative role of circulating LPS and resulting chronic inflammation in the development of diseases listed above, this review summarizes the mechanism by which curcumin affects the several layers of the intestinal barrier and, despite negligible absorption, can beneficially modulate these diseases.

Oxygen self-diffusion mechanisms in monoclinic Zr O2 revealed and quantified by density functional theory, random walk analysis, and kinetic Monte Carlo calculations

NASA Astrophysics Data System (ADS)

Yang, Jing; Youssef, Mostafa; Yildiz, Bilge

2018-01-01

In this work, we quantify oxygen self-diffusion in monoclinic-phase zirconium oxide as a function of temperature and oxygen partial pressure. A migration barrier of each type of oxygen defect was obtained by first-principles calculations. Random walk theory was used to quantify the diffusivities of oxygen interstitials by using the calculated migration barriers. Kinetic Monte Carlo simulations were used to calculate diffusivities of oxygen vacancies by distinguishing the threefold- and fourfold-coordinated lattice oxygen. By combining the equilibrium defect concentrations obtained in our previous work together with the herein calculated diffusivity of each defect species, we present the resulting oxygen self-diffusion coefficients and the corresponding atomistically resolved transport mechanisms. The predicted effective migration barriers and diffusion prefactors are in reasonable agreement with the experimentally reported values. This work provides insights into oxygen diffusion engineering in Zr O2 -related devices and parametrization for continuum transport modeling.

Cohesiveness tunes assembly and morphology of FG nucleoporin domain meshworks – Implications for nuclear pore permeability

PubMed Central

Eisele, Nico B.; Labokha, Aksana A.; Frey, Steffen; Görlich, Dirk; Richter, Ralf P.

2013-01-01

Nuclear pore complexes control the exchange of macromolecules between the cytoplasm and the nucleus. A selective permeability barrier that arises from a supramolecular assembly of intrinsically unfolded nucleoporin domains rich in phenylalanine-glycine dipeptides (FG domains) fills the nuclear pore. There is increasing evidence that selective transport requires cohesive FG domain interactions. To understand the functional roles of cohesive interactions, we studied monolayers of end-grafted FG domains as a bottom-up nanoscale model system of the permeability barrier. Based on detailed physicochemical analysis of the model films and comparison of the data with polymer theory, we propose that cohesiveness is tuned to promote rapid assembly of the permeability barrier and to generate a stable and compact pore-filling meshwork with a small mesh size. Our results highlight the functional importance of weak interactions, typically a few kBT per chain, and contribute important information to understand the mechanism of size-selective transport. PMID:24138862

Chiral tunneling in gated inversion symmetric Weyl semimetal.

PubMed

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.

Potential of Lactobacillus plantarum CCFM639 in Protecting against Aluminum Toxicity Mediated by Intestinal Barrier Function and Oxidative Stress.

PubMed

Yu, Leilei; Zhai, Qixiao; Tian, Fengwei; Liu, Xiaoming; Wang, Gang; Zhao, Jianxin; Zhang, Hao; Narbad, Arjan; Chen, Wei

2016-12-02

Aluminum (Al) is a ubiquitous metal that can seriously harm the health of animals and humans. In our previous study, we demonstrated that Lactobacillus plantarum CCFM639 can decrease Al burden in the tissues of mice by inhibiting intestinal Al absorption. The main aim of the present research was to investigate whether the protection by the strain is also associated with enhancement of the intestinal barrier, alleviation of oxidative stress and modulation of the inflammatory response. In an in vitro cell model, two protection modes (intervention and therapy) were examined and the results indicated that L. plantarum CCFM639 alleviated Al-induced cytotoxicity. In a mouse model, L. plantarum CCFM639 treatment was found to significantly alleviate oxidative stress in the intestinal tract, regulate the function of the intestinal mucosal immune system, restore the integrity of tight junction proteins and maintain intestinal permeability. These results suggest that in addition to Al sequestration, L. plantarum CCFM639 can also inhibit Al absorption by protecting the intestinal barrier, alleviating Al-induced oxidative stress and inflammatory response. Therefore, L. plantarum CCFM639 has the potential to be a dietary supplement ingredient that provides protection against Al-induced gut injury.

Bifidobacterium breve prevents necrotising enterocolitis by suppressing inflammatory responses in a preterm rat model.

PubMed

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.

Chiral tunneling in gated inversion symmetric Weyl semimetal

PubMed Central

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

Tuning the tunneling magnetoresistance by using fluorinated graphene in graphene based magnetic junctions

NASA Astrophysics Data System (ADS)

Meena, Shweta; Choudhary, Sudhanshu

2017-12-01

Spin polarized properties of fluorinated graphene as tunnel barrier with CrO2 as two HMF electrodes are studied using first principle methods based on density functional theory. Fluorinated graphene with different fluorine coverages is explored as tunnel barriers in magnetic tunnel junctions. Density functional computation for different fluorine coverages imply that with increase in fluorine coverages, there is increase in band gap (Eg) of graphene, Eg ˜ 3.466 e V was observed when graphene sheet is fluorine adsorbed on both-side with 100% coverage (CF). The results of CF graphene are compared with C4F (fluorination on one-side of graphene sheet with 25% coverage) and out-of-plane graphene based magnetic tunnel junctions. On comparison of the results it is observed that CF graphene based structure offers high TMR ˜100%, and the transport of carrier is through tunneling as there are no transmission states near Fermi level. This suggests that graphene sheet with both-side fluorination with 100% coverages acts as a perfect insulator and hence a better barrier to the carriers which is due to negligible spin down current (I ↓ ) in both Parallel Configuration (PC) and Antiparallel Configuration (APC).

Experimental investigation of defect-assisted and intrinsic water vapor permeation through ultrabarrier films

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

Barrier properties of cultured retinal pigment epithelium.

PubMed

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.

Universal functions of nuclear proximity potential for Skyrme nucleus-nucleus interaction in a semiclassical approach

NASA Astrophysics Data System (ADS)

Gupta, Raj K.; Singh, Dalip; Kumar, Raj; Greiner, Walter

2009-07-01

The universal function of the nuclear proximity potential is obtained for the Skyrme nucleus-nucleus interaction in the semiclassical extended Thomas-Fermi (ETF) approach. This is obtained as a sum of the spin-orbit-density-independent and spin-orbit-density-dependent parts of the Hamiltonian density, since the two terms behave differently, the spin-orbit-density-independent part mainly attractive and the spin-orbit-density-dependent part mainly repulsive. The semiclassical expansions of kinetic energy density and spin-orbit density are allowed up to second order, and the two-parameter Fermi density, with its parameters fitted to experiments, is used for the nuclear density. The universal functions or the resulting nuclear proximity potential reproduce the 'exact' Skyrme nucleus-nucleus interaction potential in the semiclassical approach, within less than ~1 MeV of difference, both at the maximum attraction and in the surface region. An application of the resulting interaction potential to fusion excitation functions shows clearly that the parameterized universal functions of nuclear proximity potential substitute completely the 'exact' potential in the Skyrme energy density formalism based on the semiclassical ETF method, including also the modifications of interaction barriers at sub-barrier energies in terms of modifying the constants of the universal functions.

Impact of humidity on functionality of on-paper printed electronics.

PubMed

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.

A Key Claudin Extracellular Loop Domain is Critical for Epithelial Barrier Integrity

PubMed Central

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

Defenders and Challengers of Endothelial Barrier Function

PubMed Central

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

The Functions of Grainy Head-Like Proteins in Animals and Fungi and the Evolution of Apical Extracellular Barriers

PubMed Central

Paré, Adam; Kim, Myungjin; Juarez, Michelle T.; Brody, Stuart; McGinnis, William

2012-01-01

The Grainy head (GRH) family of transcription factors are crucial for the development and repair of epidermal barriers in all animals in which they have been studied. This is a high-level functional conservation, as the known structural and enzymatic genes regulated by GRH proteins differ between species depending on the type of epidermal barrier being formed. Interestingly, members of the CP2 superfamily of transcription factors, which encompasses the GRH and LSF families in animals, are also found in fungi – organisms that lack epidermal tissues. To shed light on CP2 protein function in fungi, we characterized a Neurospora crassa mutant lacking the CP2 member we refer to as grainy head-like (grhl). We show that Neurospora GRHL has a DNA-binding specificity similar to that of animal GRH proteins and dissimilar to that of animal LSF proteins. Neurospora grhl mutants are defective in conidial-spore dispersal due to an inability to remodel the cell wall, and we show that grhl mutants and the long-known conidial separation-2 (csp-2) mutants are allelic. We then characterized the transcriptomes of both Neurospora grhl mutants and Drosophila grh mutant embryos to look for similarities in the affected genes. Neurospora grhl appears to play a role in the development and remodeling of the cell wall, as well as in the activation of genes involved in defense and virulence. Drosophila GRH is required to activate the expression of many genes involved in cuticular/epidermal-barrier formation. We also present evidence that GRH plays a role in adult antimicrobial defense. These results, along with previous studies of animal GRH proteins, suggest the fascinating possibility that the apical extracellular barriers of some animals and fungi might share an evolutionary connection, and that the formation of physical barriers in the last common ancestor was under the control of a transcriptional code that included GRH-like proteins. PMID:22590528

Effect of barrier perturbation on cutaneous penetration of salicylic acid in hairless rats: in vivo pharmacokinetics using microdialysis and non-invasive quantification of barrier function.

PubMed

Benfeldt, E; Serup, J

1999-09-01

The penetration of topically applied drugs is altered in diseased or barrier-damaged skin. We used microdialysis in the dermis to measure salicylic acid (SA) penetration in hairless rats following application to normal (unmodified) skin (n = 11) or skin with perturbed barrier function from (1) tape-stripping (n = 5), (2) sodium lauryl sulphate (SLS) 2% for 24 h (n = 3) or (3) delipidization by acetone (n = 4). Prior to the experiment, transepidermal water loss (TEWL) and erythema were measured. Two microdialysis probes were inserted into the dermis on the side of the trunk and 5% SA in ethanol was applied in a chamber overlying the probes. Microdialysis sampling was continued for 4 h, followed by measurements of probe depth by ultrasound scanning. SA was detectable in all samples and rapidly increasing up to 130 min. Microdialysates collected between 80 and 200 min showed mean SA concentrations of 3 microg/ml in unmodified and acetone-treated skin, whereas mean SA concentrations were 280 microg/ml in SLS-pretreated skin and 530 microg/ml in tape-stripped skin (P < 0.001). The penetration of SA correlated with barrier perturbation measured by TEWL (P < 0.001) and erythema (P < 0.001). A correlation between dermal probe depth and SA concentration was found in unmodified skin (P = 0.04). Microdialysis sampling in anatomical regions remote from the dosed site excluded the possibility that SA levels measured were due to systemic absorption. Microdialysis sampling of cutaneous penetration was highly reproducible. Impaired barrier function, caused by irritant dermatitis or tape stripping, resulted in an 80- to 170-fold increase in the drug level in the dermis. This dramatic increase in drug penetration could be relevant to humans, in particular to topical treatment of skin diseases and to occupational toxicology.

Suitability of polystyrene as a functional barrier layer in coloured food contact materials.

PubMed

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.

Wet Work and Barrier Function.

PubMed

Fartasch, Manigé

2016-01-01

Wet work defined as unprotected exposure to humid environments/water; high frequencies of hand washing procedures or prolonged glove occlusion is believed to cause irritant contact dermatitis in a variety of occupations. This review considers the recent studies on wet-work exposure and focuses on its influence on barrier function. There are different methods to study the effect of wet work on barrier function. On the one hand, occupational cohorts at risk can be monitored prospectively by skin bioengineering technology and clinical visual scoring systems; on the other hand, experimental test procedures with defined application of water, occlusion and detergents are performed in healthy volunteers. Both epidemiological studies and the results of experimental procedures are compared and discussed. A variety of epidemiological studies analyze occupational cohorts at risk. The measurement of transepidermal water loss, an indicator of the integrity of the epidermal barrier, and clinical inspection of the skin have shown that especially the frequencies of hand washing and water contact/contact to aqueous mixtures seem to be the main factors for the occurrence of barrier alterations. On the other hand, in a single cross-sectional study, prolonged glove wearing (e.g. occlusion for 6 h per shift in clean-room workers) without exposure to additional hazardous substances seemed not to affect the skin negatively. But regarding the effect of occlusion, there is experimental evidence that previously occluded skin challenged with sodium lauryl sulfate leads to an increased susceptibility to the irritant with an aggravation of the irritant reaction. These findings might have relevance for the real-life situation in so far as after occupational glove wearing, the skin is more susceptible to potential hazards to the skin even during leisure hours. © 2016 S. Karger AG, Basel.

Dysfunctions at human intestinal barrier by water-borne protozoan parasites: lessons from cultured human fully differentiated colon cancer cell lines.

PubMed

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.

Optimizing Barrier Removal to Restore Connectivity in Utah's Weber Basin

NASA Astrophysics Data System (ADS)

Kraft, M.; Null, S. E.

2016-12-01

Instream barriers, such as dams, culverts and diversions are economically important for water supply, but negatively affect river ecosystems and disrupt hydrologic processes. Removal of uneconomical and aging in-stream barriers to improve habitat connectivity is increasingly used to restore river connectivity. Most past barrier removal projects focused on individual barriers using a score-and-rank technique, ignoring cumulative change from multiple, spatially-connected barrier removals. Similarly, most water supply models optimize either human water use or aquatic connectivity, failing to holistically represent human and environmental benefits. In this study, a dual objective optimization model identified in-stream barriers that impede aquatic habitat connectivity for trout, using streamflow, temperature, and channel gradient as indicators of aquatic habitat suitability. Water scarcity costs are minimized using agricultural and urban economic penalty functions to incorporate water supply benefits and a budget monetizes costs of removing small barriers like culverts and road crossings. The optimization model developed is applied to a case study in Utah's Weber basin to prioritize removal of the most environmentally harmful barriers, while maintaining human water uses. The dual objective solution basis was developed to quantify and graphically visualize tradeoffs between connected quality-weighted habitat for Bonneville cutthroat trout and economic water uses. Modeled results include a spectrum of barrier removal alternatives based on budget and quality-weighted reconnected habitat that can be communicated with local stakeholders. This research will help prioritize barrier removals and future restoration decisions. The modeling approach expands current barrier removal optimization methods by explicitly including economic and environmental water uses.

Gut barrier in health and disease: focus on childhood.

PubMed

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.

Neuroglian, Gliotactin, and the Na+/K+ ATPase are essential for septate junction function in Drosophila

PubMed Central

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

Neuroglian, Gliotactin, and the Na+/K+ ATPase are essential for septate junction function in Drosophila.

PubMed

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.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robledo, L. M.; Baldo, M.; Schuck, P.

We explore the deformation properties of the newly postulated Barcelona-Catania-Paris (BCP) energy density functional (EDF). The results obtained for three isotope chains of Mg, Dy, and Ra are compared to the available experimental data as well as to the results of the Gogny-D1S force. Results for the fission barrier of {sup 240}Pu are also discussed.

Relationships between chemical structure and rat repellency. II. Compounds screened between 1950 and 1960

USGS Publications Warehouse

Bowles, W.A.; Adomaitis, V.A.; DeWitt, J.B.; Pratt, J.J.

1974-01-01

Over 4,600 compounds, chiefly organic types, were evaluated using both a food acceptance test (Part A) and a barrier penetration bioassay (Part B), to correlate relationships between chemical structure and rodent repellency.These chemicals are indexed and classified according to the functional groups present and to the degree of substitution within their molecular structures. The results of reduction in foot consumption for each compound appraised are calculated and their K values listed in Table I.The repellent activities of the functional groups represented, alone or in combinations, are expressed in Table II by a Functional Group Repellency Index. A ranking of these indices suggests that acyclic and heteroyclic compounds containing tri- or pentavalent nitrogen would be a parent compound of choice for synthesizing novel repellents. Other molecular arrangements, spatial configurations and combinations of functional groups are compared.There were 123 active, interesting or promising compounds included in the 699 having K values of 85 or greater, which were selected for the barrier appraisal study. These chemicals were formulated in selective solvents at several concentrations and applied to burlap. Small foot bags were fashioned using the fabric impregnated with the candidate formulation, and exposed to rodent attack following storage periods of varying intervals. The results of these tests are listed in Table III. Again, those compounds containing nitrogen in the functional groupings indicated a high order of effectiveness. Several commercial patents covering rodent repellents were issued using the data from the food acceptance and barrier studies.Organizations and cooperators which supplied samples for the program are listed in Appendix I. The Wiswesser cipher for compounds in Table I is used in Appendix II to facilitate location of chemicals by sample code number as they appear under the index headings, and for computer storage and analysis.

Relationships between chemical structure and rat repellency: II. compounds screened between 1950 and 1960

USGS Publications Warehouse

Bowles, Walter A.; Adomaitis, V.A.; DeWitt, J.B.; Pratt, J.J.

1974-01-01

Over 4,600 compounds, chiefly organic types, were evaluated using both a food acceptance test (Part A) and a barrier penetration bioassay (Part B), to correlate relationships between chemical structure and rodent repellency. These chemicals are indexed and classified according to the functional groups present and to the degree of substitution within their molecular structures. The results of reduction in food consumption for each compound appraised are calculated and their K values listed in Table 1. The repellent activities of the functional groups represented, alone or in combinations, are expressed in Table II by a Functional Group Repellency Index.. A ranking of these indices suggests that acyclic and heteroyclic compounds containing tri- or pentavalent nitrogen would be a parent compound of choice for synthesizing novel repellents. Other molecular arrangements, spatial configurations and combinations of functional groups are compared. There were 123 active, interesting or promising compounds included in the 699 having K values of 85 or greater, which were selected for the barrier appraisal study. These chemicals were formulated in selective solvents at several concentrations and applied to burlap. Small food bags were fashioned using the fabric impregnated with the candidate formulation, and exposed to rodent attack following storage periods of varying intervals. The results of these tests are listed in Table III. Again, those compounds containing nitrogen in the functional groupings indicated a high order of effectiveness. Several commercial patents covering rodent repellents were issued using the data from the food acceptance and barrier studies. Organizations and cooperators which supplied samples for the program are listed in Appendix I. The Wiswesser cipher for compounds in Table I is used in Appendix II to facilitate location of chemicals by sample code number as they appear under the index headings, and for computer storage and analysis.

Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System.

PubMed

Withers, David R; Hepworth, Matthew R

2017-01-01

The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of "exogenous" signals, such as dietary metabolites and commensal microbes, and "endogenous" host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a "communications hub" in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell-cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases.

Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System

PubMed Central

Withers, David R.; Hepworth, Matthew R.

2017-01-01

The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of “exogenous” signals, such as dietary metabolites and commensal microbes, and “endogenous” host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a “communications hub” in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell–cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases. PMID:29085366

Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

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

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.

Biosensor Technology Reveals the Disruption of the Endothelial Barrier Function and the Subsequent Death of Blood Brain Barrier Endothelial Cells to Sodium Azide and Its Gaseous Products.

PubMed

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.

Resonant activation in a colored multiplicative thermal noise driven closed system.

PubMed

Ray, Somrita; Mondal, Debasish; Bag, Bidhan Chandra

2014-05-28

In this paper, we have demonstrated that resonant activation (RA) is possible even in a thermodynamically closed system where the particle experiences a random force and a spatio-temporal frictional coefficient from the thermal bath. For this stochastic process, we have observed a hallmark of RA phenomena in terms of a turnover behavior of the barrier-crossing rate as a function of noise correlation time at a fixed noise variance. Variance can be fixed either by changing temperature or damping strength as a function of noise correlation time. Our another observation is that the barrier crossing rate passes through a maximum with increase in coupling strength of the multiplicative noise. If the damping strength is appreciably large, then the maximum may disappear. Finally, we compare simulation results with the analytical calculation. It shows that there is a good agreement between analytical and numerical results.

Feasibility of antihydrogen atom containment in helium: a problem of electron-positron correlation investigated by the Monte Carol method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jackman, T.M.

1987-01-01

A theoretical investigation of the interaction potential between the helium atom and the antihydrogen atom was performed for the purpose of determining the feasibility of antihydrogen atom containment. The interaction potential showed an energy barrier to collapse of this system. A variational estimate of the height of this energy barrier and estimates of lifetime with respect to electron-positron annihilation were determined by the Variational Monte Carlo method. This calculation allowed for an improvement over an SCF result through the inclusion of explicit correlation factors in the trial wave function. An estimate of the correlation energy of this system was determinedmore » by the Green's Function Monte Carlo (GFMC) method.« less

Intestinal epithelial barrier function and tight junction proteins with heat and exercise

PubMed Central

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

Intestinal epithelial barrier function and tight junction proteins with heat and exercise.

PubMed

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.

Trajectory-based understanding of the quantum-classical transition for barrier scattering

NASA Astrophysics Data System (ADS)

Chou, Chia-Chun

2018-06-01

The quantum-classical transition of wave packet barrier scattering is investigated using a hydrodynamic description in the framework of a nonlinear Schrödinger equation. The nonlinear equation provides a continuous description for the quantum-classical transition of physical systems by introducing a degree of quantumness. Based on the transition equation, the transition trajectory formalism is developed to establish the connection between classical and quantum trajectories. The quantum-classical transition is then analyzed for the scattering of a Gaussian wave packet from an Eckart barrier and the decay of a metastable state. Computational results for the evolution of the wave packet and the transmission probabilities indicate that classical results are recovered when the degree of quantumness tends to zero. Classical trajectories are in excellent agreement with the transition trajectories in the classical limit, except in some regions where transition trajectories cannot cross because of the single-valuedness of the transition wave function. As the computational results demonstrate, the process that the Planck constant tends to zero is equivalent to the gradual removal of quantum effects originating from the quantum potential. This study provides an insightful trajectory interpretation for the quantum-classical transition of wave packet barrier scattering.

Barriers and facilitators of sports in Dutch Paralympic athletes: An explorative study.

PubMed

Jaarsma, E A; Geertzen, J H B; de Jong, R; Dijkstra, P U; Dekker, R

2014-10-01

The purpose of this study was to gain insight in barriers and facilitators of sports in paralympic athletes. An online questionnaire was distributed through the Netherlands Olympic Committee and National Sports Confederation to determine personal and environmental barriers and facilitators of sports participation. The International Classification of Functioning, Disability and Health model and theory of planned behavior were used to respectively categorize the results in environmental and personal factors, and attitude, subjective norm and perceived behavioral control. Seventy-six Dutch Paralympic athletes completed the questionnaire (51% response rate). Barriers and facilitators experienced by ambulant and wheelchair athletes were compared. Most frequently mentioned personal barrier was dependency of others (22%), while most frequently mentioned environmental barrier was lack of sports facilities (30%). Wheelchair athletes mentioned more barriers (median = 3, interquartile range: 0.5-6), than ambulant athletes (median = 1.0,interquartile range:0.0-3.0, P = 0.023). One-third of the athletes did not experience any barriers. Most frequently mentioned personal facilitators to initiate sports participation were fun (78%), health (61%), and competition (53%). Most frequently mentioned environmental facilitator was social support (40%). This study indicated that barriers of sport were mostly environmental, while facilitators were usually personal factors. Attitude and subjective norm were considered the most important components for intention to participation in sports. The facilitators outweighed the barriers and kept the athletes being active in sports. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Workplace barriers encountered by employed persons with systemic sclerosis.

PubMed

Poole, Janet L; Anwar, Sahar; Mendelson, Cindy; Allaire, Saralynn

2016-01-01

Systemic sclerosis (SSc) is an auto-immune connective tissue disease characterized by fibrosis of skin, blood vessels, and internal organs that results in significant disability. To identify the work barriers faced by people with systemic sclerosis (SSc) in maintaining employment. Thirty-six people with SSc who were working more than 8 hours per week completed the Work Experience Survey, which contains lists of potential work barriers, including the ability to travel to and from work; get around at work; perform essential job functions, including physical, cognitive, and task-related activities; work with others; and manage work conditions. Thirty-three participants completed and returned the questionnaires, most of whom were female, and working full time and in professional careers. Principal disease symptoms included fatigue, Raynaud's phenomenon, esophageal involvement, and leg or hand/wrist pain. All participants reported some barriers with a mean of 18 barriers per participant. At least three quarters of participants cited outside temperature (82%), cold temperatures inside the workplace (76%), and household work (76%), as barriers. The next most common barriers were using both hands (64%), arranging and taking part in social activities (64%), being able to provide self-care (61%) and working 8 hours (58%). Participants reported a wide range of barriers, from cold temperatures, to physical job, fatigue related, and non-workplace demands, in maintaining the worker role. The barriers reflect the disease symptoms they reported. Identifying workplace barriers facilitates the creation of job accommodations or adaptations that will allow people with SSc to continue working.

Kinetic barriers for Cd and Te adatoms on Cd and Te terminated CdTe (111) surface using ab initio simulations

NASA Astrophysics Data System (ADS)

Naderi, Ebadollah; Nanavati, Sachin P.; Majumder, Chiranjib; Ghaisas, S. V.

2014-03-01

In the present work we have calculated using density functional theory (DFT), diffusion barrier potentials on both the CdTe (111) surfaces, Cd terminated (A-type) & Te terminated (B-type). We employ nudge elastic band method (NEB) for obtaining the barrier potentials. The barrier is computed for Cd and for Te adatoms on both A-type and B-type surfaces. We report two energetically favourable positions along the normal to the surface, one above and other below the surface. The one above the surface has binding energy slightly more the one below. According to the results of this work, binding energy (in all cases) for adatoms are reasonable and close to experimental data. The barrier potential for hopping adatoms (Cd and Te) on both the surfaces is less than 0.35 eV. Apart from these most probable sites, there are other at least two sites on both the types of surfaces which are meta stable. We have also computed barriers for hopping to and from these meta stable positions. The present results can shade light on the defect formation mechanism in CdTe thin films during growth. The authors would like to thank C-DAC for the computing time on its PARAM series of supercomputers and DST Govt. of India, for partial funding.

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

Possible origin and roles of nano-porosity in ZrO2 scales for hydrogen pick-up in Zr alloys

NASA Astrophysics Data System (ADS)

Lindgren, Mikaela; Geers, Christine; Panas, Itai

2017-08-01

A mechanistic understanding of Wagnerian build-up and subsequent non-Wagnerian break-down of barrier oxide upon oxidation of zirconium alloys by water is reiterated. Hydrogen assisted build-up of nano-porosity is addressed. Growth of sub-nanometer wide stalactitic pores owing to increasing aggregation of neutral oxygen vacancies offering a means to permeate hydrogen into the alloy is explored by density functional theory. The Wagnerian channel utilizes charge separation allowing charged oxygen vacancies and electrons to move separately from nominal anode to nominal cathode. This process becomes increasingly controlled by the charging of the barrier oxide resulting in sub-parabolic rate law for oxide growth. The break-down of the barrier oxide is understood to be preceded by avalanching hydrogen pick-up in the alloy. Pore mediated diffusion allows water to effectively short circuit the barrier oxide.

Norrin/Frizzled4 signaling in retinal vascular development and blood brain barrier plasticity.

PubMed

Wang, Yanshu; Rattner, Amir; Zhou, Yulian; Williams, John; Smallwood, Philip M; Nathans, Jeremy

2012-12-07

Norrin/Frizzled4 (Fz4) signaling activates the canonical Wnt pathway to control retinal vascular development. Using genetically engineered mice, we show that precocious Norrin production leads to premature retinal vascular invasion and delayed Norrin production leads to characteristic defects in intraretinal vascular architecture. In genetic mosaics, wild-type endothelial cells (ECs) instruct neighboring Fz4(-/-) ECs to produce an architecturally normal mosaic vasculature, a cell nonautonomous effect. However, over the ensuing weeks, Fz4(-/-) ECs are selectively eliminated from the mosaic vasculature, implying the existence of a quality control program that targets defective ECs. In the adult retina and cerebellum, gain or loss of Norrin/Fz4 signaling results in a cell-autonomous gain or loss, respectively, of blood retina barrier and blood brain barrier function, indicating an ongoing requirement for Frizzled signaling in barrier maintenance and substantial plasticity in mature CNS vascular structure. Copyright © 2012 Elsevier Inc. All rights reserved.

Barrier inhomogeneities at vertically stacked graphene-based heterostructures.

PubMed

Lin, Yen-Fu; Li, Wenwu; Li, Song-Lin; Xu, Yong; Aparecido-Ferreira, Alex; Komatsu, Katsuyoshi; Sun, Huabin; Nakaharai, Shu; Tsukagoshi, Kazuhito

2014-01-21

The integration of graphene and other atomically flat, two-dimensional materials has attracted much interest and been materialized very recently. An in-depth understanding of transport mechanisms in such heterostructures is essential. In this study, vertically stacked graphene-based heterostructure transistors were manufactured to elucidate the mechanism of electron injection at the interface. The temperature dependence of the electrical characteristics was investigated from 300 to 90 K. In a careful analysis of current-voltage characteristics, an unusual decrease in the effective Schottky barrier height and increase in the ideality factor were observed with decreasing temperature. A model of thermionic emission with a Gaussian distribution of barriers was able to precisely interpret the conduction mechanism. Furthermore, mapping of the effective Schottky barrier height is unmasked as a function of temperature and gate voltage. The results offer significant insight for the development of future layer-integration technology based on graphene-based heterostructures.

Graphene barristor, a triode device with a gate-controlled Schottky barrier.

PubMed

Yang, Heejun; Heo, Jinseong; Park, Seongjun; Song, Hyun Jae; Seo, David H; Byun, Kyung-Eun; Kim, Philip; Yoo, InKyeong; Chung, Hyun-Jong; Kim, Kinam

2012-06-01

Despite several years of research into graphene electronics, sufficient on/off current ratio I(on)/I(off) in graphene transistors with conventional device structures has been impossible to obtain. We report on a three-terminal active device, a graphene variable-barrier "barristor" (GB), in which the key is an atomically sharp interface between graphene and hydrogenated silicon. Large modulation on the device current (on/off ratio of 10(5)) is achieved by adjusting the gate voltage to control the graphene-silicon Schottky barrier. The absence of Fermi-level pinning at the interface allows the barrier's height to be tuned to 0.2 electron volt by adjusting graphene's work function, which results in large shifts of diode threshold voltages. Fabricating GBs on respective 150-mm wafers and combining complementary p- and n-type GBs, we demonstrate inverter and half-adder logic circuits.

Inclusion of Indium, with doping in the barriers of InxGa1-xN/InyGa1-yN quantum wells reveals striking modifications of the emission properties with current for better operation of LEDs

NASA Astrophysics Data System (ADS)

Gorai, Anup; Mistry, Apu; Panda, Siddhartha; Biswas, Dipankar

2018-02-01

Although that the continuous tunability of InGaN/GaN QW LEDs, carries the promise of a significant impact in optoelectronics, the reduction of the square of the overlap of electron and hole wave functions (Meh2) in InGaN/GaN QW LEDs, under certain conditions, is a sizable problem, difficult to overcome. Theoretical investigations have been carried out on the incorporation of Indium (In) in the GaN barrier layers, with an aim of increasing the overlap of electron and hole wave functions. Rigorous studies through the self consistent solution of Schrödinger and Poison equations expose some new and striking results. With suitable doping, the inclusion of In in the barriers can increase Meh2 to more than two times that of a conventional InGaN/GaN QW LED. In in the barrier along with doping may be suitably utilized to tailor the transition energy and Meh2 with current density, as desired. The transition energy and the Meh2 may be made to have a positive or a negative slope with current density or they may be made fairly constant. This paper will outline the theoretical details, computational methodologies, the parameters used, and the striking new results with suitable depictions and discussions. These new information ought to be interesting for current optoelectronics.

Numerical determination of the interfacial energy and nucleation barrier of curved solid-liquid interfaces in binary systems

NASA Astrophysics Data System (ADS)

Kundin, Julia; Choudhary, Muhammad Ajmal

2016-07-01

The phase-field crystal (PFC) technique is a widely used approach for modeling crystal growth phenomena with atomistic resolution on mesoscopic time scales. We use a two-dimensional PFC model for a binary system based on the work of Elder et al. [Phys. Rev. B 75, 064107 (2007), 10.1103/PhysRevB.75.064107] to study the effect of the curved, diffuse solid-liquid interface on the interfacial energy as well as the nucleation barrier. The calculation of the interfacial energy and the nucleation barrier certainly depends on the proper definition of the solid-liquid dividing surface and the corresponding nucleus size. We define the position of the sharp interface at which the interfacial energy is to be evaluated by using the concept of equimolar dividing surface (re) and the minimization of the interfacial energy (rs). The comparison of the results based on both radii shows that the difference re-rs is always positive and has a limit for large cluster sizes which is comparable to the Tolman length. Furthermore, we found the real nucleation barrier for small cluster sizes, which is defined as a function of the radius rs, and compared it with the classical nucleation theory. The simulation results also show that the extracted interfacial energy as function of both radii is independent of system size, and this dependence can be reasonably described by the nonclassical Tolman formula with a positive Tolman length.

Barriers to Medical Compassion as a Function of Experience and Specialization: Psychiatry, Pediatrics, Internal Medicine, Surgery, and General Practice.

PubMed

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.

Intrinsic incompatibilities evolving as a by-product of divergent ecological selection: Considering them in empirical studies on divergence with gene flow.

PubMed

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.

Skin Barrier and Calcium.

PubMed

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.

Fibroblast Growth Factor-Peptide Improves Barrier Function and Proliferation in Human Keratinocytes After Radiation

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

Multiscale Investigations of the Early Stage Oxidation on Cu Surfaces

NASA Astrophysics Data System (ADS)

Zhu, Qing; Xiao, Penghao; Lian, Xin; Yang, Shen-Che; Henkelman, Grame; Saidi, Wissam; Yang, Judith; University of Pittsburgh Team; University of Texas at Austin Team

Previous in situ TEM experiments have shown that the oxidation of the three low index Cu surfaces (100), (110) and (111) exhibit different oxide nucleation rates, and the resulting oxides have 3-dimensional (3D) island shapes or 2D rafts under different conditions. In order to better understand these results, we have investigated the early stages of Cu oxidation using a multiscale computational approach that employs density functional theory (DFT), reactive force field (ReaxFF), and kinetic Mote Carlo (KMC). With DFT calculation, we have compared O2 dissociation barriers on Cu (100), (110) and (111) surfaces at high oxygen coverage to evaluate the kinetic barrier of sublayer oxidization. We found that O2 dissociation barriers on Cu(111) surface are all lower than those on (110) and (100) surfaces. This trend agrees with experimental observations that (111) surface is easier to oxidize. These DFT calculated energy barriers are then incorporated into KMC simulations. The large scale ReaxFF molecular dynamics and KMC simulations detail the oxidation dynamics of the different Cu surfaces, and show the formation of various oxide morphologies that are consistent with experimental observations.

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.

The intestinal barrier in multiple sclerosis: implications for pathophysiology and therapeutics.

PubMed

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.

Determination of the thickness and structure of the skin barrier by in vivo laser scanning microscopy

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.

[Blood-nerve barrier and peripheral nerve regeneration].

PubMed

Kanda, Takashi

2013-01-01

Blood-nerve barrier (BNB) restricts the movement of soluble mediators and leukocytes from the blood contents to the peripheral nervous system (PNS) parenchyma and thus maintains the endoneurial homeostasis. However, it interferes the supply of various neurotrophic factors from the blood constituents and stops the drainage of toxic substances out of the PNS parenchyma, resulting in the inhibition of peripheral nerve regeneration. If the manipulation of BNB function is possible, regeneration of peripheral nerve may be facilitated via the alteration of peripheral nerve microenvironment and ample supply of neurotrophic substances. A possible method to manipulate the BNB for therapeutic purposes is to modify the endothelial function using siRNAs, oligonucleotides and virus vectors. Another possible method is to modify BNB pericytes: small hydrophobic substances that can reach the pericyte membrane through the endothelial monolayer and strengthen the pericytic activity, including the release of various cytokines/chemokines that influence endothelial function, may also be useful as drug candidates to control the BNB function.

Helminths and intestinal barrier function

PubMed Central

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

Alterations in Factors Involved in Differentiation and Barrier Function in the Epithelium in Oral and Genital Lichen Planus.

PubMed

Danielsson, Karin; Ebrahimi, Majid; Nylander, Elisabet; Wahlin, Ylva Britt; Nylander, Karin

2017-02-08

Lichen planus is a chronic recurrent inflammatory disease affecting both skin and mucosa, mainly in oral and/or genital regions. Keratinocytes go through a well-regulated process of proliferation and differentiation, alterations in which may result in defects in the protective epithelial barrier. Long-term barrier impairment might lead to chronic inflammation. In order to broaden our understanding of the differentiation process in mucosal lichen planus, we mapped the expression of 4 factors known to be involved in differentiation. Biopsies were collected from oral and genital lichen planus lesions and normal controls. Altered expression of all 4 factors in epithelium from lichen planus lesions was found, clearly indicating disturbed epithelial differentiation in lichen planus lesions.

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.

The Lattice and Thermal Radiation Conductivity of Thermal Barrier Coatings: Models and Experiments

NASA Technical Reports Server (NTRS)

Zhu, Dongming; Spuckler, Charles M.

2010-01-01

The lattice and radiation conductivity of ZrO2-Y2O3 thermal barrier coatings was evaluated using a laser heat flux approach. A diffusion model has been established to correlate the coating apparent thermal conductivity to the lattice and radiation conductivity. The radiation conductivity component can be expressed as a function of temperature, coating material scattering, and absorption properties. High temperature scattering and absorption of the coating systems can be also derived based on the testing results using the modeling approach. A comparison has been made for the gray and nongray coating models in the plasma-sprayed thermal barrier coatings. The model prediction is found to have a good agreement with experimental observations.

Blood-brain barrier transport of drugs for the treatment of brain diseases.

PubMed

Gabathuler, Reinhard

2009-06-01

The central nervous system is a sanctuary protected by barriers that regulate brain homeostasis and control the transport of endogenous compounds into the brain. The blood-brain barrier, formed by endothelial cells of the brain capillaries, restricts access to brain cells allowing entry only to amino acids, glucose and hormones needed for normal brain cell function and metabolism. This very tight regulation of brain cell access is essential for the survival of neurons which do not have a significant capacity to regenerate, but also prevents therapeutic compounds, small and large, from reaching the brain. As a result, various strategies are being developed to enhance access of drugs to the brain parenchyma at therapeutically meaningful concentrations to effectively manage disease.

THE PERMEABILITY OF RAT TRANSITIONAL EPITHELIUM

PubMed Central

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

The role of JAM-A in inflammatory bowel disease: unrevealing the ties that bind.

PubMed

Vetrano, Stefania; Danese, Silvio

2009-05-01

Tight junctions (TJ) are junctional proteins whose function is to maintain an intact intestinal epithelial barrier and regulate the paracellular movement of water and solutes. Altered TJ structure and epithelial permeability are observed in inflammatory bowel disease and seem to have an important role in the pathogenesis of these diseases. Junctional adhesion molecule-A (JAM-A) is a protein expressed at tight junctions of epithelial and endothelial cells, as well as on circulating leukocytes. Its function at tight junctions appears to be crucial as an extracellular adhesive molecule in the direct regulation of intestinal barrier function. This review focuses on the role of JAM-A in controlling mucosal homeostasis by regulating the integrity and permeability of epithelial barrier function.

Intact urothelial barrier function in a mouse model of ketamine-induced voiding dysfunction

PubMed Central

Rajandram, Retnagowri; Ong, Teng Aik; Razack, Azad H. A.; MacIver, Bryce; Zeidel, Mark

2016-01-01

Ketamine is a popular choice for young drug abusers. Ketamine abuse causes lower urinary tract symptoms, with the underlying pathophysiology poorly understood. Disruption of urothelial barrier function has been hypothesized to be a major mechanism for ketamine cystitis, yet the direct evidence of impaired urothelial barrier function is still lacking. To address this question, 8-wk-old female C57BL/6J mice were injected intraperitoneally with 30 mg·kg−1·day−1 ketamine for 12 wk to induce ketamine cystitis. A spontaneous voiding spot assay showed that ketamine-treated mice had increased primary voiding spot numbers and smaller primary voiding spot sizes than control mice (P < 0.05), indicating a contracted bladder and bladder overactivity. Consistently, significantly increased voiding frequency was observed in ketamine-treated mice on cystometrograms. These functional experiments indicate that ketamine induces voiding dysfunction in mice. Surprisingly, urothelial permeability in ketamine-treated mice was not changed when measured using an Ussing chamber system with isotopic urea and water. Mouse urothelial structure was also not altered, and intact umbrella cell structure was observed by both transmission and scanning electron microscopy. Furthermore, immunostaining and confocal microscopy confirmed the presence of a well-defined distribution of zonula occuldens-1 in tight junctions and uroplakin in umbrella cells. In conclusion, these data indicate that ketamine injection induces voiding dysfunction in mice but does not necessarily disrupt mouse bladder barrier function. Disruption of urothelial barrier function may not be the major mechanism in ketamine cystitis. PMID:26911853

Enhanced barrier functions and anti-inflammatory effect of cultured coconut extract on human skin.

PubMed

Kim, Soomin; Jang, Ji Eun; Kim, Jihee; Lee, Young In; Lee, Dong Won; Song, Seung Yong; Lee, Ju Hee

2017-08-01

Natural plant oils have been used as a translational alternative to modern medicine. Particularly, virgin coconut oil (VCO) has gained popularity because of its potential benefits in pharmaceutical, nutritional, and cosmetic applications. Cultured coconut extract (CCE) is an alternative end product of VCO, which undergoes a further bacterial fermentation process. This study aimed to investigate the effects of CCE on human skin. We analyzed the expression of skin barrier molecules and collagens after applying CCE on human explanted skin. To evaluate the anti-inflammatory properties of CCE, the expression of inflammatory markers was analyzed after ultraviolet B (UVB) irradiation. The CCE-treated group showed increased expression of cornified cell envelope components, which contribute to protective barrier functions of the stratum corneum. Further, the expression of inflammatory markers was lower in the CCE-treated group after exposure to UVB radiation. These results suggest an anti-inflammatory effect of CCE against UVB irradiation-induced inflammation. Additionally, the CCE-treated group showed increased collagen and hyaluronan synthase-3 expression. In our study, CCE showed a barrier-enhancing effect and anti-inflammatory properties against ex vivo UVB irradiation-induced inflammation. The promising effect of CCE may be attributed to its high levels of polyphenols and fatty acid components. Copyright © 2017 Elsevier Ltd. All rights reserved.

Temperature dependence of current-and capacitance-voltage characteristics of an Au/4H-SiC Schottky diode

NASA Astrophysics Data System (ADS)

Gülnahar, Murat

2014-12-01

In this study, the current-voltage (I-V) and capacitance-voltage (C-V) measurements of an Au/4H-SiC Schottky diode are characterized as a function of the temperature in 50-300 K temperature range. The experimental parameters such as ideality factor and apparent barrier height presents to be strongly temperature dependent, that is, the ideality factor increases and the apparent barrier height decreases with decreasing temperature, whereas the barrier height values increase with the temperature for C-V data. Likewise, the Richardson plot deviates at low temperatures. These anomaly behaviors observed for Au/4H-SiC are attributed to Schottky barrier inhomogeneities. The barrier anomaly which relates to interface of Au/4H-SiC is also confirmed by the C-V measurements versus the frequency measured in 300 K and it is interpreted by both Tung's lateral inhomogeneity model and multi-Gaussian distribution approach. The values of the weighting coefficients, standard deviations and mean barrier height are calculated for each distribution region of Au/4H-SiC using the multi-Gaussian distribution approach. In addition, the total effective area of the patches NAe is obtained at separate temperatures and as a result, it is expressed that the low barrier regions influence meaningfully to the current transport at the junction. The homogeneous barrier height value is calculated from the correlation between the ideality factor and barrier height and it is noted that the values of standard deviation from ideality factor versus q/3kT curve are in close agreement with the values obtained from the barrier height versus q/2kT variation. As a result, it can be concluded that the temperature dependent electrical characteristics of Au/4H-SiC can be successfully commented on the basis of the thermionic emission theory with both models.

Hydration effects on the barrier function of stratum corneum lipids: Raman analysis of ceramides 2, III and 5.

PubMed

Tfayli, Ali; Jamal, Dima; Vyumvuhore, Raoul; Manfait, Michel; Baillet-Guffroy, Arlette

2013-11-07

The stratum corneum is the outermost layer of the skin; its barrier function is highly dependent on the composition and the structure as well as the organization of lipids in its extracellular matrix. Ceramides, free fatty acids and cholesterol represent the major lipid classes present in this matrix. They play an important role in maintaining the normal hydration levels required for the normal physiological function. Despite the advancement in the understanding of the structure, composition and the function of the stratum corneum (SC), the concern of "dry skin" remains important in dermatology and care research. Most studies focus on the quantification of water in the skin using different techniques including Raman spectroscopy, while the studies that investigate the effect of hydration on the quality of the barrier function of the skin are limited. Raman spectroscopy provides structural, conformational and organizational information that could help elucidate the effect of hydration on the barrier function of the skin. In order to assess the effect of relative humidity on the lipid barrier function; we used Raman spectroscopy to follow-up the evolution of the conformation and the organization of three synthetic ceramides (CER) differing from each other by the nature of their polar heads (sphingosine, phytosphingosine and α hydroxyl sphingosine), CER 2, III and 5 respectively. CER III and 5 showed a more compact and ordered organization with stronger polar interactions at intermediate relative humidity values, while CER 2 showed opposite tendencies to those observed with CER III and 5.

Factors Influencing Amount of Weekly Exercise Time in Colorectal Cancer Survivors.

PubMed

Chou, Yun-Jen; Lai, Yeur-Hur; Lin, Been-Ren; Liang, Jin-Tung; Shun, Shiow-Ching

Performing regular exercise of at least 150 minutes weekly has benefits for colorectal cancer survivors. However, barriers inhibit these survivors from performing regular exercise. The aim of this study was to explore exercise behaviors and significant factors influencing weekly exercise time of more than 150 minutes in colorectal cancer survivors. A cross-sectional study design was used to recruit participants in Taiwan. Guided by the ecological model of health behavior, exercise barriers were assessed including intrapersonal, interpersonal, and environment-related barriers. A multiple logistic regression was used to explore the factors associated with the amount of weekly exercise. Among 321 survivors, 57.0% of them had weekly exercise times of more than 150 minutes. The results identified multiple levels of significant factors related to weekly exercise times including intrapersonal factors (occupational status, functional status, pain, interest in exercise, and beliefs about the importance of exercise) and exercise barriers related to environmental factors (lack of time and bad weather). No interpersonal factors were found to be significant. Colorectal cancer survivors experienced low levels of physical and psychological distress. Multiple levels of significant factors related to exercise time including intrapersonal factors as well as exercise barriers related to environmental factors should be considered. Healthcare providers should discuss with their patients how to perform exercise programs; the discussion should address multiple levels of the ecological model such as any pain problems, functional status, employment status, and time limitations, as well as community environment.

Barrier Requirements as the Evolutionary “Driver” of Epidermal Pigmentation in Humans

PubMed Central

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

Modeling the dynamics of a phreatic eruption based on a tilt observation: Barrier breakage leading to the 2014 eruption of Mount Ontake, Japan

NASA Astrophysics Data System (ADS)

Maeda, Yuta; Kato, Aitaro; Yamanaka, Yoshiko

2017-02-01

Although phreatic eruptions are common volcanic phenomena that sometimes result in significant disasters, their dynamics are poorly understood. In this study, we address the dynamics of the phreatic eruption of Mount Ontake, Japan, in 2014 based on analyses of a tilt change observed immediately (450 s) before the eruption onset. We conducted two sets of analysis: a waveform inversion and a modified phase-space analysis. Our waveform inversion of the tilt signal points to a vertical tensile crack at a depth of 1100 m. Our modified phase-space analysis suggests that the tilt change was at first a linear function in time that then switched to exponential growth. We constructed simple analytical models to explain these temporal functions. The linear function was explained by the boiling of underground water controlled by a constant heat supply from a greater depth. The exponential function was explained by the decompression-induced boiling of water and the upward Darcy flow of the water vapor through a permeable region of small cracks that were newly created in response to ongoing boiling. We interpret that this region was intact prior to the start of the tilt change, and thus, it has acted as a permeability barrier for the upward migration of fluids; it was a breakage of this barrier that led to the eruption.

Geophysical Assessment of the Control of a Jetty on a Barrier Beach and Estuary System

NASA Astrophysics Data System (ADS)

Ulrich, C.; Hubbard, S.; Delaney, C.; Seymour, D.; Blom, K.; Black, W.

2013-12-01

An evaluation is underway at the Goat Rock State Beach, which is located at the mouth of the Russian River near Jenner, CA. The study focuses on quantifying the influence of a man made jetty on the functioning of a barrier beach and associated implications for estuary fish habitat and flood control. Flow through the beach results from water level differences between the estuary and the ocean. When the estuary is closed or perched, one of the potential major sources of outflow from the lagoon is seepage flow through the barrier beach. The location and design of the jetty could be altering subsurface flow paths through the jetty and possibly impeding or enhancing subsurface flow where the jetty is still intact. This will result in unnatural connectivity between the ocean and the estuary leading to atypical surface water elevations and possibly salinity imbalance. Results of the assessment will enable the Sonoma County Water Agency to understand how the jetty affects formation of the barrier beach and water surface elevations within the estuary. As one aspect of the evaluation, we are using geophysical methods to monitor seepage through the jetty as well as through the beach berm. We are using multiple surface geophysical methods, including: electrical resistivity, seismic refraction, ground penetrating radar, and electromagnetic methods. In general, seismic data are being used to characterize deeper bedrock controls on beach barrier functioning such as, channeling of estuarine water beneath the barrier beach. Electrical and electromagnetic methods are being used to characterize the beach sediment layers that could contribute to preferential flow paths during tide cycles in addition to preferential flow paths created by the jetty structure. Time-lapse electrical and electromagnetic data are being used to monitor moisture changes and mixing of saline and fresh water within the beach berm. Ground penetrating radar data are being used to delineate the geometry of the (often buried) jetty. All data are being integrated with topography, tidal and hydrological information, and electrical conductivity and temperature data from monitoring wells. These results are expected to improve the overall understanding of the jetty's effects on beach permeability and will better improve the understanding of the jetty's influence on estuary habitats and flood risk.

Heavy Cigarette Smokers in a Chinese Population Display a Compromised Permeability Barrier

PubMed Central

Xin, Shujun; Ye, Li; Lv, Chengzhi; Elias, Peter M.

2016-01-01

Cigarette smoking is associated with various cutaneous disorders with defective permeability. Yet, whether cigarette smoking influences epidermal permeability barrier function is largely unknown. Here, we measured skin biophysical properties, including permeability barrier homeostasis, stratum corneum (SC) integrity, SC hydration, skin surface pH, and skin melanin/erythema index, in cigarette smokers. A total of 99 male volunteers were enrolled in this study. Smokers were categorized as light-to-moderate (<20 cigarettes/day) or heavy smokers (≥20 cigarettes/day). An MPA5 was used to measure SC hydration and skin melanin/erythema index on the dorsal hand, forehead, and cheek. Basal transepidermal water loss (TEWL) and barrier recovery rates were assessed on the forearm. A Skin-pH-Meter pH900 was used to measure skin surface pH. Our results showed that heavy cigarette smokers exhibited delayed barrier recovery after acute abrogation (1.02% ± 13.06 versus 16.48% ± 6.07), and barrier recovery rates correlated negatively with the number of daily cigarettes consumption (p = 0.0087). Changes in biophysical parameters in cigarette smokers varied with body sites. In conclusion, heavy cigarette smokers display compromised permeability barrier homeostasis, which could contribute, in part, to the increased prevalence of certain cutaneous disorders characterized by defective permeability. Thus, improving epidermal permeability barrier should be considered for heavy cigarette smokers. PMID:27437403

A Nano-Selenium Reactive Barrier Approach for Managing Mercury over the Life-Cycle of Compact Fluorescent Lamps

PubMed Central

Lee, Brian; Sarin, Love; Johnson, Natalie C.; Hurt, Robert H.

2013-01-01

Compact fluorescent lamps contain small quantities of mercury, whose release can lead to human exposures of potential concern in special cases involving multiple lamps, confined spaces, or young children. The exposure scenarios typically involve solid lamp debris that slowly releases elemental mercury vapor to indoor spaces. Here we propose and demonstrate a reactive barrier approach for the suppression of that mercury release, and demonstrate the concept using uncoated amorphous nano-selenium as the reactive component. Multi-layer structures containing an impregnated reactive layer and a mercury vapor barrier are fabricated, characterized, and evaluated in three exposure prevention scenarios: carpeted break sites, disposal/recycling bags, and boxes as used for retail sales, shipping and collection. The reactive barriers achieve significant suppression of mercury release to indoor spaces in each of the three scenarios. The nano-selenium barriers also exhibit a unique indicator function that can reveal the location of Hg-contamination by local reaction-induced change in optical properties. The article also presents results on equilibrium Hg vapor pressure above lamp debris, mathematical modeling of reaction and transport processes within reactive barriers, and landfill stability of nano-selenium and its reaction products. PMID:19731697

A nano-selenium reactive barrier approach for managing mercury over the life-cycle of compact fluorescent lamps.

PubMed

Lee, Brian; Sarin, Love; Johnson, Natalie C; Hurt, Robert H

2009-08-01

Compact fluorescent lamps contain small quantities of mercury, release of which can lead to human exposures of potential concern in special cases involving multiple lamps, confined spaces, or young children. The exposure scenarios typically involve solid lamp debris that slowly releases elemental mercury vapor to indoor spaces. Here we propose and demonstrate a reactive barrier approach for the suppression of that mercury release, and demonstrate the concept using uncoated amorphous nanoselenium as the reactive component. Multilayer structures containing an impregnated reactive layer and a mercury vapor barrier are fabricated, characterized, and evaluated in three exposure prevention scenarios: carpeted break sites, disposal/recycling bags, and boxes as used for retail sales, shipping, and collection. The reactive barriers achieve significant suppression of mercury release to indoor spaces in each of thethree scenarios. The nanoselenium barriers also exhibit a unique indicator function that can reveal the location of Hg contamination by local reaction-induced change in optical properties. The article also presents results on equilibrium Hg vapor pressure above lamp debris, mathematical modeling of reaction and transport processes within reactive barriers, and landfill stability of nanoselenium and its reaction products.

External electric field effects on Schottky barrier at Gd3N@C80/Au interface

NASA Astrophysics Data System (ADS)

Onishi, Koichi; Nakashima, Fumihiro; Jin, Ge; Eto, Daichi; Hattori, Hayami; Miyoshi, Noriko; Kirimoto, Kenta; Sun, Yong

2017-08-01

The effects of the external electric field on the height of the Schottky barrier at the Gd3N@C80/Au interface were studied by measuring current-voltage characteristics at various temperatures from 200 K to 450 K. The Gd3N@C80 sample with the conduction/forbidden/valence energy band structure had a face-centered cubic crystal structure with the average grain size of several nanometers. The height of the Gd3N@C80/Au Schottky barrier was confirmed to be 400 meV at a low electric field at room temperature. Moreover, the height decreases with the increasing external electric field through a change of permittivity in the Gd3N@C80 sample due to a polarization of the [Gd3] 9 +-[N3 -+("separators="|C80 ) 6 -] dipoles in the Gd3N@C80 molecule. The field-dependence of the barrier height can be described using a power math function of the electric field strength. The results of the field-dependent barrier height indicate that the reduction in the Schottky barrier is due to an image force effect of the transport charge carrier at the Gd3N@C80/Au interface.

Transition path time distributions for Lévy flights

NASA Astrophysics Data System (ADS)

Janakiraman, Deepika

2018-07-01

This paper presents a study of transition path time distributions for Lévy noise-induced barrier crossing. Transition paths are short segments of the reactive trajectories and span the barrier region of the potential without spilling into the reactant/product wells. The time taken to traverse this segment is referred to as the transition path time. Since the transition path is devoid of excursions in the minimum, the corresponding time will give the exclusive barrier crossing time, unlike . This work explores the distribution of transition path times for superdiffusive barrier crossing, analytically. This is made possible by approximating the barrier by an inverted parabola. Using this approximation, the distributions are evaluated in both over- and under-damped limits of friction. The short-time behaviour of the distributions, provide analytical evidence for single-step transition events—a feature in Lévy-barrier crossing as observed in prior simulation studies. The average transition path time is calculated as a function of the Lévy index (α), and the optimal value of α leading to minimum average transition path time is discussed, in both the limits of friction. Langevin dynamics simulations corroborating with the analytical results are also presented.

Fingolimod promotes blood-nerve barrier properties in vitro.

PubMed

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.

Surfactants have multi-fold effects on skin barrier function.

PubMed

Lemery, Emmanuelle; Briançon, Stéphanie; Chevalier, Yves; Oddos, Thierry; Gohier, Annie; Boyron, Olivier; Bolzinger, Marie-Alexandrine

2015-01-01

The stratum corneum (SC) is responsible for the barrier properties of the skin and the role of intercorneocyte skin lipids, particularly their structural organization, in controlling SC permeability is acknowledged. Upon contacting the skin, surfactants interact with the SC components leading to barrier damage. To improve knowledge of the effect of several classes of surfactant on skin barrier function at three different levels. The influence of treatments of human skin explants with six non-ionic and four ionic surfactant solutions on the physicochemical properties of skin was investigated. Skin surface wettability and polarity were assessed through contact angle measurements. Infrared spectroscopy allowed monitoring the SC lipid organization. The lipid extraction potency of surfactants was evaluated thanks to HPLC-ELSD assays. One anionic and one cationic surfactant increased the skin polarity by removing the sebaceous and epidermal lipids and by disturbing the organization of the lipid matrix. Another cationic surfactant displayed a detergency effect without disturbing the skin barrier. Several non-ionic surfactants disturbed the lipid matrix organization and modified the skin wettability without any extraction of the skin lipids. Finally two non-ionic surfactants did not show any effect on the investigated parameters or on the skin barrier. The polarity, the organization of the lipid matrix and the lipid composition of the skin allowed describing finely how surfactants can interact with the skin and disturb the skin barrier function.

Applications of δ-function perturbation to the pricing of derivative securities

NASA Astrophysics Data System (ADS)

Decamps, Marc; De Schepper, Ann; Goovaerts, Marc

2004-11-01

In the recent econophysics literature, the use of functional integrals is widespread for the calculation of option prices. In this paper, we extend this approach in several directions by means of δ-function perturbations. First, we show that results about infinitely repulsive δ-function are applicable to the pricing of barrier options. We also introduce functional integrals over skew paths that give rise to a new European option formula when combined with δ-function potential. We propose accurate closed-form approximations based on the theory of comonotonic risks in case the functional integrals are not analytically computable.

Health-related quality of life of children with physical disabilities: a longitudinal study

PubMed Central

2014-01-01

Background Outcomes of health and rehabilitation services for children and youth with disabilities increasingly include assessments of health-related quality of life (HRQoL). The purpose of this research was to 1) describe overall patterns of HRQoL, 2) examine changes in parent’s perceptions of child’s HRQoL across 18 months and 3) explore factors that predict these changes. Methods Participants in this study included 427 parents of children (229 boys and 198 girls) with a physically-based disability between the ages of 6 to 14 years. The Child Health Questionnaire (CHQ) was administered three times, at nine month intervals. Comparisons to the CHQ normative data were analyzed at Time 1 using t-tests, and change over time was examined using linear mixed-effects models. Possible predictors were modeled: 1) child’s factors measured by the Activities Scale for Kids, Strengths and Difficulties Questionnaire, and general health measured by SF-36, 2) family characteristics measured by the Impact on Family Scale and 3) environmental barriers measured by the Craig Hospital Inventory of Environmental Factors. Results CHQ scores of the study’s participants demonstrated significantly lower summary scores from the normative sample for both CHQ Physical and Psychosocial summary scores. On average, children did not change significantly over time for physical summary scores. There was an average increase in psychosocial health that was statistically significant, but small. However, there was evidence of heterogeneity among children. Environmental barriers, behavioral difficulties, family functioning/impact, general health and child physical functioning had negative and significant associations with physical QoL at baseline. Change in physical QoL scores over time was dependent on children’s behavioral difficulties, family functioning and environmental barriers. Environmental barriers, behavioral difficulties, family functioning/impact and general health had significant associations with psychosocial scores at baseline, but none served as predictors of change over time. Conclusions Children with physical disabilities differ from the normative group on parent ratings of their physical and psychosocial health. While there was little average change in CHQ scores over 18 months, there is evidence of heterogeneity among children. Factors such as environmental barriers, family functioning/impact, child physical functioning and behavioral difficulties and general health significantly influence QoL scores as measured by the CHQ. PMID:24476085

Adiabatic corrections to density functional theory energies and wave functions.

PubMed

Mohallem, José R; Coura, Thiago de O; Diniz, Leonardo G; de Castro, Gustavo; Assafrão, Denise; Heine, Thomas

2008-09-25

The adiabatic finite-nuclear-mass-correction (FNMC) to the electronic energies and wave functions of atoms and molecules is formulated for density-functional theory and implemented in the deMon code. The approach is tested for a series of local and gradient corrected density functionals, using MP2 results and diagonal-Born-Oppenheimer corrections from the literature for comparison. In the evaluation of absolute energy corrections of nonorganic molecules the LDA PZ81 functional works surprisingly better than the others. For organic molecules the GGA BLYP functional has the best performance. FNMC with GGA functionals, mainly BLYP, show a good performance in the evaluation of relative corrections, except for nonorganic molecules containing H atoms. The PW86 functional stands out with the best evaluation of the barrier of linearity of H2O and the isotopic dipole moment of HDO. In general, DFT functionals display an accuracy superior than the common belief and because the corrections are based on a change of the electronic kinetic energy they are here ranked in a new appropriate way. The approach is applied to obtain the adiabatic correction for full atomization of alcanes C(n)H(2n+2), n = 4-10. The barrier of 1 mHartree is approached for adiabatic corrections, justifying its insertion into DFT.

ORAL DELIVERY OF L-ARGININE STIMULATES PROSTAGLANDIN-DEPENDENT SECRETORY DIARRHEA IN C. PARVUM INFECTED NEONATAL PIGLETS

PubMed Central

Gookin, Jody L.; Foster, Derek M.; Coccaro, Maria R.; Stauffer, Stephen H.

2008-01-01

Objectives To determine if oral supplementation with L-arginine could augment nitric oxide (NO) synthesis and promote epithelial defense in neonatal piglets infected with C. parvum. Methods Neonatal piglets were fed a liquid milk replacer and on day 3 of age infected or not with 108 C. parvum oocysts and the milk replacer supplemented with L-arginine or L-alanine. Milk consumption, body weight, fecal consistency, and oocyst excretion were recorded daily. On day 3 post-infection, piglets were euthanized, and serum concentration of NO metabolites and histological severity of villous atrophy and epithelial infection were quantified. Sheets of ileal mucosa were mounted in Ussing chambers for measurement of barrier function (transepithelial resistance (TER) and permeability) and short-circuit current (Isc; an indirect measurement of Cl− secretion in this tissue). Results C. parvum infected piglets had large numbers of epithelial parasites, villous atrophy, decreased barrier function, severe watery diarrhea, and failure to gain weight. L-arginine promoted synthesis of NO by infected piglets which was unaccompanied by improvement in severity of infection but rather promoted epithelial chloride secretion and diarrhea. Epithelial secretion by infected mucosa from L-arginine supplemented piglets was fully inhibited by the cyclooxygenase inhibitor indomethacin, indicating that prostaglandin synthesis was responsible for this effect. Conclusions Results of these studies demonstrate that provision of additional NO substrate in the form of L-arginine incites prostaglandin-dependent secretory diarrhea and does not promote epithelial defense or barrier function of C. parvum infected neonatal ileum. PMID:18223372

Evaluation of confocal laser endomicroscopy for assessment and monitoring of therapeutic response in patients with inflammatory bowel disease.

PubMed

Karstensen, John Gásdal

2016-11-01

Crohn's disease (CD) and ulcerative colitis (UC) have been associated with altered intestinal barrier function. Moreover, it has been proposed that a defective barrier function is related to risk of relapse in patients with quiescent CD. Fluorescein-aided confocal laser endomicroscopy (CLE) is a novel endoscopic method, which enables real-time in vivo microscopy. Hence, the intestinal barrier function can be assessed as part of endoscopic evaluation of patients with inflammatory bowel disease (IBD) by measuring microerosions and fluorescein leakage into the intestinal lumen. Furthermore, barrier dysfunction can be correlated with biomarkers associated with intestinal barrier impairments. E-cadherin is a key factor for the adherence of epithelial cells and Smad4 is a cofactor in TGF-β signalling, which is compromised in IBD. To correlate ileal and colonic CLE parameters with endoscopy and histopathology in IBD. Further, we wanted to correlate these features with risk of relapse and evaluate whether they were reproducible and reversible after intensified medical treatment. We also wanted to analyse, whether Smad4 and E-cadherin mucosal protein expression levels were associated with impairments of intestinal barrier function. CLE was performed and correlated to histopathology and endoscopic appearance in two prospective studies in CD (n = 39, controls = 11) and UC patients (n = 22, controls = 7), respectively. In the first study, results were correlated to risk of relapse, whereas the latter assessed the reversibility of CLE features in a longitudinal setting. κ-statistics were used in both studies to assess reproducibility of the CLE findings. Furthermore, ileal biopsy specimens from CD patients and controls were stained by immunohistochemistry for Smad4 and E-cadherin and subsequently correlated to the severity of CD and intestinal barrier impairments. We found that fluorescein leakage and microerosions in the terminal ileum were significantly associated with CD com-pared to controls (p = 0.005 and p = 0.006, respectively) and that ileal fluorescein leakage and microerosions could predict relapse (log-rank p = 0.003 and p = 0.017, respectively). In UC patients with clinical relapse, an augmented crypt architecture and colonic fluorescein leakage were significantly correlated to the severity of the disease (p = 0.001 and p < 0.001, respectively). After intensified medical treatment, a correlation was found between histopathological progress and improvement of abnormal colonic crypt architecture (rs = 0.35, p = 0.016), but we did not observe a resolution of the intestinal barrier dysfunction (rs = 0.09, p = 0.56). The inter-observer variability of CLE parameters ranged from fair to substantial, while the intra-observer variability was somewhat higher. Smad4 expression (rs = 0.56, p = 0.002), but not E-cadherin (rs = 0.01, p = 0.95), was correlated with the severity of the disease; however, Smad4 expression did not correlate with a defect barrier function. CLE can visualise crypt alteration and barrier impairments in both CD and UC, which are otherwise undetectable. Further studies are warranted to incorporate CLE in the endoscopic and therapeutic management algorithm for CD and UC possibly refining the definition of mucosal healing. Smad4 expression was correlated with CD as well as disease severity and may serve as a novel treatment target.

Lactobacillus frumenti Facilitates Intestinal Epithelial Barrier Function Maintenance in Early-Weaned Piglets

PubMed Central

Hu, Jun; Chen, Lingli; Zheng, Wenyong; Shi, Min; Liu, Liu; Xie, Chunlin; Wang, Xinkai; Niu, Yaorong; Hou, Qiliang; Xu, Xiaofan; Xu, Baoyang; Tang, Yimei; Zhou, Shuyi; Yan, Yiqin; Yang, Tao; Ma, Libao; Yan, Xianghua

2018-01-01

Increased intestinal epithelial barrier function damages caused by early weaning stress have adverse effects on swine health and feed utilization efficiency. Probiotics have emerged as the promising antibiotic alternatives used for intestinal barrier function damage prevention. Our previous data showed that Lactobacillus frumenti was identified as a predominant Lactobacillus in the intestinal microbiota of weaned piglets. However, whether the intestinal epithelial barrier function in piglets was regulated by L. frumenti is still unclear. Here, piglets received a PBS vehicle or PBS suspension (2 ml, 108 CFU/ml) containing the L. frumenti by oral gavage once a day during the period of 6–20 days of age prior to early weaning. Our data demonstrated that oral administration of L. frumenti significantly improved the intestinal mucosal integrity and decreased the serum endotoxin and D-lactic acid levels in early-weaned piglets (26 days of age). The intestinal tight junction proteins (including ZO-1, Occludin, and Claudin-1) were significantly up-regulated by L. frumenti administration. The serum immunoglobulin G (IgG) levels, intestinal secretory immunoglobulin A (sIgA) levels, and interferon-γ (IFN-γ) levels were significantly increased by L. frumenti administration. Furthermore, our data revealed that oral administration of L. frumenti significantly increased the relative abundances of health-promoting microbes (including L. frumenti, Lactobacillus gasseri LA39, Parabacteroides distasonis, and Kazachstania telluris) and decreased the relative abundances of opportunistic pathogens (including Desulfovibrio desulfuricans and Candida humilis). Functional alteration of the intestinal bacterial community by L. frumenti administration was characterized by the significantly increased fatty acids and protein metabolism and decreased diseases-associated metabolic pathways. These findings suggest that L. frumenti facilitates intestinal epithelial barrier function maintenance in early-weaned piglets and may be a promising antibiotic alternative used for intestinal epithelial barrier function damage prevention in mammals. PMID:29867808

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

Helping Homeless Families Overcome Barriers to Successful Functioning

ERIC Educational Resources Information Center

Swick, Kevin J.

2005-01-01

The author articulates key stressors in the lives of families who are homeless. These stresses often combine with barriers such as lack of job opportunities and/or insensitive professionals. Strategies for helping homeless families overcome these barriers and related issues are presented.

Intestinal threonine utilization for protein and mucin synthesis is decreased in formula-fed preterm pigs

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 ...

Dissipation and traversal time in Josephson junctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cacciari, Ilaria; Ranfagni, Anedio; Moretti, Paolo

2010-05-01

The various ways of evaluating dissipative effects in macroscopic quantum tunneling are re-examined. The results obtained by using functional integration, while confirming those of previously given treatments, enable a comparison with available experimental results relative to Josephson junctions. A criterion based on the shortening of the semiclassical traversal time tau of the barrier with regard to dissipation can be established, according to which DELTAtau/tau > or approx. N/Q, where Q is the quality factor of the junction and N is a numerical constant of order unity. The best agreement with the experiments is obtained for N=1.11, as it results frommore » a semiempirical analysis based on an increase in the potential barrier caused by dissipative effects.« less

Kinetic Monte Carlo Simulation of Oxygen Diffusion in Ytterbium Disilicate

NASA Technical Reports Server (NTRS)

Good, Brian S.

2015-01-01

Ytterbium disilicate is of interest as a potential environmental barrier coating for aerospace applications, notably for use in next generation jet turbine engines. In such applications, the transport of oxygen and water vapor through these coatings to the ceramic substrate is undesirable if high temperature oxidation is to be avoided. In an effort to understand the diffusion process in these materials, we have performed kinetic Monte Carlo simulations of vacancy-mediated and interstitial oxygen diffusion in Ytterbium disilicate. Oxygen vacancy and interstitial site energies, vacancy and interstitial formation energies, and migration barrier energies were computed using Density Functional Theory. We have found that, in the case of vacancy-mediated diffusion, many potential diffusion paths involve large barrier energies, but some paths have barrier energies smaller than one electron volt. However, computed vacancy formation energies suggest that the intrinsic vacancy concentration is small. In the case of interstitial diffusion, migration barrier energies are typically around one electron volt, but the interstitial defect formation energies are positive, with the result that the disilicate is unlikely to exhibit experience significant oxygen permeability except at very high temperature.

Centromeric Barrier Disruption Leads to Mitotic Defects in Schizosaccharomyces pombe

PubMed Central

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

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.

Effect of seasonal and geographical differences on skin and effect of treatment with an osmoprotectant: Sorbitol.

PubMed

Muizzuddin, Neelam; Ingrassia, Michael; Marenus, Kenneth D; Maes, Daniel H; Mammone, Thomas

2013-01-01

Human skin maintains an optimal permeability barrier function in a terrestrial environment that varies considerably in humidity. Cells cultured under hyperosmotic stress accumulate osmolytes including sorbitol. Epidermal keratinocytes experience similar high osmolality under dry environmental conditions because of increased transepidermal water loss (TEWL) and concomitant drying of the skin. This study was designed to determine if epidermal keratinocytes, in vitro, could be protected from high osmotic stress, with the exogenous addition of sorbitol. In addition, we evaluated the effect of a formulation containing topical sorbitol on skin barrier and moisturization of subjects living in arid and humid regions in summer as well as in winter. Results from in vitro experiments showed that 50 mM sorbitol protected epidermal keratinocytes from osmotic toxicity induced by sodium chloride. Clinical studies indicated that skin chronically exposed to hot, dry environment appeared to exhibit stronger skin barrier and a lower baseline TEWL. In addition, skin barrier was stronger in summer than in winter. Sorbitol exhibited significant improvement in both barrier repair and moisturization, especially in individuals subjected to arid environmental conditions.

Disruption of the epithelial barrier during intestinal inflammation: Quest for new molecules and mechanisms.

PubMed

Lechuga, Susana; Ivanov, Andrei I

2017-07-01

The intestinal epithelium forms a key protective barrier that separates internal organs from the harmful environment of the gut lumen. Increased permeability of the gut barrier is a common manifestation of different inflammatory disorders contributing to the severity of disease. Barrier permeability is controlled by epithelial adherens junctions and tight junctions. Junctional assembly and integrity depend on fundamental homeostatic processes such as cell differentiation, rearrangements of the cytoskeleton, and vesicle trafficking. Alterations of intestinal epithelial homeostasis during mucosal inflammation may impair structure and remodeling of apical junctions, resulting in increased permeability of the gut barrier. In this review, we summarize recent advances in our understanding of how altered epithelial homeostasis affects the structure and function of adherens junctions and tight junctions in the inflamed gut. Specifically, we focus on the transcription reprogramming of the cell, alterations in the actin cytoskeleton, and junctional endocytosis and exocytosis. We pay special attention to knockout mouse model studies and discuss the relevance of these mechanisms to human gastrointestinal disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Regulation of Sertoli cell tight junction dynamics in the rat testis via the nitric oxide synthase/soluble guanylate cyclase/3',5'-cyclic guanosine monophosphate/protein kinase G signaling pathway: an in vitro study.

PubMed

Lee, Nikki P Y; Cheng, C Yan

2003-07-01

Nitric oxide (NO) synthase (NOS) catalyzes the oxidation of L-arginine to NO. NO plays a crucial role in regulating various physiological functions, possibly including junction dynamics via its effects on cAMP and cGMP, which are known modulators of tight junction (TJ) dynamics. Although inducible NOS (iNOS) and endothelial NOS (eNOS) are found in the testis and have been implicated in the regulation of spermatogenesis, their role(s) in TJ dynamics, if any, is not known. When Sertoli cells were cultured at 0.5-1.2 x 10(6) cells/cm(2) on Matrigel-coated dishes or bicameral units, functional TJ barrier was formed when the barrier function was assessed by quantifying transepithelial electrical resistance across the cell epithelium. The assembly of the TJ barrier was shown to associate with a significant plummeting in the levels of iNOS and eNOS, seemingly suggesting that their presence by producing NO might perturb TJ assembly. To further confirm the role of NOS on the TJ barrier function in vitro, zinc (II) protoporphyrin-IX (ZnPP), an NOS inhibitor and a soluble guanylate cyclase inhibitor, was added to the Sertoli cell cultures during TJ assembly. Indeed, ZnPP was found to facilitate the assembly and maintenance of the Sertoli cell TJ barrier, possibly by inducing the production of TJ-associated proteins, such as occludin. Subsequent studies by immunoprecipitation and immunoblotting have shown that iNOS and eNOS are structurally linked to TJ-integral membrane proteins, such as occludin, and cytoskeletal proteins, such as actin, vimentin, and alpha-tubulin. When the cAMP and cGMP levels in these ZnPP-treated samples were quantified, a ZnPP-induced reduction of intracellular cGMP, but not cAMP, was indeed detected. Furthermore, 8-bromo-cGMP, a cell membrane-permeable analog of cGMP, could also perturb the TJ barrier dose dependently similar to the effects of 8-bromo-cAMP. KT-5823, a specific inhibitor of protein kinase G, was shown to facilitate the Sertoli cell TJ barrier assembly. Cytokines, such as TGF-beta and TNF-alpha, known to perturb the Sertoli cell TJ barrier, were also shown to stimulate Sertoli cell iNOS and eNOS expression dose dependently in vitro. Collectively, these results illustrate NOS is an important physiological regulator of TJ dynamics in the testis, exerting its effects via the NO/soluble guanylate cyclase/cGMP/protein kinase G signaling pathway.

Density functional calculations on the effect of sulfur substitution for 2'-hydroxypropyl-p-nitrophenyl phosphate: C-O vs. P-O bond cleavage.

PubMed

Xia, Futing; Zhu, Hua

2012-02-01

Density functional theory calculations have been used to investigate the intra-molecular attack of 2'-hydroxypropyl-p-nitrophenyl phosphate (HPpNP) and its analogous compound 2-thiouridyl-p-nitrophenyl phosphate (s-2'pNP). Bulk solvent effect has been tested at the geometry optimization level with the polarized continuum model. It is found that the P-path involving the intra-molecular attack at the phosphorus atom and C-path involving the attack at the beta carbon atom proceed through the S(N)2-type mechanism for HPpNP and s-2'pNP. The calculated results indicate that the P-path with the free energy barrier of about 11 kcal/mol is more accessible than the C-path for the intra-molecular attack of HPpNP, which favors the formation of the five-membered phosphate diester. While for s-2'pNP, the C-path with the free energy barrier of about 21 kcal/mol proceeds more favorably than the P-path. The calculated energy barriers of the favorable pathways for HPpNP and s-2'pNP are both in agreement with the experimental results. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Off-Axis Driven Current Effects on ETB and ITB Formations based on Bifurcation Concept

NASA Astrophysics Data System (ADS)

Pakdeewanich, J.; Onjun, T.; Chatthong, B.

2017-09-01

This research studies plasma performance in fusion Tokamak system by investigating parameters such as plasma pressure in the presence of an edge transport barrier (ETB) and an internal transport barrier (ITB) as the off-axis driven current position is varied. The plasma is modeled based on the bifurcation concept using a suppression function that can result in formation of transport barriers. In this model, thermal and particle transport equations, including both neoclassical and anomalous effects, are solved simultaneously in slab geometry. The neoclassical coefficients are assumed to be constant while the anomalous coefficients depend on gradients of local pressure and density. The suppression function, depending on flow shear and magnetic shear, is assumed to affect only on the anomalous channel. The flow shear can be calculated from the force balance equation, while the magnetic shear is calculated from the given plasma current. It is found that as the position of driven current peak is moved outwards from the plasma center, the central pressure is increased. But at some point it stars to decline, mostly when the driven current peak has reached the outer half of the plasma. The higher pressure value results from the combination of ETB and ITB formations. The drop in central pressure occurs because ITB stats to disappear.

Potential of Lactobacillus plantarum CCFM639 in Protecting against Aluminum Toxicity Mediated by Intestinal Barrier Function and Oxidative Stress

PubMed Central

Yu, Leilei; Zhai, Qixiao; Tian, Fengwei; Liu, Xiaoming; Wang, Gang; Zhao, Jianxin; Zhang, Hao; Narbad, Arjan; Chen, Wei

2016-01-01

Aluminum (Al) is a ubiquitous metal that can seriously harm the health of animals and humans. In our previous study, we demonstrated that Lactobacillus plantarum CCFM639 can decrease Al burden in the tissues of mice by inhibiting intestinal Al absorption. The main aim of the present research was to investigate whether the protection by the strain is also associated with enhancement of the intestinal barrier, alleviation of oxidative stress and modulation of the inflammatory response. In an in vitro cell model, two protection modes (intervention and therapy) were examined and the results indicated that L. plantarum CCFM639 alleviated Al-induced cytotoxicity. In a mouse model, L. plantarum CCFM639 treatment was found to significantly alleviate oxidative stress in the intestinal tract, regulate the function of the intestinal mucosal immune system, restore the integrity of tight junction proteins and maintain intestinal permeability. These results suggest that in addition to Al sequestration, L. plantarum CCFM639 can also inhibit Al absorption by protecting the intestinal barrier, alleviating Al-induced oxidative stress and inflammatory response. Therefore, L. plantarum CCFM639 has the potential to be a dietary supplement ingredient that provides protection against Al-induced gut injury. PMID:27918411

Analytical model of threshold voltage degradation due to localized charges in gate material engineered Schottky barrier cylindrical GAA MOSFETs

NASA Astrophysics Data System (ADS)

Kumar, Manoj; Haldar, Subhasis; Gupta, Mridula; Gupta, R. S.

2016-10-01

The threshold voltage degradation due to the hot carrier induced localized charges (LC) is a major reliability concern for nanoscale Schottky barrier (SB) cylindrical gate all around (GAA) metal-oxide-semiconductor field-effect transistors (MOSFETs). The degradation physics of gate material engineered (GME)-SB-GAA MOSFETs due to LC is still unexplored. An explicit threshold voltage degradation model for GME-SB-GAA-MOSFETs with the incorporation of localized charges (N it) is developed. To accurately model the threshold voltage the minimum channel carrier density has been taken into account. The model renders how +/- LC affects the device subthreshold performance. One-dimensional (1D) Poisson’s and 2D Laplace equations have been solved for two different regions (fresh and damaged) with two different gate metal work-functions. LCs are considered at the drain side with low gate metal work-function as N it is more vulnerable towards the drain. For the reduction of carrier mobility degradation, a lightly doped channel has been considered. The proposed model also includes the effect of barrier height lowering at the metal-semiconductor interface. The developed model results have been verified using numerical simulation data obtained by the ATLAS-3D device simulator and excellent agreement is observed between analytical and simulation results.

Dissecting gene expression at the blood-brain barrier

PubMed Central

Huntley, Melanie A.; Bien-Ly, Nga; Daneman, Richard; Watts, Ryan J.

2014-01-01

The availability of genome-wide expression data for the blood-brain barrier is an invaluable resource that has recently enabled the discovery of several genes and pathways involved in the development and maintenance of the blood-brain barrier, particularly in rodent models. The broad distribution of published data sets represents a viable starting point for the molecular dissection of the blood-brain barrier and will further direct the discovery of novel mechanisms of blood-brain barrier formation and function. Technical advances in purifying brain endothelial cells, the key cell that forms the critical barrier, have allowed for greater specificity in gene expression comparisons with other central nervous system cell types, and more systematic characterizations of the molecular composition of the blood-brain barrier. Nevertheless, our understanding of how the blood-brain barrier changes during aging and disease is underrepresented. Blood-brain barrier data sets from a wider range of experimental paradigms and species, including invertebrates and primates, would be invaluable for investigating the function and evolution of the blood-brain barrier. Newer technologies in gene expression profiling, such as RNA-sequencing, now allow for finer resolution of transcriptomic changes, including isoform specificity and RNA-editing. As our field continues to utilize more advanced expression profiling in its ongoing efforts to elucidate the blood-brain barrier, including in disease and drug delivery, we will continue to see rapid advances in our understanding of the molecular mediators of barrier biology. We predict that the recently published data sets, combined with forthcoming genomic and proteomic blood-brain barrier data sets, will continue to fuel the molecular genetic revolution of blood-brain barrier biology. PMID:25414634

Effects of cognate, non-cognate and synthetic CXCR4 and ACKR3 ligands on human lung endothelial cell barrier function.

PubMed

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.

Physiological and pathophysiological factors affecting the expression and activity of the drug transporter MRP2 in intestine. Impact on its function as membrane barrier.

PubMed

Arana, Maite R; Tocchetti, Guillermo N; Rigalli, Juan P; Mottino, Aldo D; Villanueva, Silvina S M

2016-07-01

The gastrointestinal epithelium functions as a selective barrier to absorb nutrients, electrolytes and water, but at the same time restricts the passage into the systemic circulation of intraluminal potentially toxic compounds. This epithelium maintains its selective barrier function through the presence of very selective and complex intercellular junctions and the ability of the absorptive cells to reject those compounds. Accordingly, the enterocytes metabolize orally incorporated xenobiotics and secrete the hydrophilic metabolites back into the intestinal lumen through specific transporters localized apically. In the recent decades, there has been increasing recognition of the existence of the intestinal cellular barrier. In the present review we focus on the role of the multidrug resistance-associated protein 2 (MRP2, ABCC2) in the apical membrane of the enterocytes, as an important component of this intestinal barrier, as well as on its regulation. We provide a detailed compilation of significant contributions demonstrating that MRP2 expression and function vary under relevant physiological and pathophysiological conditions. Because MRP2 activity modulates the availability and pharmacokinetics of many therapeutic drugs administered orally, their therapeutic efficacy and safety may vary as well. Copyright © 2016 Elsevier Ltd. All rights reserved.

Wild jujube polysaccharides protect against experimental inflammatory bowel disease by enabling enhanced intestinal barrier function.

PubMed

Yue, Yuan; Wu, Shuangchan; Li, Zhike; Li, Jian; Li, Xiaofei; Xiang, Jin; Ding, Hong

2015-08-01

Dietary polysaccharides provide various beneficial effects for our health. We investigated the protective effects of wild jujube (Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou) sarcocarp polysaccharides (WJPs) against experimental inflammatory bowel disease (IBD) by enabling enhanced intestinal barrier function. Colitis was induced in rats by the intrarectal administration of TNBS. We found that WJPs markedly ameliorated the colitis severity, including less weight loss, decreased disease activity index scores, and improved mucosal damage in colitis rats. Moreover, WJPs suppressed the inflammatory response via attenuation of TNF-α, IL-1β, IL-6 and MPO activity in colitis rats. And then, to determine the effect of WJPs on the intestinal barrier, we measured the effect of WJPs on the transepithelial electrical resistance (TER) and FITC-conjugated dextran permeability in Caco-2 cell stimulation with TNF-α. We further demonstrated that the alleviation of WJPs to colon injury was associated with barrier function by assembly of tight junction proteins. Moreover, the effect of WJPs on TER was eliminated by the specific inhibitor of AMPK. AMPK activity was also up-regulated by WJPs in Caco-2 cell stimulation with TNF-α and in colitis rats. This study demonstrates that WJPs protect against IBD by enabling enhanced intestinal barrier function involving the activation of AMPK.

Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs.

PubMed

Truse, Richard; Hinterberg, Jonas; Schulz, Jan; Herminghaus, Anna; Weber, Andreas; Mettler-Altmann, Tabea; Bauer, Inge; Picker, Olaf; Vollmer, Christian

2017-01-01

Topical drug application is used to avoid systemic side effects. The aim of this study was to analyze whether locally applied iloprost or nitroglycerin influence gastric mucosal perfusion, oxygenation, and barrier function during physiological and hemorrhagic conditions. In repeated experiments, 5 anesthetized dogs received iloprost, nitroglycerin, or normal saline during physiological and hemorrhagic (-20% blood volume) conditions. Macro- and microcirculatory variables were recorded continuously. Gastric barrier function was assessed via translocation of sucrose into the blood. During hemorrhage, gastric mucosal oxygenation decreased from 77 ± 4 to 37 ± 7%. This effect was attenuated by nitroglycerin (78 ± 6 to 47 ± 13%) and iloprost (82 ± 4 to 54 ± 9%). Sucrose plasma levels increased during hemorrhage from 7 ± 4 to 55 ± 15 relative amounts. This was alleviated by nitroglycerin (5 ± 8 to 29 ± 38 relative amounts). These effects were independent of systemic hemodynamic variables. During hemorrhage, topical nitroglycerin and iloprost improve regional gastric oxygenation without affecting perfusion. Nitroglycerin attenuated the shock-induced impairment of the mucosal barrier integrity. Thus, local drug application improves gastric microcirculation without compromising systemic hemodynamic variables, and it may also protect mucosal barrier function. © 2017 S. Karger AG, Basel.

Crystal structure of Clostridium botulinum whole hemagglutinin reveals a huge triskelion-shaped molecular complex.

PubMed

Amatsu, Sho; Sugawara, Yo; Matsumura, Takuhiro; Kitadokoro, Kengo; Fujinaga, Yukako

2013-12-06

Clostridium botulinum HA is a component of the large botulinum neurotoxin complex and is critical for its oral toxicity. HA plays multiple roles in toxin penetration in the gastrointestinal tract, including protection from the digestive environment, binding to the intestinal mucosal surface, and disruption of the epithelial barrier. At least two properties of HA contribute to these roles: the sugar-binding activity and the barrier-disrupting activity that depends on E-cadherin binding of HA. HA consists of three different proteins, HA1, HA2, and HA3, whose structures have been partially solved and are made up mainly of β-strands. Here, we demonstrate structural and functional reconstitution of whole HA and present the complete structure of HA of serotype B determined by x-ray crystallography at 3.5 Å resolution. This structure reveals whole HA to be a huge triskelion-shaped molecule. Our results suggest that whole HA is functionally and structurally separable into two parts: HA1, involved in recognition of cell-surface carbohydrates, and HA2-HA3, involved in paracellular barrier disruption by E-cadherin binding.

Skin Barrier Disruption - A Requirement for Allergen Sensitization?

PubMed Central

De Benedetto, Anna; Kubo, Akiharu; Beck, Lisa A.

2011-01-01

For at least half a century, noninvasive techniques have been available to quantify skin barrier function, and these have shown that a number of human skin conditions and disorders are associated with defects in skin permeability. In the last decade, several genes responsible for skin barrier defects observed in both monogenetic and complex, polygenic disorders have been elucidated and functionally characterized. This has led to an explosion of work in the last six years that has identified pathways connecting epidermal barrier disruption and antigen uptake as well as the quality and/or magnitude of the antigen-specific adaptive immune response. This review will introduce the notion that diseases arise from the dynamic crosstalk that occurs between the skin barrier and immune system using atopic dermatitis or eczema as the disease prototype. Nevertheless, the concepts put forth are highly relevant to a number of antigen-driven disorders for which skin barrier is at least transiently compromised such as psoriasis, allergic contact dermatitis and blistering disorders. PMID:22217737

Oscillations above the barrier in the fusion of 28Si + 28Si

DOE PAGES

Montagnoli, G.; Stefanini, A.M.; Esbensen, H.; ...

2015-05-13

Fusion cross sections of 28Si+ 28Si have been measured in a range above the barrier with a very small energy step (Delta E lab=0.5 MeV). Regular oscillations have been observed, best evidenced in the first derivative of the energy-weighted excitation function. For the first time, quite different behaviors (the appearance of oscillations and the trend of sub-barrier cross sections) have been reproduced within the same theoretical frame, i.e., the coupled-channel model using the shallow M3Y+repulsion potential. The calculations suggest that channel couplings play an important role in the appearance of the oscillations, and that the simple relation between a peakmore » in the derivative of the energy-weighted cross section and the height of a centrifugal barrier is lost, and so is the interpretation of the second derivative of the excitation function as a barrier distribution for this system, at energies above the Coulomb barrier.« less

Effects of van der Waals density functional corrections on trends in furfural adsorption and hydrogenation on close-packed transition metal surfaces

NASA Astrophysics Data System (ADS)

Liu, Bin; Cheng, Lei; Curtiss, Larry; Greeley, Jeffrey

2014-04-01

The hydrogenation of furfural to furfuryl alcohol on Pd(111), Cu(111) and Pt(111) is studied with both standard Density Functional Theory (DFT)-GGA functionals and with van der Waals-corrected density functionals. VdW-DF functionals, including optPBE, optB88, optB86b, and Grimme's method, are used to optimize the adsorption configurations of furfural, furfuryl alcohol, and related intermediates resulting from hydrogenation of furfural, and the results are compared to corresponding values determined with GGA functionals, including PW91 and PBE. On Pd(111) and Pt(111), the adsorption geometries of the intermediates are not noticeably different between the two classes of functionals, while on Cu(111), modest changes are seen in both the perpendicular distance and the orientation of the aromatic ring with respect to the planar surface. In general, the binding energies increase substantially in magnitude as a result of van der Waals contributions on all metals. In contrast, however, dispersion effects on the kinetics of hydrogenation are relatively small. It is found that activation barriers are not significantly affected by the inclusion of dispersion effects, and a Brønsted-Evans-Polanyi relationship developed solely from PW91 calculations on Pd(111) is capable of describing corresponding results on Cu(111) and Pt(111), even when the dispersion effects are included. Finally, the reaction energies and barriers derived from the dispersion-corrected and pure GGA calculations are used to plot simple potential energy profiles for furfural hydrogenation to furfuryl alcohol on the three considered metals, and an approximately constant downshift of the energetics due to the dispersion corrections is observed.

P-glycoprotein multidrug transporter in inflammatory bowel diseases: More questions than answers

PubMed Central

Cario, Elke

2017-01-01

The gastrointestinal barrier is constantly exposed to numerous environmental substrates that are foreign and potentially harmful. These xenobiotics can cause shifts in the intestinal microbiota composition, affect mucosal immune responses, disturb tissue integrity and impair regeneration. The multidrug transporter ABCB1/MDR1 p-glycoprotein (p-gp) plays a key role at the front line of host defence by efficiently protecting the gastrointestinal barrier from xenobiotic accumulation. This Editorial discusses how altered expression and function of ABCB1/MDR1 p-gp may contribute to the development and persistence of chronic intestinal inflammation in inflammatory bowel diseases (IBD). Recent evidence implies multiple interactions between intestinal microbiota, innate immunity and xenobiotic metabolism via p-gp. While decreased efflux activity may promote disease susceptibility and drug toxicity, increased efflux activity may confer resistance to therapeutic drugs in IBD. Mice deficient in MDR1A develop spontaneously chronic colitis, providing a highly valuable murine IBD model for the study of intestinal epithelial barrier function, immunoregulation, infectious co-triggers and novel therapeutic approaches. Possible associations of human ABCB1 gene polymorphisms with IBD susceptibility have been evaluated, but results are inconsistent. Future studies must focus on further elucidation of the pathophysiological relevance and immunological functions of p-gp and how its ambiguous effects could be therapeutically targeted in IBD. PMID:28321153

P-glycoprotein multidrug transporter in inflammatory bowel diseases: More questions than answers.

PubMed

Cario, Elke

2017-03-07

The gastrointestinal barrier is constantly exposed to numerous environmental substrates that are foreign and potentially harmful. These xenobiotics can cause shifts in the intestinal microbiota composition, affect mucosal immune responses, disturb tissue integrity and impair regeneration. The multidrug transporter ABCB1/MDR1 p-glycoprotein (p-gp) plays a key role at the front line of host defence by efficiently protecting the gastrointestinal barrier from xenobiotic accumulation. This Editorial discusses how altered expression and function of ABCB1/MDR1 p-gp may contribute to the development and persistence of chronic intestinal inflammation in inflammatory bowel diseases (IBD). Recent evidence implies multiple interactions between intestinal microbiota, innate immunity and xenobiotic metabolism via p-gp. While decreased efflux activity may promote disease susceptibility and drug toxicity, increased efflux activity may confer resistance to therapeutic drugs in IBD. Mice deficient in MDR1A develop spontaneously chronic colitis, providing a highly valuable murine IBD model for the study of intestinal epithelial barrier function, immunoregulation, infectious co-triggers and novel therapeutic approaches. Possible associations of human ABCB1 gene polymorphisms with IBD susceptibility have been evaluated, but results are inconsistent. Future studies must focus on further elucidation of the pathophysiological relevance and immunological functions of p-gp and how its ambiguous effects could be therapeutically targeted in IBD.

Housing accessibility for senior citizens in Sweden: Estimation of the effects of targeted elimination of environmental barriers.

PubMed

Pettersson, Cecilia; Slaug, Björn; Granbom, Marianne; Kylberg, Marianne; Iwarsson, Susanne

2017-01-24

To estimate the effects of targeted elimination of environmental barriers (EB) in the ordinary housing stock in Sweden, and to explore the estimated effects on accessibility at a population level in relation to (a) residents with different functional profiles, (b) different housing types and (c) building periods. Data on dwellings from existing Swedish research databases were utilized. EB and accessibility were assessed by means of the Housing Enabler instrument. In simulations of EB removal, five items that correspond to the most common housing adaptations were selected. The simulations were applied to four functional profiles of different complexity. EB known to be commonly removed by housing adaptations exist in large proportions of the existing ordinary housing stock. Estimated targeted elimination of selected barriers would have the largest accessibility effects for the more complex functional profiles. The effects would be consistently larger for one-family houses, and for all types of dwellings built before 1960. The elimination of the EB most commonly addressed by housing adaptations could result in a reduction of the housing accessibility problems that community-living older people are facing. For society to solve the housing situation for the ageing population well-informed and efficient upgrading of ordinary housing is imperative.

Kinetic Migration of Diethylhexyl Phthalate in Functional PVC Films

NASA Astrophysics Data System (ADS)

Fei, Fei; Liu, Zhongwei; Chen, Qiang; Liu, Fuping

2012-02-01

Plasticizers that are generally used in plastics to produce flexible food packaging materials have proved to cause reproductive system problems and women's infertility. A long-term consumption may even cause cancer diseases. Hence a nano-scale layer, named as functional barrier layer, was deposited on the plastic surface to prevent plasticizer diethylhexyl phthalate's (DEHP) migration from plastics to foods. The feasibility of functional barrier layer i.e. SiOx coating through plasma enhanced chemical vapor deposition (PECVD) process was then described in this paper. We used Fourier transform infrared spectroscopy (FTIR) to analyze the chemical composition of coatings, scanning electron microscope (SEM) to explore the topography of the coating surfaces, surface profilemeter to measure thickness of coatings, and high-performance liquid chromatography (HPLC) to evaluate the barrier properties of coatings. The results have clearly shown that the coatings can perfectly block the migration of the DEHP from plastics to their containers. It is also concluded that process parameters significantly influence the block efficiency of the coatings. When the deposition conditions of SiOx coatings were optimized, i.e. 50 W of the discharge power, 4:1 of ratio of O2: HMDSO, and ca.100 nm thickness of SiOx, 71.2% of the DEHP was effectively blocked.

Dynamics of HIV neutralization by a microbicide formulation layer: biophysical fundamentals and transport theory.

PubMed

Geonnotti, Anthony R; Katz, David F

2006-09-15

Topical microbicides are an emerging HIV/AIDS prevention modality. Microbicide biofunctionality requires creation of a chemical-physical barrier against HIV transmission. Barrier effectiveness derives from properties of the active compound and its delivery system, but little is known about how these properties translate into microbicide functionality. We developed a mathematical model simulating biologically relevant transport and HIV-neutralization processes occurring when semen-borne virus interacts with a microbicide delivery vehicle coating epithelium. The model enables analysis of how vehicle-related variables, and anti-HIV compound characteristics, affect microbicide performance. Results suggest HIV neutralization is achievable with postcoital coating thicknesses approximately 100 mum. Increased microbicide concentration and potency hasten viral neutralization and diminish penetration of infectious virus through the coating layer. Durable vehicle structures that restrict viral diffusion could provide significant protection. Our findings demonstrate the need to pair potent active ingredients with well-engineered formulation vehicles, and highlight the importance of the dosage form in microbicide effectiveness. Microbicide formulations can function not only as drug delivery vehicles, but also as physical barriers to viral penetration. Total viral neutralization with 100-mum-thin coating layers supports future microbicide use against HIV transmission. This model can be used as a tool to analyze diverse factors that govern microbicide functionality.

Cell based metabolic barriers to glucose diffusion: macrophages and continuous glucose monitoring.

PubMed

Klueh, Ulrike; Frailey, Jackman T; Qiao, Yi; Antar, Omar; Kreutzer, Donald L

2014-03-01

It is assumed that MQ are central to glucose sensor bio-fouling and therefore have a major negative impact on continuous glucose monitoring (CGM) performance in vivo. However to our knowledge there is no data in the literature to directly support or refute this assumption. Since glucose and oxygen (O2) are key to glucose sensor function in vivo, understanding and controlling glucose and O2 metabolic activity of MQ is likely key to successful glucose sensor performance. We hypothesized that the accumulation of MQ at the glucose sensor-tissue interface will act as "Cell Based Metabolic Barriers" (CBMB) to glucose diffusing from the interstitial tissue compartment to the implanted glucose sensor and as such creating an artificially low sensor output, thereby compromising sensor function and CGM. Our studies demonstrated that 1) direct injections of MQ at in vivo sensor implantation sites dramatically decreased sensor output (measured in nA), 2) addition of MQ to glucose sensors in vitro resulted in a rapid and dramatic fall in sensor output and 3) lymphocytes did not affect sensor function in vitro or in vivo. These data support our hypothesis that MQ can act as metabolic barriers to glucose and O2 diffusion in vivo and in vitro. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tin-phthalocyanine adsorption and diffusion on Cu and Au (111) surfaces: A density functional theory study

NASA Astrophysics Data System (ADS)

Qin, Dan; Ge, Xu-Jin; Lü, Jing-Tao

2018-05-01

Through density functional theory based calculations, we study the adsorption and diffusion of tin phthalocyanine (SnPc) molecule on Au(111) and Cu(111) surfaces. SnPc has two conformers with Sn pointing to the vacuum (Sn-up) and substrate (Sn-down), respectively. The binding energies of the two conformers with different adsorption sites on the two surfaces, including top, bridge, fcc, hcp, are calculated and compared. It is found that the SnPc molecule binds stronger on Cu(111) surface, with binding energy about 1 eV larger than that on Au(111). Only the bridge and top adsorption sites are stable on Cu(111), while all the four adsorption sites are stable on Au(111), with small diffusion barriers between them. Moreover, the flipping barrier from Sn-up to Sn-down conformer is of the same magnitude on the two metal surfaces. These results are consistent with a recent experiment [Zhang, et al., Angew. Chem., 56, 11769 (2017)], which shows that conformation change from Sn-up to Sn-down on Cu(111) surface can be induced by a C60-functionalized STM tip, while similar change is difficult to realize on Au(111), due to smaller diffusion barrier on Au(111).

Molecular interactions of plant oil components with stratum corneum lipids correlate with clinical measures of skin barrier function

PubMed Central

Mack Correa, Mary Catherine; Mao, Guangru; Saad, Peter; Flach, Carol R; Mendelsohn, Richard; Walters, Russel M

2014-01-01

Plant-derived oils consisting of triglycerides and small amounts of free fatty acids (FFAs) are commonly used in skincare regimens. FFAs are known to disrupt skin barrier function. The objective of this study was to mechanistically study the effects of FFAs, triglycerides and their mixtures on skin barrier function. The effects of oleic acid (OA), glyceryl trioleate (GT) and OA/GT mixtures on skin barrier were assessed in vivo through measurement of transepidermal water loss (TEWL) and fluorescein dye penetration before and after a single application. OA's effects on stratum corneum (SC) lipid order in vivo were measured with infrared spectroscopy through application of perdeuterated OA (OA-d34). Studies of the interaction of OA and GT with skin lipids included imaging the distribution of OA-d34 and GT ex vivo with IR microspectroscopy and thermodynamic analysis of mixtures in aqueous monolayers. The oil mixtures increased both TEWL and fluorescein penetration 24 h after a single application in an OA dose-dependent manner, with the highest increase from treatment with pure OA. OA-d34 penetrated into skin and disordered SC lipids. Furthermore, the ex vivo IR imaging studies showed that OA-d34 permeated to the dermal/epidermal junction while GT remained in the SC. The monolayer experiments showed preferential interspecies interactions between OA and SC lipids, while the mixing between GT and SC lipids was not thermodynamically preferred. The FFA component of plant oils may disrupt skin barrier function. The affinity between plant oil components and SC lipids likely determines the extent of their penetration and clinically measurable effects on skin barrier functions. PMID:24372651

Intestinal Alkaline Phosphatase Regulates Tight Junction Protein Levels.

PubMed

Liu, Wei; Hu, Dong; Huo, Haizhong; Zhang, Weifeng; Adiliaghdam, Fatemeh; Morrison, Sarah; Ramirez, Juan M; Gul, Sarah S; Hamarneh, Sulaiman R; Hodin, Richard A

2016-06-01

Intestinal alkaline phosphatase (IAP) plays a pivotal role in maintaining gut health and well-being. Oral supplementation with IAP in mice improves gut barrier function and prevents luminal proinflammatory factors from gaining access to the circulation. In this study, we sought to explore the relationship between IAP and tight junction protein (TJP) expression and function. The effect of IAP deletion on TJP levels was studied in mouse embryonic fibroblasts (MEFs) generated from IAP-knockout and wild type mice. Regulation of TJPs by IAP was assayed in the human colon cancer Caco-2 and T84 cells by overexpressing the human IAP gene. Tight junction protein levels and localization were measured by using RT q-PCR and antibodies targeting the specific TJPs. Finally, the effect of IAP on inflammation-induced intestinal permeability was measured by in vitro trans-well epithelial electrical resistance (TEER). Intestinal alkaline phosphatase gene deletion in MEFs resulted in significantly lower levels of ZO-1, ZO-2, and Occludin compared with levels in wild-type control cells; IAP overexpression in Caco-2 and T84 cells resulted in approximate 2-fold increases in the mRNA levels of ZO-1 and ZO-2. The IAP treatment ameliorated lipopolysaccharide-induced increased permeability in the Caco-2 trans-well system. Furthermore, IAP treatment preserved the localization of the ZO-1 and Occludin proteins during inflammation and was also associated with improved epithelial barrier function. Intestinal alkaline phosphatase is a major regulator of gut mucosal permeability and appears to work at least partly through improving TJP levels and localization. These data provide a strong foundation to develop IAP as a novel therapy to maintain gut barrier function. Copyright © 2016. Published by Elsevier Inc.

Design and performance evaluation of a 1000-year evapotranspiration-capillary surface barrier.

PubMed

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.

A comparison of unemployed job-seekers with and without social anxiety

PubMed Central

Himle, Joseph A; Weaver, Addie; Bybee, Deborah; O'Donnell, Lisa; Vlnka, Sarah; Laviolette, Wayne; Steinberger, Edward; Zipora, Golenberg; Levine, Debra Siegel

2014-01-01

Objective Literature consistently demonstrates that social anxiety disorder has substantial negative impacts on occupational functioning. However, to date, no identified empirical work has focused on understanding the specific nature of vocational problems among persons with social anxiety disorder. This study examines the association between employment-related factors (i.e., barriers to employment; skills related to employment; and job aspirations) and social anxiety among a sample of adults seeking vocational rehabilitation services. Methods Data from intake assessments, including a screen for social anxiety disorder, of 265 low-income, unemployed adults who initiated vocational rehabilitation services in urban Michigan was examined to assess differences in barriers to employment, employment skills, job aspirations, and demographic characteristics among participants who screened positive for social anxiety disorder compared to those who did not. Bivariate and multiple logistic regression analyses were performed. Results Multiple logistic regression analysis revealed that greater perceived experience and skill barriers to employment, fewer skills related to social-type occupations, and less education were significantly associated with social anxiety, after adjusting for other factors. Bivariate analysis also suggested that participants who screened positive for social anxiety disorder were significantly less likely to aspire to social jobs. Conclusions Employment-related factors likely impacting occupational functioning were significantly different between persons with and without social anxiety problems. Identifying these differences in employment barriers, skills, and job aspirations offer potentially important functional targets for psychosocial interventions aimed at social anxiety disorder and suggest the need for vocational service professionals to assess and address social anxiety among their clients. PMID:24733524

Hippophae rhamnoides oil-in-water (O/W) emulsion improves barrier function in healthy human subjects.

PubMed

Khan, Barkat Ali; Akhtar, Naveed

2014-11-01

This study aimed to investigate the changes in skin barrier function in human subjects, following long-term topical application of Hippophae rhamnoides oil-in-water (O/W) emulsion whereas effects were measred using non-invasive probes like tewameter and corneometer. For this purpose, two stable oil-in-water (O/W) emulsions were formulated one with 5% Hippophae rhamnoides extract and other without extracts. Thirteen healthy, male subjects with a mean age 27 ± 4.8 years were enrolled after their informed consents. The subjects were instructed to apply either the active formulation or the base formulation over 84 days while they were not known with the contents of either formulation. Biometrological measurements of skin hydration and transepidermal water loss (TEWL) were performed on both sides of the face in each volunteer at baseline and on day 07, 14, 21, 28, 42, 56, 70 and 84. The statistical analysis revealed formulation with 5% plant extract was superior compared to placebo (base formulation) as formulation with extract have shown extremely significant improvements in skin hydration (p=0.0003) and TEWL (p=0.0087) throughout treatment course. Moreover, a significant (p<0.05) correlation between the active formulation and the improvement of the skin barrier functions was observed. The active formulation found to be superior to that of placebo. Results affirmed that future studies are necessary to clinically evaluate the active formulation hence it can be proposed that Hippophae rhamnoides emulsion could be an alternative pharmacological tool in treating barrier compromised conditions of skin.

In vitro effects of preserved and unpreserved anti-allergic drugs on human corneal epithelial cells.

PubMed

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.

Oral Supplementation with Non-Absorbable Antibiotics or Curcumin Attenuates Western Diet-Induced Atherosclerosis and Glucose Intolerance in LDLR−/− Mice – Role of Intestinal Permeability and Macrophage Activation

PubMed Central

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

A photoemission moments model using density functional and transfer matrix methods applied to coating layers on surfaces: Theory

NASA Astrophysics Data System (ADS)

Jensen, Kevin L.; Finkenstadt, Daniel; Shabaev, Andrew; Lambrakos, Samuel G.; Moody, Nathan A.; Petillo, John J.; Yamaguchi, Hisato; Liu, Fangze

2018-01-01

Recent experimental measurements of a bulk material covered with a small number of graphene layers reported by Yamaguchi et al. [NPJ 2D Mater. Appl. 1, 12 (2017)] (on bialkali) and Liu et al. [Appl. Phys. Lett. 110, 041607 (2017)] (on copper) and the needs of emission models in beam optics codes have lead to substantial changes in a Moments model of photoemission. The changes account for (i) a barrier profile and density of states factor based on density functional theory (DFT) evaluations, (ii) a Drude-Lorentz model of the optical constants and laser penetration depth, and (iii) a transmission probability evaluated by an Airy Transfer Matrix Approach. Importantly, the DFT results lead to a surface barrier profile of a shape similar to both resonant barriers and reflectionless wells: the associated quantum mechanical transmission probabilities are shown to be comparable to those recently required to enable the Moments (and Three Step) model to match experimental data but for reasons very different than the assumption by conventional wisdom that a barrier is responsible. The substantial modifications of the Moments model components, motivated by computational materials methods, are developed. The results prepare the Moments model for use in treating heterostructures and discrete energy level systems (e.g., quantum dots) proposed for decoupling the opposing metrics of performance that undermine the performance of advanced light sources like the x-ray Free Electron Laser. The consequences of the modified components on quantum yield, emittance, and emission models needed by beam optics codes are discussed.

Improvement of Blood-Brain Barrier Integrity in Traumatic Brain Injury and Hemorrhagic Shock Following Treatment With Valproic Acid and Fresh Frozen Plasma.

PubMed

Nikolian, Vahagn C; Dekker, Simone E; Bambakidis, Ted; Higgins, Gerald A; Dennahy, Isabel S; Georgoff, Patrick E; Williams, Aaron M; Andjelkovic, Anuska V; Alam, Hasan B

2018-01-01

Combined traumatic brain injury and hemorrhagic shock are highly lethal. Following injuries, the integrity of the blood-brain barrier can be impaired, contributing to secondary brain insults. The status of the blood-brain barrier represents a potential factor impacting long-term neurologic outcomes in combined injuries. Treatment strategies involving plasma-based resuscitation and valproic acid therapy have shown efficacy in this setting. We hypothesize that a component of this beneficial effect is related to blood-brain barrier preservation. Following controlled traumatic brain injury, hemorrhagic shock, various resuscitation and treatment strategies were evaluated for their association with blood-brain barrier integrity. Analysis of gene expression profiles was performed using Porcine Gene ST 1.1 microarray. Pathway analysis was completed using network analysis tools (Gene Ontology, Ingenuity Pathway Analysis, and Parametric Gene Set Enrichment Analysis). Female Yorkshire swine were subjected to controlled traumatic brain injury and 2 hours of hemorrhagic shock (40% blood volume, mean arterial pressure 30-35 mmHg). Subjects were resuscitated with 1) normal saline, 2) fresh frozen plasma, 3) hetastarch, 4) fresh frozen plasma + valproic acid, or 5) hetastarch + valproic acid (n = 5 per group). After 6 hours of observation, brains were harvested for evaluation. Immunofluoroscopic evaluation of the traumatic brain injury site revealed significantly increased expression of tight-junction associated proteins (zona occludin-1, claudin-5) following combination therapy (fresh frozen plasma + valproic acid and hetastarch + valproic acid). The extracellular matrix protein laminin was found to have significantly improved expression with combination therapies. Pathway analysis indicated that valproic acid significantly modulated pathways involved in endothelial barrier function and cell signaling. Resuscitation with fresh frozen plasma results in improved expression of proteins essential for blood-brain barrier integrity. The addition of valproic acid provides significant improvement to these protein expression profiles. This is likely secondary to activation of key pathways related to endothelial functions.

Lipid rafts are disrupted in mildly inflamed intestinal microenvironments without overt disruption of the epithelial barrier.

PubMed

Bowie, Rachel V; Donatello, Simona; Lyes, Clíona; Owens, Mark B; Babina, Irina S; Hudson, Lance; Walsh, Shaun V; O'Donoghue, Diarmuid P; Amu, Sylvie; Barry, Sean P; Fallon, Padraic G; Hopkins, Ann M

2012-04-15

Intestinal epithelial barrier disruption is a feature of inflammatory bowel disease (IBD), but whether barrier disruption precedes or merely accompanies inflammation remains controversial. Tight junction (TJ) adhesion complexes control epithelial barrier integrity. Since some TJ proteins reside in cholesterol-enriched regions of the cell membrane termed lipid rafts, we sought to elucidate the relationship between rafts and intestinal epithelial barrier function. Lipid rafts were isolated from Caco-2 intestinal epithelial cells primed with the proinflammatory cytokine interferon-γ (IFN-γ) or treated with methyl-β-cyclodextrin as a positive control for raft disruption. Rafts were also isolated from the ilea of mice in which colitis had been induced in conjunction with in vivo intestinal permeability measurements, and lastly from intestinal biopsies of ulcerative colitis (UC) patients with predominantly mild or quiescent disease. Raft distribution was analyzed by measuring activity of the raft-associated enzyme alkaline phosphatase and by performing Western blot analysis for flotillin-1. Epithelial barrier integrity was estimated by measuring transepithelial resistance in cytokine-treated cells or in vivo permeability to fluorescent dextran in colitic mice. Raft and nonraft fractions were analyzed by Western blotting for the TJ proteins occludin and zonula occludens-1 (ZO-1). Our results revealed that lipid rafts were disrupted in IFN-γ-treated cells, in the ilea of mice with subclinical colitis, and in UC patients with quiescent inflammation. This was not associated with a clear pattern of occludin or ZO-1 relocalization from raft to nonraft fractions. Significantly, a time-course study in colitic mice revealed that disruption of lipid rafts preceded the onset of increased intestinal permeability. Our data suggest for the first time that lipid raft disruption occurs early in the inflammatory cascade in murine and human colitis and, we speculate, may contribute to subsequent disruption of epithelial barrier function.

Inflammation in dry eye.

PubMed

Stern, Michael E; Pflugfelder, Stephen C

2004-04-01

Dry eye is a condition of altered tear composition that results from a diseased or dysfunctional lacrimal functional unit. Evidence suggests that inflammation causes structural alterations and/or functional paralysis of the tear-secreting glands. Changes in tear composition resulting from lacrimal dysfunction, increased evaporation and/or poor clearance have pro-inflammatory effects on the ocular surface. This inflammation is responsible in part for the irritation symptoms, ocular surface epithelial disease, and altered corneal epithelial barrier function in dry eye. Anti-inflammatory therapies for dry eye target one or more of the inflammatory mediators/pathways that have been identified in dry eye.

On the validity of the Arrhenius equation for electron attachment rate coefficients.

PubMed

Fabrikant, Ilya I; Hotop, Hartmut

2008-03-28

The validity of the Arrhenius equation for dissociative electron attachment rate coefficients is investigated. A general analysis allows us to obtain estimates of the upper temperature bound for the range of validity of the Arrhenius equation in the endothermic case and both lower and upper bounds in the exothermic case with a reaction barrier. The results of the general discussion are illustrated by numerical examples whereby the rate coefficient, as a function of temperature for dissociative electron attachment, is calculated using the resonance R-matrix theory. In the endothermic case, the activation energy in the Arrhenius equation is close to the threshold energy, whereas in the case of exothermic reactions with an intermediate barrier, the activation energy is found to be substantially lower than the barrier height.

Electrostatic Estimation of Intercalant Jump-Diffusion Barriers Using Finite-Size Ion Models.

PubMed

Zimmermann, Nils E R; Hannah, Daniel C; Rong, Ziqin; Liu, Miao; Ceder, Gerbrand; Haranczyk, Maciej; Persson, Kristin A

2018-02-01

We report on a scheme for estimating intercalant jump-diffusion barriers that are typically obtained from demanding density functional theory-nudged elastic band calculations. The key idea is to relax a chain of states in the field of the electrostatic potential that is averaged over a spherical volume using different finite-size ion models. For magnesium migrating in typical intercalation materials such as transition-metal oxides, we find that the optimal model is a relatively large shell. This data-driven result parallels typical assumptions made in models based on Onsager's reaction field theory to quantitatively estimate electrostatic solvent effects. Because of its efficiency, our potential of electrostatics-finite ion size (PfEFIS) barrier estimation scheme will enable rapid identification of materials with good ionic mobility.

Electronic states of aryl radical functionalized graphenes: Density functional theory study

NASA Astrophysics Data System (ADS)

Tachikawa, Hiroto; Kawabata, Hiroshi

2016-06-01

Functionalized graphenes are known as a high-performance molecular device. In the present study, the structures and electronic states of the aryl radical functionalized graphene have been investigated by the density functional theory (DFT) method to elucidate the effects of functionalization on the electronic states of graphene (GR). Also, the mechanism of aryl radical reaction with GR was investigated. The benzene, biphenyl, p-terphenyl, and p-quaterphenyl radicals [denoted by (Bz) n (n = 1-4), where n means numbers of benzene rings in aryl radical] were examined as aryl radicals. The DFT calculation of GR-(Bz) n (n = 1-4) showed that the aryl radical binds to the carbon atom of GR, and a C-C single bond was formed. The binding energies of aryl radicals to GR were calculated to be ca. 6.0 kcal mol-1 at the CAM-B3LYP/6-311G(d,p) level. It was found that the activation barrier exists in the aryl radical addition: the barrier heights were calculated to be 10.0 kcal mol-1. The electronic states of GR-(Bz) n were examined on the basis of theoretical results.

Determinants of hand dermatitis, urticaria and loss of skin barrier function in professional cleaners in New Zealand.

PubMed

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.

Perceived and objective entrance-related environmental barriers and daily out-of-home mobility in community-dwelling older people.

PubMed

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.

Infant Nutritional Status, Feeding Practices, Enteropathogen Exposure, Socioeconomic Status, and Illness Are Associated with Gut Barrier Function As Assessed by the Lactulose Mannitol Test in the MAL-ED Birth Cohort.

PubMed

Lee, Gwenyth O; McCormick, Benjamin J J; Seidman, Jessica C; Kosek, Margaret N; Haque, Rashidul; Olortegui, Maribel Paredes; Lima, Aldo A M; Bhutta, Zulfiqar A; Kang, Gagandeep; Samie, Amidou; Amour, Caroline; Mason, Carl J; Ahmed, Tahmeed; Yori, Pablo Peñataro; Oliveira, Domingos B; Alam, Didar; Babji, Sudhir; Bessong, Pascal; Mduma, Estomih; Shrestha, Sanjaya K; Ambikapathi, Ramya; Lang, Dennis R; Gottlieb, Michael; Guerrant, Richard L; Caulfield, Laura E; For The Mal-Ed Network Investigators

2017-07-01

The lactulose mannitol (LM) dual sugar permeability test is the most commonly used test of environmental enteropathy in developing countries. However, there is a large but conflicting literature on its association with enteric infection and host nutritional status. We conducted a longitudinal cohort using a single field protocol and comparable laboratory procedures to examine intestinal permeability in multiple, geographically diverse pediatric populations. Using a previously published systematic review to guide the selection of factors potentially associated with LM test results, we examined the relationships between these factors and mucosal breach, represented by percent lactulose excretion; absorptive area, represented by percent mannitol excretion; and gut barrier function, represented by the L/M ratio. A total of 6,602 LM tests were conducted in 1,980 children at 3, 6, 9, and 15 months old; percent lactulose excretion, percent mannitol excretion, and the L/M ratio were expressed as age- and sex-specific normalized values using the Brazil cohort as the reference population. Among the factors considered, recent severe diarrhea, lower socioeconomic status, and recent asymptomatic enteropathogen infections were associated with decreased percent mannitol excretion and higher L/M ratios. Poorer concurrent weight-for-age, infection, and recent breastfeeding were associated with increased percent lactulose excretion and increased L/M ratios. Our results support previously reported associations between the L/M ratio and factors related to child nutritional status and enteropathogen exposure. These results were remarkably consistent across sites and support the hypothesis that the frequency of these exposures in communities living in poverty leads to alterations in gut barrier function.

Infant Nutritional Status, Feeding Practices, Enteropathogen Exposure, Socioeconomic Status, and Illness Are Associated with Gut Barrier Function As Assessed by the Lactulose Mannitol Test in the MAL-ED Birth Cohort

PubMed Central

Lee, Gwenyth O.; McCormick, Benjamin J. J.; Seidman, Jessica C.; Kosek, Margaret N.; Haque, Rashidul; Olortegui, Maribel Paredes; Lima, Aldo A. M.; Bhutta, Zulfiqar A.; Kang, Gagandeep; Samie, Amidou; Amour, Caroline; Mason, Carl J.; Ahmed, Tahmeed; Yori, Pablo Peñataro; Oliveira, Domingos B.; Alam, Didar; Babji, Sudhir; Bessong, Pascal; Mduma, Estomih; Shrestha, Sanjaya K.; Ambikapathi, Ramya; Lang, Dennis R.; Gottlieb, Michael; Guerrant, Richard L.; Caulfield, Laura E.

2017-01-01

Abstract. The lactulose mannitol (LM) dual sugar permeability test is the most commonly used test of environmental enteropathy in developing countries. However, there is a large but conflicting literature on its association with enteric infection and host nutritional status. We conducted a longitudinal cohort using a single field protocol and comparable laboratory procedures to examine intestinal permeability in multiple, geographically diverse pediatric populations. Using a previously published systematic review to guide the selection of factors potentially associated with LM test results, we examined the relationships between these factors and mucosal breach, represented by percent lactulose excretion; absorptive area, represented by percent mannitol excretion; and gut barrier function, represented by the L/M ratio. A total of 6,602 LM tests were conducted in 1,980 children at 3, 6, 9, and 15 months old; percent lactulose excretion, percent mannitol excretion, and the L/M ratio were expressed as age- and sex-specific normalized values using the Brazil cohort as the reference population. Among the factors considered, recent severe diarrhea, lower socioeconomic status, and recent asymptomatic enteropathogen infections were associated with decreased percent mannitol excretion and higher L/M ratios. Poorer concurrent weight-for-age, infection, and recent breastfeeding were associated with increased percent lactulose excretion and increased L/M ratios. Our results support previously reported associations between the L/M ratio and factors related to child nutritional status and enteropathogen exposure. These results were remarkably consistent across sites and support the hypothesis that the frequency of these exposures in communities living in poverty leads to alterations in gut barrier function. PMID:28719336

Targeting the brain--surmounting or bypassing the blood-brain barrier.

PubMed

Potschka, Heidrun

2010-01-01

The constituents of the blood-brain barrier, including its efflux transporter system, can efficiently limit brain penetration of potential CNS therapeutics. Effective extrusion from the brain by transporters is a frequent reason for the pharmaceutical industry to exclude novel compounds from further development for CNS therapeutics. Moreover, high transporter expression levels that are present in individual patients or may be generally associated with the pathophysiology seem to be a major cause of therapeutic failure in a variety of CNS diseases including brain tumors, epilepsy, brain HIV infection, and psychiatric disorders. Increasing knowledge of the structure and function of the blood-brain barrier creates a basis for the development of strategies which aim to enhance brain uptake of beneficial pharmaceutical compounds. The different strategies discussed in this review aim to modulate blood-brain barrier function or to bypass constituents of the blood-brain barrier.

Predicting the continuum between corridors and barriers to animal movements using Step Selection Functions and Randomized Shortest Paths.

PubMed

Panzacchi, Manuela; Van Moorter, Bram; Strand, Olav; Saerens, Marco; Kivimäki, Ilkka; St Clair, Colleen C; Herfindal, Ivar; Boitani, Luigi

2016-01-01

The loss, fragmentation and degradation of habitat everywhere on Earth prompts increasing attention to identifying landscape features that support animal movement (corridors) or impedes it (barriers). Most algorithms used to predict corridors assume that animals move through preferred habitat either optimally (e.g. least cost path) or as random walkers (e.g. current models), but neither extreme is realistic. We propose that corridors and barriers are two sides of the same coin and that animals experience landscapes as spatiotemporally dynamic corridor-barrier continua connecting (separating) functional areas where individuals fulfil specific ecological processes. Based on this conceptual framework, we propose a novel methodological approach that uses high-resolution individual-based movement data to predict corridor-barrier continua with increased realism. Our approach consists of two innovations. First, we use step selection functions (SSF) to predict friction maps quantifying corridor-barrier continua for tactical steps between consecutive locations. Secondly, we introduce to movement ecology the randomized shortest path algorithm (RSP) which operates on friction maps to predict the corridor-barrier continuum for strategic movements between functional areas. By modulating the parameter Ѳ, which controls the trade-off between exploration and optimal exploitation of the environment, RSP bridges the gap between algorithms assuming optimal movements (when Ѳ approaches infinity, RSP is equivalent to LCP) or random walk (when Ѳ → 0, RSP → current models). Using this approach, we identify migration corridors for GPS-monitored wild reindeer (Rangifer t. tarandus) in Norway. We demonstrate that reindeer movement is best predicted by an intermediate value of Ѳ, indicative of a movement trade-off between optimization and exploration. Model calibration allows identification of a corridor-barrier continuum that closely fits empirical data and demonstrates that RSP outperforms models that assume either optimality or random walk. The proposed approach models the multiscale cognitive maps by which animals likely navigate real landscapes and generalizes the most common algorithms for identifying corridors. Because suboptimal, but non-random, movement strategies are likely widespread, our approach has the potential to predict more realistic corridor-barrier continua for a wide range of species. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

“You Shall Not Pass”—tight junctions of the blood brain barrier

PubMed Central

Bauer, Hans-Christian; Krizbai, István A.; Bauer, Hannelore; Traweger, Andreas

2014-01-01

The structure and function of the barrier layers restricting the free diffusion of substances between the central nervous system (brain and spinal cord) and the systemic circulation is of great medical interest as various pathological conditions often lead to their impairment. Excessive leakage of blood-borne molecules into the parenchyma and the concomitant fluctuations in the microenvironment following a transient breakdown of the blood-brain barrier (BBB) during ischemic/hypoxic conditions or because of an autoimmune disease are detrimental to the physiological functioning of nervous tissue. On the other hand, the treatment of neurological disorders is often hampered as only minimal amounts of therapeutic agents are able to penetrate a fully functional BBB or blood cerebrospinal fluid barrier. An in-depth understanding of the molecular machinery governing the establishment and maintenance of these barriers is necessary to develop rational strategies allowing a controlled delivery of appropriate drugs to the CNS. At the basis of such tissue barriers are intimate cell-cell contacts (zonulae occludentes, tight junctions) which are present in all polarized epithelia and endothelia. By creating a paracellular diffusion constraint TJs enable the vectorial transport across cell monolayers. More recent findings indicate that functional barriers are already established during development, protecting the fetal brain. As an understanding of the biogenesis of TJs might reveal the underlying mechanisms of barrier formation during ontogenic development numerous in vitro systems have been developed to study the assembly and disassembly of TJs. In addition, monitoring the stage-specific expression of TJ-associated proteins during development has brought much insight into the “developmental tightening” of tissue barriers. Over the last two decades a detailed molecular map of transmembrane and cytoplasmic TJ-proteins has been identified. These proteins not only form a cell-cell adhesion structure, but integrate various signaling pathways, thereby directly or indirectly impacting upon processes such as cell-cell adhesion, cytoskeletal rearrangement, and transcriptional control. This review will provide a brief overview on the establishment of the BBB during embryonic development in mammals and a detailed description of the ultrastructure, biogenesis, and molecular composition of epithelial and endothelial TJs will be given. PMID:25520612

Stratum corneum hydration and skin surface pH in patients with atopic dermatitis.

PubMed

Knor, Tanja; Meholjić-Fetahović, Ajša; Mehmedagić, Aida

2011-01-01

Atopic dermatitis (AD) is a chronically relapsing skin disease with genetic predisposition, which occurs most frequently in preschool children. It is considered that dryness and pruritus, which are always present in AD, are in correlation with degradation of the skin barrier function. Measurement of hydration and pH value of the stratum corneum is one of the noninvasive methods for evaluation of skin barrier function. The aim of the study was to assess skin barrier function by measuring stratum corneum hydration and skin surface pH of the skin with lesions, perilesional skin and uninvolved skin in AD patients, and skin in a healthy control group. Forty-two patients were included in the study: 21 young and adult AD patients and 21 age-matched healthy controls. Capacitance, which is correlated with hydration of stratum corneum and skin surface pH were measured on the forearm in the above areas by SM810/CM820/pH900 combined units (Courage AND Khazaka, Germany). The mean value of water capacitance measured in AD patients was 44.1 ± 11.6 AU (arbitrary units) on the lesions, 60.2 ± 12.4 AU on perilesional skin and 67.2 ± 8.8 AU on uninvolved skin. In healthy controls, the mean value was 74.1 ± 9.2 AU. The mean pH value measured in AD patients was 6.13 ± 0.52 on the lesions, 5.80 ± 0.41 on perilesional skin, and 5.54 ± 0.49 on uninvolved skin. In control group, the mean pH of the skin surface was 5.24 ± 0.40. The values of both parameters measured on lesional skin were significantly different (capacitance decreased and pH increased) from the values recorded on perilesional skin and uninvolved skin. The same held for the relation between perilesional and uninvolved skin. According to study results, the uninvolved skin of AD patients had significantly worse values of the measured parameters as compared with control group. The results of this study suggested the skin barrier function to be degraded in AD patients, which is specifically expressed in lesional skin.

Effects of in Utero Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Epidermal Permeability Barrier Development and Function

PubMed Central

Muenyi, Clarisse S.; Carrion, Sandra Leon; Jones, Lynn A.; Kennedy, Lawrence H.; Slominski, Andrzej T.

2014-01-01

Background: Development of the epidermal permeability barrier (EPB) is essential for neonatal life. Defects in this barrier are found in many skin diseases such as atopic dermatitis. Objective: We investigated the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development and function of the EPB. Methods: Timed-pregnant C57BL/6J mice were gavaged with corn oil or TCDD (10 μg/kg body weight) on gestation day 12. Embryos were harvested on embryonic day (E) 15, E16, E17, and postnatal day (PND) 1. Results: A skin permeability assay showed that TCDD accelerated the development of the EPB, beginning at E15. This was accompanied by a significant decrease in transepidermal water loss (TEWL), enhanced stratification, and formation of the stratum corneum (SC). The levels of several ceramides were significantly increased at E15 and E16. PND1 histology revealed TCDD-induced acanthosis and epidermal hyperkeratosis. This was accompanied by disrupted epidermal tight junction (TJ) function, with increased dye leakage at the terminal claudin-1–staining TJs of the stratum granulosum. Because the animals did not have enhanced rates of TEWL, a commonly observed phenotype in animals with TJ defects, we performed tape-stripping. Removal of most of the SC resulted in a significant increase in TEWL in TCDD-exposed PND1 pups compared with their control group. Conclusions: These findings demonstrate that in utero exposure to TCDD accelerates the formation of an abnormal EPB with leaky TJs, warranting further study of environmental exposures, epithelial TJ integrity, and atopic disease. Citation: Muenyi CS, Leon Carrion S, Jones LA, Kennedy LH, Slominski AT, Sutter CH, Sutter TR. 2014. Effects of in utero exposure of C57BL/6J mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin on epidermal permeability barrier development and function. Environ Health Perspect 122:1052–1058; http://dx.doi.org/10.1289/ehp.1308045 PMID:24904982

Importance of the correlation contribution for local hybrid functionals: range separation and self-interaction corrections.

PubMed

Arbuznikov, Alexei V; Kaupp, Martin

2012-01-07

Local hybrid functionals with their position-dependent exact-exchange admixture are a conceptually simple and promising extension of the concept of a hybrid functional. Local hybrids based on a simple mixing of the local spin density approximation (LSDA) with exact exchange have been shown to be successful for thermochemistry, reaction barriers, and a range of other properties. So far, the combination of this generation of local hybrids with an LSDA correlation functional has been found to give the most favorable results for atomization energies, for a range of local mixing functions (LMFs) governing the exact-exchange admixture. Here, we show that the choice of correlation functional to be used with local hybrid exchange crucially influences the parameterization also of the exchange part as well as the overall performance. A novel ansatz for the correlation part of local hybrids is suggested based on (i) range-separation of LSDA correlation into short-range (SR) and long-range (LR) parts, and (ii) partial or full elimination of the one-electron self-correlation from the SR part. It is shown that such modified correlation functionals allow overall larger exact exchange admixture in thermochemically competitive local hybrids than before. This results in improvements for reaction barriers and for other properties crucially influenced by self-interaction errors, as demonstrated by a number of examples. Based on the range-separation approach, a fresh view on the breakdown of the correlation energy into dynamical and non-dynamical parts is suggested.

Systematic study on the isotopic behavior of fusion barrier using the density-dependent nucleon-nucleon interactions

NASA Astrophysics Data System (ADS)

Ghodsi, O. N.; Khalaj, M.

By changing the neutron and nuclear matter incompressibility constant K, we investigate the isotopic behavior of the fusion barriers for the collision of large number of different isotopes with condition of 0.7 ≤ N/Z ≤ 1.36. Here, the double folding (DF) model which is accompanied by density-dependent (DD) versions of M3Y interactions is adopted as a basic heavy ion-ion potential. We show that the selected DD potentials predict a linear behavior for the calculated fusion barrier heights as a function of (N/Z - 1) for both proton- and neutron-rich systems. Moreover, the results indicate that the isotopic behavior of these values depend linearly on the change in the K constant. The isotopic studies conducted on the fusion cross-section also shows that the properties of the nuclear matter in the range of energy which is below the fusion barrier will quite affect the fusion process.

Direct visualization of the arterial wall water permeability barrier using CARS microscopy

PubMed Central

Lucotte, Bertrand M.; Powell, Chloe; Knutson, Jay R.; Combs, Christian A.; Malide, Daniela; Yu, Zu-Xi; Knepper, Mark; Patel, Keval D.; Pielach, Anna; Johnson, Errin; Borysova, Lyudmyla; Balaban, Robert S.

2017-01-01

The artery wall is equipped with a water permeation barrier that allows blood to flow at high pressure without significant water leak. The precise location of this barrier is unknown despite its importance in vascular function and its contribution to many vascular complications when it is compromised. Herein we map the water permeability in intact arteries, using coherent anti-Stokes Raman scattering (CARS) microscopy and isotopic perfusion experiments. Generation of the CARS signal is optimized for water imaging with broadband excitation. We identify the water permeation barrier as the endothelial basolateral membrane and show that the apical membrane is highly permeable. This is confirmed by the distribution of the AQP1 water channel within endothelial membranes. These results indicate that arterial pressure equilibrates within the endothelium and is transmitted to the supporting basement membrane and internal elastic lamina macromolecules with minimal deformation of the sensitive endothelial cell. Disruption of this pressure transmission could contribute to endothelial cell dysfunction in various pathologies. PMID:28373558

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.

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

PubMed Central

Liévin-Le Moal, Vanessa

2013-01-01

SUMMARY Hosts are protected from attack by potentially harmful enteric microorganisms, viruses, and parasites by the polarized fully differentiated epithelial cells that make up the epithelium, providing a physical and functional barrier. Enterovirulent bacteria interact with the epithelial polarized cells lining the intestinal barrier, and some invade the cells. A better understanding of the cross talk between enterovirulent bacteria and the polarized intestinal cells has resulted in the identification of essential enterovirulent bacterial structures and virulence gene products playing pivotal roles in pathogenesis. Cultured animal cell lines and cultured human nonintestinal, undifferentiated epithelial cells have been extensively used for understanding the mechanisms by which some human enterovirulent bacteria induce intestinal disorders. Human colon carcinoma cell lines which are able to express in culture the functional and structural characteristics of mature enterocytes and goblet cells have been established, mimicking structurally and functionally an intestinal epithelial barrier. Moreover, Caco-2-derived M-like cells have been established, mimicking the bacterial capture property of M cells of Peyer's patches. This review intends to analyze the cellular and molecular mechanisms of pathogenesis of human enterovirulent bacteria observed in infected cultured human colon carcinoma enterocyte-like HT-29 subpopulations, enterocyte-like Caco-2 and clone cells, the colonic T84 cell line, HT-29 mucus-secreting cell subpopulations, and Caco-2-derived M-like cells, including cell association, cell entry, intracellular lifestyle, structural lesions at the brush border, functional lesions in enterocytes and goblet cells, functional and structural lesions at the junctional domain, and host cellular defense responses. PMID:24006470

A controlled, three-part trial to investigate the barrier function and skin hydration properties of six skin protectants.

PubMed

Hoggarth, Andrew; Waring, Mike; Alexander, James; Greenwood, Amanada; Callaghan, Theresa

2005-12-01

In the treatment of incontinence dermatitis, a skin protectant primarily prevents skin breakdown due to moisture and biological irritants in urine and feces. To assess the barrier and skin hydration properties of six currently available skin protectants with different formulations, a controlled, three-phase study was conducted at a research facility in the UK among 18 healthy volunteers. The study addressed each product's efficacy against insult from a known irritant (sodium lauryl sulphate), skin hydration potential, and maintenance of skin barrier and barrier efficacy against maceration. Using white petrolatum (glycerin) as the positive control and untreated sites as the negative control, the results show that each one of the products tested has different performance properties. Products containing petrolatum demonstrated protection against irritants (P = 0.006 at 24 hours) and maceration (P < 0.005) and provided some skin hydration. Products containing dimethicone varied in protection against irritants (P < 0.005, or P > or = 0.806 at 24 hours) and have good skin hydration potential and low barrier efficacy (P > 0.500). Zinc oxide-based products showed protection against irritants (P < 0.005) but poor skin hydration and barrier properties to prevent maceration (P = 0.262). Overall, only the water-in-oil petrolatum- based product performed effectively within all the parameters tested. This study suggests that skin barrier protection involves more than the inclusion of an active barrier ingredient. Further testing and use of barrier products in the clinical setting will provide additional evidence for appropriate product selection.

A Comprehensive Biophysical Model of Ion and Water Transport in Plant Roots. I. Clarifying the Roles of Endodermal Barriers in the Salt Stress Response

PubMed Central

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

Oligoclonal banding of IgG in CSF, blood-brain barrier function, and MRI findings in patients with sarcoidosis, systemic lupus erythematosus, and Behçet's disease involving the nervous system.

PubMed Central

McLean, B N; Miller, D; Thompson, E J

1995-01-01

A retrospective study of CSF and serum analysis from a total of 43 patients with sarcoidosis, 20 with systemic lupus erythematosus, and 12 with Behçet's disease with neurological involvement found local synthesis of oligoclonal IgG using isoelectric focusing and immunoblotting in 51%, 25%, and 8% respectively at some stage in their disease. Blood-brain barrier breakdown, when assessed with an albumin ratio found 47% of patients with sarcoidosis, 30% of those with systemic lupus erythematosus, and 42% of patients with Behçet's disease exhibiting abnormal barrier function at some time. Serial CSF analysis showed that clinical relapses were associated with worsening barrier function and in some patients the development of local oligoclonal IgG synthesis; conversely steroid treatment led to a statistically significant improvement in barrier function, and in two patients a loss of oligoclonal IgG bands. A higher proportion of patients had MRI abnormalities than oligoclonal IgG or blood-brain barrier breakdown, MRI being abnormal in 16 of 19 patients with sarcoidosis, three of four patients with systemic lupus erythematosus, and seven of nine patients with Behçet's disease, although this may have been due to temporal factors. In the differential diagnosis of chronic neurological disorders, locally synthesised oligoclonal IgG cannot distinguish between diseases, but the loss of bands seen in two patients contrasts with what is seen in multiple sclerosis, and thus may be a useful diagnostic clue. PMID:7745401

Perceived barriers to utilizing maternal and neonatal health services in contracted-out versus government-managed health facilities in the rural districts of Pakistan

PubMed Central

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

Liposomes bi-functionalized with phosphatidic acid and an ApoE-derived peptide affect Aβ aggregation features and cross the blood-brain-barrier: implications for therapy of Alzheimer disease.

PubMed

Bana, Laura; Minniti, Stefania; Salvati, Elisa; Sesana, Silvia; Zambelli, Vanessa; Cagnotto, Alfredo; Orlando, Antonina; Cazzaniga, Emanuela; Zwart, Rob; Scheper, Wiep; Masserini, Massimo; Re, Francesca

2014-10-01

Targeting amyloid-β peptide (Aβ) within the brain is a strategy actively sought for therapy of Alzheimer's disease (AD). We investigated the ability of liposomes bi-functionalized with phosphatidic acid and with a modified ApoE-derived peptide (mApoE-PA-LIP) to affect Aβ aggregation/disaggregation features and to cross in vitro and in vivo the blood-brain barrier (BBB). Surface plasmon resonance showed that bi-functionalized liposomes strongly bind Aβ (kD=0.6 μM), while Thioflavin-T and SDS-PAGE/WB assays show that liposomes inhibit peptide aggregation (70% inhibition after 72 h) and trigger the disaggregation of preformed aggregates (60% decrease after 120 h incubation). Moreover, experiments with dually radiolabelled LIP suggest that bi-functionalization enhances the passage of radioactivity across the BBB either in vitro (permeability=2.5×10(-5) cm/min, 5-fold higher with respect to mono-functionalized liposomes) or in vivo in healthy mice. Taken together, our results suggest that mApoE-PA-LIP are valuable nanodevices with a potential applicability in vivo for the treatment of AD. From the clinical editor: Bi-functionalized liposomes with phosphatidic acid and a modified ApoE-derived peptide were demonstrated to influence Aβ aggregation/disaggregation as a potential treatment in an Alzheimer's model. The liposomes were able to cross the blood-brain barrier in vitro and in vivo. Similar liposomes may become clinically valuable nanodevices with a potential applicability for the treatment of Alzheimer's disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Geophysical Assessment of the Control of a Jetty on a Barrier Beach and Estuary System

NASA Astrophysics Data System (ADS)

Ulrich, C.; Hubbard, S. S.; Peterson, J.; Blom, K.; Black, W.; Delaney, C.; Mendoza, J.

2014-12-01

An evaluation is underway at the Goat Rock State Park, located at the mouth of the Russian River near Jenner, CA, to quantify the influence of a man made jetty on the functioning of a barrier beach and associated implications for estuary fish habitat and flood control. Flow through the beach results from water level differences between the estuary and the ocean. When the estuary is closed or perched, one of the major sources of outflow from the lagoon is seepage flow through the barrier beach. The location and design of the jetty could be altering subsurface flow paths through the jetty and possibly impeding subsurface flow where the jetty is still intact. This will result in unnatural connectivity between the ocean and the estuary leading to atypical surface water elevations and possibly salinity imbalance. We are monitoring seepage through the jetty and beach berm with multiple surface and borehole geophysical methods, including: electrical resistivity (ERT), seismic refraction (SR), ground penetrating radar (GPR), and electromagnetic methods (EM). We use SR data to characterize deeper bedrock controls on beach barrier functioning; ERT and EM methods to characterize the beach sediment layers that could contribute to preferential flow paths during tide cycles in addition to preferential flow paths created by the jetty structure; time-lapse ERT and EM data to monitor moisture changes and mixing of saline and fresh water within the beach berm, and borehole ERT and GPR data to delineate the geometry of the (often buried) jetty. Preliminary ERT and EM results indicate two preferential flow paths through zones of missing jetty structure, while time-lapse borehole ERT data is expected to image saltwater flow impedance in zones of intact jetty structure. All data are being integrated with topography, tidal, borehole, and hydrological information and the results of the assessment will enable the Sonoma County Water Agency to develop the feasibility of alternatives to the existing jetty that may help achieve target estuarine water surface elevations.

Theory and simulation of ion conduction in the pentameric GLIC channel.

PubMed

Zhu, Fangqiang; Hummer, Gerhard

2012-10-09

GLIC is a bacterial member of the large family of pentameric ligand-gated ion channels. To study ion conduction through GLIC and other membrane channels, we combine the one-dimensional potential of mean force for ion passage with a Smoluchowski diffusion model, making it possible to calculate single-channel conductance in the regime of low ion concentrations from all-atom molecular dynamics (MD) simulations. We then perform MD simulations to examine sodium ion conduction through the GLIC transmembrane pore in two systems with different bulk ion concentrations. The ion potentials of mean force, calculated from umbrella sampling simulations with Hamiltonian replica exchange, reveal a major barrier at the hydrophobic constriction of the pore. The relevance of this barrier for ion transport is confirmed by a committor function that rises sharply in the barrier region. From the free evolution of Na(+) ions starting at the barrier top, we estimate the effective diffusion coefficient in the barrier region, and subsequently calculate the conductance of the pore. The resulting diffusivity compares well with the position-dependent ion diffusion coefficient obtained from restrained simulations. The ion conductance obtained from the diffusion model agrees with the value determined via a reactive-flux rate calculation. Our results show that the conformation in the GLIC crystal structure, with an estimated conductance of ~1 picosiemens at 140 mM ion concentration, is consistent with a physiologically open state of the channel.

The blood-brain barrier: an engineering perspective

PubMed Central

Wong, Andrew D.; Ye, Mao; Levy, Amanda F.; Rothstein, Jeffrey D.; Bergles, Dwight E.; Searson, Peter C.

2013-01-01

It has been more than 100 years since Paul Ehrlich reported that various water-soluble dyes injected into the circulation did not enter the brain. Since Ehrlich's first experiments, only a small number of molecules, such as alcohol and caffeine have been found to cross the blood-brain barrier, and this selective permeability remains the major roadblock to treatment of many central nervous system diseases. At the same time, many central nervous system diseases are associated with disruption of the blood-brain barrier that can lead to changes in permeability, modulation of immune cell transport, and trafficking of pathogens into the brain. Therefore, advances in our understanding of the structure and function of the blood-brain barrier are key to developing effective treatments for a wide range of central nervous system diseases. Over the past 10 years it has become recognized that the blood-brain barrier is a complex, dynamic system that involves biomechanical and biochemical signaling between the vascular system and the brain. Here we reconstruct the structure, function, and transport properties of the blood-brain barrier from an engineering perspective. New insight into the physics of the blood-brain barrier could ultimately lead to clinical advances in the treatment of central nervous system diseases. PMID:24009582

Glycogen Synthase Kinase 3 (GSK-3) influences epithelial barrier function by regulating Occludin, Claudin-1 and E-cadherin expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Severson, Eric A.; Kwon, Mike; Hilgarth, Roland S.

2010-07-02

The Apical Junctional Complex (AJC) encompassing the tight junction (TJ) and adherens junction (AJ) plays a pivotal role in regulating epithelial barrier function and epithelial cell proliferative processes through signaling events that remain poorly characterized. A potential regulator of AJC protein expression is Glycogen Synthase Kinase-3 (GSK-3). GSK-3 is a constitutively active kinase that is repressed during epithelial-mesenchymal transition (EMT). In the present study, we report that GSK-3 activity regulates the structure and function of the AJC in polarized model intestinal (SK-CO15) and kidney (Madin-Darby Canine Kidney (MDCK)) epithelial cells. Reduction of GSK-3 activity, either by small molecule inhibitors ormore » siRNA targeting GSK-3 alpha and beta mRNA, resulted in increased permeability to both ions and bulk solutes. Immunofluorescence labeling and immunoblot analyses revealed that the barrier defects correlated with decreased protein expression of AJC transmembrane proteins Occludin, Claudin-1 and E-cadherin without influencing other TJ proteins, Zonula Occludens-1 (ZO-1) and Junctional Adhesion Molecule A (JAM-A). The decrease in Occludin and E-cadherin protein expression correlated with downregulation of the corresponding mRNA levels for these respective proteins following GSK-3 inhibition. These observations implicate an important role of GSK-3 in the regulation of the structure and function of the AJC that is mediated by differential modulation of mRNA transcription of key AJC proteins, Occludin, Claudin-1 and E-cadherin.« less

Protective effects of lactoferrin against intestinal mucosal damage induced by lipopolysaccharide in human intestinal Caco-2 cells.

PubMed

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.

Oncostatin M induces upregulation of claudin-2 in rodent hepatocytes coinciding with changes in morphology and function of tight junctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Imamura, Masafumi; Department of Pathology, Sapporo Medical University School of Medicine, S1. W17. Sapporo 060-8556; Kojima, Takashi

2007-05-15

In rodent livers, integral tight junction (TJ) proteins claudin-1, -2, -3, -5 and -14 are detected and play crucial roles in the barrier to keep bile in bile canaculi away from the blood circulation. Claudin-2 shows a lobular gradient increasing from periportal to pericentral hepatocytes, whereas claudin-1 and -3 are expressed in the whole liver lobule. Although claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells, the physiological functions and regulation of claudin-2 in hepatocytes remain unclear. Oncostatin M (OSM) is a multifunctional cytokine implicated in the differentiation of hepatocytes that induces formation of E-cadherin-based adherens junctions inmore » fetal hepatocytes. In this study, we examined whether OSM could induce expression and function of claudin-2 in rodent hepatocytes, immortalized mouse and primary cultured proliferative rat hepatocytes. In the immortalized mouse and primary cultured proliferative rat hepatocytes, treatment with OSM markedly increased mRNA and protein of claudin-2 together with formation of developed networks of TJ strands. The increase of claudin-2 enhanced the paracellular barrier function which depended on molecular size. The increase of claudin-2 expression induced by OSM in rodent hepatocytes was regulated through distinct signaling pathways including PKC. These results suggest that expression of claudin-2 in rodent hepatocytes may play a specific role as controlling the size of paracellular permeability in the barrier to keep bile in bile canaculi.« less

Ginger Extract Suppresses Inflammatory Response and Maintains Barrier Function in Human Colonic Epithelial Caco-2 Cells Exposed to Inflammatory Mediators.

PubMed

Kim, Yunyoung; Kim, Dong-Min; Kim, Ji Yeon

2017-05-01

The beneficial effects of ginger in the management of gastrointestinal disturbances have been reported. In this study, the anti-inflammatory potential of ginger extract was assessed in a cellular model of gut inflammation. In addition, the effects of ginger extract and its major active compounds on intestinal barrier function were evaluated. The response of Caco-2 cells following exposure to a mixture of inflammatory mediators [interleukin [IL]-1β, 25 ng/mL; lipopolysaccharides [LPS], 10 ng/mL; tumor necrosis factor [TNF]-α, 50 ng/mL; and interferon [INF]-γ, 50 ng/mL] were assessed by measuring the levels of secreted IL-6 and IL-8. In addition, the mRNA levels of cyclooxygenase-2 and inducible nitric oxide synthase were measured. Moreover, the degree of nuclear factor (NF)-κB inhibition was examined, and the intestinal barrier function was determined by measuring the transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)-dextran transfer. It was observed that ginger extract and its constituents improved inflammatory responses by decreasing the levels of nitrite, PGE2, IL-6, and IL-8 via NF-κB inhibition. The ginger extract also increased the TEER and decreased the transfer of FITC-dextran from the apical side of the epithelium to the basolateral side. Taken together, these results show that ginger extract may be developed as a functional food for the maintenance of gastrointestinal health. © 2017 Institute of Food Technologists®.

Hydroxyapatite nanobelt/polylactic acid Janus membrane with osteoinduction/barrier dual functions for precise bone defect repair.

PubMed

Ma, Baojin; Han, Jing; Zhang, Shan; Liu, Feng; Wang, Shicai; Duan, Jiazhi; Sang, Yuanhua; Jiang, Huaidong; Li, Dong; Ge, Shaohua; Yu, Jinghua; Liu, Hong

2018-04-15

Controllable osteoinduction maintained in the original defect area is the key to precise bone repair. To meet the requirement of precise bone regeneration, a hydroxyapatite (HAp) nanobelt/polylactic acid (PLA) (HAp/PLA) Janus membrane has been successfully prepared in this study by coating PLA on a paper-like HAp nanobelt film by a casting-pervaporation method. The Janus membrane possesses dual functions: excellent osteoinduction from the hydrophilic HAp nanobelt side and barrier function originating from the hydrophobic PLA film. The cell viability and osteogenic differentiation ability of human adipose-derived stem cells (hADSCs) on the Janus membrane were assessed. The in vitro experimental results prove that the HAp nanobelt side presents high cell viability and efficient osteoinduction without any growth factor and that the PLA side can prohibit cell attachment. The in vivo repair experiments on a rat mandible defect model prove that the PLA side can prevent postoperative adhesion between bone and adjacent soft tissues. Most importantly, the HAp side has a strong ability to promote defect repair and bone regeneration. Therefore, the HAp/PLA Janus membrane will have wide applications as a kind of tissue engineering material in precise bone repair because of its unique dual osteoinduction/barrier functions, biocompatibility, low cost, and its ability to be mass-produced. Precise bone defect repair to keeping tissue integrity and original outline shape is a very important issue for tissue engineering. Here, we have designed and prepared a novel HAp/PLA Janus membrane using a casting-pervaporation method to form a layer of PLA film on paper-like HAp nanobelt film. HAp nanobelt side of the Janus membrane can successfully promote osteogenic differentiation. PLA side of the Janus membrane exhibits good properties as a barrier for preventing the adhesion of cells in vitro. Mandible repair experiments in vivo have shown that the HAp/PLA Janus membrane can promote rat mandible repair on the HAp side and can successfully prevent postoperative adhesion on the PLA side at the same time. Therefore, the HAp/PLA Janus membrane with its osteoinduction/barrier dual functions can be applied to repair bone defect precisely. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Localized Down-regulation of P-glycoprotein by Focused Ultrasound and Microbubbles induced Blood-Brain Barrier Disruption in Rat Brain

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.

Fusion of 48Ti+58Fe and 58Ni+54Fe below the Coulomb barrier

NASA Astrophysics Data System (ADS)

Stefanini, A. M.; Montagnoli, G.; Corradi, L.; Courtin, S.; Bourgin, D.; Fioretto, E.; Goasduff, A.; Grebosz, J.; Haas, F.; Mazzocco, M.; Mijatović, T.; Montanari, D.; Pagliaroli, M.; Parascandolo, C.; Scarlassara, F.; Strano, E.; Szilner, S.; Toniolo, N.; Torresi, D.

2015-12-01

Background: No data on the fusion excitation function of 48Ti+58Fe in the energy region near the Coulomb barrier existed prior to the present work, while fusion of 58Ni+54Fe was investigated in detail some years ago, down to very low energies, and clear evidence of fusion hindrance was noticed at relatively high cross sections. 48Ti and 58Fe are soft and have a low-lying quadrupole excitation lying at ≈800 -900 keV only. Instead, 58Ni and 54Fe have a closed shell (protons and neutrons, respectively) and are rather rigid. Purpose: We aim to investigate (1) the possible influence of the different structures of the involved nuclei on the fusion excitation functions far below the barrier and, in particular, (2) whether hindrance is observed in 48Ti+58Fe , and to compare the results with current coupled-channels models. Methods: 48Ti beams from the XTU Tandem accelerator of INFN-Laboratori Nazionali di Legnaro were used. The experimental setup was based on an electrostatic beam separator, and fusion-evaporation residues (ERs) were detected at very forward angles. Angular distributions of ERs were measured. Results: Fusion cross sections of 48Ti+58Fe have been obtained in a range of nearly six orders of magnitude around the Coulomb barrier, down to σ ≃2 μ b . The sub-barrier cross sections of 48Ti+58Fe are much larger than those of 58Ni+54Fe . Significant differences are also observed in the logarithmic derivatives and astrophysical S factors. No evidence of hindrance is observed, because coupled-channels calculations using a standard Woods-Saxon potential are able to reproduce the data in the whole measured energy range. Analogous calculations for 58Ni+54Fe predict clearly too large cross sections at low energies. The two fusion barrier distributions are wide and display a complex structure that is only qualitatively fit by calculations. Conclusions: It is pointed out that all these different trends originate from the dissimilar low-energy nuclear structures of the involved nuclei. In particular, the strong quadrupole excitations in 48Ti and 58Fe produce the relative cross section enhancement and make the barrier distribution ≈2 MeV wider, thus probably pushing the threshold for hindrance below the measured limit.

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.

Environmental barriers, person-environment fit and mortality among community-dwelling very old people.

PubMed

Rantakokko, Merja; Törmäkangas, Timo; Rantanen, Taina; Haak, Maria; Iwarsson, Susanne

2013-08-28

Environmental barriers are associated with disability-related outcomes in older people but little is known of the effect of environmental barriers on mortality. The aim of this study was to examine whether objectively measured barriers in the outdoor, entrance and indoor environments are associated with mortality among community-dwelling 80- to 89-year-old single-living people. This longitudinal study is based on a sample of 397 people who were single-living in ordinary housing in Sweden. Participants were interviewed during 2002-2003, and 393 were followed up for mortality until May 15, 2012.Environmental barriers and functional limitations were assessed with the Housing Enabler instrument, which is intended for objective assessments of Person-Environment (P-E) fit problems in housing and the immediate outdoor environment. Mortality data were gathered from the public national register. Cox regression models were used for the analyses. A total of 264 (67%) participants died during follow-up. Functional limitations increased mortality risk. Among the specific environmental barriers that generate the most P-E fit problems, lack of handrails in stairs at entrances was associated with the highest mortality risk (adjusted RR 1.55, 95% CI 1.14-2.10), whereas the total number of environmental barriers at entrances and outdoors was not associated with mortality. A higher number of environmental barriers indoors showed a slight protective effect against mortality even after adjustment for functional limitations (RR 0.98, 95% CI 0.96-1.00). Specific environmental problems may increase mortality risk among very-old single-living people. However, the association may be confounded by individuals' health status which is difficult to fully control for. Further studies are called for.

A Qualitative Study of Barriers to Accessing Water, Sanitation and Hygiene for Disabled People in Malawi.

PubMed

White, Sian; Kuper, Hannah; Itimu-Phiri, Ambumulire; Holm, Rochelle; Biran, Adam

2016-01-01

Globally, millions of people lack access to improved water, sanitation and hygiene (WASH). Disabled people, disadvantaged both physically and socially, are likely to be among those facing the greatest inequities in WASH access. This study explores the WASH priorities of disabled people and uses the social model of disability and the World Health Organization's International Classification of Functioning, Disability and Health (ICF) framework to look at the relationships between impairments, contextual factors and barriers to WASH access. 36 disabled people and 15 carers from urban and rural Malawi were purposively selected through key informants. The study employed a range of qualitative methods including interviews, emotion mapping, free-listing of priorities, ranking, photo voice, observation and WASH demonstrations. A thematic analysis was conducted using nVivo 10. WASH access affected all participants and comprised almost a third of the challenges of daily living identified by disabled people. Participants reported 50 barriers which related to water and sanitation access, personal and hand hygiene, social attitudes and participation in WASH programs. No two individuals reported facing the same set of barriers. This study found that being female, being from an urban area and having limited wealth and education were likely to increase the number and intensity of the barriers faced by an individual. The social model proved useful for classifying the majority of barriers. However, this model was weaker when applied to individuals who were more seriously disabled by their body function. This study found that body function limitations such as incontinence, pain and an inability to communicate WASH needs are in and of themselves significant barriers to adequate WASH access. Understanding these access barriers is important for the WASH sector at a time when there is a global push for equitable access.

A Qualitative Study of Barriers to Accessing Water, Sanitation and Hygiene for Disabled People in Malawi

PubMed Central

Kuper, Hannah; Itimu-Phiri, Ambumulire; Holm, Rochelle; Biran, Adam

2016-01-01

Globally, millions of people lack access to improved water, sanitation and hygiene (WASH). Disabled people, disadvantaged both physically and socially, are likely to be among those facing the greatest inequities in WASH access. This study explores the WASH priorities of disabled people and uses the social model of disability and the World Health Organization’s International Classification of Functioning, Disability and Health (ICF) framework to look at the relationships between impairments, contextual factors and barriers to WASH access. 36 disabled people and 15 carers from urban and rural Malawi were purposively selected through key informants. The study employed a range of qualitative methods including interviews, emotion mapping, free-listing of priorities, ranking, photo voice, observation and WASH demonstrations. A thematic analysis was conducted using nVivo 10. WASH access affected all participants and comprised almost a third of the challenges of daily living identified by disabled people. Participants reported 50 barriers which related to water and sanitation access, personal and hand hygiene, social attitudes and participation in WASH programs. No two individuals reported facing the same set of barriers. This study found that being female, being from an urban area and having limited wealth and education were likely to increase the number and intensity of the barriers faced by an individual. The social model proved useful for classifying the majority of barriers. However, this model was weaker when applied to individuals who were more seriously disabled by their body function. This study found that body function limitations such as incontinence, pain and an inability to communicate WASH needs are in and of themselves significant barriers to adequate WASH access. Understanding these access barriers is important for the WASH sector at a time when there is a global push for equitable access. PMID:27171520

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.

The Lattice and Thermal Radiation Conductivity of Thermal Barrier Coatings

NASA Technical Reports Server (NTRS)

Zhu, Dongming; Spuckler, Charles M.

2008-01-01

The lattice and radiation conductivity of thermal barrier coatings was evaluated using a laser heat flux approach. A diffusion model has been established to correlate the apparent thermal conductivity of the coating to the lattice and radiation conductivity. The radiation conductivity component can be expressed as a function of temperature and the scattering and absorption properties of the coating material. High temperature scattering and absorption of the coating systems can also be derived based on the testing results using the modeling approach. The model prediction is found to have good agreement with experimental observations.

Exploration of the Esophageal Mucosal Barrier in Non-Erosive Reflux Disease

PubMed Central

Rinsma, Nicolaas F.; Farré, Ricard; Troost, Fred J.; Elizalde, Montserrat; Keszthelyi, Daniel; Helyes, Zsuzsanna; Masclee, Ad A.; Conchillo, José M.

2017-01-01

In the absence of visible mucosal damage, it is hypothesized that the esophageal mucosal barrier is functionally impaired in patients with non-erosive reflux disease (NERD). The aim of the present study was to perform an exploratory analysis of the mucosal barrier in NERD compared to erosive esophagitis (EE) and controls. A second aim was to explore TRPV1 gene transcription in relation to the mucosal barrier function and heartburn symptoms. In this prospective study, 10 NERD patients, 11 patients with active erosive esophagitis and 10 healthy volunteers were included. Biopsies from non-eroded mucosa were obtained for (1) ex vivo analyses (Ussing chamber) of transepithelial electrical resistance (TEER) and permeability (2) gene transcription of tight-junction proteins and transient receptor potential vanilloid subfamily member 1 (TRPV1). No differences in TEER or permeability were found between NERD and healthy volunteers, whereas TEER was lower in patients with erosive esophagitis. TRPV1 gene transcription was not significantly different between EE, NERD and controls. Conclusions: esophageal mucosal barrier function and TRPV1 transcription is not significantly altered in NERD patients. Future research is needed to explore other potential mechanisms that may account for the high symptom burden in these patients. PMID:28534850

Chromium-induced skin damage among Taiwanese cement workers.

PubMed

Chou, Tzu-Chieh; Wang, Po-Chih; Wu, Jyun-De; Sheu, Shiann-Cherng

2016-10-01

Little research has been done on the relationships between chromium exposure, skin barrier function, and other hygienic habits in cement workers. Our purpose was to investigate chromium-induced skin barrier disruption due to cement exposure among cement workers. One hundred and eight cement workers were recruited in this study. Urinary chromium concentration was used to characterize exposure levels. The biological exposure index was used to separate high and low chromium exposure. Transepidermal water loss (TEWL) was used to assess the skin barrier function. TEWL was significantly increased in workers with high chromium exposure levels than those with low chromium exposure levels (p = 0.048). A positive correlation was also found between urinary chromium concentration and TEWL (R = 0.28, p = 0.004). After adjusting for smoking status and glove use, a significant correlation between urinary chromium concentrations and TEWL remained. Moreover, workers who smoked and had a high chromium exposure had significantly increased TEWL compared to nonsmokers with low chromium exposure (p = 0.01). Skin barrier function of cement workers may have been disrupted by chromium in cement, and smoking might significantly enhance such skin barrier perturbation with chromium exposure. Decreased chromium skin exposure and smoking cessation should be encouraged at work. © The Author(s) 2015.

Leaky gut and diabetes mellitus: what is the link?

PubMed

de Kort, S; Keszthelyi, D; Masclee, A A M

2011-06-01

Diabetes mellitus is a chronic disease requiring lifelong medical attention. With hundreds of millions suffering worldwide, and a rapidly rising incidence, diabetes mellitus poses a great burden on healthcare systems. Recent studies investigating the underlying mechanisms involved in disease development in diabetes point to the role of the dys-regulation of the intestinal barrier. Via alterations in the intestinal permeability, intestinal barrier function becomes compromised whereby access of infectious agents and dietary antigens to mucosal immune elements is facilitated, which may eventually lead to immune reactions with damage to pancreatic beta cells and can lead to increased cytokine production with consequent insulin resistance. Understanding the factors regulating the intestinal barrier function will provide important insight into the interactions between luminal antigens and immune response elements. This review analyses recent advances in the mechanistic understanding of the role of the intestinal epithelial barrier function in the development of type 1 and type 2 diabetes. Given our current knowledge, we may assume that reinforcing the intestinal barrier can offer and open new therapeutic horizons in the treatment of type 1 and type 2 diabetes. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.

Modeling traceability information and functionality requirement in export-oriented tilapia chain.

PubMed

Zhang, Xiaoshuan; Feng, Jianying; Xu, Mark; Hu, Jinyou

2011-05-01

Tilapia has been named as the 'food fish of the 21st century' and has become the most important farmed fish. China is the world leader in tilapia production and export. Identifying information and functional requirements is critical in developing an efficient traceability system because traceability has become a fundamental prerequisite for exporting aquaculture products. This paper examines the export-oriented tilapia chains and information flow in the chains, and identifies the key actors, information requirements and information-capturing points. Unified Modeling Language (UML) technology is adopted to describe the information and functionality requirement for chain traceability. The barriers of traceability system adoption are also identified. The results show that the traceability data consist of four categories that must be recorded by each link in the chain. The functionality requirement is classified into four categories from the fundamental information record to decisive quality control; the top three barriers to the traceability system adoption are: high costs of implementing the system, lack of experienced and professional staff; and low level of government involvement and support. Copyright © 2011 Society of Chemical Industry.

Possible involvement of gap junctions in the barrier function of tight junctions of brain and lung endothelial cells.

PubMed

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.

Nanomaterial interactions with biomembranes: Bridging the gap between soft matter models and biological context.

PubMed

Werner, Marco; Auth, Thorsten; Beales, Paul A; Fleury, Jean Baptiste; Höök, Fredrik; Kress, Holger; Van Lehn, Reid C; Müller, Marcus; Petrov, Eugene P; Sarkisov, Lev; Sommer, Jens-Uwe; Baulin, Vladimir A

2018-04-03

Synthetic polymers, nanoparticles, and carbon-based materials have great potential in applications including drug delivery, gene transfection, in vitro and in vivo imaging, and the alteration of biological function. Nature and humans use different design strategies to create nanomaterials: biological objects have emerged from billions of years of evolution and from adaptation to their environment resulting in high levels of structural complexity; in contrast, synthetic nanomaterials result from minimalistic but controlled design options limited by the authors' current understanding of the biological world. This conceptual mismatch makes it challenging to create synthetic nanomaterials that possess desired functions in biological media. In many biologically relevant applications, nanomaterials must enter the cell interior to perform their functions. An essential transport barrier is the cell-protecting plasma membrane and hence the understanding of its interaction with nanomaterials is a fundamental task in biotechnology. The authors present open questions in the field of nanomaterial interactions with biological membranes, including: how physical mechanisms and molecular forces acting at the nanoscale restrict or inspire design options; which levels of complexity to include next in computational and experimental models to describe how nanomaterials cross barriers via passive or active processes; and how the biological media and protein corona interfere with nanomaterial functionality. In this Perspective, the authors address these questions with the aim of offering guidelines for the development of next-generation nanomaterials that function in biological media.

Tests of potential functional barriers for laminated multilayer food packages. Part II: Medium molecular weight permeants.

PubMed

Simal-Gándara, J; Sarria-Vidal, M; Rijk, R

2000-09-01

Experiments were performed to characterize the kinetics of the permeation of different medium molecular weight model permeants: bisphenol A, warfarin and anthracene, from liquid paraffin, through a surrogate potential functional barrier (25 microns-thick orientated polypropylene--OPP) into the food simulants olive oil and 3% (w/v) acetic acid. The characterization of permeation kinetics generally observed the permeation models previously reported to explain the experimental permeation results obtained for a low molecular weight group of model permeants. In general, the model permeants exhibited behaviour consistent with their relative molecular weights with respect to (a) the time taken to attain steady-state permeation into the food simulant in which they were more soluble, (b) their subsequent steady-state permeation rates, and (c) their partition between liquid paraffin and the OPP membrane.

Theoretical study of water-gas shift reaction on the silver nanocluster

NASA Astrophysics Data System (ADS)

Arab, Ali; Sharafie, Darioush; Fazli, Mostafa

2017-10-01

The kinetics of water gas shift reaction (WGSR) on the silver nanocluster was investigated using density functional theory according to the carboxyl associative mechanism. The hybrid B3PW91 functional along with the 6-31+G* and LANL2DZ basis sets were used throughout the calculations. It was observed that CO and H2O molecules adsorb physically on the Ag5 cluster without energy barrier as the initial steps of WGSR. The next three steps including H2Oads dissociation, carboxyl (OCOHads) formation, and CO2(ads) formation were accompanied by activation barrier. Transition states, as well as energy profiles of these three steps, were determined and analyzed. Our results revealed that the carboxyl and CO2(ads) formation were fast steps whereas H2Oads dissociation was the slowest step of WGSR.

The rotational barrier in ethane: a molecular orbital study.

PubMed

Quijano-Quiñones, Ramiro F; Quesadas-Rojas, Mariana; Cuevas, Gabriel; Mena-Rejón, Gonzalo J

2012-04-20

The energy change on each Occupied Molecular Orbital as a function of rotation about the C-C bond in ethane was studied using the B3LYP, mPWB95 functional and MP2 methods with different basis sets. Also, the effect of the ZPE on rotational barrier was analyzed. We have found that σ and π energies contribution stabilize a staggered conformation. The σ(s) molecular orbital stabilizes the staggered conformation while the stabilizes the eclipsed conformation and destabilize the staggered conformation. The π(z) and molecular orbitals stabilize both the eclipsed and staggered conformations, which are destabilized by the π(v) and molecular orbitals. The results show that the method of calculation has the effect of changing the behavior of the energy change in each Occupied Molecular Orbital energy as a function of the angle of rotation about the C-C bond in ethane. Finally, we found that if the molecular orbital energy contribution is deleted from the rotational energy, an inversion in conformational preference occurs.

Switching Hole and Electron Transports of Molecules on Metal Oxides by Energy Level Alignment Tuning.

PubMed

Bao, Zhong-Min; Xu, Rui-Peng; Li, Chi; Xie, Zhong-Zhi; Zhao, Xin-Dong; Zhang, Yi-Bo; Li, Yan-Qing; Tang, Jian-Xin

2016-08-31

Charge transport at organic/inorganic hybrid contacts significantly affects the performance of organic optoelectronic devices because the unfavorable energy level offsets at these interfaces can hinder charge injection or extraction due to large barrier heights. Herein, we report a technologically relevant method to functionalize a traditional hole-transport layer of solution-processed nickel oxide (NiOx) with various interlayers. The photoemission spectroscopy measurements reveal the continuous tuning of the NiOx substrate work function ranging from 2.5 to 6.6 eV, enabling the alignment transition of energy levels between the Schottky-Mott limit and Fermi level pinning at the organic/composite NiOx interface. As a result, switching hole and electron transport for the active organic material on the composite NiOx layer is achieved due to the controlled carrier injection/extraction barriers. The experimental findings indicate that tuning the work function of metal oxides with optimum energy level offsets can facilitate the charge transport at organic/electrode contacts.

An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting: The importance of selective blood-brain barrier uptake.

PubMed

Bode, Gerard H; Coué, Gregory; Freese, Christian; Pickl, Karin E; Sanchez-Purrà, Maria; Albaiges, Berta; Borrós, Salvador; van Winden, Ewoud C; Tziveleka, Leto-Aikaterini; Sideratou, Zili; Engbersen, Johan F J; Singh, Smriti; Albrecht, Krystyna; Groll, Jürgen; Möller, Martin; Pötgens, Andy J G; Schmitz, Christoph; Fröhlich, Eleonore; Grandfils, Christian; Sinner, Frank M; Kirkpatrick, C James; Steinbusch, Harry W M; Frank, Hans-Georg; Unger, Ronald E; Martinez-Martinez, Pilar

2017-04-01

Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo. We used an ELISA-based method for the detection of nanoparticles in biological fluids, investigating the blood clearance rate and in vivo biodistribution of labeled nanoparticles in the brain after intravenous injection in Wistar rats. Herein, we provide a detailed report of in vitro and in vivo observations. Copyright © 2016 Elsevier Inc. All rights reserved.

Type I interferon promotes alveolar epithelial type II cell survival during pulmonary Streptococcus pneumoniae infection and sterile lung injury in mice.

PubMed

Maier, Barbara B; Hladik, Anastasiya; Lakovits, Karin; Korosec, Ana; Martins, Rui; Kral, Julia B; Mesteri, Ildiko; Strobl, Birgit; Müller, Mathias; Kalinke, Ulrich; Merad, Miriam; Knapp, Sylvia

2016-09-01

Protecting the integrity of the lung epithelial barrier is essential to ensure respiration and proper oxygenation in patients suffering from various types of lung inflammation. Type I interferon (IFN-I) has been associated with pulmonary epithelial barrier function, however, the mechanisms and involved cell types remain unknown. We aimed to investigate the importance of IFN-I with respect to its epithelial barrier strengthening function to better understand immune-modulating effects in the lung with potential medical implications. Using a mouse model of pneumococcal pneumonia, we revealed that IFN-I selectively protects alveolar epithelial type II cells (AECII) from inflammation-induced cell death. Mechanistically, signaling via the IFN-I receptor on AECII is sufficient to promote AECII survival. The net effects of IFN-I are barrier protection, together with diminished tissue damage, inflammation, and bacterial loads. Importantly, we found that the protective role of IFN-I can also apply to sterile acute lung injury, in which loss of IFN-I signaling leads to a significant reduction in barrier function caused by AECII cell death. Our data suggest that IFN-I is an important mediator in lung inflammation that plays a protective role by antagonizing inflammation-associated cell obstruction, thereby strengthening the integrity of the epithelial barrier. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using Free Internet Videogames in Upper Extremity Motor Training for Children with Cerebral Palsy.

PubMed

Sevick, Marisa; Eklund, Elizabeth; Mensch, Allison; Foreman, Matthew; Standeven, John; Engsberg, Jack

2016-06-07

Movement therapy is one type of upper extremity intervention for children with cerebral palsy (CP) to improve function. It requires high-intensity, repetitive and task-specific training. Tedium and lack of motivation are substantial barriers to completing the training. An approach to overcome these barriers is to couple the movement therapy with videogames. This investigation: (1) tested the feasibility of delivering a free Internet videogame upper extremity motor intervention to four children with CP (aged 8-17 years) with mild to moderate limitations to upper limb function; and (2) determined the level of intrinsic motivation during the intervention. The intervention used free Internet videogames in conjunction with the Microsoft Kinect motion sensor and the Flexible Action and Articulated Skeleton Toolkit software (FAAST) software. Results indicated that the intervention could be successfully delivered in the laboratory and the home, and pre- and post- impairment, function and performance assessments were possible. Results also indicated a high level of motivation among the participants. It was concluded that the use of inexpensive hardware and software in conjunction with free Internet videogames has the potential to be very motivating in helping to improve the upper extremity abilities of children with CP. Future work should include results from additional participants and from a control group in a randomized controlled trial to establish efficacy.

Connecting the irreversible capacity loss in Li-ion batteries with the electronic insulating properties of solid electrolyte interphase (SEI) components.

DOE PAGES

Leung, Kevin; Lin, Yu -Xiao; Liu, Zhe; ...

2016-01-01

The formation and continuous growth of a solid electrolyte interphase (SEI) layer are responsible for the irreversible capacity loss of batteries in the initial and subsequent cycles, respectively. In this article, the electron tunneling barriers from Li metal through three insulating SEI components, namely Li 2CO 3, LiF and Li 3PO 4, are computed by density function theory (DFT) approaches. Based on electron tunneling theory, it is estimated that sufficient to block electron tunneling. It is also found that the band gap decreases under tension while the work function remains the same, and thus the tunneling barrier decreases under tensionmore » and increases under compression. A new parameter, η, characterizing the average distances between anions, is proposed to unify the variation of band gap with strain under different loading conditions into a single linear function of η. An analytical model based on the tunneling results is developed to connect the irreversible capacity loss, due to the Li ions consumed in forming these SEI component layers on the surface of negative electrodes. As a result, the agreement between the model predictions and experimental results suggests that only the initial irreversible capacity loss is due to the self-limiting electron tunneling property of the SEI.« less

Hybrid plasmachemical reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lelevkin, V. M., E-mail: lelevkin44@mail.ru; Smirnova, Yu. G.; Tokarev, A. V.

2015-04-15

A hybrid plasmachemical reactor on the basis of a dielectric barrier discharge in a transformer is developed. The characteristics of the reactor as functions of the dielectric barrier discharge parameters are determined.

49 CFR 38.23 - Mobility aid accessibility.

Code of Federal Regulations, 2013 CFR

2013-10-01

... maneuvering into or out of the aisle. The loading-edge barrier (outer barrier) which functions as a loading.... The outer barrier of the lift shall automatically raise or close, or a supplementary system shall... accessible entrance as practicable and shall have a clear floor area of 30 inches by 48 inches. Such space...

Leaky gut and mycotoxins: Aflatoxin B1 does not increase gut permeability in broiler chickens

USDA-ARS?s Scientific Manuscript database

Previous studies conducted in our laboratory have demonstrated that intestinal barrier function can be adversely affected by diet ingredients or feed restriction, resulting in increased intestinal inflammation-associated permeability. Two experiments were conducted in broilers to evaluate the effect...

Human vascular tissue models formed from human induced pluripotent stem cell derived endothelial cells

PubMed Central

Belair, David G.; Whisler, Jordan A.; Valdez, Jorge; Velazquez, Jeremy; Molenda, James A.; Vickerman, Vernella; Lewis, Rachel; Daigh, Christine; Hansen, Tyler D.; Mann, David A.; Thomson, James A.; Griffith, Linda G.; Kamm, Roger D.; Schwartz, Michael P.; Murphy, William L.

2015-01-01

Here we describe a strategy to model blood vessel development using a well-defined iPSC-derived endothelial cell type (iPSC-EC) cultured within engineered platforms that mimic the 3D microenvironment. The iPSC-ECs used here were first characterized by expression of endothelial markers and functional properties that included VEGF responsiveness, TNF-α-induced upregulation of cell adhesion molecules (MCAM/CD146; ICAM1/CD54), thrombin-dependent barrier function, shear stress-induced alignment, and 2D and 3D capillary-like network formation in Matrigel. The iPSC-ECs also formed 3D vascular networks in a variety of engineering contexts, yielded perfusable, interconnected lumen when co-cultured with primary human fibroblasts, and aligned with flow in microfluidics devices. iPSC-EC function during tubule network formation, barrier formation, and sprouting was consistent with that of primary ECs, and the results suggest a VEGF-independent mechanism for sprouting, which is relevant to therapeutic anti-angiogenesis strategies. Our combined results demonstrate the feasibility of using a well-defined, stable source of iPSC-ECs to model blood vessel formation within a variety of contexts using standard in vitro formats. PMID:25190668

Home and Health in the Third Age — Methodological Background and Descriptive Findings

PubMed Central

Kylén, Maya; Ekström, Henrik; Haak, Maria; Elmståhl, Sölve; Iwarsson, Susanne

2014-01-01

Background: The understanding of the complex relationship between the home environment, well-being and daily functioning in the third age is currently weak. The aim of this paper is to present the methodological background of the Home and Health in the Third Age Study, and describe a sample of men and women in relation to their home and health situation. Methods and Design: The study sample included 371 people aged 67–70, living in ordinary housing in the south of Sweden. Structured interviews and observations were conducted to collect data about objective and perceived aspects of home and health. Results: The majority of the participants were in good health and had few functional limitations. Women had more functional limitations and reported more symptoms than men. Environmental barriers were found in every home investigated; the most were found in the kitchen and hygiene area. Environmental barriers were more common in multi-family than in one-family dwellings. Discussion: This study will increase our knowledge on home and health dynamics among people in the third age. The results have potential to contribute to societal planning related to housing provision, home care and social services for senior citizens. PMID:25019267

Management of Patients with Atopic Dermatitis: The Role of Emollient Therapy

PubMed Central

Catherine Mack Correa, M.; Nebus, Judith

2012-01-01

Atopic dermatitis is a common inflammatory skin disorder that afflicts a growing number of young children. Genetic, immune, and environmental factors interact in a complex fashion to contribute to disease expression. The compromised stratum corneum found in atopic dermatitis leads to skin barrier dysfunction, which results in aggravation of symptoms by aeroallergens, microbes, and other insults. Infants—whose immune system and epidermal barrier are still developing—display a higher frequency of atopic dermatitis. Management of patients with atopic dermatitis includes maintaining optimal skin care, avoiding allergic triggers, and routinely using emollients to maintain a hydrated stratum corneum and to improve barrier function. Flares of atopic dermatitis are often managed with courses of topical corticosteroids or calcineurin inhibitors. This paper discusses the role of emollients in the management of atopic dermatitis, with particular emphasis on infants and young children. PMID:23008699

ROS-activated calcium signaling mechanisms regulating endothelial barrier function.

PubMed

Di, Anke; Mehta, Dolly; Malik, Asrar B

2016-09-01

Increased vascular permeability is a common pathogenic feature in many inflammatory diseases. For example in acute lung injury (ALI) and its most severe form, the acute respiratory distress syndrome (ARDS), lung microvessel endothelia lose their junctional integrity resulting in leakiness of the endothelial barrier and accumulation of protein rich edema. Increased reactive oxygen species (ROS) generated by neutrophils (PMNs) and other inflammatory cells play an important role in increasing endothelial permeability. In essence, multiple inflammatory syndromes are caused by dysfunction and compromise of the barrier properties of the endothelium as a consequence of unregulated acute inflammatory response. This review focuses on the role of ROS signaling in controlling endothelial permeability with particular focus on ALI. We summarize below recent progress in defining signaling events leading to increased endothelial permeability and ALI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human Intestinal Barrier Function in Health and Disease

PubMed Central

König, Julia; Wells, Jerry; Cani, Patrice D; García-Ródenas, Clara L; MacDonald, Tom; Mercenier, Annick; Whyte, Jacqueline; Troost, Freddy; Brummer, Robert-Jan

2016-01-01

The gastrointestinal tract consists of an enormous surface area that is optimized to efficiently absorb nutrients, water, and electrolytes from food. At the same time, it needs to provide a tight barrier against the ingress of harmful substances, and protect against a reaction to omnipresent harmless compounds. A dysfunctional intestinal barrier is associated with various diseases and disorders. In this review, the role of intestinal permeability in common disorders such as infections with intestinal pathogens, inflammatory bowel disease, irritable bowel syndrome, obesity, celiac disease, non-celiac gluten sensitivity, and food allergies will be discussed. In addition, the effect of the frequently prescribed drugs proton pump inhibitors and non-steroidal anti-inflammatory drugs on intestinal permeability, as well as commonly used methods to assess barrier function will be reviewed. PMID:27763627

Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer

PubMed Central

Landy, Jonathan; Ronde, Emma; English, Nick; Clark, Sue K; Hart, Ailsa L; Knight, Stella C; Ciclitira, Paul J; Al-Hassi, Hafid Omar

2016-01-01

Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. PMID:27003989

A homolog of Drosophila grainy head is essential for epidermal integrity in mice.

PubMed

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.

Barriers to the free diffusion of proteins and lipids in the plasma membrane

PubMed Central

Trimble, William S.

2015-01-01

Biological membranes segregate into specialized functional domains of distinct composition, which can persist for the entire life of the cell. How separation of their lipid and (glyco)protein components is generated and maintained is not well understood, but the existence of diffusional barriers has been proposed. Remarkably, the physical nature of such barriers and the manner whereby they impede the free diffusion of molecules in the plane of the membrane has rarely been studied in depth. Moreover, alternative mechanisms capable of generating membrane inhomogeneity are often disregarded. Here we describe prototypical biological systems where membrane segregation has been amply documented and discuss the role of diffusional barriers and other processes in the generation and maintenance of their structural and functional compartmentalization. PMID:25646084

Barriers to the free diffusion of proteins and lipids in the plasma membrane.

PubMed

Trimble, William S; Grinstein, Sergio

2015-02-02

Biological membranes segregate into specialized functional domains of distinct composition, which can persist for the entire life of the cell. How separation of their lipid and (glyco)protein components is generated and maintained is not well understood, but the existence of diffusional barriers has been proposed. Remarkably, the physical nature of such barriers and the manner whereby they impede the free diffusion of molecules in the plane of the membrane has rarely been studied in depth. Moreover, alternative mechanisms capable of generating membrane inhomogeneity are often disregarded. Here we describe prototypical biological systems where membrane segregation has been amply documented and discuss the role of diffusional barriers and other processes in the generation and maintenance of their structural and functional compartmentalization. © 2015 Trimble and Grinstein.

Visualizing Molecular Diffusion through Passive Permeability Barriers in Cells: Conventional and Novel Approaches

PubMed Central

Lin, Yu-Chun; Phua, Siew Cheng; Lin, Benjamin; Inoue, Takanari

2013-01-01

Diffusion barriers are universal solutions for cells to achieve distinct organizations, compositions, and activities within a limited space. The influence of diffusion barriers on the spatiotemporal dynamics of signaling molecules often determines cellular physiology and functions. Over the years, the passive permeability barriers in various subcellular locales have been characterized using elaborate analytical techniques. In this review, we will summarize the current state of knowledge on the various passive permeability barriers present in mammalian cells. We will conclude with a description of several conventional techniques and one new approach based on chemically-inducible diffusion trap (C-IDT) for probing permeable barriers. PMID:23731778

Glucose Transporters at the Blood-Brain Barrier: Function, Regulation and Gateways for Drug Delivery.

PubMed

Patching, Simon G

2017-03-01

Glucose transporters (GLUTs) at the blood-brain barrier maintain the continuous high glucose and energy demands of the brain. They also act as therapeutic targets and provide routes of entry for drug delivery to the brain and central nervous system for treatment of neurological and neurovascular conditions and brain tumours. This article first describes the distribution, function and regulation of glucose transporters at the blood-brain barrier, the major ones being the sodium-independent facilitative transporters GLUT1 and GLUT3. Other GLUTs and sodium-dependent transporters (SGLTs) have also been identified at lower levels and under various physiological conditions. It then considers the effects on glucose transporter expression and distribution of hypoglycemia and hyperglycemia associated with diabetes and oxygen/glucose deprivation associated with cerebral ischemia. A reduction in glucose transporters at the blood-brain barrier that occurs before the onset of the main pathophysiological changes and symptoms of Alzheimer's disease is a potential causative effect in the vascular hypothesis of the disease. Mutations in glucose transporters, notably those identified in GLUT1 deficiency syndrome, and some recreational drug compounds also alter the expression and/or activity of glucose transporters at the blood-brain barrier. Approaches for drug delivery across the blood-brain barrier include the pro-drug strategy whereby drug molecules are conjugated to glucose transporter substrates or encapsulated in nano-enabled delivery systems (e.g. liposomes, micelles, nanoparticles) that are functionalised to target glucose transporters. Finally, the continuous development of blood-brain barrier in vitro models is important for studying glucose transporter function, effects of disease conditions and interactions with drugs and xenobiotics.

Homeostasis of the gut barrier and potential biomarkers.

PubMed

Wells, Jerry M; Brummer, Robert J; Derrien, Muriel; MacDonald, Thomas T; Troost, Freddy; Cani, Patrice D; Theodorou, Vassilia; Dekker, Jan; Méheust, Agnes; de Vos, Willem M; Mercenier, Annick; Nauta, Arjen; Garcia-Rodenas, Clara L

2017-03-01

The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions through the production of short-chain fatty acids (SCFAs) and interactions with innate pattern recognition receptors in the mucosa, driving the steady-state expression of mucus and antimicrobial factors. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability, and dysbiosis of the microbiota, which are recognized to play a role in the pathophysiology of a variety of gastrointestinal disorders. Additionally, gut-brain signaling may be affected by prolonged mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the hypothalamus-pituitary-adrenal axis and both mast cell-dependent and mast cell-independent mechanisms. The modulation of gut barrier function through nutritional interventions, including strategies to manipulate the microbiota, is considered a relevant target for novel therapeutic and preventive treatments against a range of diseases. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases, but there remains a need to explore their use in assessing the effect of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of available biomarkers and their predictive value for gut health in human cohorts. Copyright © 2017 the American Physiological Society.

Homeostasis of the gut barrier and potential biomarkers

PubMed Central

Brummer, Robert J.; Derrien, Muriel; MacDonald, Thomas T.; Troost, Freddy; Cani, Patrice D.; Theodorou, Vassilia; Dekker, Jan; Méheust, Agnes; de Vos, Willem M.; Mercenier, Annick; Nauta, Arjen; Garcia-Rodenas, Clara L.

2017-01-01

The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions through the production of short-chain fatty acids (SCFAs) and interactions with innate pattern recognition receptors in the mucosa, driving the steady-state expression of mucus and antimicrobial factors. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability, and dysbiosis of the microbiota, which are recognized to play a role in the pathophysiology of a variety of gastrointestinal disorders. Additionally, gut-brain signaling may be affected by prolonged mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the hypothalamus-pituitary-adrenal axis and both mast cell-dependent and mast cell-independent mechanisms. The modulation of gut barrier function through nutritional interventions, including strategies to manipulate the microbiota, is considered a relevant target for novel therapeutic and preventive treatments against a range of diseases. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases, but there remains a need to explore their use in assessing the effect of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of available biomarkers and their predictive value for gut health in human cohorts. PMID:27908847

The endothelial glycocalyx

PubMed Central

Yang, Yimu; Schmidt, Eric P.

2013-01-01

Once thought to be a structure of small size and uncertain significance, the endothelial glycocalyx is now known to be an important regulator of endothelial function. Studies of the systemic vasculature have demonstrated that the glycocalyx forms a substantial in vivo endothelial surface layer (ESL) critical to inflammation, barrier function and mechanotransduction. The pulmonary ESL is significantly thicker than the systemic ESL, suggesting unique physiologic function. We have recently demonstrated that the pulmonary ESL regulates exposure of endothelial surface adhesion molecules, thereby serving as a barrier to neutrophil adhesion and extravasation. While the pulmonary ESL is not a critical structural component of the endothelial barrier to fluid and protein, it serves a major role in the mechanotransduction of vascular pressure, with impact on the active regulation of endothelial permeability. It is likely that the ESL serves numerous additional functions in vascular physiology, representing a fertile area for future investigation. PMID:24073386

Analysis of Schottky Barrier Parameters and Current Transport Properties of V/p-Type GaN Schottky Junction at Low Temperatures

NASA Astrophysics Data System (ADS)

Asha, B.; Harsha, Cirandur Sri; Padma, R.; Rajagopal Reddy, V.

2018-05-01

The electrical characteristics of a V/p-GaN Schottky junction have been investigated by current-voltage (I-V) and capacitance-voltage (C-V) characteristics under the assumption of the thermionic emission (TE) theory in the temperature range of 120-280 K with steps of 40 K. The zero-bias barrier height (ΦB0), ideality factor (n), flat-band barrier height (ΦBF) and series resistance (R S) values were evaluated and were found to be strongly temperature dependent. The results revealed that the ΦB0 values increase, whereas n, ΦFB and R S values decrease, with increasing temperature. Using the conventional Richardson plot, the mean barrier height (0.39 eV) and Richardson constant (8.10 × 10-10 Acm-2 K-2) were attained. The barrier height inhomogeneities were demonstrated by assuming a Gaussian distribution function. The interface state density (N SS) values were found to decrease with increasing temperature. The reverse leakage current mechanism of the V/p-GaN Schottky junction was found to be governed by Poole-Frenkel emission at all temperatures.

Community environmental factors are associated with disability in older adults with functional limitations: the MOST study.

PubMed

Keysor, Julie J; Jette, Alan M; LaValley, Michael P; Lewis, Cora E; Torner, James C; Nevitt, Michael C; Felson, Dave T

2010-04-01

There is limited evidence supporting the hypothesized environment-disability link. The objectives of this study were to (a) identify the prevalence of community mobility barriers and transportation facilitators and (b) examine whether barriers and facilitators were associated with disability among older adults with functional limitations. Four hundred and thirty-five participants aged 65+ years old with functional limitations were recruited from the Multicenter Osteoarthritis Study, a prospective study of community-dwelling adults with or at risk of developing symptomatic knee osteoarthritis. Presence of community barriers and facilitators was ascertained by the Home and Community Environment survey. Two domains of disability, (a) daily activity limitation (DAL) and (b) daily activity frequency (DAF), were assessed with the Late-Life Disability Instrument. Covariates included age, gender, education, race, comorbidity, body mass index, knee pain, and functional limitation. Multivariable logistic regression was used to examine adjusted associations of community factors with presence of DAL and DAF. Approximately one third of the participants lived in a community with high mobility barriers and low transportation facilitators. High mobility barriers was associated with greater odds of DAL (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.2-3.1) after adjusting for covariates, and high transportation facilitators was associated with lower odds of DAL (OR = 0.5, 95% CI 0.3-0.8) but not with DAF in adjusted models. People with functional limitations who live in communities that were more restrictive felt more limited in doing daily activities but did not perform these daily activities any less frequently.

Roll-to-roll suitable short-pulsed laser scribing of organic photovoltaics and close-to-process characterization

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.

Sex differences in NSAID-induced perturbation of human intestinal barrier function and microbiota.

PubMed

Edogawa, Shoko; Peters, Stephanie A; Jenkins, Gregory D; Gurunathan, Sakteesh V; Sundt, Wendy J; Johnson, Stephen; Lennon, Ryan J; Dyer, Roy B; Camilleri, Michael; Kashyap, Purna C; Farrugia, Gianrico; Chen, Jun; Singh, Ravinder J; Grover, Madhusudan

2018-06-13

Intestinal barrier function and microbiota are integrally related and play critical roles in maintenance of host physiology. Sex is a key biologic variable for several disorders. Our aim was to determine sex-based differences in response to perturbation and subsequent recovery of intestinal barrier function and microbiota in healthy humans. Twenty-three volunteers underwent duodenal biopsies, mucosal impedance, and in vivo permeability measurement. Permeability testing was repeated after administration of indomethacin, then 4 to 6 wk after its discontinuation. Duodenal and fecal microbiota composition was determined using 16S rRNA amplicon sequencing. Healthy women had lower intestinal permeability and higher duodenal and fecal microbial diversity than healthy men. Intestinal permeability increases after indomethacin administration in both sexes. However, only women demonstrated decreased fecal microbial diversity, including an increase in Prevotella abundance, after indomethacin administration. Duodenal microbiota composition did not show sex-specific changes. The increase in permeability and microbiota changes normalized after discontinuation of indomethacin. In summary, women have lower intestinal permeability and higher microbial diversity. Intestinal permeability is sensitive to perturbation but recovers to baseline. Gut microbiota in women is sensitive to perturbation but appears to be more stable in men. Sex-based differences in intestinal barrier function and microbiome should be considered in future studies.-Edogawa, S., Peters, S. A., Jenkins, G. D., Gurunathan, S. V., Sundt, W. J., Johnson, S., Lennon, R. J., Dyer, R. B., Camilleri, M., Kashyap, P. C., Farrugia, G., Chen, J., Singh, R. J., Grover, M. Sex differences in NSAID-induced perturbation of human intestinal barrier function and microbiota.

Gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice

PubMed Central

Fang, Yu; Chen, Hao; Hu, Yuhui; Djukic, Zorka; Tevebaugh, Whitney; Shaheen, Nicholas J.; Orlando, Roy C.; Hu, Jianguo

2013-01-01

The barrier function of the esophageal epithelium is a major defense against gastroesophageal reflux disease. Previous studies have shown that reflux damage is reflected in a decrease in transepithelial electrical resistance associated with tight junction alterations in the esophageal epithelium. To develop novel therapies, it is critical to understand the molecular mechanisms whereby contact with a refluxate impairs esophageal barrier function. In this study, surgical models of duodenal and mixed reflux were developed in mice. Mouse esophageal epithelium was analyzed by gene microarray. Gene set enrichment analysis showed upregulation of inflammation-related gene sets and the NF-κB pathway due to reflux. Significance analysis of microarrays revealed upregulation of NF-κB target genes. Overexpression of NF-κB subunits (p50 and p65) and NF-κB target genes (matrix metalloproteinases-3 and -9, IL-1β, IL-6, and IL-8) confirmed activation of the NF-κB pathway in the esophageal epithelium. In addition, real-time PCR, Western blotting, and immunohistochemical staining also showed downregulation and mislocalization of claudins-1 and -4. In a second animal experiment, treatment with an NF-κB inhibitor, BAY 11-7085 (20 mg·kg−1·day−1 ip for 10 days), counteracted the effects of duodenal and mixed reflux on epithelial resistance and NF-κB-regulated cytokines. We conclude that gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice and that targeting the NF-κB pathway may strengthen esophageal barrier function against reflux. PMID:23639809

Selection on plant male function genes identifies candidates for reproductive isolation of yellow monkeyflowers.

PubMed

Aagaard, Jan E; George, Renee D; Fishman, Lila; Maccoss, Michael J; Swanson, Willie J

2013-01-01

Understanding the genetic basis of reproductive isolation promises insight into speciation and the origins of biological diversity. While progress has been made in identifying genes underlying barriers to reproduction that function after fertilization (post-zygotic isolation), we know much less about earlier acting pre-zygotic barriers. Of particular interest are barriers involved in mating and fertilization that can evolve extremely rapidly under sexual selection, suggesting they may play a prominent role in the initial stages of reproductive isolation. A significant challenge to the field of speciation genetics is developing new approaches for identification of candidate genes underlying these barriers, particularly among non-traditional model systems. We employ powerful proteomic and genomic strategies to study the genetic basis of conspecific pollen precedence, an important component of pre-zygotic reproductive isolation among yellow monkeyflowers (Mimulus spp.) resulting from male pollen competition. We use isotopic labeling in combination with shotgun proteomics to identify more than 2,000 male function (pollen tube) proteins within maternal reproductive structures (styles) of M. guttatus flowers where pollen competition occurs. We then sequence array-captured pollen tube exomes from a large outcrossing population of M. guttatus, and identify those genes with evidence of selective sweeps or balancing selection consistent with their role in pollen competition. We also test for evidence of positive selection on these genes more broadly across yellow monkeyflowers, because a signal of adaptive divergence is a common feature of genes causing reproductive isolation. Together the molecular evolution studies identify 159 pollen tube proteins that are candidate genes for conspecific pollen precedence. Our work demonstrates how powerful proteomic and genomic tools can be readily adapted to non-traditional model systems, allowing for genome-wide screens towards the goal of identifying the molecular basis of genetically complex traits.

Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice

PubMed Central

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

Impaired Intestinal Mucosal Barrier upon Ischemia-Reperfusion: “Patching Holes in the Shield with a Simple Surgical Method”

PubMed Central

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

Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13-Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation.

PubMed

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.

Meprin A impairs epithelial barrier function, enhances monocyte migration, and cleaves the tight junction protein occludin

PubMed Central

Bao, Jialing; Yura, Renee E.; Matters, Gail L.; Bradley, S. Gaylen; Shi, Pan; Tian, Fang

2013-01-01

Meprin metalloproteases are highly expressed at the luminal interface of the intestine and kidney and in certain leukocytes. Meprins cleave a variety of substrates in vitro, including extracellular matrix proteins, adherens junction proteins, and cytokines, and have been implicated in a number of inflammatory diseases. The linkage between results in vitro and pathogenesis, however, has not been elucidated. The present study aimed to determine whether meprins are determinative factors in disrupting the barrier function of the epithelium. Active meprin A or meprin B applied to Madin-Darby canine kidney (MDCK) cell monolayers increased permeability to fluorescein isothiocyanate-dextran and disrupted immunostaining of the tight junction protein occludin but not claudin-4. Meprin A, but not meprin B, cleaved occludin in MDCK monolayers. Experiments with recombinant occludin demonstrated that meprin A cleaves the protein between Gly100 and Ser101 on the first extracellular loop. In vivo experiments demonstrated that meprin A infused into the mouse bladder increased the epithelium permeability to sodium fluorescein. Furthermore, monocytes from meprin knockout mice on a C57BL/6 background were less able to migrate through an MDCK monolayer than monocytes from their wild-type counterparts. These results demonstrate the capability of meprin A to disrupt epithelial barriers and implicate occludin as one of the important targets of meprin A that may modulate inflammation. PMID:23804454

Efficacy of IPL device combined with intralesional corticosteroid injection for the treatment of keloids and hypertrophic scars with regards to the recovery of skin barrier function: A pilot study.

PubMed

Kim, Dong Young; Park, Hyun Sun; Yoon, Hyun-Sun; Cho, Soyun

2015-10-01

Keloids and hypertrophic scars are prevalent and psychologically distressful dermatologic conditions. Various treatment modalities have been tried but without complete success by any one method. We evaluated the efficacy of a combination of intense pulsed light (IPL) device and intralesional corticosteroid injection for the treatment of keloids and hypertrophic scars with respect to the recovery of skin barrier function. Totally 52 Korean patients were treated by the combined treatment at 4-8-week intervals. Using digital photographs, changes in scar appearance were assessed with modified Vancouver Scar Scale (MVSS), physicians' global assessment (PGA) and patient's satisfaction score. In 12 patients, the stratum corneum (SC) barrier function was assessed by measuring transepidermal water loss (TEWL) and SC capacitance. Most scars demonstrated significant clinical improvement in MVSS, PGA and patient's satisfaction score after the combined therapy. A significant decrease of TEWL and elevation of SC capacitance were also documented after the treatment. The combination therapy (IPL + corticosteroid injection) not only improves the appearance of keloids and hypertrophic scars but also increases the recovery level of skin hydration status in terms of the skin barrier function.

The blood-brain barrier of the chick glycogen body (corpus gelatinosum) and its functional implications.

PubMed

Möller, Wilhelm; Kummer, Wolfgang

2003-07-01

Among recent vertebrates only birds possess a glycogen body (corpus gelatinosum), located in the rhomboidal sinus of the lumbosacral region of the spinal cord and separated from the neural tissue proper. Because of the specific topographical situation of this circumventricular organ, the structure of its vascular system is of special interest with respect to the still unsolved functional problems. The existence of a blood-brain barrier is demonstrated by the exclusion of intravascularly injected tracer (horseradish peroxidase), and immunocytochemical demonstration of glucose transporter-1 as a functional marker and of neurothelin, occludin and ZO-1 as structural markers. Alkaline phosphatase and gamma-glutamyltransferase activities, two enzyme reactions frequently used for demonstration of an established blood-brain barrier in vitro, were localized histochemically on the plasmalemma of glycogen body cells and were absent from the endothelium. In addition, local enlargements of the intercellular space were observed by transmission and scanning electron microscopy. In accordance with the concept of a third circulation the cerebrospinal fluid may be the vehicle for distributing substances originating in the glycogen body to the CNS, while the vascular endothelium maintains the internal milieu by virtue of its dynamic barrier functions.

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

Alterations in Gut Microbiome Composition and Barrier Function Are Associated with Reproductive and Metabolic Defects in Women with Polycystic Ovary Syndrome (PCOS): A Pilot Study

PubMed Central

Bashir, Mina; Münzker, Julia; Trummer, Christian; Zachhuber, Verena; Leber, Bettina; Horvath, Angela; Pieber, Thomas R.; Gorkiewicz, Gregor; Stadlbauer, Vanessa; Obermayer-Pietsch, Barbara

2017-01-01

Background Polycystic ovary syndrome (PCOS) is a common female endocrinopathy of unclear origin characterized by hyperandrogenism, oligo-/anovulation, and ovarian cysts. Women with PCOS frequently display overweight, insulin resistance, and systemic low-grade inflammation. We hypothesized that endotoxemia resulting from a leaky gut is associated with inflammation, insulin resistance, fat accumulation, and hyperandrogenemia in PCOS. In this pilot study, we compared the stool microbiome, gut permeability, and inflammatory status of women with PCOS and healthy controls. Methods 16S rRNA gene amplicon sequencing was performed on stool samples from 24 PCOS patients and 19 healthy controls. Data processing and microbiome analysis were conducted in mothur and QIIME using different relative abundance cut-offs. Gut barrier integrity, endotoxemia, and inflammatory status were evaluated using serum and stool markers and associations with reproductive, metabolic, and anthropometric parameters were investigated. Results The stool microbiome of PCOS patients showed a lower diversity and an altered phylogenetic composition compared to controls. We did not observe significant differences in any taxa with a relative abundance>1%. When looking at rare taxa, the relative abundance of bacteria from the phylum Tenericutes, the order ML615J-28 (phylum Tenericutes) and the family S24-7 (phylum Bacteroidetes) was significantly lower and associated with reproductive parameters in PCOS patients. Patients showed alterations in some, but not all markers of gut barrier function and endotoxemia. Conclusion Patients with PCOS have a lower diversity and an altered phylogenetic profile in their stool microbiome, which is associated with clinical parameters. Gut barrier dysfunction and endotoxemia were not driving factors in this patient cohort, but may contribute to the clinical phenotype in certain PCOS patients. PMID:28045919

A photoemission moments model using density functional and transfer matrix methods applied to coating layers on surfaces: Theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Kevin L.; Finkenstadt, Daniel; Shabaev, Andrew

Recent experimental measurements of a bulk material covered with a small number of graphene layers reported by Yamaguchi et al. [NPJ 2D Mater. Appl. 1, 12 (2017)] (on bialkali) and Liu et al.[Appl. Phys. Lett. 110, 041607 (2017)] (on copper) and the needs of emission models in beam optics codes have lead to substantial changes in a Moments model of photoemission. The changes account for (i) a barrier profile and density of states factor based on density functional theory (DFT) evaluations, (ii) a Drude-Lorentz model of the optical constants and laser penetration depth, and (iii) a transmission probability evaluated bymore » an Airy Transfer Matrix Approach. Importantly, the DFT results lead to a surface barrier profile of a shape similar to both resonant barriers and reflectionless wells: the associated quantum mechanical transmission probabilities are shown to be comparable to those recently required to enable the Moments (and Three Step) model to match experimental data but for reasons very different than the assumption by conventional wisdom that a barrier is responsible. The substantial modifications of the Moments model components, motivated by computational materials methods, are developed. The results prepare the Moments model for use in treating heterostructures and discrete energy level systems (e.g., quantum dots) proposed for decoupling the opposing metrics of performance that undermine the performance of advanced light sources like the x-ray Free Electron Laser. The consequences of the modified components on quan-tum yield, emittance, and emission models needed by beam optics codes are discussed. Published by AIP Publishing. https://doi.org/10.1063/1.5008600« less

A photoemission moments model using density functional and transfer matrix methods applied to coating layers on surfaces: Theory

DOE PAGES

Jensen, Kevin L.; Finkenstadt, Daniel; Shabaev, Andrew; ...

2018-01-28

Recent experimental measurements of a bulk material covered with a small number of graphene layers reported by Yamaguchi et al. [NPJ 2D Mater. Appl. 1, 12 (2017)] (on bialkali) and Liu et al.[Appl. Phys. Lett. 110, 041607 (2017)] (on copper) and the needs of emission models in beam optics codes have lead to substantial changes in a Moments model of photoemission. The changes account for (i) a barrier profile and density of states factor based on density functional theory (DFT) evaluations, (ii) a Drude-Lorentz model of the optical constants and laser penetration depth, and (iii) a transmission probability evaluated bymore » an Airy Transfer Matrix Approach. Importantly, the DFT results lead to a surface barrier profile of a shape similar to both resonant barriers and reflectionless wells: the associated quantum mechanical transmission probabilities are shown to be comparable to those recently required to enable the Moments (and Three Step) model to match experimental data but for reasons very different than the assumption by conventional wisdom that a barrier is responsible. The substantial modifications of the Moments model components, motivated by computational materials methods, are developed. The results prepare the Moments model for use in treating heterostructures and discrete energy level systems (e.g., quantum dots) proposed for decoupling the opposing metrics of performance that undermine the performance of advanced light sources like the x-ray Free Electron Laser. The consequences of the modified components on quan-tum yield, emittance, and emission models needed by beam optics codes are discussed. Published by AIP Publishing. https://doi.org/10.1063/1.5008600« less

The role of the blood-brain barrier in the development and treatment of migraine and other pain disorders.

PubMed

DosSantos, Marcos F; Holanda-Afonso, Rosenilde C; Lima, Rodrigo L; DaSilva, Alexandre F; Moura-Neto, Vivaldo

2014-01-01

The function of the blood-brain barrier (BBB) related to chronic pain has been explored for its classical role in regulating the transcellular and paracellular transport, thus controlling the flow of drugs that act at the central nervous system, such as opioid analgesics (e.g., morphine) and non-steroidal anti-inflammatory drugs. Nonetheless, recent studies have raised the possibility that changes in the BBB permeability might be associated with chronic pain. For instance, changes in the relative amounts of occludin isoforms, resulting in significant increases in the BBB permeability, have been demonstrated after inflammatory hyperalgesia. Furthermore, inflammatory pain produces structural changes in the P-glycoprotein, the major efflux transporter at the BBB. One possible explanation for these findings is the action of substances typically released at the site of peripheral injuries that could lead to changes in the brain endothelial permeability, including substance P, calcitonin gene-related peptide, and interleukin-1 beta. Interestingly, inflammatory pain also results in microglial activation, which potentiates the BBB damage. In fact, astrocytes and microglia play a critical role in maintaining the BBB integrity and the activation of those cells is considered a key mechanism underlying chronic pain. Despite the recent advances in the understanding of BBB function in pain development as well as its interference in the efficacy of analgesic drugs, there remain unknowns regarding the molecular mechanisms involved in this process. In this review, we explore the connection between the BBB as well as the blood-spinal cord barrier and blood-nerve barrier, and pain, focusing on cellular and molecular mechanisms of BBB permeabilization induced by inflammatory or neuropathic pain and migraine.

The role of the blood–brain barrier in the development and treatment of migraine and other pain disorders

PubMed Central

DosSantos, Marcos F.; Holanda-Afonso, Rosenilde C.; Lima, Rodrigo L.; DaSilva, Alexandre F.; Moura-Neto, Vivaldo

2014-01-01

The function of the blood–brain barrier (BBB) related to chronic pain has been explored for its classical role in regulating the transcellular and paracellular transport, thus controlling the flow of drugs that act at the central nervous system, such as opioid analgesics (e.g., morphine) and non-steroidal anti-inflammatory drugs. Nonetheless, recent studies have raised the possibility that changes in the BBB permeability might be associated with chronic pain. For instance, changes in the relative amounts of occludin isoforms, resulting in significant increases in the BBB permeability, have been demonstrated after inflammatory hyperalgesia. Furthermore, inflammatory pain produces structural changes in the P-glycoprotein, the major efflux transporter at the BBB. One possible explanation for these findings is the action of substances typically released at the site of peripheral injuries that could lead to changes in the brain endothelial permeability, including substance P, calcitonin gene-related peptide, and interleukin-1 beta. Interestingly, inflammatory pain also results in microglial activation, which potentiates the BBB damage. In fact, astrocytes and microglia play a critical role in maintaining the BBB integrity and the activation of those cells is considered a key mechanism underlying chronic pain. Despite the recent advances in the understanding of BBB function in pain development as well as its interference in the efficacy of analgesic drugs, there remain unknowns regarding the molecular mechanisms involved in this process. In this review, we explore the connection between the BBB as well as the blood–spinal cord barrier and blood–nerve barrier, and pain, focusing on cellular and molecular mechanisms of BBB permeabilization induced by inflammatory or neuropathic pain and migraine. PMID:25339863

Apical electrolyte concentration modulates barrier function and tight junction protein localization in bovine mammary epithelium.

PubMed

Quesnell, Rebecca R; Erickson, Jamie; Schultz, Bruce D

2007-01-01

In vitro mammary epithelial cell models typically fail to form a consistently tight barrier that can effectively separate blood from milk. Our hypothesis was that mammary epithelial barrier function would be affected by changes in luminal ion concentration and inflammatory cytokines. Bovine mammary epithelial (BME-UV cell line) cells were grown to confluence on permeable supports with a standard basolateral medium and either high-electrolyte (H-elec) or low-electrolyte (L-elec) apical medium for 14 days. Apical media were changed to/from H-elec medium at predetermined times prior to assay. Transepithelial electrical resistance (R(te)) was highest in monolayers continuously exposed to apical L-elec. A time-dependent decline in R(te) began within 24 h of H-elec medium exposure. Change from H-elec medium to L-elec medium time-dependently increased R(te). Permeation by FITC-conjugated dextran was elevated across monolayers exposed to H-elec, suggesting compromise of a paracellular pathway. Significant alteration in occludin distribution was evident, concomitant with the changes in R(te), although total occludin was unchanged. Neither substitution of Na(+) with N-methyl-d-glucosamine (NMDG(+)) nor pharmacological inhibition of transcellular Na(+) transport pathways abrogated the effects of apical H-elec medium on R(te). Tumor necrosis factor alpha, but not interleukin-1beta nor interleukin-6, in the apical compartment caused a significant decrease in R(te) within 8 h. These results indicate that mammary epithelium is a dynamic barrier whose cell-cell contacts are acutely modulated by cytokines and luminal electrolyte environment. Results not only demonstrate that BME-UV cells are a model system representative of mammary epithelium but also provide critical information that can be applied to other mammary model systems to improve their physiological relevance.

Myosin light chain kinase knockout improves gut barrier function and confers a survival advantage in polymicrobial sepsis.

PubMed

Lorentz, C Adam; Liang, Zhe; Meng, Mei; Chen, Ching-Wen; Yoseph, Benyam P; Breed, Elise R; Mittal, Rohit; Klingensmith, Nathan J; Farris, Alton B; Burd, Eileen M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

2017-06-07

Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK -/- and wild type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies. Survival was significantly increased in MLCK -/- mice (95% vs. 24%, p<0.0001). Intestinal permeability increased in septic WT mice compared to unmanipulated mice. In contrast, permeability in septic MLCK -/- mice was similar to that seen in unmanipulated animals. Improved gut barrier function in MLCK -/- mice was associated with increases in the tight junction mediators ZO-1 and claudin 15 without alterations in claudin 1, 2, 3, 4, 5, 7, 8, 13, occludin or JAM-A. Other components of intestinal integrity (apoptosis, proliferation and villus length) were unaffected by MLCK deletion as were local peritoneal inflammation and distant lung injury. Systemic IL-10 was decreased greater than 10-fold in MLCK -/- mice; however, survival was similar between septic MLCK -/- mice given exogenous IL-10 or vehicle. These data demonstrate that deletion of MLCK improves survival following sepsis, associated with normalization of intestinal permeability and selected tight junction proteins.

Effect of Standardized Boesenbergia pandurata Extract and Its Active Compound Panduratin A on Skin Hydration and Barrier Function in Human Epidermal Keratinocytes.

PubMed

Woo, Seon Wook; Rhim, Dong-Bin; Kim, Changhee; Hwang, Jae-Kwan

2015-03-01

The skin plays a key role in protecting the body from the environment and from water loss. Cornified envelope (CE) and natural moisturizing factor (NMF) are considered as the primary regulators of skin hydration and barrier function. The CE prevents loss of water from the body and is formed by cross-linking of several proteins. Among these proteins, filaggrin is an important protein because NMF is produced by the degradation of filaggrin. Proteases, including matriptase and prostasin, stimulate the generation of filaggrin from profilaggrin and caspase-14 plays a role in the degradation of filaggrin. This study elucidated the effects of an ethanol extract of Boesenbergia pandurata (Roxb.) Schltr., known as fingerroot, and its active compound panduratin A on CE formation and filaggrin processing in HaCaT, human epidermal keratinocytes. B. pandurata extract (BPE) and panduratin A significantly stimulated not only CE formation but also the expression of CE proteins, such as loricrin, involucrin, and transglutaminase, which were associated with PPARα expression. The mRNA and protein levels of filaggrin and filaggrin-related enzymes, such as matriptase, prostasin, and caspase-14 were also up-regulated by BPE and panduratin A treatment. These results suggest that BPE and panduratin A are potential nutraceuticals which can enhance skin hydration and barrier function based on their CE formation and filaggrin processing.

Effects of moisturizing skincare on skin barrier function and the prevention of skin problems in 3-month-old infants: A randomized controlled trial.

PubMed

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.

Dietary glucosylceramide enhances tight junction function in skin epidermis via induction of claudin-1.

PubMed

Kawada, Chinatsu; Hasegawa, Tatsuya; Watanabe, Mutsuto; Nomura, Yoshihiro

2013-01-01

Dietary glucosylceramide increased the expression of claudin-1 in UVB-irradiated mouse epidermis. Sphingosine and phytosphingosine, metabolites of glucosylceramide, increased trans-epithelial electrical resistance, and phytosphingosine increased claudin-1 mRNA expression in cultured keratinocytes. Our results indicate that the skin barrier improvement induced by dietary glucosylceramide might be due to enhancement of tight junction function, mediated by increased expression of claudin-1 induced by sphingoid metabolites.

Near Two-Decade Instrument Performance for Hydrological Monitoring at the Prototype Hanford Barrier

NASA Astrophysics Data System (ADS)

Zhang, Z. F.; Strickland, C. E.; Clayton, R. E.

2012-12-01

Surface barriers have been proposed for use at the Department of Energy's Hanford Site as a means to isolate certain radioactive waste sites that, for reasons of cost or worker safety, may not be exhumed. The Hanford Prototype Barrier was constructed in 1994 using mostly natural materials to demonstrate its long-term performance. The barrier is expected to perform for at least 1000 years by limiting water, plant, animal, and human intrusion and minimizing erosion. Extensive instrumentation is used to monitor the hydrological regime above, within, below, and around the barrier. Specifically, natural precipitation and irrigation are measured with rain gauges, runoff water with a runoff flume, soil water content within the barrier at 12 stations with a neutron probe, a capacitance probe, and time-domain-reflectometry probes, and soil water pressure with gypsum blocks and heat-dissipation-units. Drainage through the barrier and the side slopes is measured with 12 water collection vaults, respectively, for 12 zones. Each drainage vault is equipped with a dosing siphon, a dose counter, a pressure transducer to measure the water level, and a tipping bucket to measure the inflow. During the near two-decade monitoring period, some of the instruments stopped functioning, while others still function normally till present. This presentation will summarize the performance of these instruments. Recommendations for future barrier monitoring will be given.

Physiology and molecular biology of barrier mechanisms in the fetal and neonatal brain.

PubMed

Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld; Habgood, Mark D

2018-05-17

Properties of the local internal environment of the adult brain are tightly controlled providing a stable milieu essential for its normal function. The mechanisms involved in this complex control are structural, molecular and physiological (influx and efflux transporters) frequently referred to as the "blood-brain barrier". These mechanisms include regulation of ion levels in brain interstitial fluid essential for normal neuronal function, supply of nutrients, removal of metabolic products and prevention of entry or elimination of toxic agents. A key feature is cerebrospinal fluid secretion and turnover. This is much less during development, allowing greater accumulation of permeating molecules. The overall effect of these mechanisms is to tightly control the exchange of molecules into and out of the brain. This review presents experimental evidence currently available on the status of these mechanisms in developing brain. It has been frequently stated for over nearly a century that the blood-brain barrier is not present or at least is functionally deficient in the embryo, fetus and newborn. We suggest the alternative hypothesis that the barrier mechanisms in developing brain are likely to be appropriately matched to each stage of its development. The contributions of different barrier mechanisms, such as changes in constituents of cerebrospinal fluid in relation to specific features of brain development, for example neurogenesis, are only beginning to be studied. The evidence on this previously neglected aspect of brain barrier function is outlined. We also suggest future directions this field could follow with special emphasis on potential applications in a clinical setting. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Placenta-on-a-chip: a novel platform to study the biology of the human placenta.

PubMed

Lee, Ji Soo; Romero, Roberto; Han, Yu Mi; Kim, Hee Chan; Kim, Chong Jai; Hong, Joon-Seok; Huh, Dongeun

2016-01-01

Studying the biology of the human placenta represents a major experimental challenge. Although conventional cell culture techniques have been used to study different types of placenta-derived cells, current in vitro models have limitations in recapitulating organ-specific structure and key physiological functions of the placenta. Here we demonstrate that it is possible to leverage microfluidic and microfabrication technologies to develop a microengineered biomimetic model that replicates the architecture and function of the placenta. A "Placenta-on-a-Chip" microdevice was created by using a set of soft elastomer-based microfabrication techniques known as soft lithography. This microsystem consisted of two polydimethylsiloxane (PDMS) microfluidic channels separated by a thin extracellular matrix (ECM) membrane. To reproduce the placental barrier in this model, human trophoblasts (JEG-3) and human umbilical vein endothelial cells (HUVECs) were seeded onto the opposite sides of the ECM membrane and cultured under dynamic flow conditions to form confluent epithelial and endothelial layers in close apposition. We tested the physiological function of the microengineered placental barrier by measuring glucose transport across the trophoblast-endothelial interface over time. The permeability of the barrier study was analyzed and compared to that obtained from acellular devices and additional control groups that contained epithelial or endothelial layers alone. Our microfluidic cell culture system provided a tightly controlled fluidic environment conducive to the proliferation and maintenance of JEG-3 trophoblasts and HUVECs on the ECM scaffold. Prolonged culture in this model produced confluent cellular monolayers on the intervening membrane that together formed the placental barrier. This in vivo-like microarchitecture was also critical for creating a physiologically relevant effective barrier to glucose transport. Quantitative investigation of barrier function was conducted by calculating permeability coefficients and metabolic rates in varying conditions of barrier structure. The rates of glucose transport and metabolism were consistent with previously reported in vivo observations. The "Placenta-on-a-Chip" microdevice described herein provides new opportunities to simulate and analyze critical physiological responses of the placental barrier. This system may be used to address the major limitations of existing placenta model systems and serve to enable research platforms for reproductive biology and medicine.

Blood-brain barrier and its function during inflammation and autoimmunity.

PubMed

Sonar, Sandip Ashok; Lal, Girdhari

2018-05-01

The blood-brain barrier (BBB) is an important physiologic barrier that separates CNS from soluble inflammatory mediators and effector immune cells from peripheral circulation. The optimum function of the BBB is necessary for the homeostasis, maintenance, and proper neuronal function. The clinical and experimental findings have shown that BBB dysfunction is an early hallmark of various neurologic disorders ranging from inflammatory autoimmune, neurodegenerative, and traumatic diseases to neuroinvasive infections. Significant progress has been made in the understanding of the regulation of BBB function under homeostatic and neuroinflammatory conditions. Several neurologic disease-modifying drugs have shown to improve the BBB function. However, they have a broad-acting immunomodulatory function and can increase the risk of life-threatening infections. The recent development of in vitro multicomponent 3-dimensional BBB models coupled with fluidics chamber as well as a cell-type specific reporter and knockout mice gave a new boost to our understanding of the dynamics of the BBB. In the review, we discuss the current understanding of BBB composition and recent findings that illustrate the critical regulatory elements of the BBB function under physiologic and inflammatory conditions, and also suggested the strategies to control BBB structure and function. ©2018 Society for Leukocyte Biology.

Barriers to Liposomal Gene Delivery: from Application Site to the Target.

PubMed

Saffari, Mostafa; Moghimi, Hamid Reza; Dass, Crispin R

2016-01-01

Gene therapy is a therapeutic approach to deliver genetic material into cells to alter their function in entire organism. One promising form of gene delivery system (DDS) is liposomes. The success of liposome-mediated gene delivery is a multifactorial issue and well-designed liposomal systems might lead to optimized gene transfection particularly in vivo. Liposomal gene delivery systems face different barriers from their site of application to their target, which is inside the cells. These barriers include presystemic obstacles (epithelial barriers), systemic barriers in blood circulation and cellular barriers. Epithelial barriers differ depending on the route of administration. Systemic barriers include enzymatic degradation, binding and opsonisation. Both of these barriers can act as limiting hurdles that genetic material and their vector should overcome before reaching the cells. Finally liposomes should overcome cellular barriers that include cell entrance, endosomal escape and nuclear uptake. These barriers and their impact on liposomal gene delivery will be discussed in this review.

Activation of amino-based monolayers for electroless metallization of high-aspect-ratio through-silicon vias by using a simple ultrasonic-assisted plating solution

NASA Astrophysics Data System (ADS)

Chen, Sung-Te; Cheng, Yu-Syun; Chang, Yiu-Hsiang; Yang, Tzu-Ming; Lee, Jyun-Ting; Chen, Giin-Shan

2018-05-01

In this paper, we present the method and results of electroless plating of through-silicon via (TSV) contacts using Ni nanoparticle seeds on self-assembled monolayers (SAMs). This approach where the nanoparticles are evenly distributed and stabilized on the SAM allows the successive electroless metallization schemes such as Co-alloy barrier and Cu plug used typically in TSV as interconnects. The seeding was tested on SiO2 layers with surfaces functionalized by an amino-based aminopropyltrimethoxysilane (APTMS) SAM. APTMS-SAM after a suitable SC-1 treatment yielded a remarkably good barrier layer, with high adhesion strength (70 MPa) and low electrical resistivity (28 μΩ-cm). Moreover, the SAM assisted seeding protocol was followed by an ultrasonic-assisted (or mechanically agitated) electroless-plating stage together with a relatively simple plating solution. Conformal plating of Co-alloy barrier and seem/void-free Cu-plug filling into high-aspect-ratio TSVs (>10) was only achieved by using an ultrasonic-assisted plating process. The SAM layers were characterized by X-ray photoelectron spectroscopy to elucidate the surface functionalization effect.

Designing solid-liquid interphases for sodium batteries.

PubMed

Choudhury, Snehashis; Wei, Shuya; Ozhabes, Yalcin; Gunceler, Deniz; Zachman, Michael J; Tu, Zhengyuan; Shin, Jung Hwan; Nath, Pooja; Agrawal, Akanksha; Kourkoutis, Lena F; Arias, Tomas A; Archer, Lynden A

2017-10-12

Secondary batteries based on earth-abundant sodium metal anodes are desirable for both stationary and portable electrical energy storage. Room-temperature sodium metal batteries are impractical today because morphological instability during recharge drives rough, dendritic electrodeposition. Chemical instability of liquid electrolytes also leads to premature cell failure as a result of parasitic reactions with the anode. Here we use joint density-functional theoretical analysis to show that the surface diffusion barrier for sodium ion transport is a sensitive function of the chemistry of solid-electrolyte interphase. In particular, we find that a sodium bromide interphase presents an exceptionally low energy barrier to ion transport, comparable to that of metallic magnesium. We evaluate this prediction by means of electrochemical measurements and direct visualization studies. These experiments reveal an approximately three-fold reduction in activation energy for ion transport at a sodium bromide interphase. Direct visualization of sodium electrodeposition confirms large improvements in stability of sodium deposition at sodium bromide-rich interphases.The chemistry at the interface between electrolyte and electrode plays a critical role in determining battery performance. Here, the authors show that a NaBr enriched solid-electrolyte interphase can lower the surface diffusion barrier for sodium ions, enabling stable electrodeposition.

Inhibition of cyclooxygenase-2 alleviates liver cirrhosis via improvement of the dysfunctional gut-liver axis in rats.

PubMed

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.

Pirin Inhibits Cellular Senescence in Melanocytic Cells

PubMed Central

Licciulli, Silvia; Luise, Chiara; Scafetta, Gaia; Capra, Maria; Giardina, Giuseppina; Nuciforo, Paolo; Bosari, Silvano; Viale, Giuseppe; Mazzarol, Giovanni; Tonelli, Chiara; Lanfrancone, Luisa; Alcalay, Myriam

2011-01-01

Cellular senescence has been widely recognized as a tumor suppressing mechanism that acts as a barrier to cancer development after oncogenic stimuli. A prominent in vivo model of the senescence barrier is represented by nevi, which are composed of melanocytes that, after an initial phase of proliferation induced by activated oncogenes (most commonly BRAF), are blocked in a state of cellular senescence. Transformation to melanoma occurs when genes involved in controlling senescence are mutated or silenced and cells reacquire the capacity to proliferate. Pirin (PIR) is a highly conserved nuclear protein that likely functions as a transcriptional regulator whose expression levels are altered in different types of tumors. We analyzed the expression pattern of PIR in adult human tissues and found that it is expressed in melanocytes and has a complex pattern of regulation in nevi and melanoma: it is rarely detected in mature nevi, but is expressed at high levels in a subset of melanomas. Loss of function and overexpression experiments in normal and transformed melanocytic cells revealed that PIR is involved in the negative control of cellular senescence and that its expression is necessary to overcome the senescence barrier. Our results suggest that PIR may have a relevant role in melanoma progression. PMID:21514450

Numerical Study for a Large-Volume Droplet on the Dual-Rough Surface: Apparent Contact Angle, Contact Angle Hysteresis, and Transition Barrier.

PubMed

Dong, Jian; Jin, Yanli; Dong, He; Liu, Jiawei; Ye, Senbin

2018-06-26

The profile, apparent contact angle (ACA), contact angle hysteresis (CAH), and wetting state transmission energy barrier (WSTEB) are important static and dynamic properties of a large-volume droplet on the hierarchical surface. Understanding them can provide us with important insights into functional surfaces and promote the application in corresponding areas. In this paper, we establish three theoretical models (models 1-3) and the corresponding numerical methods, which were obtained by the free energy minimization and the nonlinear optimization algorithm, to predict the profile, ACA, CAH, and WSTEB of a large-volume droplet on the horizontal regular dual-rough surface. In consideration of the gravity, the energy barrier on the contact circle, the dual heterogeneous structures and their roughness on the surface, the models are more universal and accurate than the previous models. It showed that the predictions of the models were in good agreement with the results from the experiment or literature. The models are promising to become novel design approaches of functional surfaces, which are frequently applied in microfluidic chips, water self-catchment system, and dropwise condensation heat transfer system.

Density functional theory studies of methyl dissociation on a Ni(111) surface in the presence of an external electric field.

PubMed

Che, Fanglin; Zhang, Renqin; Hensley, Alyssa J; Ha, Su; McEwen, Jean-Sabin

2014-02-14

To provide a basis for understanding the reactive processes on nickel surfaces at fuel cell anodes, we investigate the influence of an external electric field on the dehydrogenation of methyl species on a Ni(111) surface using density functional theory calculations. The structures, adsorption energies and reaction barriers for all methyl species dissociation on the Ni(111) surface are identified. Our results show that the presence of an external electric field does not affect the structures and favorable adsorption sites of the adsorbed species, but causes the adsorption energies of the CHx species at the stable site to fluctuate around 0.2 eV. Calculations give an energy barrier of 0.692 eV for CH3* → CH2* + H*, 0.323 eV for CH2* → CH* + H* and 1.373 eV for CH* → C* + H*. Finally, we conclude that the presence of a large positive electric field significantly increases the energy barrier of the CH* → C* + H* reaction more than the other two reactions, suggesting that the presence of pure C atoms on Ni(111) are impeded in the presence of an external positive electric field.

The Blood–Brain Barrier

PubMed Central

Daneman, Richard; Prat, Alexandre

2015-01-01

Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood–brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease. PMID:25561720

Wnt/β-catenin signaling controls development of the blood–brain barrier

PubMed Central

Liebner, Stefan; Corada, Monica; Bangsow, Thorsten; Babbage, Jane; Taddei, Andrea; Czupalla, Cathrin J.; Reis, Marco; Felici, Angelina; Wolburg, Hartwig; Fruttiger, Marcus; Taketo, Makoto M.; von Melchner, Harald; Plate, Karl Heinz; Gerhardt, Holger; Dejana, Elisabetta

2008-01-01

The blood–brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/β-catenin (β-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of β-cat in vivo enhances barrier maturation, whereas inactivation of β-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of β-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of β-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of β-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown. PMID:18955553

Advancements in the maintenance of skin barrier/skin lipid composition and the involvement of metabolic enzymes.

PubMed

Cui, Le; Jia, Yan; Cheng, Zhi-Wei; Gao, Ying; Zhang, Gao-Lei; Li, Jing-Yi; He, Cong-Fen

2016-12-01

The human skin barrier has an important role in protection and defense, reflected not only in the ability to resist entry of harmful substances into the human body, but also in the ability to prevent loss of water and nutrients. Once the skin barrier is damaged, the skin may become dry, scaly, and wrinkled, and a series of skin problems may occur. In this article, we review the composition of lipids, such as ceramides, cholesterol, and free fatty acids, in the skin and examine the expression of enzymes related to lipid metabolism, such as kallikreins, elongase of elongation of very long-chain fatty acids, hydrolases, and lipid synthases. Additionally, we discuss the involvement of these proteins in skin barrier function and structure. The information presented in this review is expected to provide a theoretical basis for the development of skin care products facilitating the maintenance and repair of skin barrier function. © 2016 Wiley Periodicals, Inc.

Origin of hydrogen-inclusion-induced critical current deviation in Nb/AlOx/Al/Nb Josephson junctions

NASA Astrophysics Data System (ADS)

Hinode, Kenji; Satoh, Tetsuro; Nagasawa, Shuichi; Hidaka, Mutsuo

2010-04-01

We investigated the mechanisms that change the critical current density (Jc) of Nb/AlOx/Al/Nb Josephson junctions due to the inclusion of hydrogen in the Nb electrodes. Our investigations were performed according to three aspects: the superconductivity change, the change in thickness of the barrier layer, and the change in the barrier height due to the electronic effect. The results are as follows: (a) the hydrogen-inclusion-accompanied changes in the superconductivity parameters, such as the junction gap voltage, were much less than those of the critical current density, (b) the effect of hydrogen inclusion on Jc varied depending on the electrodes, i.e., the upper electrode above the barrier layer was the most affected, (c) the junctions with increased Ics due to hydrogen exclusion showed the identical amount of decrease in the junction resistance measured at room temperature, and (d) the hydrogen exclusion from the junction electrodes had no influence on the Nb/Al/AlOx/Al/Nb junctions, which had an extra Al layer. Based on these results we conclude that the Jc change is mainly caused by the change in junction resistance. A one order of magnitude smaller effect is caused by the superconductivity change. We believe the Jc change is caused by a Nb work function increase due to the hydrogen inclusion, resulting in an increase in barrier height.

The biological significance of brain barrier mechanisms: help or hindrance in drug delivery to the central nervous system?

PubMed Central

Saunders, Norman R.; Habgood, Mark D.; Møllgård, Kjeld; Dziegielewska, Katarzyna M.

2016-01-01

Barrier mechanisms in the brain are important for its normal functioning and development. Stability of the brain’s internal environment, particularly with respect to its ionic composition, is a prerequisite for the fundamental basis of its function, namely transmission of nerve impulses. In addition, the appropriate and controlled supply of a wide range of nutrients such as glucose, amino acids, monocarboxylates, and vitamins is also essential for normal development and function. These are all cellular functions across the interfaces that separate the brain from the rest of the internal environment of the body. An essential morphological component of all but one of the barriers is the presence of specialized intercellular tight junctions between the cells comprising the interface: endothelial cells in the blood-brain barrier itself, cells of the arachnoid membrane, choroid plexus epithelial cells, and tanycytes (specialized glial cells) in the circumventricular organs. In the ependyma lining the cerebral ventricles in the adult brain, the cells are joined by gap junctions, which are not restrictive for intercellular movement of molecules. But in the developing brain, the forerunners of these cells form the neuroepithelium, which restricts exchange of all but the smallest molecules between cerebrospinal fluid and brain interstitial fluid because of the presence of strap junctions between the cells. The intercellular junctions in all these interfaces are the physical basis for their barrier properties. In the blood-brain barrier proper, this is combined with a paucity of vesicular transport that is a characteristic of other vascular beds. Without such a diffusional restrain, the cellular transport mechanisms in the barrier interfaces would be ineffective. Superimposed on these physical structures are physiological mechanisms as the cells of the interfaces contain various metabolic transporters and efflux pumps, often ATP-binding cassette (ABC) transporters, that provide an important component of the barrier functions by either preventing entry of or expelling numerous molecules including toxins, drugs, and other xenobiotics. In this review, we summarize these influx and efflux mechanisms in normal developing and adult brain, as well as indicating their likely involvement in a wide range of neuropathologies. There have been extensive attempts to overcome the barrier mechanisms that prevent the entry of many drugs of therapeutic potential into the brain. We outline those that have been tried and discuss why they may so far have been largely unsuccessful. Currently, a promising approach appears to be focal, reversible disruption of the blood-brain barrier using focused ultrasound, but more work is required to evaluate the method before it can be tried in patients. Overall, our view is that much more fundamental knowledge of barrier mechanisms and development of new experimental methods will be required before drug targeting to the brain is likely to be a successful endeavor. In addition, such studies, if applied to brain pathologies such as stroke, trauma, or multiple sclerosis, will aid in defining the contribution of brain barrier pathology to these conditions, either causative or secondary. PMID:26998242

Participants' barriers to diagnostic resolution and factors associated with needing patient navigation.

PubMed

Krok-Schoen, Jessica L; Brewer, Brittany M; Young, Gregory S; Weier, Rory C; Tatum, Cathy M; DeGraffinreid, Cecilia R; Paskett, Electra D

2015-08-15

Patient navigation (PN) may improve cancer care by identifying and removing patient-reported barriers to care. In 2012, the American College of Surgeons Commission on Cancer (CoC) announced that health care facilities seeking CoC accreditation must have PN processes in place by January 1, 2015. Given these unfunded mandates, hospitals are looking for cost-effective ways to implement PN. This study examined demographic and psychosocial predictors of barriers to diagnostic resolution among individuals with a cancer screening abnormality enrolled in the Ohio Patient Navigation Research Project. Data were obtained from patients who received care at 1 of 9 Ohio Patient Navigation Research Project intervention clinics. Descriptive statistics and logistic regression models were used. There were 424 participants, and 151 (35.6%) reported a barrier to diagnostic resolution within 90 days of study consent. The most commonly reported barriers were misconceptions about a test or treatment (16.4%), difficulty in communicating with the provider (15.0%), and scheduling problems (11.5%). Univariate analyses indicated that race, education, employment, income, insurance, clinic type, friend support, and physical and psychological functioning were significantly associated with reporting a barrier to diagnostic resolution. Multivariate analyses found that comorbidities (odds ratio, 1.65; 95% confidence interval, 1.04-2.61) and higher intrusive thoughts and feelings (odds ratio, 1.25; 95% confidence interval, 1.10-1.41) were significantly associated with reporting a barrier to diagnostic resolution. The results suggest that demographic and psychosocial factors are associated with barriers to diagnostic resolution. To ensure compliance with the CoC mandate and provide timely care to all patients, CoC-accredited facilities can systematically identify the patients most likely to have barriers to care and assign them to PN. © 2015 American Cancer Society.